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This study aims to explore the effects of arbuscular mycorrhizal fungi (AMF) on the growth of Iris pseudacorus L. and treatment efficacy in constructed wetlands (CWs) subjected to stress from per-and poly-fluoroalkyl substances (PFASs). The findings reveal that PFASs exposure induces oxidative damage and inhibits the growth of I. pseudacorus. However, AMF symbiosis enhances plant tolerance to PFAS stress by modulating oxidative responses. AMF treatment not only promoted plant growth but also improved photosynthetic efficiency under PFAS exposure. Compared to non-AMF treatment, those with AMF treatment exhibited significantly increased levels of peroxidases and antioxidant enzymes, including peroxidase and superoxide dismutase, along with a notable reduction in lipid peroxidation. Additionally, AM symbiosis markedly enhanced the efficacy of CWs in the remediation of wastewater under PFASs-induced stress, with removal efficiencies for COD, TP, TN, and NH 4 + -N increasing by 19-34%, 67-180%, 106-137%, and 25-95%, respectively, compared to the AMF- treatments. In addition, the metabolic pathways of PFASs appeared to be influenced by their carbon chain length, with long-chain PFASs like perfluorooctanoic acid (PFOA) and perfluoro anionic acid (PFNA) exhibiting more complex pathways compared to short-chain PFASs such as perfluoro acetic acid (PFPeA), and perfluoro hexanoic acid (PFHpA). These results suggest that AMF-plant symbiosis can enhance plant resilience against PFAS-induced stress and improve the pollutant removal efficiency of CWs. This study highlights the significant potential of AMF in enhancing environmental remediation strategies, providing new insights for the more effective management of PFAS-contaminated ecosystems., 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.)

Age-related macular degeneration (AMD) is a representative age-related ophthalmic disease, and the pathogenesis of AMD remains unclear. This research intended to determine whether epigallocatechin gallate (EGCG) could alleviate the progression of AMD and the possible mechanism. We constructed three groups of mice (young, aged, and EGCG), and HE and TUNEL staining of retinal tissues was performed to observe the structural changes in the retinal pigment epithelial (RPE) layer and the level of apoptosis, respectively. Through RNA-Sequencing analysis of retinal tissues and by RT-qPCR, GO, KEGG, and literature analyses, we identified cytoplasmic fragile X mental retardation 1-interacting protein 2 (CYFIP2) as a possible effector gene for EGCG action and validated its role by immunofluorescent and western blotting experiments. The CCK-8 and Hoechst 33342 apoptosis assays, and western blotting and qRT-PCR assays showed that EGCG reduced hydrogen peroxide (H 2 O 2 )-induced apoptosis in adult human RPE (ARPE-19) cells, and the expression of Cyfip2 was changed accordingly. RNA interference analysis indicated that Cyfip2 knockdown alleviated H 2 O 2 -induced ARPE apoptosis, while its overexpression weakened EGCG's protective effect. Western blot analysis showed that Cyfip2 mediated the anti-apoptotic effect of EGCG by modulating the level of protein kinase B (Akt) phosphorylation in ARPE cells, and the activation level of phosphorylated AKT (p-AKT Ser473) in retinal tissue of the EGCG-fed group was higher than that of the aged group. Taken together, this study suggests that EGCG plays a protective role in the development of AMD and the apoptosis of ARPE cells through the Cyfip2/AKT pathway., Competing Interests: Declaration of competing interest All authors disclosed no relevant relationships., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: Insulin icodec is a first once-weekly administration basal insulin analogue for type 2 diabetes. This study aimed to investigate the price range of icodec for type 2 diabetes in the Chinese market, taking insulin degludec as reference., Materials and Methods: Long-term health outcomes and costs for icodec and degludec were simulated using the United Kingdom Prospective Diabetes Study Outcomes Model (version 2.1) over 40 years from the Chinese healthcare provider's perspective. The efficacy and safety data were obtained from the ONWARDS 2 trial (Switching to once-weekly insulin icodec versus once-daily insulin degludec in individuals with basal insulin-treated type 2 diabetes (ONWARDS 2): a phase 3a, randomised, open label, multicentre, treat-to-target trial). Cost-utility analysis and a binary search were used to investigate the price range of icodec. Sensitivity analyses were performed to verify the robustness of the base-case analysis results., Results: After a 40-year simulation, the quality-adjusted life years (QALY) of icodec and degludec were 10.32 and 10.28 years, respectively. At the initial assumption of the same annual costs of icodec and degludec of $455.40, icodec was the dominant therapy compared with degludec, with higher QALYs and lower total cost. After the binary search, we observed that the annual cost range of icodec was $625.17-$855.25. This cost range was finally adjusted to be $597.66-$736.34 using one-way sensitivity analysis and confirmed using probabilistic sensitivity analysis and scenario analysis. The scenario analysis revealed that the annual cost range of icodec could be $506.70-$736.34 if the price of degludec decreased by 20% in the future., Conclusion: Insulin icodec appears to be more cost effective than degludec if the annual cost of icodec ranges from $597.66 to $736.34 for patients with type 2 diabetes in China., (© 2024 John Wiley & Sons Ltd.)

Backgrounds: The role of miR-191-5p in cerebral ischemia-reperfusion (I/R) injury has been established, with its expression in endothelial cells demonstrating anti-angiogenic effects. A potential circular RNA, circRNA_0003307, has been identified through bioinformatics analysis as a candidate for interaction with miR-191-5p, yet its functional significance in brain I/R injury remains unexplored. We aimed to investigate whether circRNA_0003307 regulates brain microvascular endothelial cell (BMEC) vascular tube formation, invasion, and migration by regulating the miR-191-5p cascade., Methods: Mouse BMECs (bEnd.3) were culturedand exposed to oxygen-glucose deprivation (OGD). The effects of circRNA_0003307 on vessel-like tube formation and cellular migration were examined. In addition, we investigated the protective effects of circRNA_0003307 on I/R injury in mice., Results: The results showed the level of circRNA_0003307 was concentration-dependently increased in OGD-induced bEnd.3 cells. ODG-induction enhanced angiogenesis, migration, and invasion of bEnd.3 cells, which were further promoted by the transfection of pcDNA-0003307. Silencing circRNA_0003307 expression showed the opposite results. The dual luciferase assay demonstrated miRNA-191-5p interacted with circRNA_00033073' UTR, and miRNA-191-5p could bind with CDK6. Meanwhile, circRNA_0003307 promoted the expression of CDK6 by sponging miRNA-191-5p. The overexpression of circRNA_0003307 activated the angiogenesis, migration, and invasion of OGD-induced bEnd.3 cells, which were hindered by miRNA-191-5p mimic or siRNA-CDK6. Thus, circRNA_0003307 promoted ODG-induced angiogenesis, migration, and invasion of bEnd.3 cells by targeting miR-191-5p/CDK6 axis. In vivo, circRNA_0003307 had protective effects on brain I/R injury, including neuroprotection, anti-apoptosis and angiogenesis., Conclusion: CircRNA_0003307 may be a promisingtherapeutictarget forthe treatment of cerebral I/R injury., 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 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)

Introduction: Stiff person syndrome (SPS) is a rare disease characterized by axial and lower-extremity muscle rigidity, muscle spasm, and pain. Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a variant of SPS. This case is particularly notable for its uncommon initial symptom: orthostatic hypotension, coupled with the presence of multiple antibodies. Such a presentation is a rarity in the context of PERM, thus providing a fresh and unique angle for both diagnosis and treatment., Case Presentation: This case presents a 71-year-old man who was ultimately diagnosed with progressive encephalomyelitis with rigidity and myoclonus (PERM). His initial symptom was orthostatic hypotension, and we detected multiple antibodies such as GlyR antibody, GAD antibody, GM1-IgG and GQ1b-IgG in his serum. The patient showed partial response to glucocorticoid and immunoglobulin therapies, but as the disease recurred and progressed, plasma exchange, rituximab, and cyclophosphamide immunosuppressive therapy was administered, the prognosis remained poor. During follow-up after treatment, the patient developed pulmonary embolism and cardiac arrest, and died., Conclusion: PERM exhibits diverse manifestation and pathogenic mechanisms. Immune heterogeneity affects clinical symptoms and prognosis. Cases of PERM combined with orthostatic hypotension and various antibodies have rarely been reported, the incidence and the specific mechanism is unknown, underscoring the need for further research. This case report underscores the importance of recognizing the diverse clinical presentations of PERM and the challenges in its diagnosis and management. It highlights autonomic dysfunction may be as the initial symptom of PERM. Moreover, it emphasizes the limitations of current treatment modalities and the necessity for further research to elucidate the underlying mechanisms and optimize therapeutic approaches for this debilitating autoimmune condition., (© 2024. The Author(s).)

Anxiety disorders are one of the most epidemic and chronic psychiatric disorders. An incomplete understanding of anxiety pathophysiology has limited the development of highly effective drugs against these disorders. GPR17 has been shown to be involved in multiple sclerosis and some acute brain injury disorders. However, no study has investigated the role of GPR17 in psychiatric disorders. In a well-established chronic restraint stress (CRS) mouse model, using a combination of pharmacological and molecular biology techniques, viral tracing, in vitro electrophysiology recordings, in vivo fiber photometry, chemogenetic manipulations and behavioral tests, we demonstrated that CRS induced anxiety-like behaviors and increased the expression of GPR17 in basolateral amygdala (BLA) glutamatergic neurons. Inhibition of GPR17 by cangrelor or knockdown of GPR17 by adeno-associated virus in BLA glutamatergic neurons effectively improved anxiety-like behaviors. Overexpression of GPR17 in BLA glutamatergic neurons increased the susceptibility to anxiety-like behaviors. What's more, BLA glutamatergic neuronal activity was required for anxiolytic-like effects of GPR17 antagonist and GPR17 modulated anxiety-like behaviors via BLA to ventral hippocampal CA1 glutamatergic projection. Our study finds for the first and highlights the new role of GPR17 in regulating anxiety-like behaviors and it might be a novel potential target for therapy of anxiety disorders., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors.)

To inhibit the growth and metastasis of triple-negative breast cancer (TNBC), two Fe(III) thiosemicarbazone complexes (Fe1 and Fe2) were designed and synthesized. The structures of the Fe(III) complexes were characterized by single crystal X-ray diffraction. The antiproliferative activity of Fe1 and Fe2 against four cancer lines (MDA-MB-231, T98G, HepG2, 143B) and human renal proximal tubular epithelial cell line (HK-2) was evaluated by MTT assay. Among all cells, Fe2 showed significant cytotoxicity to TNBC cells (MDA-MB-231), with an IC 50 value of 12.38 μM. Furthermore, Fe2 showed less toxicity to HK-2 cells. The two Fe(III) complexes can produce excess of reactive oxygen species, decrease of mitochondrial membrane potential, and induce DNA damage, then lead to apoptosis of MDA-MB-231 cells. In addition, Fe1 and Fe2 can also inhibit migration and invasion of MDA-MB-231 cells. This study provides guidance for the development of metal complexes that inhibit the growth and metastasis of TNBC., (© 2024 Wiley Periodicals LLC.)

Identifying infected stones is crucial due to their rapid growth and high recurrence rate. Here, the calcium-magnesium dual-responsive aggregation-induced emission (AIE)-active probe TCM-5COOH (Tricyano-methlene-pyridine-5COOH), distinctively engineered to distinguish high-threat infection calculi from metabolic stones, is presented. Upon incorporation of flexible alkyl carboxyl group, TCM-5COOH featuring five carboxyl moieties demonstrates excellent water solubility and enhanced penetration into porous infectious stones. The robust chelation of TCM-5COOH with stone surface-abundant Ca 2+ and Mg 2+ inhibits vibrational relaxation, thus triggering intense AIE signals. Remarkably, the resulting complex exhibits high insolubility, effectively anchoring within the porous structure of the infection calculi and offering prolonged illumination. Jobs' plot method reveals similar response characteristics for Ca 2+ and Mg 2+ , with a 1:2 coordination number for both ions. Isothermal titration calorimetry (ITC) results demonstrate higher enthalpy change (ΔH) and lower entropy change (ΔS) for the reaction, indicating enhanced selectivity compared to TCM-4COOH lacking the alkyl carboxyl group. Synchrotron X-ray absorption fine spectroscopy (XAFS) validates TCM-5COOH's interaction with Ca 2+ and Mg 2+ at the microlevel. This dual-responsive probe excels in identifying infectious and metabolic calculi, compatible with endoscopic modalities and laser excitation, thereby prompting clinical visualization and diagnostic assessment., (© 2024 Wiley‐VCH GmbH.)

Gray mold caused by Botrytis elliptica is one of the most determinative factors of lily growth and has become a major threat to lily productivity. However, the nature of the lily B. elliptica interaction remains largely unknown. Here, comparative transcriptomic and metabolomic were used to investigate the defense responses of resistant ('Sorbonne') and susceptible ('Tresor') lily cultivars to B. elliptica infection at 24 hpi. In total, 1326 metabolites were identified in 'Sorbonne' and 'Tresor' after infection, including a large number of phenylpropanoids. Specifically, the accumulation of four phenylpropanes, including eriodictyol, hesperetin, ferulic acid, and sinapyl alcohol, was significantly upregulated in the B. elliptica -infected 'Sorbonne' compared with the infected 'Tresor', and these phenylpropanes could significantly inhibit B. elliptica growth. At the transcript level, higher expression levels of F3'M , COMT , and CAD led to a higher content of resistance-related phenylpropanes (eriodictyol, ferulic acid, and sinapyl alcohol) in 'Sorbonne' following B. elliptica infection. It can be assumed that these phenylpropanes cause the resistance difference between 'Sorbonne' and 'Tresor', and could be the potential marker metabolites for gray mold resistance in the lily. Further transcriptional regulatory network analysis suggested that members of the AP2/ERF, WRKY, Trihelix, and MADS-M-type families positively regulated the biosynthesis of resistance-related phenylpropanes. Additionally, the expression patterns of genes involved in phenylpropanoid biosynthesis were confirmed using qRT-PCR. Therefore, we speculate that the degree of gray mold resistance in the lily is closely related to the contents of phenylpropanes and the transcript levels of the genes in the phenylpropanoid biosynthesis pathway. Our results not only improve our understanding of the lily's resistance mechanisms against B. elliptica , but also facilitate the genetic improvement of lily cultivars with gray mold resistance.

Background: The relationship between non-alcoholic fatty liver disease (NAFLD) and cholelithiasis is intricate, with alterations in the microenvironment potentially mediating this interplay. Thus, this study aimed to explore the biliary microbiota and metabolites of patients with cholelithiasis and detect changes induced by comorbid NAFLD., Methods: In this study, 16S rRNA gene sequencing and metabolome analysis were performed on biliary samples collected from 35 subjects. Then, patients were stratified into two groups: the comorbidity group (n = 18), consisting of cholelithiasis patients with NAFLD, and the non-comorbidity group (n = 17), comprising cholelithiasis patients without NAFLD., Results: Comorbid NAFLD did not significantly increase α-diversity but affected β-diversity. A statistically significant difference was observed in the abundance of biliary metabolites between the two groups. Specifically, differences in the abundance of 4 phyla, 19 genera, and 28 metabolites were significant between the two groups. Correlation analysis demonstrated positive associations among 12α-hydroxylated bile acid levels, Pyramidobacter and Fusobacterium abundance, AST levels, and the fibrosis-4 index (p < 0.05, r > 0.3), all of which were increased in patients with cholelithiasis and comorbid NAFLD., Conclusions: The relationship between cholelithiasis and NAFLD influences the biliary microbial and metabolic profile, creating a detrimental microenvironment that promotes the disease progression., 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 Masson SAS.)

The gut microbiota plays a key role in the brain function impairment caused by chronic stress, yet its exact mechanism remains unclear. Many studies have revealed the important role of miR-124 in the central nervous system. Meanwhile, previous studies have indicated that miR-124 may be regulated by chronic stress and gut microbiota. Here, we aimed to explore whether miR-124 serves as a mediator for the impacts of gut microbial dysbiosis on brain function in mice subjected to chronic stress. Repeated daily restraint stress for 4 weeks was used to induce chronic stress in mice. Chronic stress resulted in gut microbial dysbiosis, abnormal behaviors, and a decrease in hippocampal miR-124 levels. Treatment with different probiotic mixtures significantly alleviated the effects of chronic stress on hippocampal miR-124 levels and mouse behaviors. Suppression of hippocampal miR-124 expression reversed the beneficial effects of probiotics on cognitive function, neurogenesis, and related molecular markers in chronically stressed mice. Bioinformatics analysis and qPCR suggested that Ptpn11 might be a target gene for miR-124 in mediating the effects of gut microbial dysbiosis on brain function in these mice. These findings suggest that miR-124 is a pivotal regulator that mediates the detrimental effects of gut microbial dysbiosis on brain function and the subsequent cognitive impairment during chronic stress., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Patients with glioblastoma (GBM) have a poor prognosis and limited treatment options. The mRNA decapping enzyme scavenger (DCPS) is a cap-hydrolyzing enzyme. The DCPS inhibitor RG3039 exhibited excellent central nervous system bioavailability in vivo and was safe and well tolerated in healthy volunteers in a phase 1 clinical trial. In this study, we investigated the expression of DCPS in GBM and the anti-tumor activity of RG3039 in various preclinical models of GBM., Methods: DCPS expression was examined in human GBM and paired peritumoral tissues. Its prognostic role was evaluated together with clinicopathological characteristics of patients. The anti-GBM effect of RG3039 was determined using GBM cell lines, patient-derived organoids, and orthotopic mouse models. The therapeutic mechanisms of DCPS inhibition were explored., Results: DCPS is overexpressed in GBM and is associated with poor survival of patients with GBM. The DCPS inhibitor RG3039 exhibited robust anti-GBM activities in GBM cell lines, patient-derived organoids and orthotopic mouse models, with drug exposure achievable in humans. Mechanistically, RG3039 downregulated STAT5B expression, thereby suppressing proliferation, survival and colony formation of GBM cells., Conclusions: DCPS is a promising target for GBM. Inhibition of DCPS with RG3039 at doses achievable in humans downregulates STAT5B expression and reduces proliferation, survival and colony formation of GBM cells. Given the excellent anti-cancer activity and central nervous system bioavailability in vivo and good tolerance in humans, RG3039 warrants further study as a potential GBM therapy., (© 2024. The Author(s).)

Aim: To assess the real-world impact of glucose-lowering drugs (GLDs) as an adjunct to insulin in Chinese patients with type 1 diabetes (T1DM)., Methods: This dual-center, observational, retrospective study included 121 T1DM patients receiving GLDs as adjuncts and 56 participants with insulin-only drugs as comparators. Glycated hemoglobin A1c (HbA1c), daily insulin dosage, fasting blood glucose (FBG), postprandial blood glucose (PBG), nocturnal blood glucose (NBG) and the difference in trough and peak blood glucose levels on the same day (Δ TP) were assessed at baseline and at the end of the study., Results: In total, HbA1c decreased by 1.14% in the GLD+insulin group (p < 0.0001) and 0.36% in the insulin-only group (p = 0.0423, mean adjusted difference, -0.09% [95% CI, -0.55 to 0.37]). The total daily insulin concentration was reduced by 7.34 U per day in the GLD+insulin group vs. 5.55 U per day in the insulin-only group (mean adjusted difference, -2.32 U [95% CI, -4.97 to 0.33]). In particular, among patients with fasting C-peptide levels < 17 pmol/L, the total daily insulin concentration was significantly reduced by 9.22 U vs. 5.09 U per day (mean adjusted difference, -3.84 [95% CI, -6.85-0.84]; p = 0.0129). There were no notable differences in the other glycemic indices between the two groups. A gradual downward trend in changes in glycemic outcomes was observed among patients treated with various combinations of metformin, acarbose, and dipeptidyl peptidase 4 inhibitor (DPP-4i). Similar reductions in the daily insulin dose were also detected in most of the GLD+insulin group in addition to the DPP-4i-only group. No severe hypoglycemia was induced by additional GLDs., Conclusions: The use of additional GLDs tends to improve glycemic outcomes and reduce insulin requirements in patients with T1DM. These results indicate that the use of GLDs as an adjunctive therapy may have been an effective treatment strategy among adults with T1DM in China., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Metal-organic frameworks (MOFs), as porous materials, have great potential for exploring high-performance electrochemiluminescence (ECL) probes. However, the constrained applicability of MOFs in the realm of ECL biosensing is primarily attributed to their inadequate water stability, which consequently impairs the overall ECL efficiency. Herein, we developed a competitive ECL biosensor based on a novel tightest structural ruthenium-based organic framework emitter combining the proximity hybridization-induced catalytic hairpin assembly (CHA) strategy and the quenching effect between the Ru-MOF and ferrocene for detecting paraquat (PQ). Through a simple hydrothermal synthesis strategy, ruthenium and 2,2'-bipyrimidine (bpm) are head-to-head self-assembled to obtain a novel tightest structural Ru-MOF. Due to the metal-ligand charge-transfer (MLCT) effect between ruthenium and the bpm ligand and the connectivity between the internal chromophore units, the Ru-MOF exhibits strong ECL emissions. Meanwhile, the coordination-driven Ru-MOF utilizes strong metal-organic coordination bonds as building blocks, which effectively solves the problem of serious leakage of chromophores caused by water solubility. The sensitive analysis of PQ is realized in the range of 1 pg/mL to 1 ng/mL with a detection limit of 0.352 pg/mL. The tightest structural Ru-MOF driven by the coordination of ruthenium and bridging ligands (2,2'-bipyrimidine, bpm) provides new horizons for exploring high-performance MOF-based ECL probes for quantitative analysis of biomarkers., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Exosomes play a crucial role in regulating crosstalk between tumor and tumor stem-like cells through their cargo molecules. Circular RNAs (circRNAs) have recently been demonstrated to be critical factors in tumorigenesis. This study focuses on the molecular mechanism by which circRNAs from glioma stem-like cell (GSLC) exosomes regulate glioblastoma (GBM) tumorigenicity. In this study, we validated that GSLC exosomes accelerated the malignant phenotype of GBM. Subsequently, we found that circZNF800 was highly expressed in GSLC exosomes and was negatively associated with GBM patients. CircZNF800 promoted GBM cell proliferation and migration and inhibited GBM cell apoptosis in vitro. Silencing circZNF800 could improve the GBM xenograft model survival rate. Mechanistic studies revealed that circZNF800 activated the PIEZO1/Akt signaling pathway by sponging miR-139-5p. CircZNF800 derived from GSLC exosomes promoted GBM cell tumorigenicity and predicted poor prognosis in GBM patients. CircZNF800 has the potential to serve as a promising target for further therapeutic exploration., (© 2024. The Author(s).)

The pancreatic tumor microenvironment presents multiple obstacles for polymer-based drug delivery systems, limiting tumor penetration and treatment efficacy. Here, we engineer a hyaluronidase/reactive oxygen species cascade-responsive size/charge bidirectional-tunable nanodelivery (btND, G/R@TKP/HA) for co-delivery of gemcitabine and KRAS siRNA, capable of navigating through tumor barriers and augmenting anticancer efficiency. When penetrating the tumor stroma barrier, the hyaluronic acid shell of the nanodelivery undergoes degradation by hyaluronidase in an extracellular matrix, triggering size tuning from large to small and charge tuning from negative to positive, thereby facilitating deeper penetration and cellular internalization. After endocytosis, the nanodelivery protonizes in the endo/lysosome, prompting rapid endo/lysosomal escape, effectively overcoming the lysosome barrier. Intracellular ROS further disrupt the nanodelivery, inducing its size tuning again from small to large and a positive charge decrease for high tumor retention and controlled drug release. The btND shows remarkable antitumor activity in pancreatic cancer mouse models, highlighting the efficacy of this approach in penetrating tumor barriers and enhancing anticancer outcomes., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Objective: To explore the impact of intergenerational connections on cognitive function in middle-aged and older adults (45-60 years and over 60 years, respectively) and analyze the urban-rural and sex differences in the effects of intergenerational connections on cognitive function., Method: Based on China Health and Retirement Longitudinal Study data (CHARLS), this study conducted ID matching for four waves of data from 2011, 2013, 2015, and 2018. Cognitive function was measured via Telephone Interview for Cognitive Status-modified (TICS-m), word recall, and imitation drawing. Using a combination of cross-sectional and longitudinal research, we constructed the cross-lagged panel model (CLPM) with a sample of 1,480 participants to explore the relationship between intergenerational connections and cognitive function., Results: This study examines the impact of intergenerational connections on cognitive function in middle-aged (45-60 years) and older adults (over 60 years) using data from the CHARLS. It identifies urban-rural and sex differences, with notable effects among rural female participants. The frequency of meeting with one child negatively predicts cognitive function ( β  = -0.040, p  = 0.041), and the frequency of communication with one child positively predicts cognitive function ( β  = 0.102, 0.068, 0.041, p  < 0.001, p  = 0.001, 0.045). Meanwhile, intergenerational connections with multiple children positively predicts cognitive function ( β  = 0.044, p  = 0.031), ( β  = 0.128, 0.084, and 0.056, p  < 0.001, 0.001, p  = 0.008). There are urban-rural and sex differences in the effects of intergenerational connections on cognitive function; additionally, the effects of intergenerational connections on cognitive function are significant in rural female middle-aged and older adults., Discussion: This study proposes the theory of skewed intergenerational support, which suggests that as middle-aged and older adults age, the responsibility for intergenerational support is skewed toward one child. This leads to conflicts between middle-aged and older parents and the child, which further affects cognitive function. In addition, this study put forward the boat-carrying theory of intergenerational relations and "to hold a bowl of water level" is the art of dealing with intergenerational relationships., 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 Hu, Ge, Fang and Yang.)

Silver nanoparticles (AgNPs) are commonly utilized in the medical sector, particularly in cardiovascular applications. Nevertheless, there is a studies scarcity examining the impact of AgNPs on myocardial infarction protection. A green formulation of AgNPs was documented in the research. Different spectroscopic methods were utilized to examine the AgNPs, and their potential for treating myocardial infarction was explored. The NPs exhibited a spherical morphology upon formation. Isoproterenol (85 mg/kg) was administered to induce myocardial infarction in mice. The mice were categorized into four distinct groups (n = 15): (1) untreated; (2) normal; (3,4) AgNPs + isoproterenol at various doses (5 and 50 µg/kg). The activation of PPAR-Υ/NF-κB and subsequent cytokine release induced by lipopolysaccharide were quantified using real-time PCR and western blot techniques. Subsequent to the administration of AgNPs at different doses, the evaluation of cardiac function was conducted through biochemical, histochemical, and electrocardiogram (ECG) analysis. AgNPs significantly inhibit the levels of myocardial injury markers, reduce the incidence of mortality, and improve the condition of ventricular wall infarction. In addition, the administration of AgNPs effectively prevents the characteristic ST segment depression when compared to animals with myocardial infarction. The positive effects of AgNPs could potentially be attributed to the restoration of normal gene expression in PPAR-Υ/NF-κB/ΙκB-α/ΙΚΚα/β and PPAR-Υ phosphorylation pathways. Additionally, the application of AgNPs led to a reduction in the levels of pro-inflammatory cytokines in the hearts of mice suffering from myocardial infarction. The expression suppression of inflammation cytokines and cell death was significantly reduced by AgNPs. Recent findings suggest that AgNPs possess cardioprotective properties on isoproterenol-induced myocardial infarction, possibly by the inhibition of NF-κB signaling and activation of PPAR-γ. To summarize, the present study introduces a contemporary therapeutic approach for treating myocardial infarction in clinical settings., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A three-partition distributed force platform (3P-DFP) is proposed to measure the plantar pressure distribution, and foot support characteristics are evaluated with the obtained pressure distribution information. Twenty-seven young adults and 40 elderly adults were randomly recruited to perform the test in three phases: double-leg stance with eyes closed, double-leg stance with eyes opened, and single-leg stance with eyes opened. The evaluation parameters of foot support surface characteristics and support point characteristics were calculated based on the average position information of the center of pressure in the lateral of sole, media of sole, posterior of heel, and entire pelma. The results showed that the support width of the foot sole was significantly greater in the elderly group (p <0.01), but the overall support area showed a decreasing trend. The CoP excursion in the media-lateral direction was significantly higher in the elderly group from double-leg stance to single-leg stance (p <0.01). The CoP trajectory in the elderly group tends to shift in a medial direction with increasing age or postural difficulty., 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.)

Aim: To investigate the most matchable price of tirzepatide (TIRZ) compared with semaglutide (SEMA) in the treatment of type 2 diabetes in China., Methods: The patient cohort and clinical efficacy data were derived from the SURPASS-2 trial. Cost-utility analysis and a binary search were performed to identify the most matchable price of TIRZ from a Chinese healthcare provider's perspective., Results: After lifetime simulation, the quality-adjusted life years of TIRZ 5, 10, 15 mg and SEMA 1 mg were 11.17, 11.21, 11.27 and 11.12 years, respectively. Despite an initial assumption that the annual cost of TIRZ equals that of SEMA, our analysis revealed that TIRZ is probably more cost-effective than SEMA. A thorough evaluation of pricing showed that the cost ranges for TIRZ at doses of 5, 10 and 15 mg were $1628.61-$1846.23, $1738.40-$2140.95 and $1800.30-$2430.81, respectively. After adjustment in the univariate sensitivity analysis, the cost ranges for TIRZ 5, 10 and 15 mg were $1542.68-$1757.57, $1573.00-$1967.16 and $1576.54-$2133.96, respectively. These cost intervals were validated through robust probabilistic sensitivity analysis and scenario analysis, except for the cost range for TIRZ 5 mg., Conclusions: This study shows that, using SEMA as a reference, the annual costs for TIRZ 10 and 15 mg are $1573.00-$1967.16 and $1576.54-$2133.96, respectively, for patients with type 2 diabetes in China., (© 2024 John Wiley & Sons Ltd.)

Introduction: Studies have shown that microplastics (MPs) and nanoplastics (NPs) could accumulate in the human body and pose a potential threat to human health. The purpose of this study is to evaluate the biodistribution and toxicity of MPs/NPs with different particle sizes comprehensively and thoroughly., Methods: The purpose of this study was to investigate the biodistribution and in vivo toxicity of polystyrene (PS) MPs/NPs with different sizes (50 nm, 100 nm, and 500 nm). The BALB/c mice were given 100 μL of PS50, PS100 and PS500 at the dosage of 1 mg/kg BW or 10 mg/kg BW, respectively, by gavage once a day. After 28 consecutive days of treatment, the biodistribution of differently sized PS MPs/NPs was determined through cryosection fluorescence microscopy and fluorescent microplate reader analysis, and the subsequent effects of differently sized PS MPs/NPs on histopathology, hematology and blood biochemistry were also evaluated., Results: The results showed that the three different sizes of PS MPs/NPs were distributed in the organs of mice, mainly in the liver, spleen, and intestine. At the same time, the smaller the particle size, the more they accumulate in the body and more easily penetrate the tissue. During the whole observation period, no abnormal behavior and weight change were observed. The results of H&E staining showed that no severe histopathological abnormalities were observed in the main organs in the low-dose exposure group, while. Exposure of three sizes of PS MPs/NPs could cause some changes in hematological parameters or biochemical parameters related to heart, liver, and kidney function; meanwhile, there were size- and dose-dependencies., Conclusion: The biological distribution and toxicity of plastic particles in mice were more obvious with the decrease of particle size and the increase of concentration of plastic particles. Compared with MPs, NPs were easier to enter the tissues and produce changes in liver, kidney, and heart functions. Therefore, more attention should be paid to the toxicity of NPs., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Du et al.)

Diabetes mellitus is a common chronic metabolic disease characterized by a high incidence and disability rate. Intestinal flora refers to the microbial community that lives in the intestines and plays a crucial role in maintaining intestinal health and the human immune system. In recent years, an increasing body of research has revealed a close relationship between intestinal flora and diabetes. The pathophysiological mechanisms between them have also been constantly uncovered, and the regulation of intestinal flora has shown promising efficacy in the adjuvant treatment of diabetes. This study mainly summarized the characteristics and mechanisms of intestinal flora in patients with diabetes in recent years, as well as the methods of regulating intestinal flora to prevent and treat diabetes, and prospected the future research direction. This will offer a theoretical basis for the clinical adjuvant treatment of diabetes with intestinal flora and the development of new drugs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cerebral infarction is a common neurological disease with high rates of morbidity, mortality, and recurrence, posing a great threat to human life and health. Cerebral infarction is the second leading cause of death in the world and the leading cause of long-term disability in humans. The results of the third national retrospective sampling survey on causes of death in 2008 showed that cerebral infarction has become the leading cause of death in China and its mortality rate is 4-5 times that of European and American countries. Therefore, this article proposed a study on the predictive value of Cmmi-MHR combined with thromboelastography parameters that was performed for acute cerebral infarction. This paper mainly proposed a high frame rate imaging technology and analyzed its algorithm. In this article, in the experimental part, an in-depth analysis of the predictive value of the Monocyte-to-high-density lipoprotein cholesterol ratio (MHR) combined with thromboelastography parameters was performed for acute cerebral infarction. The final experimental results showed that HDL (OR = 1.695%, P-trend = 0.049) had a probability of death within 90 days of hospitalization (OR = 0.81, 95% CI = 1.06-3.11, P-trend = 0.523). There were no significant differences in mortality rate after 90 days. Regardless of adjusting for confounders such as age, gender, and NIHSS score, there was no significant difference in the risk of MHR or monocyte count within 90 days of hospitalization. The conclusion indicates that the combination of Cmmi-MHR and thromboelastography parameters provides a new perspective and method for the diagnosis and treatment of cerebral infarction, and provides important support for personalized treatment and management of cerebral infarction., (© 2024. The Author(s).)

Objectives: Soccer heading is adversely associated with neurocognitive performance, but whether greater neck strength or anthropometrics mitigates these outcomes is controversial. Here, we examine the effect of neck strength or anthropometrics on associations of soccer heading with neurocognitive outcomes in a large cohort of adult amateur players., Methods: 380 adult amateur league soccer players underwent standardized measurement of neck strength (forward flexion, extension, left lateral flexion, right lateral flexion) and head/neck anthropometric measures (head circumference, neck length, neck circumference and neck volume). Participants were assessed for heading (HeadCount) and cognitive performance (Cogstate) on up to 7 visits over a period of two years. Principal components analysis (PCA) was performed on 8 neck strength and anthropometric measures. We used generalized estimating equations to test the moderation effect of each of the three PCs on 8 previously identified adverse associations of 2-week and 12-month heading estimates with cognitive performance (psychomotor speed, immediate verbal recall, verbal episodic memory, attention, working memory) and of unintentional head impacts on moderate to severe central nervous system symptoms., Results: 3 principal components (PC's) account for 80% of the variance in the PCA. In men, PC1 represents head/neck anthropometric measures, PC2 represents neck strength measures, and PC3 represents the flexor/extensor (F/E) ratio. In women, PC1 represents neck strength, PC2 represents anthropometrics, and PC3 represents the F/E ratio. Of the 48 moderation effects tested, only one showed statistical significance after Bonferroni correction, which was not robust to extensive sensitivity analyses., Conclusion: Neither neck strength nor anthropometrics mitigate adverse associations of soccer heading with cognitive performance in adult amateur players., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Rationale: Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy caused by reduced activity of the von Willebrand factor-cleaving protease (ADAMTS13), which can be life-threatening. The patient reported in this case study also had concurrent Sjögren syndrome and renal impairment, presenting multiple symptoms and posing a great challenge in treatment., Patient Concerns: A 25-year-old woman in the postpartum period visited the hospital due to indifference in consciousness for more than 1 day following cesarean section 8 days prior., Diagnosis: Notable decreases were observed in platelets, hemoglobin, creatinine, and ADAMTS13 levels. After a consultative examination by an ophthalmologist, she was diagnosed with retinal hemorrhage in the right eye and dry eye syndrome in both eyes., Interventions: Having been diagnosed with TTP with Sjögren syndrome and renal impairment, she received repeated treatments with plasmapheresis combined with rituximab., Outcomes: Following treatment and during the follow-up period, the patient's platelet counts and bleeding symptoms significantly improved., Lessons: TTP has a high mortality rate, and when combined with Sjögren syndrome and renal impairment, it poses an even greater challenge in treatment. However, after administering standard plasmapheresis combined with rituximab treatment, the treatment outcome is favorable., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Hepatocellular carcinoma (HCC) is a highly vascularized tumor, one of the most common and lethal cancer-related tumor deaths worldwide, with cell proliferation playing a key role. In this study our western blot results and data from TAGC demonstrate a strong association between Sorcin (SRI) overexpression and poor outcomes in HCC. Moreover, SRI overexpression was remarkably effective in promoting proliferation in vitro and increasing tumor growth in vivo, which were attenuated by knocking down SRI. Mechanistically, SRI regulated vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor B (VEGFB) through PI3K/Akt/FOXO1 signal pathway. Overall, our study indicates that SRI stimulates HCC growth by controlling VEGFA/B, which presents a fresh insight into the pathogenesis of hepatocarcinogenesis and a new therapeutic target for HCC., (© 2024. The Author(s) under exclusive licence to University of Navarra.)

Background: Sacituzumab govitecan (SG) has recently been approved in China for the post-line treatment of metastatic triple-negative breast cancer (mTNBC). SG substantially improves progression-free survival and overall survival compared with single-agent chemotherapy for pretreated mTNBC. However, in view of the high price of SG, it is necessary to consider its value in terms of costs and outcomes. This study aimed to estimate the cost-effectiveness of SG versus single-agent treatment of physician's choice (TPC) in the post-line setting for patients with mTNBC from a Chinese healthcare system perspective., Methods: The cohort characteristics were sourced from the ASCENT randomized clinical trial, which enrolled 468 heavily pretreated patients with mTNBC between November 2017 and September 2019. A partitioned survival model was constructed to assess the long-term costs and effectiveness of SG versus TPC in the post-line treatment of mTNBC. Quality-adjusted life-months (QALMs) and total costs in 2022 US dollars were used to derive incremental cost effectiveness ratio (ICER). QALMs and costs were discounted at 5% annually. The willingness-to-pay (WTP) threshold was defined as $3188 per QALM, three times China's average monthly per capita gross domestic product in 2022. One-way sensitivity analysis, probabilistic sensitivity analysis, and scenario analyses were performed to estimate the robustness of the results., Results: Treatment with SG yielded an incremental 5.17 QALMs at a cost of $44,792 per QALM, much above the WTP threshold of $3188/QALM in China. One-way sensitivity analysis showed that SG price was a crucial factor in the ICER. Probabilistic sensitivity analysis revealed that the cost-effective acceptability of SG was 0% in the current setting. Scenario analyses indicated that the result was robust in all subgroups in ASCENT or under different time horizons. Furthermore, SG must reduce the price to enter the Chinese mainland market. When the monthly cost of SG reduce to $2298, SG has about 50% probability to be a preferred choice than TPC., Conclusions: SG was estimated to be not cost-effective compared with TPC for post-line treatment for mTNBC in China by the current price in HK under a WTP threshold of $3188 per QALM. A drastic price reduction is necessary to improve its cost-effectiveness., (© 2024. The Author(s).)

Changes in the chemical composition of white tea during storage have been studied extensively; however, whether such chemical changes impact the efficacy of white tea in ameliorating colitis remains unclear. In this study, we compared the effects of new (2021 WP) and 10-year-old (2011 WP) white tea on 3% dextrose sodium sulfate (DSS)-induced ulcerative colitis in mice by gavaging mice with the extracts at 200 mg kg -1 day -1 . Chemical composition analysis showed that the levels of 50 compounds, such as flavanols, dimeric catechins, and amino acids, were significantly lower in the 2011 WP extract than in the 2021 WP extract, whereas the contents of 21 compounds, such as N -ethyl-2-pyrrolidinone-substituted flavan-3-ols, theobromine, and (-)-epigallocatechin-3-(3''- O -methyl) gallate, were significantly higher. Results of the animal experiments showed that 2011 WP ameliorated the pathological symptoms of colitis, which was superior to the activity of 2021 WP, and this effect was likely enhanced based on the decreasing of the relative abundance of the g&#95;bacteroides and g&#95;Escherichia-Shigella flora in mice with colitis and promoting the conversion of primary bile acids to secondary bile acids in the colon. These results will facilitate the development of novel functional products from white tea.

The use of static solution-assisted laser drilling can effectively improve hole roundness, decrease taper angle, and reduce recast layer thickness and hole wall slag adhesion. However, the enormous energy of the laser will evaporate the solution to form a suspension droplet and reduce the quality and efficiency of laser drilling. To deal with this defect, the mist-blowing method was used to reduce the influence of droplets on the taper angle and recast layer. In this work, the effect of wind speed on drilling quality was examined, and laser drilling in air, water, and NaCl solution was carried out to analyse the effect of solution composition on hole wall morphology. The results showed that a speed fan with a proper wind speed that disperses the droplets formed in the processing area can significantly reduce the refraction and scattering of the laser, and the taper angle and roundness of the drilling hole were also reduced by 15.6% and improved by 2.4%, respectively, under the wind speed of 2 m/s. The hole wall morphology showed a thicker recast layer and cracking in air, while it was thinner in water and there was little or no layer in the NaCl solution in the same current. When drilling in NaCl, the taper angle and roundness of the drilling hole were reduced by 4.13% and improved by 2.11%, respectively, compared to water. Due to the mechanical effect of the laser in the NaCl solution, the impact force on the material was much greater than that in water. The solution cavitation effect, generated by the absorption of laser energy, caused an explosive impact on the molten material adhered to the surface of the hole wall. Above all, drilling in the NaCl solution with a current of 200 A and a wind speed of 2 m/s was the optimal condition for obtaining the best processing quality.

Polysaccharides are generally considered to have immune enhancing functions, and mulberry leaf polysaccharide is the main active substance in mulberry leaves, while there are few studies on whether mulberry leaf polysaccharide (MLP) has an effect on immunosuppression and intestinal damage caused by cyclophosphamide (CTX), we investigated whether MLP has an ameliorative effect on intestinal damage caused by CTX. A total of 210 1-day-old Mahuang cocks were selected for this experiment. Were equally divided into six groups and used to evaluate the immune effect of MLP. Our results showed that MLP significantly enhanced the growth performance of chicks and significantly elevated the secretion of cytokines (IL-1β, IL-10, IL-6, TNF-α, and IFN-γ), immunoglobulins and antioxidant enzymes in the serum of immunosuppressed chicks. It attenuated jejunal damage and elevated the expression of jejunal tight junction proteins Claudin1, Zo-1 and MUC2, which protected intestinal health. MLP activated TLR4-MyD88-NF-κB pathway and enhanced the expression of TLR4, MyD88 and NF-κB, which served to protect the intestine. 16S rDNA gene high-throughput sequencing showed that MLP increased species richness, restored CTX-induced gut microbiome imbalance, and enhanced the abundance of probiotic bacteria in the gut. MLP improves cyclophosphamide-induced growth inhibition and intestinal damage in chicks by modulating intestinal flora and enhancing immune regulation and antioxidant capacity. In conclusion, this study provides a scientific basis for MLP as an immune enhancer to regulate chick intestinal flora and protect chick intestinal mucosal damage., 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 Cheng, Shi, Cheng, Hu, Liu, Xu, He, Hu, Lu, Chen, Li and Si.)

It has been shown that exposure to hexavalent Chromium, Cr (Ⅵ), via nasal cavity can have neurotoxicological effects and induces behavioral impairment due to the fact that blood brain barrier (BBB) does not cover olfactory bulb. But whether Cr (Ⅵ) can cross the BBB and have a toxicological effects in central nervous system (CNS) remains unclear. Therefore, we investigated the effects of Cr (Ⅵ) on mice treated with different concentrations and exposure time (14 days and 28 days) of Cr (Ⅵ) via intraperitoneal injection. Results revealed that Cr accumulated in hypothalamus (HY) in a timely dependent manner. Much more severer neuropathologies was observed in the group of mice exposed to Cr (Ⅵ) for 28 days than that for 14 days. Gliosis, neuronal morphological abnormalities, synaptic degeneration, BBB disruption and neuronal number loss were observed in HY. In terms of mechanism, the Nrf2 related antioxidant stress signaling dysfunction and activated NF-κB related inflammatory pathway were observed in HY of Cr (Ⅵ) intoxication mice. And these neuropathologies and signaling defects appeared in a timely dependent manner. Taking together, we proved that Cr (Ⅵ) can enter HY due to weaker BBB in HY and HY is the most vulnerable CNS region to Cr (Ⅵ) exposure. The concentration of Cr in HY increased along with time. The accumulated Cr in HY can cause BBB disruption, neuronal morphological abnormalities, synaptic degeneration and gliosis through Nrf2 and NF-κB signaling pathway. This finding improves our understanding of the neurological dysfunctions observed in individuals who have occupational exposure to Cr (Ⅵ), and provided potential therapeutic targets to treat neurotoxicological pathologies induced by Cr (Ⅵ)., 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.)

Glioblastoma multiforme (GBM) is the highest grade of glioma. Tumours, including GBM, possess reprogrammed metabolism, such as altered aerobic glycolysis and aberrant energy production. Lycorine hydrochloride (LH) was extracted from the bulb of Lycoris radiata. The previous study indicated that LH exerts antiviral, anti-inflammatory and antitumour effects. However, the effect of LH on GBM and the underlying molecular mechanism remain unclear. Our study revealed that LH restrained chemoresistant GBM cells growth by inhibiting PDK3 expression in vitro and in vivo. Functionally, LH inhibited the proliferation and invasive capacity of chemoresistant GBM cells in dose-dependent manner. Metabolomics and cellular energy analyses showed that LH decreased extracellular acidification rates while increased oxidative respiration and ROS levels. Mechanistically, LH inhibits the growth of GBM chemoresistant cells by regulating the expression of apoptosis-related proteins, while overexpression of of PDK3 can reverse the antitumor effect of LH. In conclusion, our study revealed that LH could reprogramme cell energy metabolism, including aerobic glycolysis suppression and oxidative phosphorylation hyperactivation by inhibiting PDK3. PDK3 may be a candidate therapeutic target for chemoresistant GBM treatment with LH., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

DNA methylation plays an important role in the occurrence and development of age-related cataracts (ARC). This study aims to reveal potential epigenetic biomarkers of ARC by detecting modifications to the DNA methylation patterns of genes shown to be related to ARC by transcriptomics. The MethylationEPIC BeadChip (850 K) was used to analyze the DNA methylation levels in ARC patients and unaffected controls, and the Pearson correlation test was used to perform genome-wide integration analysis of DNA methylation and transcriptome data. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to perform functional analysis of the whole genome, promoter regions (TSS1500/TSS200), and the associated differentially methylated genes (DMG). Pyrosequencing was used to verify the methylation levels of the selected genes. The results showed that, compared with the control group, a total of 52,705 differentially methylated sites were detected in the ARC group, of which 13,858 were hypermethylated and 38,847 were hypomethylated. GO and KEGG analyses identified functions related to the cell membrane, the calcium signaling pathway, and their possible molecular mechanisms. Then, 57 DMGs with negative promoter methylation correlations were screened by association analysis. Pyrosequencing verified that the ARC group had higher methylation levels of C3 and CCKAR and lower methylation levels of NLRP3, LEFTY1, and GPR35 compared with the control group. In summary, our study reveals the whole-genome DNA methylation patterns and gene expression profiles in ARC, and the molecular markers of methylation identified herein may aid in the prevention, diagnosis, treatment, and prognosis of ARC., 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 Elsevier B.V. All rights reserved.)

Background: Obesity and psychological factors were identified as risk factors for female infertility. The study investigated the correlation between WWI, depression, and secondary infertility, focusing on the potential mediating role of depression., Methods: According to the data from NHANES, this cross-sectional study used multiple regression analysis, subgroup analysis, and smooth curve fitting to explore the relationship between WWI, depression, and secondary infertility. The diagnostic ability of WWI was evaluated and compared to other obesity indicators using the ROC curve. The mediating effect test adopted the distribution of the product., Results: This study involved 2778 participants, including 381 (13.7%) women with secondary infertility. Results showed that higher WWI (OR = 1.31; 95% CI, 1.11-1.56) and depression scores (OR = 1.03; 95% CI, 1.01-1.06) were associated with secondary infertility. There was a positive correlation between WWI and secondary infertility (nonlinear p = 0.8272) and this association was still consistent in subgroups (all P for interaction> 0.05). Compared with other obesity indicators, WWI (AUC = 0.588) also shows good predictive performance for secondary infertility. Mediation analysis showed that depression mediated the relationship between 3.94% of WWI and secondary infertility, with a confidence interval of Z a * Z b excluding 0., Conclusion: WWI exhibited a relatively good correlation in predicting secondary infertility than other obesity indicators, and depression may be a mediator between WWI and secondary infertility. Focusing on the potential mediating role of depression, the risk of secondary infertility due to obesity may be beneficially reduced in women., 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 Sun, Liu, Hu, Xie, Chen, Sun and Bi.)

Metabolic reprogramming is one of the prominent features that distinguishes tumor cells from normal cells. The role of metabolic abnormalities in regulating innate immunity is poorly understood. In this study, we found that IDI1 is significantly upregulated in liver cancer. IDI1 has no significant effect on the growth or invasion of liver cancer cells but significantly promotes liver cancer development in mice. Through molecular mechanism studies, we found that IDI1 interacts with the important regulator of innate immunity cGAS and recruits the E3 ligase TRIM41 to promote cGAS ubiquitination and degradation, inhibiting the cGAS-Sting signaling pathway. IDI1 inhibits the phosphorylation of TBK1 and the downstream factor IRF3 as well as the expression of CCL5 and CXCL10. In summary, this study revealed the important role of the metabolic enzyme IDI1 in the regulation of innate immunity, suggesting that it may be a potential target for liver cancer treatment., Competing Interests: 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., (© 2024 The Authors.)

As a Chinese folk health product, Abrus cantoniensis exhibits good immunomodulatory activity because of its polysaccharide components (ACP), and carboxymethylation of polysaccharides can often further improve the biological activity of polysaccharides. In this study, we explored the impact of prophylactic administration of carboxymethylated Abrus cantoniensis polysaccharide (CM-ACP) on immunosuppression and intestinal damage induced by cyclophosphamide (CTX) in mice. Our findings demonstrated that CM-ACP exhibited a more potent immunomodulatory activity compared to ACP. Additionally, CM-ACP effectively enhanced the abundance of short-chain fatty acid (SCFA)-producing bacteria in immunosuppressed mice and regulated the gene expression of STAT6 and STAT3 mediated pathway signals. In order to further explore the relationship among polysaccharides, intestinal immunity and intestinal flora, we performed a pseudo-sterile mouse validation experiment and fecal microbiota transplantation (FMT) experiment. The findings suggest that CM-FMT and butyrate attenuate CTX-induced immunosuppression and intestinal injury. CM-FMT and butyrate show superior immunomodulatory ability, and may effectively regulate intestinal cell metabolism and repair the damaged intestine by activating STAT6 and STAT3-mediated pathways. These findings offer new insights into the mechanisms by which CM-ACP functions as functional food or drug, facilitating immune response regulation and maintaining intestinal health., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Diabetic retinopathy (DR) is a main factor affecting vision of patients, and its pathogenesis is not completely clear. The purpose of our study was to investigate correlations between MST2 and DR progression, and to study the possible mechanism of MST2 and its down pathway in high glucose (HG)-mediated RGC-5 apoptosis. The diabetic rat model was established by intraperitoneal injection of streptozotocin (STZ) 60 mg/kg. HE and TUNEL staining were used to evaluate the pathological changes and apoptosis of retinal cells in rats. Western blot, qRT-PCR and immunohistochemistry showed that levels of MST2 were increased in diabetic group (DM) than control. In addition, the differential expression of MST2 is related to HG-induced apoptosis of RGC-5 cells. CCK-8 and Hoechst 33,342 apoptosis experiments showed that MST2 was required in HG-induced apoptosis of RGC-5 cells. Further research revealed that MST2 regulated the protein expression of YAP1 at the level of phosphorylation in HG-induced apoptosis. Simultaneously, we found that Xmu-mp-1 acts as a MST2 inhibitor to alleviate HG-induced apoptosis. In summary, our study indicates that the MST2/YAP1 signaling pathway plays an important role in DR pathogenesis and RGC-5 apoptosis. This discovery provides new opportunities for future drug development targeting this pathway to prevent DR., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Although porphyrins make up a promising class of electrochemiluminescence (ECL) luminophors, their aggregation-caused quenching (ACQ) characteristics lead to inferior ECL efficiency (Φ ECL ). Furthermore, current application of porphyrins is limited to cathodic emission. This work creatively exploited a cage-like porous complex (referred to as SWU-1) as the microreactor to recede the ACQ effect while modulating dual ECL emission of meso-tetra(4-carboxyphenyl)porphine (TCPP), which self-assembled with SWU-1 to form TCPP@SWU-1 nanocapsules (TCPP@SWU-1 NCs). As the microreactor, SWU-1 not only effectively constrained TCPP aggregation to improve electron-hole recombination efficiency but also improved stability of anion and cation radicals, thus significantly enhancing the dual emission of TCPP. Compared with TCPP aggregates, the resulting TCPP@SWU-1 NCs exhibited significantly enhanced anodic and cathodic emission, and their Φ ECL was increased by 8.7-fold and 3.9-fold, respectively. Furthermore, black hole quencher-2 (BHQ2) can simultaneously quench anodic and cathodic signals. TCPP@SWU-1 NCs coupling BHQ2 conveniently achieved an ECL ratio detection of miRNA-126, and the limit of detection (S/N = 3) was 4.1 aM. This work pioneered the development of the cage-like porous complex SWU-1 as the microreactor to alleviate defects of the ACQ effect and mediate dual emission of TCPP. The coupling of dual-emitting TCPP@SWU-1 NCs and dual-function moderator BHQ2 created a novel single-luminophor-based ratio system for bioanalysis and provided a promising ECL analysis approach for miRNA-126.

Head and neck squamous cell carcinoma (HNSC) represents nearly 90% of all head and neck tumors. The current treatment modality for HNSC patients primarily involves surgical intervention and radiotherapy, but its therapeutic efficacy remains limited. The mRNA vaccine based on tumor antigens seems promising for cancer treatment. Ferroptosis, a novel form of cell death, is linked to tumor progression and cancer immunotherapy. Nevertheless, the effectiveness of ferroptosis-associated tumor antigens in treating HNSC remains uncertain. In this study, we identified three ferroptosis-associated tumor antigens, namely caveolin1 (CAV1), ferritin heavy chain (FTH1), and solute carrier 3A2 (SLC3A2), as being overexpressed and mutated based on data obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. These antigens were strongly associated with poor prognosis and infiltration of antigen-presenting cells in HNSC. We further identified two ferroptosis subtypes (FS1 and FS2) with distinct molecular, cellular, and clinical properties to identify antigen-sensitive individuals. Our findings indicate that FS1 exhibits an immune "hot" phenotype, whereas FS2 displays an immune "cold" phenotype. Additionally, differential expression of immunogenic cell death modulators and immune checkpoints was observed between these two immune subtypes. Further exploration of the HNSC's immune landscape revealed significant heterogeneity among individual patients. Our findings suggest that CAV1, FTH1, and SLC3A2 are potential targets to prevent HNSC in FS2 patients. Overall, our research reveals the potential of ferroptosis-associated mRNA vaccines for HNSC and identifies an effective patient population for vaccine treatment., (© 2024 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

Background: The six-transmembrane epithelial antigen of prostate (STEAP) family members are known to be involved in various tumor-related biological processes and showed its huge potential role in tumor immunotherapy., Methods: Biological differences were investigated through Gene set enrichment analysis (GSEA) and tumor microenvironment analysis by CIBERSORT. Tumor mutation burden (TMB), immunotherapy response and chemotherapeutic drugs sensitivity were estimated in R., Results: We established a prognostic signature with the formula: risk score = STEAP1 × 0.3994 + STEAP4 × (- 0.7596), which had a favorable concordance with the prediction. The high-risk group were enriched in cell cycle and RNA and protein synthesis related pathways, while the low-risk group were enriched in complement and metabolic related pathways. And the risk score was significantly correlated with immune cell infiltration. Most notably, the patients in the low-risk group were characterized with increased TMB and decreased tumor immune dysfunction and exclusion (TIDE) score, indicating that these patients showed better immune checkpoint blockade response. Meanwhile, we found the patients with high-risk were more sensitive to some drugs related to cell cycle and apoptosis., Conclusions: The novel signature based on STEAPs may be effective indicators for predicting prognosis, and provides corresponding clinical treatment recommendations for HCC patients based on this classification., (© 2024. The Author(s).)

Competing Interests: Conflicts of interest: The authors declare no conflicts of interest.

Excessive lipid intake is linked to an elevated risk of health problems. However, reducing lipid contents may influence food structure and flavor. Some alternatives are needed to control the lipid absorption. Emulsions are common carriers for lipids, which can control the hydrolysis and absorption of lipids. Chitin (Ch) and chitosan (CS) are natural polysaccharides with good biodegradability, biocompatibility, and unique cationic properties. They have been reported to be able to delay lipolysis, which can be regarded as one of the most promising agents that regulates lipid digestion (LiD). The application of Ch/CS and their derivatives in emulsions are summarized in this review with a focus on their performances and mechanisms for LiD regulation, aiming to provide theoretical guidance for the development of novel Ch/CS emulsions, and the regulation of LiD. A reasonable design of emulsion interface can provide its resistance to the external environment and then control LiD. The properties of emulsion interface are the key factors affecting LiD. Therefore, systematic study on the relationship between Ch/CS-based emulsion structure and LiD can not only instruct the reasonable design of emulsion interface to accurately regulate LiD, but also provide scientific guidelines for applying Ch/CS in functional food, medicine and other fields.

Background: Stanford type B aortic dissection (TB-AD) is a life-threatening vascular condition with high rates of morbidity and mortality. Currently, thoracic endovascular aortic repair (TEVAR) is widely performed to treat TB-AD, and some studies have analyzed the influence of stents on hemodynamics using computational fluid dynamics (CFD) models. However, the accuracy of TB-AD simulation models are not satisfactory, they are often constructed as a regular ideal model. Furthermore, it is unclear which tear should be closed for the best treatment when there are multi entry tears., Purpose: The aims of this paper were to provide an assessment method for the selection of the surgical closure location for type B aortic dissection. Five 3D models of multiple entry tears in type B aortic dissection were produced using real patient computed tomography (CT) images to perform hemodynamic analyses of flow velocity streamlines, wall pressure, and wall shear stress., Methods: A Boolean operation was adopted to establish 3D models with multiple entry tears in type B aortic dissection based on patient-specific CT images. The Mimics and Ansys plug-in The Integrated Computer Engineering and Manufacturing code for Computational Fluid Dynamics (ICEM CFD) software were applied to mesh the 3D models. The flow velocity streamlines, wall pressures, and wall shear stresses were then analyzed in the finite element analysis software Fluent. Five 3D models were produced to compare the hemodynamic characteristics of different entry tear numbers, as well as the changes of different closure positions before and after closure., Results: The false lumen of the model with two entry tears had a higher wall pressure than that of model with multiple entry tears, which may tend to squeeze the true lumen and expand the false lumen. The load distribution of the vessel in the model with multiple entry tears had a more balanced flow velocity, and its wall pressure and shear stress were lower than that of model with two entry tears. For aortic dissection with two entry tears, the closure of the proximal entry tear was recommended, which helped to isolate and thrombose the false lumen, thereby improving the blood supply function of the true lumen. Because the postoperative vascular flow velocity and mechanical load performance of the vascular wall were still higher than those of normal blood vessels, the postoperative blood vessels remained pathological, and TEVAR did not restore the blood vessels to their original healthy state., Conclusions: Type B aortic dissection with two entry tears tend to squeeze the true lumen and expand the false lumen, resulting in a new entry tear and deterioration into multiple entry type B aortic dissection. The model of the vessel with multiple entry tears had a more balanced distribution in flow velocity and a smaller wall pressure and shear stress than that of the vessel with two entry tears. The closure of the proximal entry tear was considered an ideal solution for type B aortic dissection with two entry tears., (© 2023 American Association of Physicists in Medicine.)

Minimally invasive puncture combined with urokinase is widely used in the treatment of hypertensive intracerebral hemorrhage (HICH). However, the appropriate frequency of urokinase following minimally invasive puncture in patients is still unclear. In total, 55 patients were enrolled in this study. According to the frequency of urokinase (10.0 ​× ​10 4 units) administration, 30 patients received urokinase at Q4h, while the other 25 patients received urokinase at Q8h. In the univariate analysis, preoperative GCS (p ​= ​0.0002), postoperative GCS (p ​= ​0.0007), the volume of residual hematoma (p ​= ​0.0179), and the frequency of urokinase (p ​= ​0.0110) were associated with unfavorable outcomes in patients with HICH in the basal ganglia. The multivariate analysis revealed that the frequency of urokinase was independently associated with unfavorable outcomes in patients with HICH in the basal ganglia (p ​= ​0.038, 1.109-35.380). The drainage time was significantly shorter in the Q4h group (14.17 ​± ​0.86 ​h) than in the Q8h group (27.36 ​± ​1.39 ​h) (p ​< ​0.0001). The GOS (4.37 ​± ​0.18), BI (75.52 ​± ​2.39), and mRS (1.67 ​± ​0.24) in the Q4h group were significantly ameliorated compared to those in the Q8h group (GOS 3.56 ​± ​0.18, BI 64.13 ​± ​2.22, and mRS 2.64 ​± ​0.28, respectively) (p ​= ​0.0004, p ​= ​0.0002, and p ​= ​0.0018) at 3 months of follow-up. Thus, minimally invasive puncture combined with urokinase is safe and efficient. Increasing the frequency of urokinase administration can produce faster and better postoperative recovery for patients with HICH in the basal ganglia., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Age-related cataract (ARC) is a common eye disease, the main cause of which is oxidative stress-mediated apoptosis of lens epithelial cells (LECs). Epigallocatechin gallate (EGCG) is the most potent antioxidant in green tea. Our results demonstrated that EGCG could effectively reduce apoptosis of LECs and retard lens clouding in aged mice. By comparing transcriptome sequencing results of three groups of mice (young control, untreated aged, and EGCG-treated) and screening using GO and KEGG analyses, we selected RASSF2 as the effector gene of EGCG for mechanistic exploration. We verified that the differential expression of RASSF2 was associated with the occurrence of ARC in clinical samples and mouse tissues by immunohistochemistry and western blotting, respectively. We showed that high RASSF2 expression plays a crucial role in the oxidative induction of apoptosis in LECs, as revealed by overexpression and interference experiments. Further studies showed that RASSF2 mediates the inhibitory effect of EGCG on apoptosis and ARCogenesis in LECs by regulating AKT (Ser473) phosphorylation. In this study, we found for the first time the retarding effect of EGCG on lens clouding in mice and revealed the mechanism of action of RASSF2/AKT in it, which provides a theoretical basis for the targeted treatment of EGCG., Competing Interests: Declaration of competing interest All authors disclosed no relevant relationships., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To explore the association between weight-adjusted-waist index (WWI) and sarcopenic obesity (SO) in patients with maintenance hemodialysis (MHD). Methods: A multicenter, cross-sectional study that included 3311 adult MHD patients was conducted in 20 hemodialysis (HD) centers from June 1, 2021, to August 30, 2021. Body composition was evaluated by body composition monitor based on bioimpedance spectroscopy. Hand grip strength was measured by CAMRY ® dynamometer. WWI was calculated as waist circumference (cm) divided by the square root of body weight (kg). Multiple logistic regression models, spearman correlation analysis, and receiver-operating characteristic (ROC) analyses were conducted. Results: The median age of the study was 55 years, and 39.4% of patients were female. The prevalence of SO was 22.7% in the total population, and patients with SO had higher WWI. Higher WWI quartiles were independently associated with a higher risk of SO in men after adjusting for potential confounders, including age, dialysis vintage, body mass index, biochemical indicators, and various medical histories; the odds ratio (OR) of SO was highest in the fourth quartile of the WWI (OR: 4.08, 95% confidence interval: 2.65-6.27, P for trend <0.001). Age-adjusted WWI provided a better diagnostic power than WWI only for SO in men (area under the ROC curve: 0.72 vs. 0.68, P  < 0.001). WWI was not associated with SO in female HD patients. Conclusion: WWI is independently associated with SO in male but not female MHD patients. This anthropometric index is simple to calculate, making it applicable in clinical practice.