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Lei Lyu, Wei Xiang, Jin-Yan Zhu, Tao Huang, Jing-Dong Yuan, Chuan-Hua ZhangDepartment of Urology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, People’s Republic of ChinaBackground: Long noncoding RNAs (lncRNAs) play important roles in competing endogenous RNA (ceRNA) networks involved in the development and progression of various cancers, including muscle-invasive bladder cancer (MIBC).Purpose: This study aims to construct the lncRNA-associated ceRNA network and identify lncRNA signatures correlated with the clinical features of MIBC tissue samples from The Cancer Genome Atlas (TGCA) database.Methods: The differential expression profiles of MIBC associated lncRNAs, miRNAs and mRNAs were obtained from TCGA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to determine the principal functions of significantly dysregulated mRNAs. The dysregulated lncRNA-associated ceRNA network of MIBC was constructed based on the bioinformatics data, and the correlations between lncRNA expression and clinical features were analyzed using a weighted gene coexpression network analysis (WGCNA). Six cancer specific lncRNAs from the ceRNA network were randomly selected to detect their expression in 32 paired MIBC tissue samples and 5 bladder cancer cell lines using quantitative real-time polymerase chain reaction (qRT-PCR).Results: The ceRNA network was constructed with 30 lncRNAs, 13 miRNAs and 32 mRNAs. Seventeen lncRNAs in the ceRNA network correlated with certain clinical features, and only 1 lncRNA (MIR137HG) correlated with the overall survival (OS) of patients with MIBC (log-rank test P

Abstract Background Nonspecific (nonproductive) binding (adsorption) of cellulase by lignin has been identified as a key barrier to reduce cellulase loading for economical sugar and biofuel production from lignocellulosic biomass. Sulfite Pretreatment to Overcome Recalcitrance of Lignocelluloses (SPORL) is a relatively new process, but demonstrated robust performance for sugar and biofuel production from woody biomass especially softwoods in terms of yields and energy efficiencies. This study demonstrated the role of lignin sulfonation in enhancing enzymatic saccharification of lignocelluloses – lignosulfonate from SPORL can improve enzymatic hydrolysis of lignocelluloses, contrary to the conventional belief that lignin inhibits enzymatic hydrolysis due to nonspecific binding of cellulase. Results The study found that lignosulfonate from SPORL pretreatment and from a commercial source inhibits enzymatic hydrolysis of pure cellulosic substrates at low concentrations due to nonspecific binding of cellulase. Surprisingly, the reduction in enzymatic saccharification efficiency of a lignocellulosic substrate was fully recovered as the concentrations of these two lignosulfonates increased. We hypothesize that lignosulfonate serves as a surfactant to enhance enzymatic hydrolysis at higher concentrations and that this enhancement offsets its inhibitive effect from nonspecific binding of cellulase, when lignosulfonate is applied to lignocellulosic solid substrates. Lignosulfonate can block nonspecific binding of cellulase by bound lignin on the solid substrates, in the same manner as a nonionic surfactant, to significantly enhance enzymatic saccharification. This enhancement is linearly proportional to the amount of lignosulfonate applied which is very important to practical applications. For a SPORL-pretreated lodgepole pine solid, 90% cellulose saccharification was achieved at cellulase loading of 13 FPU/g glucan with the application of its corresponding pretreatment hydrolysate coupled with increasing hydrolysis pH to above 5.5 compared with only 51% for the control run without lignosulfonate at pH 5.0. The pH-induced lignin surface modification at pH 5.5 further reduced nonspecific binding of cellulase by lignosulfonate. Conclusions The results reported in this study suggest significant advantages for SPORL-pretreatment in terms of reducing water usage and enzyme dosage, and simplifying process integration, i.e., it should eliminate washing of SPORL solid fraction for direct simultaneous enzymatic saccharification and combined fermentation of enzymatic and pretreatment hydrolysates (SSCombF). Elevated pH 5.5 or higher, rather than the commonly believed optimal and widely practiced pH 4.8-5.0, should be used in conducting enzymatic saccharification of lignocelluloses.

CD44, an extracellular matrix (ECM) receptor, has been described as a cancer stem cell marker in multiple cancers, including head and neck squamous cell carcinoma (HNSCC). HNSCC orasphere formation or stemness was characterized by cleavage of CD44, and thu

This paper describes measurments of the local temperature field near a combusting stream of methanol droplets using coherent anti-Stokes Raman scattering (CARS). Synchronizing the CARS measurements with the droplets in the stream allows correlations between the temperature field and the droplet position. These measurements describe the thermal structure of the droplet stream flame and can help validate detailed spray combustion models. The diameter of the droplets in the stream is 120 μm, which is comparable to the droplet size in a practical spray. The droplet spacing is approximately 1.0 mm (8 droplet diameters). The CARS measurements indicate a flame surrounding the droplet stream located I mm (8 droplet diameters) from the stream centerline. The temperature profile shows a local minimum temperature a the stream centerline. Moving radially outward from the centerline, the temperature rises at the flame (about 2000 K), and then falls gradually to room temperature. The local minimum temperature is more pronounced on lines through droplet centers than on lines between adjacent droplets. The results also show that the temperature profile between adjacent droplets becomes more uniform as the droplets move downstream. © 1992, Taylor & Francis Group, LLC. All rights reserved.

Objective: To investigate the changes and effects of arginine vasopressin (AVP) in patients with acute traumatic subarachnoid hemorrhage (tSAH).Methods: The plasma and cerebrospinal fluid (CSF) level of AVP, and intracranial pressure (ICP) were measured in a total of 21 patients within 24 hours after tSAH. The neurological status of the patients was evaluated by Glasgow Coma Scale (GCS). Correlation between AVP and ICP, GCS was analyzed respectively. Meanwhile, 18 healthy volunteers were recruited as control group.Results: Compared with control group, the levels (pg/ml) of AVP in plasma and CSF (x+/-s) in tSAH group were significantly increased within 24 hours (38.72+/-24.71 vs 4.54+/-1.38 and 34.61+/-21.43 vs 4.13+/-.26, P less than 0.01), and was remarkably higher in GCS less than or equal to 8 group than GCS larger than 8 group (50.96+/-36.81 vs 25.26+/-12.87 and 44.68+/-31.72 vs 23.53+/-10.94, P less than 0.05). The CSF AVP level was correlated with ICP (r eqaul to 0.46, P less than 0.05), but no statistically significant correlation was found between plasma AVP, CSF AVP and initial GCS (r equal to -0.29, P larger than 0.05 and r equal to -0.32, P larger than 0.05, respectively). The ICP (mm Hg) in tSAH patients was elevated and higher in GCS less than or equal to 8 group than in GCS larger than 8 group (25.9+/-9.7 vs 17.6+/-5.2, P less than 0.05).Conclusion: Our research suggests that AVP is correlated with the severity of tSAH, and may be involved in the pathophysiological process of brain damage in the early stage after tSAH. It seems that compared with the plasma AVP concentration, CSF AVP is more related to the severity of tSAH. [ABSTRACT FROM AUTHOR]

Diabetes is a major risk factor for compromised visual health, leading to retinal vasculopathy and neuropathy, both of which are hallmarks of neurovascular unit dysfunction. Despite the critical impact of diabetic retinopathy, the precise mechanism underlying neurovascular coupling and effective strategies to suppress neurovascular dysfunction remain unclear. In this study, the up-regulation of a tRNA-derived stress-induced RNA, 5'tiRNA-His-GTG, in response to diabetic stress is revealed. 5'tiRNA-His-GTG directly regulates Müller glia action and indirectly alters endothelial angiogenic effects and retinal ganglion cell (RGC) survival in vitro. Downregulation of 5'tiRNA-His-GTG alleviates diabetes-induced retinal neurovascular dysfunction, characterized by reduced retinal vascular dysfunction, decreased retinal neurodegeneration, and improved visually-guided behaviors in vivo. Mechanistically, 5'tiRNA-His-GTG acts as a key regulator of retinal neurovascular dysfunction, primarily by modulating arachidonic acid (AA) metabolism via the CYPs pathway. The 5'tiRNA-His-GTG-CYP2E1-19(S)-HETE signaling axis is identified as a key driver of retinal neurovascular dysfunction. Thus, targeting 5'tiRNA-His-GTG presents a promising therapeutic strategy for treating vasculopathy and neuropathy associated with diabetes mellitus. Modulating this novel signaling pathway can open up new avenues for intervention in diabetic retinopathy and its related complications., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background/Objectives: The COVID-19 pandemic has led to a global health crisis, impacting physical, and mental well-being, particularly among those who have recovered from the illness. This study aimed to assess the mental health status of patients recovered from COVID-19 in Macau, focusing on the impact of sequelae of COVID-19, and identifying demographic factors associated with poor mental health. Methods: A cross-sectional online survey was conducted involving 494 adults who had recovered from COVID-19, with 426 participants included in the final analysis. Mental health was evaluated using the 12-item General Health Questionnaire (GHQ-12), with scores ≥3 indicating poor mental health. Results: This study revealed a high prevalence of poor mental health, affecting 71.8% of the respondents. Binary logistic regression identified experiencing COVID-19 sequelae (OR = 5.727, 95% CI: 2.973-11.031), being in the age groups of 26-45 (OR = 4.227, 95% CI: 1.754-10.185), or 61, and above (OR = 18.072, 95% CI: 3.590-90.962), being male (OR = 0.501, 95% CI: 0.257-0.979), being married (OR = 5.714, 95% CI: 1.919-17.016), and dissatisfaction with family relationships (OR = 2.957, 95% CI: 1.228-7.119) as significant risk factors for poor mental health. Conclusions: This study underscores the critical need for targeted psychological support for patients recovered from COVID-19 in Macau, particularly for those with sequelae, and those in vulnerable demographic groups. The findings suggest that specific age groups and individuals with sequelae may face higher mental health risks, indicating the necessity for prioritized interventions.

Objective: Physical activity (PA) plays an important role in human health. However, the relationship between the PA and dysthyreosis was not clear. This study aimed to explore this question., Methods: We performed a population-based study on the basis of the participant's information that was collected from the National Health and Nutrition Examination Survey (NHANES) database. The association of the thyroid hormone and total PA metabolic equivalent task (MET) were assessed via linear regression analysis with adjusting for different covariates. Moreover, we also used path analysis to explore the causality between PA, thyroid hormone index, and dysthyreosis. The restricted cubic spline analysis was used to explore the non-linear relationship between the thyroid hormone index and the PA total MET., Results: A total of 2118 participants aged≥20, including 969 females and 1149 males, were collected from NHANES. The linear regression with multivariate adjustment suggested a linear relationship between the PA total MET and Thyroid-Stimulating Hormone Index (TSHI), and Thyroid Feedback Quantile-Based Index (TFQI), respectively. And TFQI and dysthyresis occurrence were significantly correlated (P<0.05). The path analysis showed that the PA total MET affected dysthyreosis occurrence by TFQI. In addition, we found a non-linear relationship between the total PA met and dysthyreosis via restricted cubic spline analysis., Conclusions: PA was significantly correlated with dysthyreosis via thyroid hormone sensitivity. Therefore, it can be considered to prevent the occurrence of dysthyreosis by regulating thyroid hormone sensitivity through PA in daily life., 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 Zhang, Hu, Xiang, Xiang, Guo, Zhi, Zhao, Zhu and Zhang.)

Breast cancer has become the malignant tumor with the first incidence and the second mortality among female cancers. Most female breast cancers belong to luminal-type breast cancer and HER2-positive breast cancer. These breast cancer cells all have different driving genes, which constantly promote the proliferation and metastasis of breast cancer cells. Signal transducer and activator of transcription 3 (STAT3) is an important breast cancer-related gene, which can promote the progress of breast cancer. It has been proved in clinical and basic research that over-expressed and constitutively activated STAT3 is involved in the progress, proliferation, metastasis and chemotherapy resistance of breast cancer. STAT3 is an important key target in luminal-type breast cancer and HER2-positive cancer, which has an important impact on the curative effect of related treatments. In breast cancer, the activation of STAT3 will change the spatial position of STAT3 protein and cause different phenotypic changes of breast cancer cells. In the current basic research and clinical research, small molecule inhibitors activated by targeting STAT3 can effectively treat breast cancer, and enhance the efficacy level of related treatment methods for luminal-type and HER2-positive breast cancers., (© 2024. The Author(s).)

Background: Extracorporeal shock wave therapy (ESWT) is increasingly being recognized as an advantageous alternative for treating non-union due to its efficacy and minimal associated complications. Non-union following Bernese periacetabular osteotomy (PAO) is particularly challenging, with a reported 55% delayed union and 8% non-union. Herein, we highlight a unique case of ischial non-union post-PAO treated successfully with a structured ESWT regimen., Case Summary: A 50-year-old patient, diagnosed with left ischial non-union following the PAO, underwent six cycles of ESWT treatment across ten months. Each cycle, spaced four weeks apart, consisted of five consecutive ESWT sessions without anesthesia. Regular X-ray follow-ups showed progressive disappearance of the fracture line and fracture union. The patient ultimately achieved a satisfactory asymptomatic recovery and bone union., Conclusion: The results from this case suggest that this ESWT regimen can be a promising non-invasive treatment strategy for non-union following PAO., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objectives: To summarize and discuss3-days MRI changes after uterine artery embolization (UAE) and their predictive value for efficacy., Methods: From August 2016 to April 2023, 52 patients underwent enhanced MRI within 3 days post-embolization. We retrospectively analyzed clinical and imaging data, focusing on MR characteristics at the 3-day mark, comparing pre- and post-embolization images. Patients were categorized based on 3-day MR findings into complete and incomplete necrosis groups, with clinical efficacy compared over 6 months., Results: Our study included 30 cases of multiple leiomyomas and 22 of single leiomyomas. Postoperative MRI revealed complete necrosis in 31 tumors and incomplete necrosis in 21 tumors. At 3 days, MR ADC imaging showed increased signals in necrotic areas, mildly increased signals on T2-weighted images, and minimal changes on T1-weighted images. Six-month follow-up showed no significant difference in symptom improvement between groups (p = 0.524, p = 0.587, p = 0.615). However, a significant difference was found in leiomyoma volume reduction, with 70.63 ± 15.53% in the complete necrosis group and 51.36 ± 25.20% in the incomplete necrosis group (p＜0.001), highlighting the impact of necrosis extent on volumetric reduction., Conclusion: Short-term MRI changes after UAE can reflect changes in blood supply to fibroids and normal uterine tissue, and have good predictive value for medium-term embolization efficacy., Advances in Knowledge: This study describes short-term MR manifestations of complete and incomplete embolism, aiding in predicting long-term outcome., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

With SARS-CoV-2 N protein as a model target, a signal-enhanced LFIA based on Au@Pt nanoparticles (NPs) as labels is proposed. This Au@Pt NPs combined the distinguished localized surface plasma resonance (LSPR) effect of Au NPs and the ultrahigh peroxidase-like catalytic activity of Pt NPs. Au@Pt NPs could trigger substrate chromogenic reaction, generating a color signal orders of magnitude darker than their intrinsic color. In the detection, after the coloration of the strips, 3,3',5,5'-tetramethylbenzidine (TMB) and H 2 O 2 were added, and a dark blue chelate (OxTMB) was produced soon, enhancing the band color significantly. After the signal amplification, the naked-eye detection limit for N protein reached 40 pg/mL. The detection sensitivity enhanced more than 1000 times than that without signal amplification. Compared with mainstream LFIA requiring complex readout instruments, the Au@Pt-based LFIA achieved a comparable sensitivity using naked eyes detection. This point is crucial, especially for unprofessional users or low-resource areas. Hence, this signal-enhanced LFIA may serve as a sensitive, cost-effective, and user-friendly detection method. It can shorten the testing window period and help identify early infections., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

A novel reaction of cyclic and acyclic secondary amines with in situ-generated allene intermediate species from nitro-substituted donor-acceptor cyclopropanes is reported. In the presence of a simple inorganic base, NaOH, tetrasubstituted enamine derivatives can be obtained in moderate to excellent yields. The reaction is operationally easy, features mild reaction conditions and simple inorganic bases, and is free of transition metals.

Background: Early-onset rectal cancer (EORC) is characterized by a unique disease process with different clinicopathological features compared with late-onset rectal cancer (LORC). Research on the risk of recurrence in EORC patients, however, is limited. We aim to develop a predictive model to accurately predict EORC recurrence risk., Materials and Methods: Rectal cancer patients who underwent radical surgery and T2-weighted imaging and diffusion-weighted imaging magnetic resonance imaging (MRI) were retrospectively enrolled from three medical institutions from November 2012 to November 2018. Differences in clinicopathological characteristics between EORC and LORC were compared. Five prediction models for disease-free survival were constructed based on clinicopathological variables and five radiomic features from pretreatment MRI of the EORC. A fixed cut-off value calculated in the training set was used to stratify EORC patients into high-risk and low-risk groups of post-operative recurrence. Model performance was evaluated by concordance index (C-index) and receiver operating characteristic curve., Results: A total of 264 EORC patients (median age, 43 years, 163 males) and 778 LORC patients (median age, 62 years, 520 males) were enrolled. Pretreatment positive carcinoembryonic antigen [hazard ratio (HR) = 2.84, P = 0.006], pathological positive lymph node status (pN positive) [HR = 2.86, P = 0.011] and MRI-based radiomics score [HR = 2.72, P < 0.001] are independent risk factors for disease-free survival in EORC patients. The EORC-ClinPathRadiom model, constructed by integrating the clinicopathological characteristics and MRI-based radiomics features of EORC, showed C-index of 0.82, 0.82, and 0.81 in the training, internal, and external test sets, respectively. This model effectively stratified EORC patients into high risk and low risk of recurrence (HRs for the training, internal, and external test sets were 8.96, 6.81, and 7.46, respectively)., Conclusion: The EORC-ClinPathRadiom model can effectively predict and stratify the risk of post-operative recurrence in EORC patients., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To sum up clinical researches and the rule of acupoint selection on the treatment of psoriasis by acupuncture and moxibustion in the past 20 years, so as to provide new ideas and reference for improving the clinical effect of acupuncture for psoriasis., Methods: Research papers, published from January 1, 2002 to December 31, 2022 in both Chinese and English, were searched from databases of China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform (WanFang), and Chinese Science and Technology Journal (CSTJ), PubMed, Embase and Web of Science by using key words of psoriasis, psoriases, psoriasis vulgaris, acupuncture, needle, acupoint and moxibustion. Then, Microsoft Excel 2021 was used for data entry, extraction and sorting of the included literature, data extraction mainly includes diagnostic criteria, treatment methods, treatment frequency, total course of treatment, selection of acupoints, efficacy evaluation and outcomes. SPSS Modeler 18.1 software was used to make analysis on the association rules of acupoints., Results: A total of 26 papers were included, and the diagnostic criteria of clinical studies on acupuncture treatment of psoriasis are constantly updated. Of the 26 clinical studies, 23 had both treatment group and control group, 21 were randomized controlled trials. The main methods for treatment of psoriasis included fire needle, acupuncture, electroacupuncture, acupuncture combined with moxibustion or fire needle, fire needle plus western medicines, etc. with the acupuncture combined with moxibustion, and fire needle combined with western medicines being most frequently used. The observation index and clinical efficacy evaluation were effective rate, psoriasis area and severity index, dermatology life quality index, Traditional Chinese Medicine syndrome score, etc., with the effective rate being about 40% to 100%. Comparison of clinical efficacy of acupuncture in treating psoriasis showed that the simple fire needle, simple acupuncture, acupuncture combined with moxibustion, fire needle or acupuncture combined with western medicines were superior to simple western medicines, etc. In regard to acupoint selection, a total of 35 acupoints were found in the 26 studies included, among which the top 5 frequently used were Ashi points (skin lesion region), Geshu (BL17), Feishu (BL13), Ganshu (BL18) and Quchi (LI11), and there were strong association rules among BL17, BL13, BL18 and Shenshu (BL23)., Conclusions: Acupuncture is safe and effective in the treatment of psoriasis, and acupuncture combined with moxibustion and fire acupuncture needle combined with western medicines are recommended as the main intervention method, with Ashi-point, BL13, BL17, BL18 and BL23 as the main acupoints.

Objectives: This study aims to develop a robust predictive model for survival in AML patients undergoing allo-HSCT., Methods: It was performed a retrospective analysis of 336 AML patients who underwent allo-HSCT at Peking University First Hospital between September 2003 and March 2023. Univariable and multivariable Cox regression analyses were conducted to determine hazard ratios (HR) for overall survival. A predictive model was developed based on multivariable analysis results. Internal validation was carried out through bootstrap resampling, and the model's performance was assessed using the Concordance Index (C-index), Receiver Operating Characteristics (ROC) curve, calibration plots, and Decision Curve Analysis (DCA)., Results: Our prognostic model, which includes age, disease stage, donor/recipient gender, mononuclear cell counts, and the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), effectively stratified patients into low-risk and high-risk groups. The two groups showed significant differences in overall survival (P<0.0001), disease-free survival (P<0.0001), non-relapse mortality (NRM) (P<0.0001), and relapse rates (P=0.08). The model achieved a C-index of 0.71. Calibration plots and DCA confirmed strong alignment between predicted and observed outcomes. Subgroup analysis revealed that overall survival was significantly lower in the high-risk group compared to the low-risk group in both measurable residual disease (MRD) negative and MRD positive subgroups (P=0.015 for both)., Conclusion: The developed prognostic model, which integrates comprehensive disease and patient characteristics, enhances risk stratification for AML patients undergoing allo-HSCT. This model effectively stratifies risk in both MRD-negative and MRD-positive subgroups and may facilitate more informed MRD-based treatment decisions., 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. Production and hosting by Elsevier B.V.)

Objective: We present a case of phosphaturic mesenchymal tumor (PMT) in the left ethmoid without any nasal symptoms in a 63-year-old woman. Initially diagnosed with postmenopausal osteoporosis, 2-year history of hypophosphatemia and a significantly higher uptake of Fluorine-18 ( 18 F)-AlF-NOTA-octreotide ( 18 F-OC) in the left ethmoid sinus, provided crucial information for accurate diagnosis., Methods: We presented a case with chart review and conducted review of the literature., Results: The patient endured 1-year history of weakness and bone pain but without any nasal symptoms before a tissue diagnosis was eventually reached. It is a challenging diagnosis to make-patients present with non-specific clinical symptoms and the culprit neoplasm is often tiny in size and difficult to detect. It emphasizes the importance of thorough patient history-taking and the whole-body functional imaging., Conclusions: Sinonasal PMTs are rare, and because of this most otolaryngologists are unfamiliar with its clinical presentation. This case highlights the importance of early diagnosis to enable prompt intervention and reduce the burden of associated symptoms., 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.

Purpose: Our purpose was to investigate and test the causal relationship between type 1 diabetes (T1D) and inflammatory bowel disease (IBD) and its major phenotypes, including ulcerative colitis (UC) and Crohn's disease (CD), in two large datasets., Methods: We obtained IBD samples from the largest publicly available genome-wide association study (GWAS), as well as the FinnGen database and the publicly accessible IEU GWAS database of T1D. We employed a two-sample Mendelian randomization approach to assess bidirectional causality using the inverse variance weighting (IVW) method as the primary outcome., Results: Genetic predisposition to T1D was associated with reduced risk of IBD (IVW: odds ratio (OR), 0.867; 95% confidence interval (CI), [0.852, 0.883]; P < 0.001), UC (OR = 0.879 [0.823, 0.939], P < 0.001), and CD (OR = 0.925 [0.872, 0.981], P = 0.009). The republication results found IBD genetically possessed negative association with T1D (OR = 0.781 [0.684, 0.891], P < 0.001). Additionally, a meta-analysis of results was conducted to prove the strong evidence between T1D and CD (OR = 0.95 [0.91, 0.98]; p = 0.01)., Conclusions: This study first demonstrated a causal effect of TID on the reduced risk of CD in the mendelian randomization study., Competing Interests: Compliance with ethical standards Ethics approval and Consent to participate No ethical approval from an ethics committee or Equator Network checklist was necessary as our study did not involve any human or animal research or observational studies. Our investigation utilized Mendelian randomization analysis and draw data from open databases. All of the projects and datasets cited in our study were approved by the respective ethics committees of the corresponding published articles. Conflict of interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

One new lathyrane-type diterpenoid, euphlathin A ( 1 ), and 11 known analogues ( 2-12 ), were isolated from the fruits of Euphorbia lathyris . Their structures were elucidated by spectroscopic data. The absolute configurations of 1 were established by single-crystal X-ray crystallography. All diterpenoids ( 1-12 ) were evaluated for antiproliferative activity against the human hypertrophic scar (HTS) cells. Compound 1 exhibited significantly against HTS cells growth with an IC 50 value of 6.33 μM. Morphological features of apoptosis were evaluated in 1 -treated HTS cells. Wound healing assays indicated that 1 significantly inhibited the migration of HTS at 24 h and 48 h. Compound 1 effectively induced apoptosis of HTS, which was associated with G 2 /M or S phase cell cycle arrest. Flow cytometric analysis showed that the treatment by 1 significantly induced HTS cell apoptosis in a dose-dependent manner. Overall, euphlathin A ( 1 ) has the potential to be a therapeutic agent for the treatment of hyperplastic scar therapy.

Background: The safety and efficacy of neoadjuvant immunochemotherapy (nICT) for locally advanced gastric cancer (LAGC) remain controversial., Methods: Patients with LAGC who received either nICT or neoadjuvant chemotherapy (nCT) at 3 tertiary referral teaching hospitals in China between January 2016 and October 2022 were analyzed. After propensity-score matching (PSM), comparing the radiological response, pathological response rate, perioperative outcomes, and early recurrence between the two groups., Results: After PSM, 585 patients were included, with 195 and 390 patients comprising the nICT and nCT groups, respectively. The nICT group exhibited a higher objective response rate (79.5% vs. 59.0%; P <0.001), pathological complete response rate (14.36% vs. 6.41%; P =0.002) and major pathological response rate (39.49% vs. 26.15%; P =0.001) compared with the nCT group. The incidence of surgical complications (17.44% vs. 16.15%, P =0.694) and the proportion of perioperative textbook outcomes (80.0% vs. 81.0%; P =0.767) were similar in both groups. The nICT group had a significantly lower proportion of early recurrence than the nCT group (29.7% vs. 40.8%; P =0.047). Furthermore, the multivariable logistic analysis revealed that immunotherapy was an independent protective factor against early recurrence [odds ratio 0.62 (95% CI 0.41-0.92); P =0.018]. No significant difference was found in neoadjuvant therapy drug toxicity between the two groups (51.79% vs. 45.38%; P =0.143)., Conclusions: Compared with nCT, nICT is safe and effective, which significantly enhanced objective and pathological response rates and reduced the risk for early recurrence among patients with LAGC., Trial Registration: Clinical Trials.gov., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Ligand-receptor recognition serves as the fundamental driving force for active targeting, yet it is still constrained by off-target effects. Herein, we demonstrate that circumventing or blocking the mononuclear phagocyte system (MPS) are both viable strategies to address off-target effects. Naturally derived lignin nanoparticles (LNPs) show great potential to block MPS due to its good stability, low toxicity, and degradability. We further demonstrate the impact of LNPs dosage on in vivo tumor targeting and antitumor efficacy. Our results show that a high dose of LNPs (300 mg/kg) leads to significant accumulation at the tumor site for a duration of 14 days after intravenous administration. In contrast, the low-dose counterparts (e.g., 50, 150 mg/kg) result in almost all LNPs accumulating in the liver. This discovery indicates that the liver is the primary site of LNP capture, leaving only the surplus LNPs the chance to reach the tumor. In addition, although cell membrane-engineered LNPs can rapidly penetrate tumors, they are still prone to capture by the liver during subsequent circulation in the bloodstream. Excitingly, comparable therapeutic efficacy is obtained for the above two strategies. Our findings may offer valuable insights into the targeted delivery of drugs for disease treatment., 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.)

Three new prenylated dihydroflavones, moralbaflavones A-C ( 1 - 3 ), together with four known ones ( 4a/4b , 5 , and 6 ) were isolated from the root barks of Morus alba L. Their structures including the absolute configurations were determined by the analysis of HRMS, NMR, and ECD data. The neuroprotective properties of these prenylated dihydroflavones were screened at the concentration of 10  µ M in the sodium nitroprusside-induced rat pheochromocytoma PC-12 cells, and the results showed moralbaflavone C ( 3 ) possessed significant neuroprotective activity, being more potent than the positive control edaravone.

Liver cancer with portal vein tumor thrombus (PVTT) is a frequent finding and is related to poor prognosis. Surgical resection provides a more promising prognosis in selected patients. The purpose of this study was to explore the application of 3D (3-dimensional) visualization and image fusion technology in liver cancer with PVTT surgery. 12 patients were treated with surgery between March 2019 and August 2022. The preoperative standard liver volume (SLV), estimated future liver remnant (FLR), FLR/SLV, 3D visualization models, PVTT classification, operation programs, surgical results, and prognosis were collected and analyzed. Twelve patients who had complete data of 3D visualization and underwent hemihepatectomy combined with portal vein tumor thrombectomy. The operation plan was formulated by 3D visualization and was highly consistent with the actual surgery. The SLV was 1208.33 ± 63.22 mL, FLR was 734.00 mL and FLR/SLV was 61.62 ± 19.38%. The accuracy of classification of PVTT by 3D visualization was 100%, Cheng type Ⅱa (4 cases), Ⅱb (2 cases), Ⅲa (4 cases), and Ⅲb (2 cases). The 3D visualization model was a perfect fusion with the intraoperative live scene and precise guidance for hepatectomy. No patient was suffering from postoperative liver failure and without procedure‑associated death. 6 patients died of tumor recurrence, and 2 patients died of other reasons. The 12-month cumulative survival rate was 25.9%. 3D visualization and image fusion technology could be used for precise assessment of FLR, classification of PVTT, surgery navigation, and which was helpful in improving the safety of hepatectomy., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Mitochondria are crucial for cellular ATP production. They are highly dynamic organelles, whose morphology and function are controlled through mitochondrial fusion and fission. The specific roles of mitochondria in podocytes, the highly specialized cells of the kidney glomerulus, remain less understood. Given the significant structural, functional, and molecular similarities between mammalian podocytes and Drosophila nephrocytes, we employed fly nephrocytes to explore the roles of mitochondria in cellular function. Our study revealed that alterations in the Pink1-Park (mammalian PINK1-PRKN) pathway can disrupt mitochondrial dynamics in Drosophila nephrocytes. This disruption led to either fragmented or enlarged mitochondria, both of which impaired mitochondrial function. The mitochondrial dysfunction subsequently triggered defective intracellular endocytosis, protein aggregation, and cellular damage. These findings underscore the critical roles of mitochondria in nephrocyte functionality.

The multiprotein complexes known as the complex of proteins associated with Set1 (COMPASS) play a crucial role in the methylation of histone 3 lysine 4 (H3K4). In Drosophila, the COMPASS series complexes comprise core subunits Set1, Trx, and Trr, which share several common subunits such as ash2, Dpy30-L1, Rbbp5, and wds, alongside their unique subunits: Wdr82 for Set1/COMPASS, Mnn1 for Trx/COMPASS-like, and Ptip for Trr/COMPASS-like. Our research has shown that flies deficient in any of these common or unique subunits exhibited high lethality at eclosion (the emergence of adult flies from their pupal cases) and significantly shortened lifespans of the few adults that do emerge. Silencing these common or unique subunits led to severe heart morphological and functional defects. Moreover, specifically silencing the unique subunits of the COMPASS series complexes, Wdr82, Mnn1, and Ptip, in the heart results in decreased levels of H3K4 monomethylation and dimethylation, consistent with effects observed from silencing the core subunits Set1, Trx, and Trr. These findings underscore the critical roles of each subunit of the COMPASS series complexes in regulating histone methylation during heart development and provide valuable insights into their potential involvement in congenital heart diseases, thereby informing ongoing research in heart disease., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)