Search

Background: Epithelial stromal interaction 1 (EPSTI1) plays an important role in M1 macrophages, which induce osteoclastogenesis. One recent genome-wide association study (GWAS) involving 426,824 individuals has shown that EPSTI1 is strongly associated with osteoporosis (P < 5E-8). Therefore, we speculate that EPSTI1 participates in the modulation of osteoporosis through osteoclastogenesis. The roles of EPSTI1 in osteoclastogenesis and bone resorption remain unclear., Methods: Femur specimens were collected from osteoporotic patients and control patients. Immunofluorescence staining was used to detect the expression of EPSTI1 and signaling pathways. The osteoclastic potential of RAW264.7 cells with Sh-EPSTI1 lentivirus infection was tested using tartrate-resistant acid phosphatase (TRAP) staining, western blotting, and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western blotting was also used to examine signaling pathways., Results: In this study, EPSTI1 was found to be significantly increased in tartrate-resistant acid phosphatase positive (ACP5 + ) osteoclasts of bone sections from osteoporotic patients. Next, we identified EPSTI1 as a positive regulator of osteoclastogenesis and osteoclast differentiation capability. Diminished EPSTI1 expression resulted in reduced osteoclastic resorption. Mechanistically, EPSTI1-driven osteoclastogenesis was regulated by NF-κB pathway, which was mediated by the phosphorylation of protein kinase R (p-PKR). Furthermore, EPSTI1 participating in the modulation of osteoporosis via PKR/NF-κB pathway was also verified in the bone samples of osteoporotic patients., Conclusions: Collectively, our findings suggest that EPSTI1 may regulate osteoclast differentiation and bone resorption through PKR/NF-κB pathway and in vivo experiments are needed to further verify EPSTI1 as the therapy target for osteoporosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The aim of this study was to develop a long-acting transdermal patch of levamlodipine (LAM) using an ion-pair strategy to reduce the skin irritation induced by topical application of LAM and explore the mechanism underlying the improvement of skin irritation. The formulation was optimized through porcine in vitro transdermal experiments and rabbit in vivo skin irritation tests. The obtained formulation consisted of poly (2-Ethylhexyl acrylate-co-N-Vinyl-2-pyrrolidone-co-N-(2-Hydroxyethyl) acrylamide) (PENH) as the adhesive matrix, 13.00 % levamlodipine-sorbic acid ion-pair complex (LAM-SA) (w/w), and 10 % isopropyl myristate (IPM) (w/w), with a patch thickness of 70 μm, achieving an erythema index of 188 for rabbit skin and 117-187 for human skin (264 for rabbit skin and 110-260 for human skin in the absence of sorbic acid (SA)). In vivo rabbit and human skin erythema analysis and H&E staining verified that the optimized ion-pair patch effectively reduced skin irritation. Drug distribution experiments in the skin, ATR-FTIR, and molecular simulation were used to characterize the mechanism by which the ion-pair reduced skin irritation. Excessive accumulation of LAM in the epidermis induced secondary structural changes in keratin, resulting in skin barrier damage and inflammatory response. The formation of the LAM-SA ion pair altered physicochemical properties of LAM, reducing drug retention in the epidermis and, thereby, reducing skin irritation. This study demonstrated the potential of the ion-pair strategy to improve the safety of transdermal drug delivery system (TDDS) and provided a means for reducing skin irritation caused by the active pharmaceutical ingredient (API) itself., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Emotions play an important role in fostering positive parenting and healthy child development. This qualitative study explored the affective experiences of racially diverse US fathers with low income across the prenatal, postnatal, and early childhood periods. Semi-structured interviews were conducted with 24 fathers. Interview questions asked about fathers' early parenting experiences that elicit parenting emotions of different valence. Results from thematic analysis demonstrated activation of multiple emotions depending on different proximal and distal experiences. Specific to proximal experiences, fathers reported feeling both excited and anxious about pregnancy and joyful and disappointed at childbirth. Related to distal experiences, fathers reported feeling encouraged by their social support networks that further aid their parenting, but feeling marginalized given systematic barriers (e.g., societal bias, high incarceration rates of Black fathers). Most importantly, fathers' parenting emotions, especially negative ones, led to them resolving to stay involved in their children's lives, gaining a sense of responsibility, and changing behaviors to do right by their children. Fathers resorted to various coping strategies to regulate their negative emotions. Overall, fathers with low income are emotionally resilient. Infant and early childhood health professionals should support fathers' mental health to promote father-child engagement and thus, ultimately, young children's mental health and wellbeing., (© 2024 The Author(s). Infant Mental Health Journal published by Wiley Periodicals LLC on behalf of Michigan Association for Infant Mental Health.)

Aim: The current study aims to characterize the longitudinal patterns of depression subtypes and investigate the associations among the stability of depression subtypes, COVID-19-related stressors, and depression severity., Methods: The study utilized data from the Canadian Longitudinal Study on Aging, which is a national, long-term study of Canadian adults aged 45 and older (n = 12,957). Latent profile analysis was used to identify latent depression subtypes. Latent transition analysis was then applied to assess the stability of these subtypes over time. Hierarchical multivariate linear regression was used to explore the relationships among these identified depression subtypes, COVID-19-related stressors, and depression severity among males and females, respectively., Results: Distinct depression subtypes were identified. Except for atypical depression, other depression subtypes showed greater stability over time. We also found that melancholic depression (B = 9.432) and typical depression (B = 6.677) were strongly associated with depression severity during the pandemic. Health-related stressors (B = 0.840), conflict (B = 3.639), difficulties accessing resources (B = 0.927), separation from family (B = 0.840), and caregiving experience (B = 0.764), were significantly associated with increased depression severity. Sex-specific analyses also revealed differences in the associations between stressors and depression severity between males and females., Conclusions: This study contributes valuable insights into the latent clustering of depression subtypes and their stability. Stressors were associated with increased depression severity, with distinct associations observed among males and females. These findings have implications for targeted early interventions and integrated clinical management strategies by providing the evidence base for tailored mental health care during and after the pandemic., (© 2024 The Author(s). Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

To enhance the intestinal targeted release of kidney tea saponins, a simple delivery system was designed through the use of porous starch (PS), sodium alginate (ALG) and xanthan gum (XG). Porous starch was prepared by hydrolysis with a combination of α-amylase and amyloglucosidase and it was characterized by scanning electron microscopy, which revealed the formation of porous structures in the starch granules. The results of one-way optimisation illustrated that this unique delivery system achieved 79.00 ± 1.22 % of the optimal encapsulation rate. The carrier structure was subjected to analysis using Fourier transform infrared spectroscopy and X-ray diffraction. The α-glucosidase inhibition assay showed better inhibition of kidney tea saponin compared to the positive control acarbose. In addition, the effectiveness of this delivery design was confirmed via an in vitro simulated digestion method. It was showed that only a 15.57 ± 1.27 % release rate of kidney tea saponin was observed in the upper gastrointestinal tract, whereas release rates of 17.51 ± 1.29 % and 41.07 ± 0.76 % were observed for xanthan gum/sodium alginate/kidney tea saponin and sodium alginate/kidney tea saponin beads, respectively. It was concluded that the utilization of PS and a xanthan gum/sodium alginate coating represents an efficacious methodology for the development of an intestinal targeted delivery system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Prey can use several information sources (cues) to assess predation risk and avoid predation with a variety of behavioural responses (e.g., changes in activity, foraging, vigilance, social behaviour, space use, and reproductive behaviour). Direct cues produced by predators and indirect cues from environmental features or conspecific and heterospecific prey generally provide different types of information about predation risk. Despite widespread interest in understanding behavioural antipredator responses to direct and indirect cues, a clear general pattern of relative response strength across taxa and environments has yet to emerge. We conducted a meta-analysis of studies (N = 113 articles and 999 effect sizes taken from a search of over 7500 articles) testing behavioural responses to direct and indirect cues of predation risk, and their combination, across terrestrial and aquatic ecosystems. We further contrasted if effects were moderated by ecosystem type (terrestrial, marine, or freshwater), cue source (predator, conspecific, heterospecific, or environmental feature), or sensory modality (visual, auditory, or chemosensory). Overall, there were strong effects of risk cues on prey behaviour. We found that prey responded more strongly when both types of cues were presented together compared with either cue in isolation, which was driven by changes in prey activity levels but not other behaviours. There was no general pattern in response strength to direct compared with indirect cues. Responses to these cues were moderated by interactions between environment, cue source, and cue sensory modality (e.g., visual cues elicited stronger responses than other modalities, and responses to conspecific chemosensory cues were stronger than those to predator chemosensory cues in aquatic systems). These results suggest that rather than a broad framework of direct and indirect cues, the specific context of the system should be considered in tests and predictions of how prey respond to risk to elucidate general patterns of antipredator responses., (© 2024 The Author(s). Journal of Animal Ecology © 2024 British Ecological Society.)

TMEM106B is a lysosomal/late endosome protein that is a potent genetic modifier of multiple neurodegenerative diseases as well as general aging. Recently, TMEM106B was shown to form insoluble aggregates in postmortem human brain tissue, drawing attention to TMEM106B pathology and the potential role of TMEM106B aggregation in disease. In the context of neurodegenerative diseases, TMEM106B has been studied in vivo using animal models of neurodegeneration, but these studies rely on overexpression or knockdown approaches. To date, endogenous TMEM106B pathology and its relationship to known canonical pathology in animal models has not been reported. Here, we analyze histological patterns of TMEM106B in murine models of C9ORF72 -related amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD), SOD1-related ALS, and tauopathy and compare these to postmortem human tissue from patients with C9-ALS/FTD, Alzheimer's disease (AD), and AD with limbic-predominant age-related TDP-43 encephalopathy (AD/LATE). We show that there are significant differences between TMEM106B pathology in mouse models and human patient tissue. Importantly, we also identified convergent evidence from both murine models and human patients that links TMEM106B pathology to TDP-43 nuclear clearance specifically in C9-ALS. Similarly, we find a relationship at the cellular level between TMEM106B pathology and phosphorylated Tau burden in Alzheimer's disease. By characterizing endogenous TMEM106B pathology in both mice and human postmortem tissue, our work reveals considerations that must be taken into account when analyzing data from in vivo mouse studies and elucidates new insights supporting the involvement of TMEM106B in the pathogenesis and progression of multiple neurodegenerative diseases.

Background: Preoperative chemotherapy (PC) is an important component of Colorectal cancer (CRC) treatment, but its effects on the biological functions of fibroblasts and epithelial cells in CRC are unclear., Methods: This study utilized bulk, single-cell, and spatial transcriptomic sequencing data from 22 independent cohorts of CRC. Through bioinformatics analysis and in vitro experiments, the research investigated the impact of PC on fibroblast and epithelial cells in CRC. Subpopulations associated with PC and CRC prognosis were identified, and a predictive model was constructed using machine learning., Results: PC significantly attenuated the pathways related to tumor progression in fibroblasts and epithelial cells. NOTCH3 + Fibroblast (NOTCH3 + Fib), TNNT1 + Epithelial (TNNT1 + Epi), and HSPA1A + Epithelial (HSPA1A + Epi) subpopulations were identified in the adjacent spatial region and were associated with poor prognosis in CRC. PC effectively diminished the presence of these subpopulations, concurrently inhibiting pathway activity and intercellular crosstalk. A risk signature model, named the Preoperative Chemotherapy Risk Signature Model (PCRSM), was constructed using machine learning. PCRSM emerged as an independent prognostic indicator for CRC, impacting both overall survival (OS) and recurrence-free survival (RFS), surpassing the performance of 89 previously published CRC risk signatures. Additionally, patients with a high PCRSM risk score showed sensitivity to fluorouracil-based adjuvant chemotherapy (FOLFOX) but resistance to single chemotherapy drugs (such as Bevacizumab and Oxaliplatin). Furthermore, this study predicted that patients with high PCRSM were resistant to anti-PD1therapy., Conclusion: In conclusion, this study identified three cell subpopulations (NOTCH3 + Fib, TNNT1 + Epi, and HSPA1A + Epi) associated with PC, which can be targeted to improve the prognosis of CRC patients. The PCRSM model shows promise in enhancing the survival and treatment of CRC patients., Competing Interests: Declaration of competing interest All authors declare that no conflict of interest exists., (Copyright © 2024. Published by Elsevier B.V.)

Background: Stressors across the lifespan are associated with the onset of major depressive disorder (MDD) and increased severity of depressive symptoms. However, it is unclear how lifetime stressors are related to specific MDD subtypes. The present study aims to examine the relationships between MDD subtypes and stressors experienced across the lifespan while considering potential confounders., Methods: Data analyzed were from the Zone d'Épidémiologie Psychiatrique du Sud-Ouest de Montréal ( N = 1351). Lifetime stressors included childhood maltreatment, child-parent bonding, and stressful life events. Person-centered analyses were used to identify the clusters/profiles of the studied variables and multinomial logistic regression analyses were performed to examine the relationships between stressors and identified MDD subtypes. Intersectional analysis was applied to further examine how distal stressors interact with proximal stressors to impact the development of MDD subtypes., Results: There was a significant association between proximal stressors and melancholic depression, whereas severe atypical depression and moderate depression were only associated with some domains of stressful life events. Additionally, those with severe atypical depression and melancholic depression were more likely to be exposed to distal stressors such as childhood maltreatment. The combinations of distal and proximal stressors predicted a greater risk of all MDD subtypes except for moderate atypical depression., Conclusions: MDD was characterized into four subtypes based on depressive symptoms and severity. Different stressor profiles were linked with various MDD subtypes. More specific interventions and clinical management are called to provide precision treatment for MDD patients with unique stressor profiles and MDD subtypes.

Introduction and Importance: As the obesity rate continues to rise, portal vein thrombosis (PVT) has emerged as a more frequent complication following bariatric surgery, with an incidence reported at approximately 0.4 % according to recent meta-analyses. PVT, characterized by the development of a thrombus within the portal vein, can be life-threatening due to its subtle and often nonspecific symptoms, complicating timely diagnosis and treatment., Case Presentation: In this case report, we present a 45-year-old female patient with a history of morbid obesity who underwent robotic-assisted laparoscopic sleeve gastrectomy and hiatal hernia repair. On postoperative day 16, she developed symptoms of severe abdominal pain and intolerance to oral intake, suggesting the presence of portal vein thrombosis. Laboratory findings showed significantly elevated D-dimer levels, and contrast-enhanced CT imaging confirmed an extensive thrombus within the portal vein. The patient was promptly admitted to the critical care unit, where she was managed conservatively with therapeutic anticoagulation, including subcutaneous heparin preoperatively and postoperatively, and discharged with a prescription for apixaban., Clinical Discussion: Early diagnosis of PVT in the post-bariatric population is critical, as it allows for timely intervention with evidence-based therapeutic options such as anticoagulation, thereby improving both short- and long-term patient outcomes. This case not only underscores the importance of heightened vigilance for PVT in patients presenting with nonspecific abdominal symptoms after bariatric surgery but also highlights the potential risk factors unique to this patient, such as prolonged operative time and underlying comorbidities, which may have contributed to the thrombotic event. A multidisciplinary approach, involving both medical and surgical teams, is essential for optimal management of such complex cases., Conclusion: This case underscores the critical importance of early recognition and prompt management of portal vein thrombosis in post-bariatric surgery patients. By emphasizing the role of thorough perioperative DVT prophylaxis, including the use of heparin and sequential compression devices, this report not only aims to improve patient outcomes but also contributes to the growing body of knowledge on the prevention and treatment of PVT in the bariatric population. These insights may serve as a valuable framework for managing similar clinical scenarios in the future., Competing Interests: Conflict of interest statement N/A., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: We aim to explore the prevalence of coronary artery calcification (CAC) and ascending/descending thoracic aorta (AA/DA) dilation in idiopathic inflammatory myopathies (IIM) and systemic lupus erythematosus (SLE) patients, and to assess associations between cardiovascular disease (CVD) risk factors and these imaging signatures., Methods: This study recruited 151 IIM patients, 140 SLE patients, and 195 controls. The CAC and AA/DA diameters were quantified using non-gated chest CT images. The independent samples t-test or Mann-Whitney test was chosen for comparisons of continuous variables between patients and healthy controls. For categorical data, comparisons were made using the chi-square test or Fisher's exact test. Multivariate regression or Spearman's correlation analysis was employed to probe the associations between CVD risk factors and Framingham risk score (FRS) with imaging signatures., Results: The IIM and SLE patients showed significantly higher prevalence of CAC and AA/DA dilatation (P < 0.01). Age was a risk factor for both CAC and AA/DA dilatation in all cohorts (P < 0.01). In IIM patients, the AA/DA dilatation was associated with BMI (P = 0.05). In SLE patients, CAC was associated with the elevated CRP level (P = 0.05). Without CAC, both IIM and SLE patients showed significant correlations between AA/DA diameters and FRS (P < 0.01, P < 0.01). Only in SLE patients, the interleukin-6 (IL-6) level correlated with AA/DA diameters., Conclusion: The IIM and SLE patients more commonly exhibit CAC and AA/DA dilation. These subclinical atherosclerosis signs are associated with traditional CVD risk factors. For AID patients without CAC, AA/DA diameters could serve as a potential biomarker for early CVD risk. Key Points • The study characterized the manifestation of subclinical atherosclerosis imaging biomarkers (CAC, AA/DA dilation) in IIM and SLE patients. • AA/DA diameters could serve as an early imaging biomarker in clinical management for IIM and SLE patients with early-onset and no CAC present., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

In this study, high temperature thermotolerant nitrifying bacteria (TNB) and high temperature thermotolerant sulfide oxidizing bacteria (TSOB) were obtained from compost samples and inoculated into sewage sludge (SS) compost. The effects of inoculation on physical and chemical parameters, ammonia and hydrogen sulfide release, nitrogen form and sulfur compound content change and physical-chemical properties during nitrogen and sulfur conversion were studied. The results showed that inoculation of TNB and TSOB increased the temperature, pH, OM degradation, C/N ratio and germination index (GI) of compost. Compared with the control treatment (CK), the addition of inoculants reduced the release of NH 3 and H 2 S, and transformed them into nitrogen and sulfur compounds, the hydrolysis of polymeric ferrous sulfate was promoted, resulting in relatively high content of sulfite and sulfate. At the same time, the physical and chemical properties of SS have a strong correlation with nitrogen and sulfur compounds., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Vaccines represent an effective tool for controlling disease infection. As a key component of vaccines, many types of adjuvants have been developed and used today. This study is designed to investigate the efficacy of single-walled carbon nanotubes (SWCNTs) as a new adjuvant. The results showed that SWCNT could adsorb the antigen by intermolecular action, and the adsorption rate was significantly higher after dispersion of the SWCNTs in a sonic bath. The titer of specific antibody of mice in the SWCNTs group was higher than that of the mice in the antigen control group, confirming the adjuvant efficacy of SWCNTs. During immunisation, the specific antibody was detected earlier in the mice of the SWCNTs group, especially when the amount of antigen was reduced. And it was proved that the titer of antibodies was higher after subcutaneous and intraperitoneal injection compared to intramuscular injection. Most importantly, the mice immunised with SWCNTs showed almost the same level of immunity as the mice in the FCA (Freund's complete adjuvant) group, indicating that the SWCNTs were an effective adjuvant. In addition, the mice in the SWCNT group maintained antibody levels for 90 days after the last booster vaccination and showed a good state of health during the observed period. We also found that the SWCNTs were able to induce macrophages activation and enhance antigen uptake by mouse peritoneal macrophages., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Type D trichothecene toxins represent a class of macrocyclic trichothecene toxins with significant cytotoxicities towards human and crops. These toxins can also be used as anti-tumor compounds by the combination of antibody-drug conjugate. Therefore, it is urgent to investigate the biosynthetic routine of type D trichothecene toxins and explore type D trichothecene toxin-resistant genes, in order to ameliorate the hazard of trichothecene toxins and to facilitate the heterologous expression of toxin-biosynthetic cluster. In this study, tri18 gene was firstly knocked out in Paramyrothecium roridum, leading to the complete absence of type D trichothecene toxin epiroridin E, which can be restored by the complement of tri18 gene. Additionally, the knockout of tri18 gene led to a significant reduction in the pathogenicity of P. roridum towards pumpkin. Meanwhile, the enzymatic properties of Tri18 protein towards trichothecene deoxynivalenol (DON) toxin were also characterized. Moreover, tri3 and tri17KR with broad spectrum toxin-resistance function within the tri cluster were initially discovered through heterologous expression in toxin-sensitive Saccharomyces cerevisiae. And this study provides innovative type D trichothecene toxin resistant enzymes, which can provides green platform for the production of type D trichothecene toxins, thus promoting the application of these toxins in biomedical field., Competing Interests: Declaration of competing interest All the authors declare no conflict of interest for this article., (Copyright © 2024. Published by Elsevier B.V.)

Background: The pathogenesis exploration and timely intervention of hepatocellular carcinoma (HCC) are crucial due to its global impact on human health. As a general tumor biomarker, stanniocalcin 2 (STC2), its role in HCC remains unclear. We aimed to analyze the effect and mechanism of STC2 on HCC., Methods: STC2 expressions in HCC tissues and cell lines were measured. si-STC2 and oe-STC2 transfections were utilized to analyze how STC2 affected cell functions. Functional enrichment analysis of STC2 was performed by Gene Set Enrichment Analysis (GSEA). The regulatory mechanism of STC2 on HCC was investigated using 2-DG, 3-MA, IGF-1, Rap, and LY294002. The impact of STC2 on HCC progression in vivo was evaluated by the tumor formation experiment., Results: Higher levels of STC2 expression were observed in HCC tissues and cell lines. Besides, STC2 knockdown reduced proliferation, migration, and invasion, while inducing cell apoptosis. Further analysis indicated a positive correlation between STC2 and glycolysis. STC2 knockdown inhibited glycolysis progression and down-regulated the expressions of PKM2, GLUT1, and HK2 in HCC cells. However, treatment with glycolysis inhibitor (2-DG) prevented oe-STC2 from promoting the growth of HCC cells. Additionally, STC2 knockdown up-regulated the levels of LC3II/LC3I and Beclin1 and reduced the phosphorylation of PI3K, AKT, and mTOR. Treatment with 3-MA, IGF-1, Rap, and LY294002 altered the function of STC2 on proliferation and glycolysis in HCC cells. Tumor formation experiment results revealed that STC2 knockdown inhibited HCC progression., Conclusions: STC2 knockdown inhibited cell proliferation and glycolysis in HCC through the PI3K/Akt/mTOR pathway-mediated autophagy induction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Self-trapped exciton (STE) emission, typified by antimony (Sb), with broadband characteristics, represents the next generation of materials for solid-state lighting and radiation detection. However, little is known about the multiexciton behavior of the Sb emission center. Here, we proposed a general approach for designing antimony-centered multi-exciton emitting materials through self-assembly. Benefitting from controllable multiexciton behavior, dual-band white light emission spanning the entire visible spectrum was achieved. Relying on the reduction of an effective atomic number brought by self-assembly, excellent scintillation response to β-rays was attained. This study offers unprecedented insight into hybrid single/triple STE emission and unveils new avenues for single-emitter white-light emission, as well as radiographic testing using low-risk β-rays as sources., (© 2024 Wiley-VCH GmbH.)

Neonicotinoids pose significant environmental risks due to their widespread use, persistence, and challenges in elimination. This study explores the effectiveness of Fe/Mn biochar in enhancing the removal efficiency of neonicotinoids in recirculating constructed wetlands (RCWs). Results demonstrated that incorporating Fe/Mn biochar into RCWs significantly improved the removal of COD, NH 4 + -N, TN, TP, imidacloprid (IMI), and acetamiprid (ACE). However, the simultaneous presence of IMI and ACE in the RCWs hindered the elimination of NH 4 + -N, TN, and TP from wastewater. The enhanced removal of nutrients and pollutants by Fe/Mn biochar was attributed to its promotion of carbon, nitrogen, and phosphorus cycling in RCWs, along with its facilitation of the adsorption and biodegradation of IMI and ACE. Metagenomics analysis demonstrated that Fe/Mn biochar altered the structure and diversity of microbial communities in RCWs. A total of 17 biodegradation genes (BDGs) and two pesticide degradation genes (PDGs) were identified within RCWs, with Fe/Mn biochar significantly increasing the abundance of BDGs such as cytochrome P450. The potential host genera for these BDGs/PDGs were identified as Betaproteobacteria, Acidobacteria, Nitrospiraceae, Gemmatimonadetes, and Bacillus. This study offers valuable insights into how Fe/Mn biochar enhances pesticide removal and its potential application in constructed wetland systems for treating pesticide-contaminated wastewater., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. No interests to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Oral insulin delivery is considered a revolutionary alternative to daily subcutaneous injection. However, the oral bioavailability of insulin is very low due to the poor oral absorption into blood circulation. Methods: To promote penetration across the intestinal epithelium and achieve enhanced and safe glucose-responsive oral insulin delivery, pH and H 2 O 2 dual-sensitive nanoparticles (NPs) were constructed. The NPs were loaded of glucose oxidase (GOx) and insulin by pH and H 2 O 2 dual-sensitive amphiphilic polymer incorporated with phenylboronic ester-conjugated poly(2-hydroxyethyl methacrylate) and poly(carboxybetaine) (PCB). The dual-sensitive NPs were utilized for the treatment of type 1 diabetes mellitus (T1DM) after oral administration. Results: The dual-sensitive NPs could enhance the transport of insulin across the intestinal epithelium into blood facilitated by zwitterionic PCB. By virtue of the generated low pH and high H 2 O 2 with GOx in hyperglycemic environment, the pH and H 2 O 2 dual-sensitive NPs were disassembled to achieve rapid and sustained release of insulin. After oral administration of the dual-sensitive NPs in enteric capsules into T1DM mouse model, the oral bioavailability of insulin reached 20.24%, and the NPs achieved hypoglycemic effect for a few hours longer than subcutaneously injected insulin. Importantly, the pH and H 2 O 2 dual-sensitive NPs could ameliorate the local decline of pH and rise of H 2 O 2 to avoid the toxic side effect. Conclusion: Therefore, this work would provide a promising platform for the enhanced and safe treatment of diabetes mellitus., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The unique physicochemical properties and fascinating bioisosterism of tetrazole scaffolds have received significant attention in medicinal chemistry. We report recent efforts using tetrazoles in drug design strategies in this context. Despite the increasing prevalence of tetrazoles in FDA-approved drugs for various conditions such as cancer, bacterial viral and fungal infections, asthma, hypertension, Alzheimer's disease, malaria, and tuberculosis, our understanding of their structure-activity relationships, multifunctional mechanisms, binding modes, and biochemical properties remains limited. We explore the potential of tetrazole bioisosteres in optimising lead molecules for innovative therapies, discussing applications, trends, advantages, limitations, and challenges. Additionally, we assess future research directions to drive further progress in this field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Carboxy-terminal domain small phosphatase like 2 (CTDSPL2), one of the haloacid dehalogenase phosphatases, is associated with several diseases including cancer. However, the role of CTDSPL2 and its regulatory mechanism in lung cancer remain unclear. Here, we aimed to explore the clinical implications, biological functions, and molecular mechanisms of CTDSPL2 in non-small cell lung cancer (NSCLC). CTDSPL2 was identified as a novel target of the tumor suppressor miR-193a-3p. CTDSPL2 expression was significantly elevated in NSCLC tissues. Database analysis showed that CTDSPL2 expression was negatively correlated with patient survival. Depletion of CTDSPL2 inhibited the proliferation, migration, and invasion of NSCLC cells, as well as tumor growth and metastasis in mouse models. Additionally, silencing of CTDSPL2 enhanced CD4 + T cell infiltration into tumors. Moreover, CTDSPL2 interacted with JAK1 and positively regulated JAK1 expression. Subsequent experiments indicated that CTDSPL2 activated the PI3K/AKT signaling pathway through the upregulation of JAK1, thereby promoting the progression of NSCLC. In conclusion, CTDSPL2 may play an oncogenic role in NSCLC progression by activating PI3K/AKT signaling via JAK1. These findings may provide a potential target for the diagnosis and treatment of NSCLC., (© 2024. The Author(s).)

Background: Colorectal cancer (CRC) is the third most malignant tumor in the world. 5-fluorouracil (5‑FU) -based chemotherapy is the first-line chemotherapy scheme for CRC, whereas acquired drug resistance poses a huge obstacle to curing CRC patients and the mechanism is still obscure. Therefore, identification of genes associated with 5‑FU chemotherapy and seeking second-line treatment are necessary means to improve survival and prognosis of patients with CRC., Methods: The Cancer Therapeutics Response Portal (CTRP) database and Genomics of Drug Sensitivity in Cancer (GDSC) database were used to identify CRC-related genes and potential second-line therapies for 5-FU-resistant CRC. The single-cell RNA sequencing data for CRC tissues were obtained from a GEO dataset. The relationship between ITGA2 and 5-FU-resistant was investigated in vitro and in vivo models., Results: ACOX1 and ITGA2 were identified as risk biomarkers associated with 5-FU-resistance. We developed a risk signature, consisting of ACOX1 and ITGA2, that was able to distinguish well between 5-FU-resistance and 5-FU-sensitive. The single-cell sequencing data showed that ITGA2 was mainly enriched in malignant cells. ITGA2 was negatively correlated with IC50 values of most small molecule inhibitors, of which selumetinib had the highest negative correlation. Finally, knocking down ITGA2 can make 5-FU-resistant CRC cells sensitive to 5-FU and combining with selumetinib can improve the therapeutic effect of 5-FU resistant cells., Conclusion: In summary, our findings demonstrated the critical role of ITGA2 in enhancing chemotherapy resistance in CRC cells and suggested that selumetinib can restore the sensitivity of chemotherapy-resistant CRC cells to 5-FU by inhibiting ITGA2 expression., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: China has made considerable efforts to promote the development of maternal and child health (MCH) care since the new health system reform in 2009. This study aims to evaluate the trend and equity of MCH resources allocation in China from 2008 to 2020 and provide a reference for rational distribution of MCH resources., Methods: Data were collected from the China Health Statistics Yearbook and China Statistics Yearbook. The number of MCH hospitals, licensed (assistant) physicians, registered nurses and beds were selected for the measurement of the equity of MCH resources allocation. The Health Resource Agglomeration Degree and Theil index were used in evaluating MCH resource allocation equity and to compare differences among regions., Results: From 2008 to 2020, the average annual growth rates for MCH hospitals, beds, licensed (assistant) physicians, and registered nurses were 0.72%, 6.95%, 5.04%, and 9.57%, respectively. However, regional disparities in the equity of MCH resource allocation have been identified. Although the western region has shown growth in MCH resource allocation by geography, the agglomeration degree of the four indicators remains less than 1, significantly lower than the average value of greater than 2 in the eastern region. Additionally, the equity of human resource allocation in the western region is lower than the equity in the allocation of institutions. In the densely populated eastern region, the equity of MCH resource allocation by population is decreasing, with the agglomeration degree of all four indicators below 1 in 2020. The disparity in healthcare resource allocation within regions is the main cause of inequitable MCH resource allocation in China., Conclusion: The allocation of MCH resources in China has improved since 2009, however, geographic equity needs further improvement, particularly in densely populated regions. Population and geographic balances should be considered in the development and implementation of MCH resource allocation policies, and improving intraregional equity should be the focus., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Zhou et al.)

This case report presented the details of the case and outcomes of the relevant literature review to offer insights into how hyperkalemia triggers cardiac arrest and the resuscitation rate of patients with hyperkalemia. This report discusses how conditions such as hyperkalemia and necrotic bowel can lower patients' heart rate, with regard to patients' baseline cardiac condition. This report also justifies the possibility of patients experiencing cardiac arrest episodes before and after chest/abdomen surgeries., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Xu et al.)

The past decades have seen large numbers of Somali women migrate across the globe. It is critical for healthcare workers in host countries to understand healthcare needs of Somali women. The majority of Somali female migrants experience female genital cutting (FGC). The most common type in Somalia is Type 3 or infibulation, the narrowing of the vaginal introitus. Deinfibulation opens the introitus to reduce poor health outcomes and/or allow for vaginal births. In this study, we explored the perspectives of Somali women living in the United States about deinfibulation. We recruited 75 Somali women who had experienced FGC through community-based participatory research methods. Bilingual community researchers conducted qualitative interviews in Somali or English. University faculty and community-based researchers coded data together in a participatory-analysis process. We identified four themes. (1) Personal Views: participants reported positive attitudes toward deinfibulation and varied on the appropriateness of deinfibulation before marriage. (2) Benefits: identified benefits included alleviation of health problems; improved sexual health, in particular reduction or prevention of sexual pain; and reclamation of body and womanhood. (3) Barriers: these included associated stigma and lack of knowledge by providers. (4) Decision-Making: most reported that husbands, healthcare providers, and elder female community members may provide advice about if and/or when to seek deinfibulation, though some felt deinfibulation decisions are solely up to the impacted woman. An ecological framework is used to frame the findings and identify the importance of healthcare workers in assisting women who have been infibulated make decisions., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Most bacteria will use their toxins to interact with the host cell, causing damage to the cell and then escaping from it. When bacteria enter the cell, they will be transported via the endosomal pathway. Rab GTPases are involved in bacterial transport as major components of endosomes that bind to their downstream effector proteins. The bacteria manipulate some Rab GTPases, escape the cell, and get to survive. In this review, we will focus on summarizing the many processes of how bacteria manipulate Rab GTPases to control their escape., (© 2024. The Author(s), under exclusive licence to Microbiological Society of Korea.)

Fusarium head blight (FHB) is a devastating disease that occurs in warm and humid environments. The German wheat 'Centrum' has displayed moderate to high levels of FHB resistance in the field for many years. In this study, an F 6:8 recombinant inbred line (RIL) population derived from cross 'Centrum' × 'Xinong 979' was evaluated for FHB response following point inoculation in five environments. The population and parents were genotyped using the GenoBaits Wheat 16 K Panel. Stable quantitative trait loci (QTL) associated with FHB resistance in 'Centrum' were mapped on chromosome arms 2DS and 5BS. The most effective QTL, located in 2DS, was identified as a new chromosome region represented by a 1.4 Mb interval containing 17 candidate genes. Another novel QTL was mapped in chromosome arm 5BS of a 5BS to 7BS translocation chromosome. In addition, two environmentally sensitive QTL were mapped on chromosome arms 2BL from 'Centrum' and 5AS from 'Xinong 979'. Polymorphisms of flanking phenotypic variance explained (PVE) markers (allele-specific quantitative PCR [AQP]) AQP-6 for QFhb.nwafu-2DS and 16K-13073 for QFhb.nwafu-5BS were validated in a panel of 217 cultivars and breeding lines. These markers could be useful for marker-assisted selection (MAS) of FHB resistance and provide a starting point for fine mapping and marker-based cloning of the resistance genes., Competing Interests: The author(s) declare no conflict of interest.

Objectives: Given the plausible mechanisms and the lacking of empirical evidence, the study aims to investigate how gestational sleep behaviors and the development of sleep disorders, such as restless legs syndrome, influence ultrasonographic measures of fetal growth., Methods: The study included 2457 pregnant women from the NICHD Fetal Growth Studies - Singletons (2009-2013), who were recruited between 8-13 gestational weeks and followed up to five times during pregnancy. Women were categorized into six groups based on their total sleep hours and napping frequency. The trajectory of estimated fetal weight from 10-40weeks was derived from three ultrasonographic measures. Linear mixed effect models were applied to model the estimated fetal weight in relation to self-reported sleep-napping behaviors and restless legs syndrome status, adjusting for age, race and ethnicity, education, parity, prepregnancy body mass index category, infant sex, and prepregnancy sleep-napping behavior., Results: From enrollment to near delivery, pregnant women's total sleep duration and nap frequency declined and restless legs syndrome symptoms frequency increased generally. No significant differences in estimated fetal weight were observed by sleep-napping group or by restless legs syndrome status. Results remained similar in sensitivity analyses and stratified analyses by women's prepregnancy body mass index category (normal vs. overweight/obese) or by infant sex., Conclusions: Our data indicate that there is no association between sleep during pregnancy-assessed as total sleep duration and napping frequency, nor restless legs syndrome symptoms-and fetal growth from weeks 10 to 40 in healthy pregnant women., Competing Interests: Declaration of conflicts of interest None., (Copyright © 2024. Published by Elsevier Inc.)

Immune thrombocytopenic purpura (ITP) is a challenging condition to manage especially when conventional treatment methods, including splenectomy, fail. This report evaluates the effectiveness of laparoscopic removal of accessory spleen for chronic refractory ITP after an initial splenectomy. A 73-year-old African American male with a history of ITP, previously treated with laparoscopic splenectomy nine years ago, presented with severe thrombocytopenia that was found to be refractory to medical therapies. Platelet counts were monitored, and the absence of Howell-Jolly bodies was noted in the peripheral blood smear. Imaging studies over the past eight years indicated the growth of a mass in the left upper abdomen, suggesting a possible accessory spleen. Given the overwhelming evidence of a splenule in refractory thrombocytopenia, laparoscopic exploration and mass removal were conducted. Histologic analysis of the removed mass confirmed a splenule. Despite the complete removal of the mass, postoperative platelet counts remained consistently low and unresponsive to the resumption of medical therapies. This study emphasizes the limitations of accessory splenectomy for refractory ITP and highlights the need for further research to clarify the long-term effectiveness of this surgical procedure in these patients., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Meng et al.)

Background: The Chinese Society of Clinical Oncology Artificial Intelligence System (CSCO AI) serves as a clinical decision support system developed utilizing Chinese breast cancer data. Our study delved into the congruence between breast cancer treatment recommendations provided by CSCO AI and their practical application in clinical settings., Methods: A retrospective analysis encompassed 537 breast cancer patients treated at the Second Affiliated Hospital of Anhui Medical University between January 2017 and December 2022. Proficient senior oncology researchers manually input patient data into the CSCO AI system. "Consistent" and "Inconsistent" treatment categories were defined by aligning our treatment protocols with the classification system in the CSCO AI recommendations. Cases that initially showed inconsistency underwent a second evaluation by the Multi-Disciplinary Treatment (MDT) team at the hospital. Concordance was achieved when MDTs' treatment suggestions were in the 'Consistent' categories., Results: An impressive 80.4% concurrence was observed between actual treatment protocols and CSCO AI recommendations across all breast cancer patients. Notably, the alignment was markedly higher for stage I (85.02%) and stage III (88.46%) patients in contrast to stage II patients (76.06%, P=0.023). Moreover, there was a significant concordance between invasive ductal carcinoma and lobular carcinoma (88.46%). Interestingly, triple-negative breast cancer (TNBC) exhibited a high concordance rate (87.50%) compared to other molecular subtypes. When contrasting MDT-recommended treatments with CSCO AI decisions, an overall 92.4% agreement was established. Furthermore, a logistic multivariate analysis highlighted the statistical significance of age, menstrual status, tumor type, molecular subtype, tumor size, and TNM stage in influencing consistency., Conclusion: In the realm of breast cancer treatment, the alignment between recommendations offered by CSCO AI and those from MDT is predominant. CSCO AI can be a useful tool for breast cancer treatment decisions., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Xu et al.)

Roundup®, a prominent glyphosate-based herbicide (GBH), holds a significant position in the global market. However, studies of its effects on aquatic invertebrates, including molluscs are limited. Pomacea canaliculata, a large freshwater snail naturally thrives in agricultural environments where GBH is extensively employed. Our investigation involved assessing the impact of two concentrations of GBH (at concentrations of 19.98 mg/L and 59.94 mg/L, corresponding to 6 mg/L and 18 mg/L glyphosate) during a 96 h exposure experiment on the intestinal bacterial composition and metabolites of P. canaliculata. Analysis of the 16 S rRNA gene demonstrated a notable reduction in the alpha diversity of intestinal bacteria due to GBH exposure. Higher GBH concentration caused a significant shift in the relative abundance of dominant bacteria, such as Bacteroides and Paludibacter. We employed widely-targeted metabolomics analysis to analyze alterations in the hepatopancreatic metabolic profile as a consequence of GBH exposure. The shifts in metabolites primarily affected lipid, amino acid, and glucose metabolism, resulting in compromised immune and adaptive capacities in P. canaliculata. These results suggested that exposure to varying GBH concentrations perpetuates adverse effects on intestinal and hepatopancreatic health of P. canaliculata. This study provides an understanding of the negative effects of GBH on P. canaliculata and may sheds light on its potential implications for other molluscs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Qingfu Juanbi Tang (QFJBT), a novel and improved Chinese herbal formulation, has surged in recent years for its potential in the therapy of rheumatoid arthritis (RA). Anti-arthritic effects and underlying molecular mechanisms of QFJBT have increasingly become a focal point in research., Aim of the Study: This study utilized network pharmacology, molecular docking, and experimental validation to elucidate effective ingredients and anti-arthritic mechanisms of QFJBT., Materials and Methods: Targets associated with QFJBT and RA were identified from relevant databases and standardized using the Uniprot for gene nomenclature. A "QFJBT-ingredient-target network" and a "Venn diagram of QFJBT and RA targets" were created from the data. The overlap in the Venn diagram highlighted potential targets of QFJBT in the treatment of RA. These targets were subjected to PPI network, GO, and KEGG pathway analysis. The findings were subsequently confirmed through molecular docking and pharmacological experiments to propose the mechanism of action of QFJBT., Results: The study identified 236 active ingredients in QFJBT, with 120 predicted to be effective against RA. Molecular docking showed high binding affinity of key targets (JUN, PTGS2, and TNF-α) with bioactive compounds (rhein, sinomenine, calycosin, and paeoniflorin) of QFJBT. Pharmacodynamic evaluation demonstrated the effects of QFJBT at the dose of 4.56 g/kg in ameliorating symptoms of AIA rats and in reducing levels of JUN, PTGS2, and TNF-α in synovial tissues. In vitro studies further exhibited that rhein, paeoniflorin, sinomenine, calycosin, and QFJBT-containing serum significantly inhibited abnormal proliferation of RA fibroblast-like synoviocytes. Interestingly, rhein and paeoniflorin specifically decreased p-JUN/JUN expression and TNF-α release, respectively, while sinomenine and calycosin selectively increased PTGS2 expression. Consistently, QFJBT-containing serum demonstrated similar effects as those active ingredients identified in QFJBT did., Conclusions: QFJBT, QFJBT-containing serum, and its active ingredients (rhein, paeoniflorin, sinomenine, and calycosin) suppress inflammatory responses in RA. Anti-arthritic effects of QFJBT and its active ingredients are likely linked to their modulatory impact on identified hub targets., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors of this review manuscript have directly participated in the conception, design, or analysis this study, and finally have read and approved the final version submitted., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Abstract: Leukocyte immunoglobulin-like receptor (LILR) B4 (also known as ILT3/CD85k) is an immune checkpoint protein that is highly expressed in solid tumors and hematological malignancies and plays a significant role in the pathophysiology of cancer. LILRB4 is highly expressed in acute myeloid leukemia (AML), and this phenotype is associated with adverse patient outcomes. Its differential expression in tumors compared to normal tissues, its presence in tumor stem cells, and its multifaceted roles in tumorigenesis position it as a promising therapeutic target in AML. Currently, several immunotherapies targeting LILRB4 are undergoing clinical trials. This review summarizes advancements made in the study of LILRB4 in AML, focusing on its structure, ligands, expression, and significance in normal tissues and AML; its protumorigenic effects and mechanisms in AML; and the application of LILRB4-targeted therapies in AML. These insights highlight the potential advantages of LILRB4 as an immunotherapeutic target in the context of AML., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Background: Cardiovascular diseases (CVDs) are the leading age-related disorders worldwide, with their prevalence increasing annually. Cathepsins are protein-degrading enzymes essential for processes such as intracellular protein breakdown, apoptosis, and immune responses. Recent studies suggest a potential link between cathepsins and CVDs, yet the exact causal relationship remains to be elucidated. To address this, we propose using Mendelian randomization (MR) to explore the causal relationships between cathepsins and CVDs. Methods: We obtained single nucleotide polymorphism (SNP) data for cathepsins from the INTERVAL study, a publicly accessible genome-wide association study (GWAS) dataset. Outcome SNP data were sourced from seven distinct GWAS datasets, ensuring a comprehensive analysis across multiple cardiovascular outcomes. For MR analysis, we primarily employed the inverse variance weighted (IVW) method, known for its efficiency when all SNPs are valid instruments. This was supplemented by the weighted median and MR-Egger methods to provide robustness against potential violations of MR assumptions, such as pleiotropy. The IVW method offers precision and efficiency, the weighted median method adds robustness against invalid instruments, and the MR-Egger method helps identify and correct for pleiotropic biases. Cochran's Q test was utilized to assess heterogeneity, and sensitivity analyses were conducted using MR-PRESSO and the leave-one-out approach. Results: The strength of the associations between exposure and outcome was measured using odds ratios (ORs), and results were presented with 95% confidence intervals (CIs). The cathepsin E increases the risk of myocardial infarction (MI) (OR = 1.053%, 95% CI: 1.007-1.101, p = 0.024) and ischemic stroke (IS) (OR = 1.06%, 95% CI: 1.019-1.103, p = 0.004). Conversely, cathepsin L2 decreases the risk of chronic heart failure (CHF) (OR = 0.922%, 95% CI: 0.859-0.99, p = 0.025) and atrial fibrillation (AF) (OR = 0.956%, 95% CI: 0.918-0.996, p = 0.033). Cathepsin O was associated with an increased risk of IS (OR = 1.054%, 95% CI: 1.008-1.102, p = 0.021) and AF (OR = 1.058%, 95% CI: 1.02-1.098, p = 0.002). Conclusion: Our MR analysis reveals that cathepsin E is a risk factor for MI and IS, cathepsin L2 offers protective effects against CHF and AF, and cathepsin O increases the risk for IS and AF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Zhou, Xu, Gao, Lou, Chen, Zhang, Fang, Tan and Huang.)

In Brief: Abnormal glucose metabolism may be involved in the pathogenesis of endometriosis. The present study identifies that highly expressed H19 leads to increased aerobic glycolysis and histone lactylation levels in endometriosis., Abstract: Previous studies from our group and others have shown increased IncRNA H19 expression in both the eutopic endometrium and the ectopic endometriosis tissue during endometriosis. In this study, we use immunofluorescence, immunohistochemistry, and protein quantification to determine that levels of aerobic glycolysis and histone lactylation are increased in endometriosis tissues. In human endometrial stromal cells, we found that high H19 expression resulted in abnormal glucose metabolism by examining the levels of glucose, lactate, and ATP and measuring protein levels of enzymes that participate in glycolysis. At the same time, immunofluorescence and western blotting demonstrated increased histone lactylation in H19 overexpressing cells. Altering aerobic glycolysis and histone lactylation levels through the addition of sodium lactate and 2-deoxy-d-glucose demonstrated that increased aerobic glycolysis and histone lactylation levels resulted in enhanced cell proliferation and cell migration, contributing to endometriosis. To validate these findings in vivo, we constructed an endometriosis mouse model, demonstrating similar changes in endometriosis tissues in vivo. Both aerobic glycolysis and histone lactylation levels were elevated in endometriotic lesions. Taken together, these data demonstrate elevated expression levels of H19 in endometriosis patients promote abnormal glucose metabolism and elevated histone lactylation levels in vivo, enhancing cell proliferation and migration and promoting the progression of endometriosis. Our study provides a functional link between H19 expression and histone lactylation and glucose metabolism in endometriosis, providing new insights into disease mechanisms that could result in novel therapeutic approaches.

The current diagnostic criteria for depression do not sufficiently reflect its heterogeneous clinical presentations. Associations between adverse childhood experiences (ACEs), allostatic load (AL), and depression subtypes have not been extensively studied. Depression subtypes were determined based on clinical presentations, and their relationships to AL biomarkers and ACEs were elucidated in a sample of middle-aged and older adults. Participants from the Canadian Longitudinal Study on Aging who screened positive for depression were included (n = 3966). Depression subtypes, AL profiles and ACE profiles were determined with latent profile analyses, and associations between them were determined using multinomial logistic regression. Four depression subtypes were identified: positive affect, melancholic, typical, and atypical. Distinct associations between depression subtypes, stressor profiles and covariates were observed. Among the subtypes compared to positive affect, atypical subtype had the most numerous significant associations, and the subtypes had unique relationships to stressor profiles. Age, sex, smoking status, chronic conditions, marital status, and physical activity were significant covariates. The present study describes distinct associations between depression subtypes and measures of stress (objective and self-reported), as well as related factors that differentiate subtypes. The findings may inform more targeted and integrated clinical management strategies for depression in individuals exposed to multiple stressors., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Blast-related mild traumatic brain injury (blast-mTBI) can result in a spectrum of persistent symptoms leading to substantial functional impairment and reduced quality of life. Clinical evaluation and discernment from other conditions common to military service can be challenging and subject to patient recall bias and the limitations of available assessment measures. The need for objective biomarkers to facilitate accurate diagnosis, not just for symptom management and rehabilitation but for prognostication and disability compensation purposes is clear. Toward this end, we compared regional brain [ 18 F]fluorodeoxyglucose-positron emission tomography ([ 18 F]FDG-PET) intensity-scaled uptake measurements and motor, neuropsychological, and behavioral assessments in 79 combat Veterans with retrospectively recalled blast-mTBI with 41 control participants having no lifetime history of TBI. Using an agnostic and unbiased approach, we found significantly increased left pallidum [ 18 F]FDG-uptake in Veterans with blast-mTBI versus control participants, p < 0.0001; q = 3.29 × 10 -9 [Cohen's d , 1.38, 95% confidence interval (0.96, 1.79)]. The degree of left pallidum [ 18 F]FDG-uptake correlated with the number of self-reported blast-mTBIs, r 2 = 0.22; p < 0.0001. Greater [ 18 F]FDG-uptake in the left pallidum provided excellent discrimination between Veterans with blast-mTBI and controls, with a receiver operator characteristic area under the curve of 0.859 ( p < 0.0001) and likelihood ratio of 21.19 (threshold:SUVR ≥ 0.895). Deficits in executive function assessed using the Behavior Rating Inventory of Executive Function-Adult Global Executive Composite T-score were identified in Veterans with blast-mTBI compared with controls, p < 0.0001. Regression-based mediation analyses determined that in Veterans with blast-mTBI, increased [ 18 F]FDG-uptake in the left pallidum-mediated executive function impairments, adjusted causal mediation estimate p = 0.021; total effect estimate, p = 0.039. Measures of working and prospective memory (Auditory Consonant Trigrams test and Memory for Intentions Test, respectively) were negatively correlated with left pallidum [ 18 F]FDG-uptake, p < 0.0001, with mTBI as a covariate. Increased left pallidum [ 18 F]FDG-uptake in Veterans with blast-mTBI compared with controls did not covary with dominant handedness or with motor activity assessed using the Unified Parkinson's Disease Rating Scale. Localized increased [ 18 F]FDG-uptake in the left pallidum may reflect a compensatory response to functional deficits following blast-mTBI. Limited imaging resolution does not allow us to distinguish subregions of the pallidum; however, the significant correlation of our data with behavioral but not motor outcomes suggests involvement of the ventral pallidum, which is known to regulate motivation, behavior, and emotions through basal ganglia-thalamo-cortical circuits. Increased [ 18 F]FDG-uptake in the left pallidum in blast-mTBI versus control participants was consistently identified using two different PET scanners, supporting the generalizability of this finding. Although confirmation of our results by single-subject-to-cohort analyses will be required before clinical deployment, this study provides proof of concept that [ 18 F]FDG-PET bears promise as a readily available noninvasive biomarker for blast-mTBI. Further, our findings support a causative relationship between executive dysfunction and increased [ 18 F]FDG-uptake in the left pallidum.

Catalytic asymmetric dearomatization (CADA) reactions have evolved into an efficient strategy for accessing chiral polycyclic and spirocyclic scaffolds from readily available planar aromatics. Despite the significant developments, the CADA reaction of naphthalenes remains underdeveloped. Herein, we report a Gd(III)-catalyzed asymmetric dearomatization reaction of naphthalene with a chiral PyBox ligand via visible-light-enabled [4 + 2] cycloaddition. This reaction features application of a chiral Gd/PyBox complex, which regulates the reactivity and selectivity simultaneously, in excited-state catalysis. A wide range of functional groups is compatible with this protocol, giving the highly enantioenriched bridged polycycles in excellent yields (up to 96%) and selectivity (up to >20:1 chemoselectivity, >20:1 dr, >99% ee). The synthetic utility is demonstrated by a 2 mmol scale reaction, removal of directing group, and diversifications of products. Preliminary mechanistic experiments are performed to elucidate the reaction mechanism.

We leveraged the potential of high χ-low N block copolymer (BCP), namely, poly[2-(perfluorobutyl) ethyl methacrylate]- block -poly(2-vinylpyridine) (P2PFBEMA- b -P2VP), and demonstrated its utility in next-generation nanomanufacturing. By combining molecular dynamics simulations with experiments, the χ value was calculated to be as high as 0.4 (at 150 °C), surpassing similar structures. Highly ordered features suitable for application were observed, ranging in periods from 19.0 nm down to 12.1 nm, with feature sizes as small as 6 nm. Transmission electron microscopy images of the BCP solutions indicated that preformed micelles in the solution facilitated the self-assembly process of the thin film. In addition, the vertical or parallel orientation of the cylindrical structure was determined by manipulating the solvent, substrate, and annealing conditions. Finally, guided by a wide topographical template, nearly defect-free directed self-assembly (DSA) lines with a resolution of 8 nm were achieved, highlighting its potential practical application in DSA lithography technology.

Background: Physical activity was suggested to be related to sleep health, while the gardening-sleep association among the community population remained unrevealed. Therefore, this study aimed to explore whether gardening was associated with sleep complaints., Methods: A total of 62,098 adults from the 2017 Behavioral Risk Factor Surveillance System (BRFSS) were included in this study and further categorized as non-exercisers, gardeners, and other exercisers, based on their self-reported exercise status. Sleep complaints including short/prolonged sleep duration, probable insomnia, daytime sleepiness, and sleep apnea were surveyed via a questionnaire. Primary outcome was multiple sleep complaints (coexistence of ≥2 sleep complaints) and secondary outcomes referred to individual sleep complaints. The adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated to assess the associations between gardening or tertiles of gardening duration and the outcomes using multivariable logistic regression models., Results: The sample included 16,707 non-exercisers, 4243 gardeners, and 41,148 other exercisers. Relative to non-exercisers, gardeners (OR 0.58, 95%CI 0.49-0.67) and other exercisers (OR 0.67, 95%CI 0.61-0.72) had a lower likelihood of experiencing multiple sleep complaints. The adjusted OR comparing the highest gardening duration tertile to non-exercise was 0.45 (95%CI 0.33-0.63) for multiple sleep complaints (P for trend <0.001). Similar patterns persisted in several individual sleep complaints, such as short sleep duration, probable insomnia, daytime sleepiness, and sleep apnea., Limitations: Cross-sectional study design and use of self-reported variables., Conclusions: This nationwide study observed an inverse association of gardening with multiple sleep complaints and several individual sleep complaints, in a dose-response manner., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The identification and expression of germ cells are important for studying sex-related mechanisms in fish. The vasa gene, encoding an ATP-dependent RNA helicase, is recognized as a molecular marker of germ cells and plays a crucial role in germ cell development. Silurus asotus , an important freshwater economic fish species in China, shows significant sex dimorphism with the female growing faster than the male. However, the molecular mechanisms underlying these sex differences especially involving in the vasa gene in this fish remain poorly understood. In this work, the vasa gene sequence of S. asotus (named as Savasa ) was obtained through RT-PCR and rapid amplification of cDNA end (RACE), and its expression in embryos and tissues was analyzed using qRT-PCR and an in situ hybridization method. Letrozole (LT) treatment on the larvae fish was also conducted to investigate its influence on the gene. The results revealed that the open reading frame (ORF) of Savasa was 1989 bp, encoding 662 amino acids. The SaVasa protein contains 10 conserved domains unique to the DEAD-box protein family, showing the highest sequence identity of 95.92% with that of Silurus meridionalis . In embryos, Savasa is highly expressed from the two-cell stage to the blastula stage in early embryos, with a gradually decreasing trend from the gastrula stage to the heart-beating stage. Furthermore, Savasa was initially detected at the end of the cleavage furrow during the two-cell stage, later condensing into four symmetrical cell clusters with embryonic development. At the gastrula stage, Savasa -positive cells increased and began to migrate towards the dorsal side of the embryo. In tissues, Savasa is predominantly expressed in the ovaries, with almost no or lower expression in other detected tissues. Moreover, Savasa was expressed in phase I-V oocytes in the ovaries, as well as in spermatogonia and spermatocytes in the testis, implying a specific expression pattern of germ cells. In addition, LT significantly upregulated the expression of Savasa in a concentration-dependent manner during the key gonadal differentiation period of the fish. Notably, at 120 dph after LT treatment, Savasa expression was the lowest in the testis and ovary of the high concentration group. Collectively, findings from gene structure, protein sequence, phylogenetic analysis, RNA expression patterns, and response to LT suggest that Savasa is maternally inherited with conserved features, serving as a potential marker gene for germ cells in S.asotus , and might participate in LT-induced early embryonic development and gonadal development processes of the fish. This would provide a basis for further research on the application of germ cell markers and the molecular mechanisms of sex differences in S. asotus .

Sclerosing mesenteritis (SM) is a rare inflammatory disorder characterized by chronic inflammation and fibrosis of the mesenteric adipose tissue. While SM can manifest with various gastrointestinal symptoms, its association with small bowel obstruction (SBO) is infrequent. We present a case of a 78-year-old male with a history of systemic lupus erythematosus (SLE) who presented with acute abdominal pain and distention. The patient had multiple admissions with the same symptoms. A CT scan showed swirling of the proximal central mesentery, small bowel malrotation with volvulus, and high-grade mechanical obstruction of the proximal jejunum. The patient underwent exploratory laparotomy, with findings significant for multiple inflammatory nodules in the mesentery. These were causing adhesions between the bowel and mesentery, resulting in a volvulus of the bowel. One segment was resected, and subsequent histopathological examination revealed subserosal fibrosis and chronic inflammation. The clinical scenario was consistent with a diagnosis of SM. This case highlights the challenges of diagnosing and managing SBO in the presence of SM and SLE. Further research is needed to understand the underlying pathophysiological mechanisms and improve management techniques for this rare clinical condition., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Meng et al.)

Auxin response factors (ARFs), as the main components of auxin signaling, play a crucial role in various processes of plant growth and development, as well as in stress response. So far, there have been no reports on the genome-wide identification of the ARF transcription factor family in Cyclocarya paliurus , a deciduous tree plant in the family Juglaceae. In this study, a total of 34 CpARF genes were identified based on whole genome sequence, and they were unevenly distributed on 16 chromosomes, with the highest distribution on chromosome 6. Domain analysis of CpARF proteins displayed that 31 out of 34 CpARF proteins contain a typical B3 domain (DBD domain), except CpARF12/ CpARF14/CpARF31, which all belong to Class VI. And 20 CpARFs (58.8%) contain an auxin&#95;IAA binding domain, and are mainly distributed in classes I, and VI. Phylogenetic analysis showed that CpARF was divided into six classes (I-VI), each containing 4, 4, 1, 8, 4, and 13 members, respectively. Gene duplication analysis showed that there are 14 segmental duplications and zero tandem repeats were identified in the CpARF gene family of the C. paliurus genome. The Ka/Ks ratio of duplicate gene pairs indicates that CpARF genes are subjected to strong purification selection pressure. Synteny analysis showed that C. paliurus shared the highest homology in 74 ARF gene pairs with Juglans regi a, followed by 73, 51, 25, and 11 homologous gene pairs with Populus trichocarpa , Juglans cathayensis , Arabidopsis , and rice, respectively. Promoter analysis revealed that 34 CpARF genes had cis- elements related to hormones, stress, light, and growth and development except for CpARF12 . The expression profile analysis showed that almost all CpARF genes were differentially expressed in at least one tissue, and several CpARF genes displayed tissue-specific expression. Furthermore, 24 out of the 34 CpARF genes have significantly response to drought stress ( P  < 0.05), and most of them (16) being significantly down-regulated under moderate drought treatment. Meanwhile, the majority of CpARF genes (28) have significantly response to drought stress ( P  < 0.05), and most of them (26) are significantly down-regulated under severe drought treatment. Furthermore, 32 out of the 34 CpARF genes have significantly response to high, middle, and low salt stress under salt treatment ( P  < 0.05). Additionally, subcellular localization analysis confirmed that CpARF16 and CpARF32 were all localized to nucleus. Thus, our findings expand the understanding of the function of CpARF genes and provide a basis for further functional studies on CpARF genes in C. paliurus ., Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01474-1., Competing Interests: Conflict of interestThe authors declare no competing interests., (© Prof. H.S. Srivastava Foundation for Science and Society 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Ammonia in aquatic environments is toxic to fish, directly impacting their growth performance and development. Activation of autophagy can facilitate intracellular component renewal and enhance an organism's adaptability to adverse environments. Therefore, this study investigates the impact of autophagy on the yellow catfish under acute ammonia stress. In this study, the yellow catfish intraperitoneally injected with 0.9 % sodium chloride were placed with 0 (CON group) and 125 (HA group) mg/L T-AN (Total ammonia nitrogen) dechlorinated water. The yellow catfish intraperitoneally injected with 30 mg/kg fish CQ (Chloroquine, HA + CQ group) and 1.5 mg/kg fish RAPA (rapamycin, HA + RAPA group) were placed in dechlorinated water containing 125 mg/L T-AN. The results showed that activation of autophagy by injecting with RAPA can alleviate oxidative stress (catalase, superoxide dismutase, total antioxidant capacity significantly increased, H 2 O 2 content significantly decreased), and inflammatory response (pro-inflammatory factors TNF-α, MyD88, IL 1-β gene expression decreased significantly), apoptosis (baxa, Bcl2, Tgf-β, Smad2, Caspase3, Caspase 9 gene expression decreased significantly) induced by ammonia stress. In addition, activation of autophagy in yellow catfish can enhance ammonia detoxification by promoting the urea cycle and synthesis of glutamine (the mRNA level of CPS Ⅰ, ARG, OTC, ASS, ASL, and GS increased in the HA + RAPA group). The data above demonstrates that activating autophagy can alleviate oxidative stress, inflammatory responses, and cell apoptosis induced by ammonia stress. Therefore, enhancing autophagy is proposed as a potential strategy to mitigate the detrimental impacts of ammonia stress on yellow catfish., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To develop and evaluate a nomogram prediction model for recurrence of acute ischemic stroke (AIS) within one year., Method: Patients with AIS treated at the second affiliated hospital of Xuzhou Medical University from August 2017 to July 2019 were enrolled. Clinical data such as demographic data, risk factors, laboratory tests, TOAST etiological types, MRI features, and treatment methods were collected. Cox regression analysis was done to determine the parameters for entering the nomogram model. The performance of the model was estimated by receiver operating characteristic curves, decision curve analysis, calibration curves, and C-index., Result: A total of 645 patients were enrolled in this study. Side of hemisphere (SOH, Bilateral, HR = 0.35, 95 % CI = 0.15-0.84, p = 0.018), homocysteine (HCY, HR = 1.38, 95 % CI = 1.29-1.47, p < 0.001), c-reactive protein (CRP, HR = 1.04, 95 % CI = 1.01-1.07, p = 0.013) and stroke severity (SS, HR = 3.66, 95 % CI = 2.04-6.57, p < 0.001) were independent risk factors. The C-index of the nomogram model was 0.872 (se = 0.016). The area under the receiver operating characteristic (ROC)curve at one-year recurrence was 0.900. Calibration curve, decision curve analysis showed good performance of the nomogram. The cutoff value for low or high risk of recurrence score was 1.73., Conclusion: The nomogram model for stroke recurrence within one year developed in this study performed well. This useful tool can be used in clinical practice to provide important guidance to healthcare professionals., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kai Wang reports administrative support, article publishing charges, equipment, drugs, or supplies, statistical analysis, travel, and writing assistance were provided by Scientific Research Project of Jiangsu Health Committee (No.H2019054). Kai Wang reports administrative support, article publishing charges, equipment, drugs, or supplies, statistical analysis, travel, and writing assistance were provided by Xuzhou Science and Technology Planning Project (No. KC21220). Kai Wang reports administrative support, equipment, drugs, or supplies, and statistical analysis were provided by Development Fund of Affiliated Hospital of Xuzhou Medical University (No.XYFY2020013). Wenle Li reports statistical analysis was provided by Shaanxi Provincial Health and Health Research Fund Project (2022E006). Qian Zhou reports writing assistance was provided by The First batch of key Disciplines On Public Health in Chongqing. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: The volume of the implant is the most critical element of breast reconstruction, so it is necessary to accurately assess the preoperative volume of the healthy and affected breasts and select the appropriate implant for placement. Accurate and automated methods for quantitative assessment of breast volume can optimize breast reconstruction surgery and assist physicians in clinical decision making. The aim of this study was to develop an artificial intelligence model for automated segmentation of the breast and measurement of volume., Material and Methods: A total of 249 subjects undergoing breast reconstruction surgery were enrolled in this study. Subjects underwent preoperative breast MRI, and the breast region manually outlined by the imaging physician served as the gold standard for volume measurement by the automated segmentation model. In this study, we developed three automated algorithms for automatic segmentation of breast regions, including a simple alignment model, an alignment dynamic encoding model, and a deep learning model. The volumetric agreement between the three automated segmentation algorithms and the breast regions manually segmented by imaging physicians was evaluated by calculating the mean square error (MSE) and intragroup correlation coefficient (ICC), and the reproducibility of the automated segmentation of the breast regions was assessed by the test-retest step., Results: The three breast automated segmentation models developed in this study (simple registration model, dynamic programming model, and deep learning model) showed strong ICC with manual segmentation of the breast region, with MSEs of 1.124, 0.693, and 0.781, and ICCs of 0.975 (95% CI, 0.869-0.991), 0.986 (95% CI, 0.967-0.996), and 0.983 (95% CI, 0.961-0.992), respectively. Regarding the test-retest results of breast volume, the dynamic programming model performed the best with an MSE of 0.370 and an ICC of 0.993 (95% CI, 0.982-0.997), followed by the deep learning algorithm with an MSE of 0.741 and an ICC of 0.983 (95% CI, 0.956-0.993), and the simple registration algorithm with an MSE of 0.763 and an ICC of 0.982 (95% CI, 0.949-0.993). The reproducibility of the breast region segmented by the three automated algorithms was higher than that of manual segmentation by different radiologists., Conclusion: The three automated breast segmentation algorithms developed in this study generate accurate and reliable breast regions, enable highly reproducible breast region segmentation and automated volume measurements, and provide a valuable tool for surgical selection of appropriate prostheses., No Level Assigned: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Background: Heart failure (HF) is a significant health problem that is often associated with major morbidity and mortality. Metabolic abnormalities occur in HF and may be used to identify individuals at risk of developing the condition. Furthermore, these metabolic changes may play a role in the pathogenesis and progression of HF. Despite this knowledge, the utility of metabolic changes in diagnosis, management, prognosis, and therapy for patients with chronic HF has not been systematically reviewed., Objective: This scoping review aims to systematically appraise the literature on metabolic changes in patients with HF, describe the role of these changes in pathogenesis, progression, and care, and identify knowledge gaps to inform future research., Methods: This review will be conducted using a strategy based on previous reports, the JBI Manual for Evidence Synthesis, and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR) guidelines. A comprehensive search of electronic databases (Medline, EBSCOhost, Scopus, and Web of Science) will be conducted using keywords related to HF, myocardial failure, metabolomes, metabonomics, and analytical chemistry techniques. The search will include original peer-reviewed research papers (clinical studies conducted on humans and systematic reviews with or without a meta-analysis) published between January 2010 and September 2023. Studies that include patients with HF younger than 18 years or those not published in English will be excluded. Two authors (UGA and MB) will screen the titles and abstracts independently and perform a full-text screen of the relevant and eligible papers. Relevant data will be extracted and synthesized, and a third author or group will be consulted to resolve discrepancies., Results: This scoping review will span from January 2010 to September 2023, and the results will be published in a peer-reviewed, open-access journal as a scoping review in 2024. The presentation of the findings will use the PRISMA-ScR flow diagram and descriptive and narrative formats, including tables and graphical displays, to provide a comprehensive overview of the extracted data., Conclusions: This review aims to collect and analyze the available evidence on metabolic changes in patients with HF, aiming to enhance our current understanding of this topic. Additionally, this review will identify the most commonly used and suitable sample, analytical method, and specific metabolomes to facilitate standardization, reproducibility of results, and application in the diagnosis, treatment, and risk stratification of patients with HF. Finally, it is hoped that this review's outcomes will inspire further research into the metabolomes of patients with HF in low- and middle-income countries., Trial Registration: Open Science Framework; https://osf.io/sp6xj., International Registered Report Identifier (irrid): DERR1-10.2196/53905., (©Umar Gati Adamu, Marheb Badianyama, Dineo Mpanya, Muzi Maseko, Nqoba Tsabedze. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 23.05.2024.)

Hexavalent chromium [Cr(VI)] is an environmental pollutant known for its strong oxidizing and carcinogenic effects. However, its potential to induce ferroptosis in poultry remains poorly understood. This study aims to investigate the induction of ferroptosis by Cr(VI) in DF-1 cells and elucidate the underlying mechanisms. DF-1 cells exposed to Cr(VI) showed increased lipid reactive oxygen species and changes in ferroptosis marker genes (decreased expression of GPX4 and increased expression of COX2). Notably, the addition of the ferroptosis-specific inhibitor ferrostatin-1 (Fer-1) can reverse this effect. During the cell death process, Cr(VI) induced ferritinophagy, disrupting iron homeostasis and releasing labile iron ions. We predicted by docking that these iron ions would bind to mitochondrial membrane proteins through virtual docking. This binding was validated through colocalization analysis. In addition, Cr(VI) caused mitophagy, which releases additional ferrous ions. Therefore, Cr(VI) can induce the simultaneous release of ferrous ions through these pathways, thereby exacerbating lipid peroxidation and ultimately triggering ferroptosis in DF-1 cells. This study demonstrates that Cr(VI) can induce ferroptosis in DF-1 cells by disrupting intracellular iron homeostasis and providing valuable insights into the toxic effects of Cr(VI) in poultry and potentially other organisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: A greater emphasis has been placed on the part of cell cycle progression (CCP) in cancer in recent years. Nevertheless, the precise connection between CCP-related genes and bladder cancer (BCa) has remained elusive. This study endeavors to establish and validate a reliable risk model incorporating CCP-related factors, aiming to predict both the prognosis and immune landscape of BCa., Methods: Clinical information and RNA sequencing data were collected from the GEO and TCGA databases. Univariate and multivariate Cox regression analyses were conducted to construct a risk model associated with CCP. The performance of the model was assessed using ROC and Kaplan-Meier survival analyses. Functional enrichment analysis was employed to investigate potential cellular functions and signaling pathways. The immune landscape was characterized using CIBERSORT algorithms. Integration of the risk model with various clinical variables led to the development of a nomogram., Results: To build the risk model, three CCP-related genes (RAD54B, KPNA2, and TPM1) were carefully chosen. ROC and Kaplan-Meier survival analysis confirm that our model has good performance. About immunological infiltration, the high-risk group showed decreased levels of regulatory T cells and dendritic cells coupled with increased levels of activated CD4 + memory T cells, M2 macrophages, and neutrophils. Furthermore, the nomogram showed impressive predictive power for OS at 1, 3, and 5 years., Conclusion: This study provides new insights into the association between the CCP-related risk model and the prognosis of BCa, as well as its impact on the immune landscape., (© 2024. The Author(s).)

Cancer-associated fibroblasts (CAFs) play an important role in a variety of cancers. However, the role of tumor stroma in nonfunctional pancreatic neuroendocrine tumors (NF-PanNETs) is often neglected. Profiling the heterogeneity of CAFs can reveal the causes of malignant phenotypes in NF-PanNETs. Here, we found that patients with high stromal proportion had poor prognosis, especially for that with infiltrating stroma (stroma and tumor cells that presented an infiltrative growth pattern and no regular boundary). In addition, myofibroblastic CAFs (myCAFs), characterized by FAP + and α-SMA high , were spatially closer to tumor cells and promoted the EMT and tumor growth. Intriguingly, only tumor cells which were spatially closer to myCAFs underwent EMT. We further elucidated that myCAFs stimulate TGF-β expression in nearby tumor cells. Then, TGF-β promoted the EMT in adjacent tumor cells and promoted the expression of myCAFs marker genes in tumor cells, resulting in distant metastasis. Our results indicate that myCAFs cause spatial heterogeneity of EMT, which accounts for liver metastasis of NF-PanNETs. The findings of this study might provide possible targets for the prevention of liver metastasis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

One of the most important cancers in terms of worldwide prevalence is breast tumors, which have been less investigated in correlation with the enzyme Isocitrate Dehydrogenase 1 (IDH1) gene. The aim of this study was that expression of this gene could have significant effects on the progression of metastasis and invasive disease in breast cancer patients. We used the molecular method of RT-PCR with SYBR-Green to analyze breast tumor tissue from patients with metastasis and non-metastasis, the latter confirmed by the pathology department of Shohada-e Tajrish Hospital (serving as a control group). Also, patients population and its relationship with the degree of tumor in the IDH1 gene was investigated. The IDH1 gene has shown high expression in patients with metastatic breast cancer rather than in patients with non-metastatic breast cancer. The metastatic samples were compared with non-metastatic samples for IDH1 mRNA expression. In this research work, 72.5% (29 samples) were up-regulated in comparison to 27.5% of samples (11 samples) that did not exhibit high expression (P=0.000).  This study examined the IDH1 gene expression, suggesting that changes in this gene's expression could impact the prognosis of breast cancer. However, further research is needed to draw definitive conclusions.