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Competing Interests: Disclosure: Jixiang Zheng, Ting Wang, Huaiming Wang, Botao Yan, Jianbo Lai, Kemao Qiu, Xinyi Zhou, Jie Tan, Shijie Wang, Hongli Ji, Mingyuan Feng, Wei Jiang, Hui Wang, and Jun Yan have no conflicts of interest, use of off-label or unapproved drugs or products, or use of previously copyrighted material to declare that may be relevant to the contents of this study. Ethical statement: Nanfang Hospital, Guangzhou, Guangdong, People's Republic of China, and The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China, approved this study. Patient informed consent was waived by the Institutional Review Board because of the retrospective design of this study, and patient information was protected.

Background: Gastric cancer, characterized by its high morbidity and mortality rates, exhibits low levels of RAB37. The role and molecular mechanisms of RAB37, a small GTPase, in the pathogenesis of gastric cancer are still unclear., Methods: We assessed RAB37 expression in gastric cancer cells using quantitative Polymerase Chain Reaction (qPCR), Western blot, and immunohistochemical staining (IHC), and analyzed EMT marker proteins and autophagy changes via Western blot, immunofluorescence (IF), and transmission electron microscopy (TEM). Co-immunoprecipitation (co-IP) was used to identify protein-protein interactions. We studied the migration and invasion of gastric cancer cells using wound healing and transwell assays in vitro and a mouse pulmonary metastasis model in vivo., Results: Overexpression of RAB37 suppressed EMT, invasion, and migration while enhancing autophagy in gastric cancer cells, which was dependent on its GTPase activity. However, all these effects could be reversed by the autophagy inhibitor chloroquine. Regarding the molecular mechanism, RAB37 strengthened the interaction between p62 and β-catenin, which consequently enhanced the p62-mediated autophagic degradation of β-catenin. Furthermore, RAB37 curbed the pulmonary metastasis of both general and cisplatin-resistant gastric cancer cells., Conclusion: The low level of RAB37 reduces interaction between p62 and β-catenin and then the autophagic degradation of β-catenin, thereby promoting the EMT, invasion, and migration in gastric cancer cells. The low expression of RAB37 in gastric cancer suggests a potential therapeutic target, especially for cisplatin-resistant gastric cancer., Competing Interests: Declarations. Ethics approval and consent to participate: The authors state that the study has been approved by the Ethics Committee of Anhui Medical University and has followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. Informed consent was obtained from all subjects. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. Springer Nature Switzerland AG.)

Objectives: To validate the 2018 European Neuromuscular Centre classification (ENMC) criteria, compare its performance to the 1975 Bohan & Peter (B&P) and 2017 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) criteria for dermatomyositis (DM), and describe characteristics of different myositis-specific autoantibody (MSA)-positive patients defined by the ENMC-DM criteria., Methods: Medical records and data on MSAs and muscle biopsies were retrospectively obtained from 1370 Chinese patients with idiopathic inflammatory myopathy (IIM) between 2008 and 2020. Patients were diagnosed with DM by at least two rheumatologists and classified according to the ENMC-DM, EULAR/ACR, and B&P criteria., Results: Of the 1370 patients, 857, 671, 693, and 913 were diagnosed with DM using the specialists' gold standard, ENMC-DM, EULAR/ACR, and B&P criteria, respectively. Significant between-group differences were observed in the clinical symptoms, serum creatine kinase levels, and MSAs (P < 0.05). Based on muscle biopsy data, the B&P criteria had the highest sensitivity (94%) but lowest specificity (65%). Without muscle biopsy data, the ENMC-DM criteria had the highest specificity (92%) but lowest sensitivity (61%). The sensitivity and specificity of the EULAR/ACR criteria were intermediate (72% and 86%, respectively) regardless of muscle biopsy data availability. With MSA data, the sensitivity and specificity of the ENMC-DM criteria were 73% and 91% and increased to 76% and 97%, respectively, with both muscle biopsy and MSA data., Conclusions: The ENMC-DM criteria had higher specificity than the other criteria, especially in the absence of muscle biopsy data. Sensitivity and specificity improved when both muscle biopsy and MSA data were available. Key Points • Idiopathic inflammatory myopathy presents diagnostic challenges due to its variable features and dermatomyositis has distinct subtypes based on myositis-specific autoantibodies (MSAs) with unique clinical phenotypes. • This study validates the ENMC-DM criteria in Chinese patients and provides a comprehensive comparison with the B&P and EULAR/ACR criteria. • It demonstrates that the new ENMC-DM criteria exhibit higher specificity, especially noteworthy in cases without muscle biopsy, and the study further highlights the improved sensitivity and specificity when combining muscle biopsy and MSAs, offering a refined approach for accurate DM classification., Competing Interests: Declarations. Statement of ethics and consent: This study was approved by the Clinical Research Ethics Committee of the China-Japan Friendship Hospital (2020–11-K08). All patients provided written informed consent to participate in the study. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background: Ubiquitination is one of the important modification of proteins which can be reversed by deubiquitinating enzymes (DUBs). Ubiquitin specific protease 28 (USP28) belongs to the deubiquitinase family, which plays a cancer-promoting function in many types of cancers such as pancreatic cancer and breast cancer. So far, the molecular function and significance of USP 28 in cholangiocarcinoma remain unclear., Methods: In this study, we evaluated the expression of USP28 using tissue microarray (TMA), reverse transcription polymerase chain reaction (qRT-PCR), and online databases. We investigated the effect of USP28 on the progression of CCA through in vitro and in vivo functional experiments. In addition, we explored downstream molecular pathways using Western blotting (WB), immunofluorescence (IF), and mass spectrometry techniques., Results: Here, we found that cholangiocarcinoma tissue had higher USP 28 expression than normal bile duct tissue, and that high USP 28 levels were significantly associated with a malignant phenotype and poorer prognosis in cholangiocarcinoma patients. Both in vitro and in vivo, USP28 could mediate the deubiquitination of PKM2, thereby activating the downstream Hif1-α signaling pathway, promoting glycolysis and energy supply, and finally promoting tumor progression., Conclusion: In summary, USP28 activated downstream Hif1-α by reducing the ubiquitination level of PKM2, furthermore, promoting the level of glycolysis in CCA cells for tumor progression., Competing Interests: Declarations. Ethics approval and consent to participate: The studies involving human participants were reviewed and approved by the Ethics Committee of The First Affiliated Hospital of Nanjing Medical University. The patients/participants provided their written informed consent to participate in this study. Competing interests: The authors declare no competing interests., (© 2024. Springer Nature Switzerland AG.)

Background: Approximately 25% of patients with stage III colorectal cancer experience liver metastasis after radical resection; however, there is currently a lack of methods to predict liver metastasis. This study aims to develop and validate a pathomics nomogram to predict liver metastasis in patients with stage III colorectal cancer., Methods: A total of 318 enrolled patients were divided into three cohorts: a training cohort (n = 139), a validation cohort (n = 69), and an external cohort (n = 110). A competitive risk nomogram was established by the pathomics signature and clinicopathological characteristics and assessed by calibration, discrimination, and clinical usefulness., Results: A significant correlation between the pathomics signature and liver metastasis in stage III colorectal cancer was found. Multivariate Fine-Gray analysis indicated that preoperative carcinoembryonic antigen level, postoperative chemotherapy, and pathomics signature were independent predictors of liver metastasis. A competitive risk nomogram was developed to predict liver metastasis in patients with stage III colorectal cancer. The predicting nomogram shows good discrimination and calibration, with C-indexes of 0.811 (95% confidence interval [CI] 0.651-0.971), 0.759 (95% CI 0.531-0.987), and 0.845 (95% CI 0.641-0.999), with area under the receiver operating characteristic (AUROC) curves at 5 years of 0.833 (95% CI 0.742-0.925), 0.760 (95% CI 0.652-0.893), and 0.812 (95% CI 0.692-0.931) in the training, validation, and external cohorts, respectively. Compared with the clinicopathological nomogram, the nomogram combined with the pathomics signature had better performance (AUROC 0.823 [95% CI 0.764-0.881] vs. 0.678 [95% CI 0.606-0.751]; p < 0.001)., Conclusions: The pathomics signature is a predictive indicator for liver metastasis in patients with stage III colorectal cancer, and the integrated nomogram can be used to predict liver metastasis better than the clinicopathological nomogram alone., Competing Interests: Disclosure: Jixiang Zheng, Ting Wang, Huaiming Wang, Botao Yan, Jianbo Lai, Kemao Qiu, Xinyi Zhou, Jie Tan, Shijie Wang, Hongli Ji, Mingyuan Feng, Wei Jiang, Hui Wang, and Jun Yan have no conflicts of interest, use of off-label or unapproved drugs or products, or use of previously copyrighted material to disclose. Ethical approval: Nanfang Hospital, Guangzhou, Guangdong, People’s Republic of China, and The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China, approved this study. Patient informed consent was waived by the Institutional Review Board due to the retrospective design of this study, and patient information was protected., (© 2024. Society of Surgical Oncology.)

The mastitis caused by Klebsiella pneumoniae (K. pneumoniae) is increasing in the dairy cows. To investigate the epidemic of K. pneumoniae of China, 131 strains were isolated from 495 clinical mastitis milk samples (26.5%) from 14 provinces in China. Among the isolates, K57 was the dominant serotype (45.0%) and 19 (14.5%) isolates were identified as hypervirulent K. pneumoniae (hvKP). The mrkA, entB, wabG and fimH genes were prevalent virulence genes while rmpA, magA, and ycf were not found in K. pneumoniae. Furthermore, K. pneumoniae had serious antibiotic resistance and multiple β-lactamase genes, including blaTEM, blaSHV, blaNDM, blaCTX-M, blaDHA, and blaKPC. Biofilm was an important factor in bacterial resistance and persistent infection, and 77.1% isolates could form biofilm. Although acylated homoserine lactone (AHL, a Gram-negative bacterial quorum sensing signal molecule) was not confirmed among the K. pneumoniae isolates, exogenous AHLs could reduce the biofilm formation ability of the K. pneumoniae strains. Three new ST types (ST6781, ST6782, and ST6783) were first identified in this study. The MLST phylogenetic tree showed the distribution of mastitis associated K. pneumoniae strains had no regular pattern, which confirmed high genomic diversity of mastitis associated K. pneumoniae. In conclusion, the high rate of isolation and serious antibiotic resistance of K. pneumonia were found in this study and indicated a potential threat to public health from the food chain., Competing Interests: Declarations Ethical approval This study does not contain any experiments with human participants or animals. Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Key Message: PAs varied greatly in leaves of different germplasm accessions in Lotus corniculatus and over-expression of LcMYB5 led to high PA accumulation in L. japonicus hairy roots. Proanthocyanidins (PAs) content in leaves is an important quality trait in forage species. The leaves of most forage crops accumulated no or little PAs, which makes it difficult to discover key genes involved in PA biosynthesis in the leaves. We found PAs content varied greatly in leaves of different germplasm accessions in Lotus corniculatus, which is one of the most agriculturally important forage crops. Through a combination of global transcriptional analysis, GO and KEGG analysis, and phylogenetic analysis, we discovered that LcMYB5 was strongly correlated with PA accumulation in leaves of L. corniculatus. The subcellular localization and transactivation activity assays demonstrated that LcMYB5 localized to the nucleus and acted as a transcriptional activator. Over-expression of the two homologs of LcMYB5 (LcMYB5a and LcMYB5b) in the L. japonicus hairy roots resulted in a particular high level of PAs. Global transcriptional analysis and qRT-PCR assays indicated that LcMYB5a and LcMYB5b up-regulated the transcript levels of many key PA pathway genes in the transgenic hairy roots, including structural genes (eg. CHS, F3H, LAR, ANR, and TT15) and regulatory genes (eg. TT8 and TTG1). Collectively, our data suggests that LcMYB5 independently regulates PA accumulation in the leaves of Lotus as a master regulator, which can be bioengineered for PAs production in the leaves of forage species., Competing Interests: Declarations Conflict of interest The authors have no conflicts of interest to declare. Data availability All data supporting the findings of this study are available within the paper and within its supplementary data published online., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The coronavirus disease 2019 (COVID-19) pandemic has caused significant changes in lower respiratory tract infections (LRTIs). This study aimed to characterize potentially pathogenic bacterial infections in paediatric patients hospitalized for LRTIs per-, during and post-COVID-19., Methods: Sputum culture data from 85,659 children with LRTIs at the Children's Hospital of Soochow University from January 2016 to May 2024 were analyzed for eight bacteria: Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii. The data during the pandemic (2020-2022, during COVID-19) and after the pandemic (January 2023-May 2024, post-COVID-19) were compared with those before the pandemic (2016-2019)., Results: Overall, 85,659 children with LRTIs were enrolled. Of these, 42,567 cases (49.7%) were diagnosed in the pre-COVID-19 period, 22,531 cases (26.3%) during the COVID-19 period and 20,561 cases (24.0%) in the post-COVID-19 period. The overall positive rate for pathogenic bacteria was 37.1%, with the top three being S. pneumoniae (14.5%), H. influenzae (12.1%) and S. aureus (6.5%). Compared to the average pre-COVID-19 levels, the bacterial pathogen positive rate decreased by 3.5% during the COVID-19 period (OR: 0.94, 95% CI: 0.91-0.98) and by 23.4% in the post-COVID-19 period (OR: 0.66, 95% CI: 0.64-0.69). During the COVID-19 period, the positive rates for S. pneumoniae, H. influenzae, E. coli, K. pneumoniae and mixed infections decreased by 11.7%, 35.3%, 22.2%, 33.3% and 45.7% respectively, while the positive rates for S. aureus, M. catarrhalis and P. aeruginosa increased by 21.7%, 44.7% and 25% respectively. In the post-COVID-19 period, the positive rates for S. pneumoniae, H. influenzae, E. coli, P. aeruginosa, K. pneumoniae, A. baumannii and mixed infections decreased by 50.0%, 7.4%, 22.2%, 50.0%, 44.4%, 60.0% and 32.6% respectively, while there was no statistical change in the positive rates for S. aureus and M. catarrhalis. Bacteria case detection decreases in 2020 (67.0%), 2021 (60.5%), 2022 (76.3%) and 2023 (72.7%) compared to predicted cases., Conclusions: Measures to restrict COVID-19 as a driver of declining bacterial positive rates. Respiratory bacteria in children are change across COVID-19 phases, age groups and seasons. After COVID-19, clinicians should continue to increase surveillance for pathogenic bacteria, especially drug-resistant flora., Competing Interests: Declarations Ethics approval and consent to participate All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.The study was approved by the Medical Ethics Committee of the Children’s Hospital of Soochow University under approval number 2,013,002. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin. Consent to participate Informed consent was obtained from all individual participants included in this study. Clinical trial number Not applicable. Human ethics and consent to participate declarations Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Breast cancer brain metastasis (BCBM) is a deadly clinical problem, and the exact underlying mechanisms remain elusive. Junctional adhesion molecule (JAM), a tight junction protein, is a key negative regulator of cancer cell invasion and metastasis., Methods: Junction adhesion molecule 3 (JAM3) expression in breast cancer was analyzed using bioinformatics methods and confirmed by PCR, western blotting, and immunofluorescence (IF) in cell lines. The effects of exogenous expression of JAM3 using lentiviral vectors on invasion, adhesion, and apoptosis were verified using transwell assays and flow cytometry. Differentially expressed genes (DEGs) were detected by RNA sequencing and verified by q‒PCR and Western blotting. The effect of JAM3 silencing using siRNA was assessed by an adhesion assay. Kaplan‒Meier analysis was applied to calculate the impact of JAM3 expression and classic clinicopathologic characteristics on survival., Results: Bioinformatics analysis revealed that JAM3 expression was reduced in BCBM. Exogenous expression of JAM3 minimizes the ability of breast cancer cells to invade and adhere and promotes their apoptosis. Silencing JAM3 results in morphology changes and the recovery of invasion and adhesion to ECMs, and the TGF-β/Smad signaling pathway may be involved. JAM3 predicts less metastasis and good survival in patients with BCBM. Statistical analysis of BCBM samples detected by immunohistochemistry (IHC) and the associated clinicopathological characteristics revealed that low levels of JAM3 expression and high levels of TNF-β1 are linked to the clinical progression of both primary and metastatic breast tumors. Kaplan-Meier analysis revealed that a high expression level of JAM3 was associated with longer survival., Conclusion: JAM3 can serve as a key negative regulator of breast cancer cell invasion, apoptosis, and brain metastasis, possibly through the TGF/Smad signaling pathway. JAM3 is anticipated to be a promising biomarker for the diagnosis and prognosis of breast cancer., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Subdural hematoma (SDH) drains into the extracranial lymphatic system through the meningeal lymphatic vessels (mLVs) but the formation of SDH impairs mLVs. Because vitamin D (Vit D) can protect the endothelial cells, we hypothesized that Vit D may enhance the SDH clearance. SDH was induced in Sprague-Dawley rats and treated with Vit D or vehicle. Hematoma volume in each group was measured by H&E staining and hemoglobin quantification. Evans blue (EB) quantification and red blood cells injection were used to evaluated the drainage of mLVs. Western blot analysis and immunofluorescence were conducted to assess the expression of lymphatic protein markers. We also examined the inflammatory factors levels in subdural space by ELISA. Vit D treatment significantly reduced SDH volume and improved the drainage of SDH to cervical lymph nodes. The structure of mLVs in SDH rats were protected by Vit D, and the expressions of LYVE1, PROX1, FOXC2, and VE-cadherin were increased after Vit D treatment. The TNF-α, IL-6, and IL-8 levels were reduced in Vit D group. In vitro, Vit D also increased the VE-cadherin expression levels under inflammation. Vit D protects the structure of mLVs and enhances the absorption of SDH, partly by the anti-inflammatory effect of Vit D., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Postoperative morbidity in patients undergoing curative colorectal cancer surgery is high. Prehabilitation has been suggested to reduce postoperative morbidity, however its effectiveness is still lacking., Objective: The aim of this study was to investigate the effectiveness of prehabilitation in reducing postoperative morbidity and length of hospital stay in patients undergoing colorectal cancer surgery., Methods: A comprehensive electronic search was conducted in the CINAHL, Cochrane Library, Medline, PsychINFO, AMED, and Embase databases from inception to April 2023. Randomised controlled trials testing the effectiveness of prehabilitation, including exercise, nutrition, and/or psychological interventions, compared with usual care in patients undergoing colorectal cancer surgery were included. Two independent review authors extracted relevant information and assessed the risk of bias. Random-effect meta-analyses were used to pool outcomes, and the quality of evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) guidelines., Results: A total of 23 trials were identified (N = 2475 patients), including multimodal (3 trials), exercise (3 trials), nutrition (16 trials), and psychological (1 trial) prehabilitation. There was moderate-quality evidence that preoperative nutrition significantly reduced postoperative infectious complications (relative risk 0.65, 95% confidence interval [CI] 0.45-0.94) and low-quality evidence on reducing the length of hospital stay (mean difference 0.87, 95% CI 0.17-1.58) compared with control. A single trial demonstrated an effect of multimodal prehabilitation on postoperative complication., Conclusion: Nutrition prehabilitation was effective in reducing infectious complications and length of hospital stay. Whether other multimodal, exercise, and psychological prehabilitation modalities improve postoperative outcomes after colorectal cancer surgery is uncertain as the current quality of evidence is low., Protocol Registration: Open Science Framework ( https://doi.org/10.17605/OSF.IO/VW72N )., (© 2024. The Author(s).)

Purpose: Refractory hepatic encephalopathy (RHE) can occur as a consequence of excessive shunting following the creation of a transjugular intrahepatic portosystemic shunt (TIPS). We describe a technique that utilizes a suture-constrained covered stent for shunt reduction to treat TIPS-related RHE., Materials and Methods: Between January 2017 and September 2023, 25 patients with TIPS-related RHE who underwent shunt reduction utilizing a suture-constrained covered stent were reviewed. The procedure involved reducing the diameter of a polytetrafluoroethylene-covered stent from 8 to 5 mm with a non-absorbable suture and inserting it into the existing TIPS stent to reduce shunt flow., Results: Twelve of the 25 patients were evaluated. Shunt reduction was technically successful in all patients and no immediate complications related to the procedures were observed. Varying degrees of improvement in HE symptoms were observed after shunt reduction, with a mean increase in portosystemic gradient of 5 mmHg compared to pre-procedure, and complete disappearance of symptoms was observed in seven (58.3%) individuals. After a median follow-up of 8.3 months, HE recurred in 4 patients (33.3%) and TIPS indication recurred in 2 patients (16.7%) in the form of ascites and variceal bleeding, respectively. One patient (8.3%) developed shunt dysfunction detected by Doppler ultrasound and was accompanied by the presence of hepatic hydrothorax and ascites. At the end of the study, 5 patients (41.7%) were alive, 5 (41.7%) succumbed to liver failure, and 2 (16.7%) succumbed to pneumonia., Conclusions: Constraining the stent diameter with a suture is feasible, and using this suture-constrained covered stent for shunt reduction can effectively improve TIPS-related RHE. Further investigations are warranted to precisely delineate the impact of the increased portosystemic gradient and to optimize patient survival., (© 2024. The Author(s) under exclusive licence to Japan Radiological Society.)

Soft rot is one of the top ten most dangerous plant pathogens in agricultural production, storage, and transport, and the use of microorganisms and their metabolites to control soft rot is a current research hotspot. In this study, we identified the antimicrobial substance in the metabolite of Paenibacillus polymyxa KH-19, and determined that the antimicrobial substance of this strain was an active protein. The protein was completely precipitated at 40-60% ammonium sulphate saturation and showed good inhibitory effects against seven pathogenic bacteria including Pectobacterium carotovorum BC2 and seven pathogenic fungi including Pyricularia oryzae. The MIC of the protein was 51.563 µg/mL, temperature acid-base UV and light stability insensitive to protease, with high-temperature resistance. The antimicrobial protein was isolated and purified by DEAE-anion exchange column and Sephadex G-75 gel filtration chromatography, and the LC-MS/MS assay identified the protein as lysophosphatidyl esterase with a molecular weight of 25.255 kDa. The purified antimicrobial protein increased the inhibitory effect against P. carotovorum BC2, with the diameter of the circle of inhibition being 26.50 ± 0.915 mm. Bioinformatics analysis showed that the protein has the molecular formula of C 1117 H 1732 N 316 O 338 S 5 , encodes 224 amino acids, has an aliphatic index of 88.39, and belongs to the category of hydrophilic unstable proteins. The present study is the first report of an active protein with extreme thermoplastic and resistance to P. carotovorum BC2, which provides a reference for the preparation and application of the antimicrobial substances of P. polymyxa KH-19, as well as a theoretical basis for the study of the function of lysophosphodiesterase protein and its use as a microbial preparation., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Research into the potential therapeutic benefits of herbal remedies for treating chronic kidney disease (CKD), a condition marked by renal fibrosis and persistent inflammation, has become popular. Eucommiae cortex (EC) is a vital herb for strengthening bones and muscles and tonifying the kidneys and liver. In the study, C57 BL/6 mice were given a diet containing 0.2% adenine to create a CKD model. The findings demonstrated that exogenous EC supplementation successfully decreased the levels of creatinine and urea nitrogen, down-regulated the TGF-β1/Smad signaling pathway's expression levels of TGF-β1, α-SMA, Smad3, and phospho-Smad3, and prevented renal fibrosis. Consequently, it was determined that EC might have a nephroprotective impact., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

Background: The population of Aging cancer survivors in the United States has surged to over 16.9 million. Research on the relationship between statin usage and post-cancer survival rates remains limited., Aims: This study aims to investigate the association between statin use and various causes of mortality among aging cancer survivors., Methods: We analyzed NHANES data from 1999 to 2018, Statin usage, both hydrophilic and lipophilic, was derived from NHANES prescription records. We utilized Cox proportional hazards models to associate statin utilization with mortality, differentiating causes of death according to statin type and patterns of use., Results: Within a cohort of 2,968 participants, statin usage was categorized into non-users (1,738), hydrophilic statin users (216), and lipophilic statin users (982). Compared to those who did not use statins, individuals prescribed hydrophilic statins did not show a reduced risk of all-cause mortality (adjusted hazard ratio [HR] 1.01; 95% confidence interval [CI] 0.72-1.41; P = 0.960), as outlined in Model 3. In contrast, the group receiving lipophilic statins exhibited a notable decrease in all-cause mortality risk (adjusted HR, 0.77; P = 0.003). Nonetheless, both hydrophilic and lipophilic statins were effective in diminishing the risk associated with cancer from its onset until death, with hydrophilic statins showing a greater level of efficacy., Discussion: The potential of statins to reduce cancer-related mortality may provide avenues for targeted clinical interventions and management strategies., Conclusions: Our study reveals that the use of lipophilic statins is significantly associated with lower all-cause and cancer-cause mortality risks among aging cancer survivors., (© 2024. The Author(s).)

The existence of cancer stem cells (CSCs) in pancreatic ductal adenocarcinoma (PDAC) is considered to be the key factor for metastasis and chemoresistance. Thus, novel therapeutic strategies for eradicating CSCs are urgently needed. Here we aimed to explore the role of KLF15 in stemness and the feasibility of using KLF15 to inhibit CSCs and improve chemotherapy sensitivity in PDAC. In this study, we report that KLF15 is negatively associated with poor survival and advanced pathological staging of PDAC. Moreover, tumorous KLF15 suppresses the stemness of PDAC by promoting the degradation of Nanog, and KLF15 directly interacts with Nanog, inhibiting interaction between Nanog with USP21. We also demonstrate that the KLF15/Nanog complex inhibit the stemness in vivo and in PDX cells. Tazemetostat suppresses stemness and sensitizes PDAC cells to gemcitabine by promoting KLF15 expression in PDAC. In summary, the findings of our study confirm the value of KLF15 level in diagnosis and prognosis of PDAC, it is the first time to explore the inhibition role of KLF15 in stemness of PDAC and the regulation mechanism of Nanog, contributing to provide a new therapeutic strategy that using Tazemetostat sensitizes PDAC cells to gemcitabine by promoting KLF15 expression for PDAC., (© 2024. The Author(s).)

Graph neural networks (GNNs) are proficient machine learning models in handling irregularly structured data. Nevertheless, their generic formulation falls short when applied to the analysis of brain connectomes in Alzheimer's Disease (AD), necessitating the incorporation of domain-specific knowledge to achieve optimal model performance. The integration of AD-related expertise into GNNs presents a significant challenge. Current methodologies reliant on manual design often demand substantial expertise from external domain specialists to guide the development of novel models, thereby consuming considerable time and resources. To mitigate the need for manual curation, this paper introduces a novel self-guided knowledge-infused multimodal GNN to autonomously integrate domain knowledge into the model development process. We propose to conceptualize existing domain knowledge as natural language, and devise a specialized multimodal GNN framework tailored to leverage this uncurated knowledge to direct the learning of the GNN submodule, thereby enhancing its efficacy and improving prediction interpretability. To assess the effectiveness of our framework, we compile a comprehensive literature dataset comprising recent peer-reviewed publications on AD. By integrating this literature dataset with several real-world AD datasets, our experimental results illustrate the effectiveness of the proposed method in extracting curated knowledge and offering explanations on graphs for domain-specific applications. Furthermore, our approach successfully utilizes the extracted information to enhance the performance of the GNN., Competing Interests: Disclosure of Interests. The authors have no competing interests to declare that are relevant to the content of this article.

Receiver for Activated C Kinase 1 (RACK1) is a highly conserved scaffold protein that can assemble multiple kinases and proteins together to form complexes, thereby regulating signal transduction process and various cellular biological processes, including cell cycle regulation, differentiation, and immune response. However, the function and mechanism of RACK1 in cervical cancer remain incompletely understood. Here we identified that RACK1 could significantly suppress cell ferroptosis in cervical cancer cells. Mechanistically, RACK1 increased the expression of FUT8 by inhibiting miR-1275, which in turn promoted the FUT8-catalyzed core-fucosylation of cystine/glutamate antiporter SLC7A11, thereby inhibiting SLC7A11 degradation and cell ferroptosis. Our data highlight the role of RACK1 in cervical cancer progression and its suppression of ferroptosis via the RACK1/miR-1275/FUT8/SLC7A11 axis, suggesting that inhibiting this pathway may be a promising therapeutic approach for patients with cervical cancer., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Apple replant disease (ARD) is a significant factor restricting the healthy development of the apple industry. Biological control is an important and sustainable method for mitigating ARD. In this study, a strain of Paenibacillus polymyxa GRY-11 was isolated and screened from the rhizosphere soil of healthy apple trees in old apple orchards in Shandong Province, China, and the effects of strain GRY-11 on soil microbial community and ARD were studied. The result showed that P. polymyxa GRY-11 could effectively inhibit the growth of the main pathogenic fungi that caused ARD, and the inhibition rates of the strain against Fusarium moniliforme, Fusarium proliferatum, Fusarium solani, and Fusarium oxysporum were 80.00%, 71.60%, 75.00%, and 70.00%, respectively. In addition, the fermentation supernatant played an active role in suppressing the growth of pathogenic fungi. The results of the pot experiment showed that the bacterial fertilizer of the GRY-11 promoted the growth of Malus hupehensis seedlings, improved the activity of protective enzymes in plant roots, enhanced the soil enzyme content, and optimized the soil microbial environment. In general, the GRY-11 can be used as an effective microbial preparation to alleviate ARD. Our study offers novel perspectives for the prevention of ARD., (© 2024. Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i.)

Objective: The present research aims to assess the factors that influence live birth outcomes following fresh embryo transfers using antagonist protocols in individuals diagnosed with polycystic ovary syndrome (PCOS). Furthermore, it seeks to develop a predictive nomogram model to facilitate clinical decision-making and provide personalized treatment strategies., Methods: This retrospective cohort research analyzed the clinical data of 1242 individuals having PCOS who went through fresh embryo transfers employing antagonist protocols and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) at Fujian Provincial Maternal and Child Health Hospital between January 2018 and December 2022. Individuals were assigned randomly to a modeling group (869 cases) and a validation group (373 cases) in a 7:3 ratio. The Boruta algorithm and multivariable logistic regression were utilized to identify independent risk factors linked to live births after transfer. A predictive nomogram was subsequently developed. The discriminatory power of the model and its accuracy were monitored by utilizing receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis., Results: Multivariable logistic regression analysis identified several independent factors that influence live birth rates in fresh embryo transfer cycles for individuals having PCOS using antagonist protocols, including female age, body mass index (BMI), infertility duration, serum testosterone levels, progesterone levels at the time of human chorionic gonadotropin (hCG) injection, number of high-quality cleavage-stage embryos, type of embryo transferred, and the total number of embryos transferred. Based on these findings, a predictive nomogram was developed. The area under the ROC curve stood at 0.804 (95% confidence interval (CI), 0.775-0.833) for the modeling group and 0.807 (95% CI, 0.762-0.851) for the validation group. Calibration curves confirmed that the predictions of the nomogram closely matched the actual live birth outcomes. Decision curve analysis highlighted that the model provides significant net benefits for predicting live birth rates, with optimal performance across a probability range of 16.5 to 88.6%., Conclusion: Independent factors, including female age, infertility duration, BMI, serum testosterone levels, progesterone levels on the day of hCG injection, and the number and type of high-quality cleavage-stage embryos transferred are pivotal in influencing live birth outcomes in fresh embryo transfer cycles under antagonist protocols in individuals with PCOS undergoing IVF/ICSI treatments. The predictive nomogram developed from these factors offers substantial predictive accuracy and clinical utility, providing a reliable basis for clinical prognosis, targeted interventions, and the development of personalized treatment plans., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A human laryngeal model, incorporating all the cartilages and the intrinsic muscles, was reconstructed based on MRI data. The vocal fold was represented as a multilayer structure with detailed inner components. The activation levels of the thyroarytenoid (TA) and cricothyroid (CT) muscles were systematically varied from zero to full activation allowing for the analysis of their interaction and influence on vocal fold dynamics and glottal flow. The finite element method was employed to calculate the vocal fold dynamics, while the one-dimensional Bernoulli equation was utilized to calculate the glottal flow. The analysis was focused on the muscle influence on the fundamental frequency (f o ). We found that while CT and TA  activation increased the f o in most of the conditions, TA activation resulted in a frequency drop when it was moderately activated. We show that this frequency drop was associated with the sudden increase of the vertical motion when the vibration transited from involving the whole tissue to mainly in the cover layer. The transition of the vibration pattern was caused by the increased body-cover stiffness ratio that resulted from TA activation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The specific CT-related skeletal muscle parameters predictive of postoperative survival in liver transplant (LT) patients with hepatocellular carcinoma (HCC) remain unclear. There is increasing evidence supporting the role of fatty acids and their lipid intermediates in regulating skeletal muscle mass and function, the relationship between lipoprotein subfractions and body composition remains unclear., Methods: Adult patients with HCC who underwent LT between January 2015 and September 2022 were retrospectively analyzed. CT parameters, including skeletal muscle index (SMI), psoas muscle index (PMI), skeletal muscle density (SMD), visceral and subcutaneous adipose tissue (VAT and SAT), and the VAT/SAT ratio at the L3 level, and lipid profiles, were assessed prior to LT., Results: Of the 284 LT patients with HCC, 224 underwent CT (L3 level) within 3 months of LT, and 82 (37%) were diagnosed with myosteatosis. Patients with myosteatosis exhibited significantly lower 1- and 3-year survival rates (p = 0.002, p = 0.01), a trend persisting even beyond the Milan criteria (p = 0.004, p = 0.04). After adjusting for covariates, SMD demonstrated a significant negative correlation with post-transplant survival (HR: 0.90, [95% Confidence Interval(CI): 0.83-0.98], C-statistic: 0.78, p = 0.009). Pearson's correlation analysis revealed a positive correlation between high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1(ApoA1) levels and SMD. Multivariate stepwise regression analysis demonstrated that every 10 Hounsfield unit decrease in SMD was associated with a 0.16 mmol/L decrease in HDL-C and a 0.18 g/L decrease in ApoA1., Conclusion: Routine abdominal CT scans for assessing skeletal muscle density before LT were significantly associated with post-transplant mortality. Furthermore, abnormal HDL-C and ApoA1 levels before LT were associated with myosteatosis., (© 2024. Asian Pacific Association for the Study of the Liver.)

Purpose: This study explored models of monoexponential diffusion-weighted imaging (DWI), diffusion kurtosis imaging (DKI), stretched exponential (SEM), fractional-order calculus (FROC), and continuous-time random-walk (CTRW) as diagnostic tools for assessing pathological prognostic factors in patients with resectable rectal cancer (RRC)., Methods: RRC patients who underwent radical surgery were included. The apparent diffusion coefficient (ADC), the mean kurtosis (MK) and mean diffusion (MD) from the DKI model, the distributed diffusion coefficient (DDC) and α from the SEM model, D, β and u from the FROC model, and D, α and β from the CTRW model were assessed., Results: There were a total of 181 patients. The area under the receiver operating characteristic (ROC) curve (AUC) of CTRW-α for predicting histology type was significantly higher than that of FROC-u (0.780 vs. 0.671, p = 0.043). The AUC of CTRW-α for predicting pT stage was significantly higher than that of FROC-u and ADC (0.786 vs.0.683, p = 0.043; 0.786 vs. 0.682, p = 0.030), the difference in predictive efficacy of FROC-u between ADC and MK was not statistically significant [0.683 vs. 0.682, p = 0.981; 0.683 vs. 0.703, p = 0.720]; the difference between the predictive efficacy of MK and ADC was not statistically significant (p = 0.696). The AUC of CTRW (α + β) (0.781) was significantly higher than that of FROC-u (0.781 vs. 0.625, p = 0.003) in predicting pN stage but not significantly different from that of MK (p = 0.108)., Conclusion: The CTRW and DKI models may serve as imaging biomarkers to predict pathological prognostic factors in RRC patients before surgery., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Nasopharyngeal carcinoma (NPC) arises from the mucosal epithelium of the nasopharynx and is frequently located in the pharyngeal crypts. This is a highly aggressive malignant tumor that frequently leads to distant metastases in many cases and poses a significant public health challenge, particularly in certain geographic regions globally. This review discusses the epidemiology, risk factors, diagnosis, and treatment options for NPC, emphasizing the importance of early detection and comprehensive management strategies in improving patient outcomes. Moreover, the article explores the intricate mechanisms that cause NPC. Comprehending these fundamental principles can assist in creating specific prevention and therapy approaches for NPC. Recent advances in diagnostic methods, including imaging tests and molecular biomarkers, are emphasized to improve early diagnosis and individualized treatment strategies for individuals with NPC. The review also explores the most recent advancements in treating early-stage (stage I and II) NPC patients, highlighting the changing landscape of individualized therapy approaches for this particular set of patients., (© 2024. The Author(s).)

Background: Cholangiocarcinoma (CCA), a primary hepatobiliary malignancy, is characterized by a poor prognosis and a lack of effective treatments. Therefore, the need to explore novel therapeutic approaches is urgent. While the role of Peptidylprolyl Cis/Trans Isomerase, NIMA-Interacting 1 (PIN1) has been extensively studied in various tumor types, its involvement in CCA remains poorly understood., Methods: In this study, we employed tissue microarray (TMA), reverse transcription-polymerase chain reaction (RT-PCR), and The Cancer Genome Atlas (TCGA) database to assess the expression of PIN1. Through in vitro and in vivo functional experiments, we investigated the impact of PIN1 on the adhesion and metastasis of CCA. Additionally, we explored downstream molecular pathways using RNA-seq, western blotting, co-immunoprecipitation, immunofluorescence, and mass spectrometry techniques., Results: Our findings revealed a negative correlation between PIN1 overexpression and prognosis in CCA tissues. Furthermore, high PIN1 expression promoted CCA cell proliferation and migration. Mechanistically, PIN1 functioned as an oncogene by regulating ANXA2 phosphorylation, thereby promoting CCA adhesion. Notably, the interaction between PIN1 and ANXA2 was facilitated by RACK1. Importantly, pharmacological inhibition of PIN1 using the FDA-approved drug all-trans retinoic acid (ATRA) effectively suppressed the metastatic potential of CCA cells in a nude mouse lung metastasis model., Conclusion: Overall, our study emphasizes the critical role of the PIN1/RACK1/ANXA2 complex in CCA growth and functionality, highlighting the potential of targeting PIN1 as a promising therapeutic strategy for CCA., (© 2024. Springer Nature Switzerland AG.)

Nod-like receptor family pyrin-containing protein 3 (NLRP3) inflammasome plays a pathologic role in metabolic dysfunction-associated steatohepatitis (MASH), but the molecular mechanism regulating the NLRP3 inflammasome activation in hepatocellular lipotoxicity remains largely unknown. Bromodomain-containing protein 4 (BRD4) has emerged as a key epigenetic reader of acetylated lysine residues in enhancer regions that control the transcription of key genes. The aim of this study is to investigate if and how BRD4 regulated the NLRP3 inflammasome activation and pyroptosis in MASH. Using the AML12 and primary mouse hepatocytes stimulated by palmitic acid (PA) as an in vitro model of hepatocellular lipotoxicity, we found that targeting BRD4 by genetic knockdown or a selective BRD4 inhibitor MS417 protected against hepatosteatosis; and this protective effect was attributed to inhibiting the activation of NLRP3 inflammasome and reducing the expression of Caspase-1, gasdermin D (GSDMD), interleukin (IL)-1β and IL-6. Moreover, BRD4 inhibition limited the voltage-dependent anion channel-1 (VDAC1) expression and oligomerization in PA-treated AML12 hepatocytes, thereby suppressing the NLRP3 inflammasome activation. Additionally, the expression of BRD4 enhanced in MASH livers of humans. Mechanistically, BRD4 was upregulated during hepatocellular lipotoxicity that in turn modulated the active epigenetic mark H3K27ac at the promoter regions of the Vdac and Gsdmd genes, thereby enhancing the expression of VDAC and GSDMD. Altogether, our data provide novel insights into epigenetic mechanisms underlying BRD4 activating the NLRP3 inflammasome and promoting GSDMD-mediated pyroptosis in hepatocellular lipotoxicity. Thus, BRD4 might serve as a novel therapeutic target for the treatment of MASH., (© 2024. The Author(s).)

Background: Collecting duct carcinoma (CDC) is a rare histological type of renal cell carcinoma that lacks a prognostic prediction model. In this study, we developed a nomogram to predict the prognosis of CDC patients., Methods: Data for patients (n = 247) diagnosed with CDC from 2004 to 2015 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database, and the patients were randomized into training (n = 165) and validation (n = 82) cohorts. Survival outcomes were evaluated by the Kaplan-Meier method. Significant variables determined by univariate and multivariate Cox regression analyses were used to construct the nomogram. C-indexes and calibration plots were applied to evaluate the performance of the nomogram., Results: CDC patients had a median overall survival (OS) of 18.0 months (95% confidence interval: 13.7-22.3); 1-year, 3-year, and 5-year OS rates were 58.7%, 34.2%, and 29.4%, respectively. Independent prognostic factors, including age at diagnosis, tumor size, tumor grade, T stage, N stage, M stage, and surgery information, were identified by multivariate analysis. The nomogram was constructed based on significant factors in the training cohort. The C-indexes were 0.769 (training cohort) and 0.767 (validation cohort). The calibration curves for survival rates showed that the predicted and observed values were consistent., Conclusions: This study constructed a nomogram to predict prognosis in patients with CDC. The nomogram performed well in predicting the 1-year, 3-year, and 5-year OS, which can help doctors actively monitor and follow up patients., (© 2024. The Author(s).)

CD320, which is a transmembrane protein responsible for facilitating the absorption of vitamin B12, plays a key role in this process. However, the relationships between CD320 and immune cell infiltration levels remain unclear, with limited studies investigating the diagnostic and prognostic significance of CD320 in hepatocellular carcinoma. We used various databases, including the TIMER, GEPIA, UALCAN and TCGA databases to investigate the expression levels of CD320 in hepatocellular carcinoma. Subsequently, we analyzed the prognosis of hepatocellular carcinoma patients with different expression levels of CD320. Furthermore, we also performed Western blot, immunohistochemistry, and immunofluorescence analyses to validate the results of the database analysis. Finally, the functions of CD320 in hepatocellular carcinoma were also confirmed via relevant cell experiments and angiogenesis assays. We found that CD320 expression was significantly upregulated in tumor vascular endothelial cells. Moreover, the knockdown of CD320 led to a reduction in angiogenesis in endothelial cells. Increased expression of CD320 was also correlated with a poor prognosis in patients with hepatocellular carcinoma, which suggested that CD320 may be a potential prognostic marker. Finally, TIMER analysis demonstrated that the infiltration of six immune cell types was significantly associated with high expression levels of CD320 in hepatocellular carcinoma. Herein, we demonstrated that CD320 may play an important role in angiogenesis in hepatocellular carcinoma. These findings suggested that CD320 may be a potential clinical prognostic marker and immunotherapy target for hepatocellular carcinoma., (© 2024. The Author(s).)

The timely degradation of tapetum, the innermost somatic anther cell layer in flowering plants, is critical for pollen development. Although several genes involved in tapetum development have been characterized, the molecular mechanisms underlying tapetum degeneration remain elusive. Here, we showed that mutation in Abnormal Degraded Tapetum 1 (ADT1) resulted in overaccumulation of Reactive Oxygen Species (ROS) and abnormal anther development, causing earlier tapetum Programmed Cell Death (PCD) and pollen abortion. ADT1 encodes a nuclear membrane localized protein, which is strongly expressed in the developing microspores and tapetal cells during early anther development. Moreover, ADT1 could interact with metallothionein MT2b, which was related to ROS scavenging and cell death regulation. These findings indicate that ADT1 is required for proper timing of tapetum PCD by regulating ROS homeostasis, expanding our understanding of the regulatory network of male reproductive development in rice., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Atrial fibrillation (AF) is a significant precursor to cerebral embolism. Our study sought to unearth new diagnostic biomarkers for atrial fibrillation-related cerebral embolism (AF-CE) by meticulously examining multiple GEO datasets and meta-analysis. The gene expression omnibus (GEO) database provided RNA sequencing data associated with AF and stroke. We began by pinpointing genes with varied expressions in AF-CE patient blood samples. A meta-analysis was subsequently undertaken using several RNA sequencing datasets to verify these genes. LASSO regression discerned key genes for AF-CE, with their diagnostic prowess verified through ROC curve examination. Active signaling pathways within stroke patients were discerned via GO and KEGG enrichment, with PPI interactions detailing gene interplay. Differential gene analysis revealed an upregulation of sixteen genes and a downregulation of four in stroke patient blood samples. Eight genes showcased varied expression in the meta-analysis. LASSO regression zeroed in on five of these, culminating in HIST1H2BH's identification as a characteristic gene. HIST1H2BH's prowess in predicting AF-CE was confirmed through ROC. Integrin signaling, platelet activation, ECM interactions, and the PI3K-Akt pathway were found active in stroke victims. HIST1H2BH's interaction with the notably upregulated ITGA2B was spotlighted by PPI. Additionally, HIST1H2BH exhibited links with NK cells and eosinophils. HIST1H2BH emerges as an insightful diagnostic beacon for AF-CE. Its presence, post AF, potentially modulates pathways, accentuating platelet activation and consequent thrombus generation, leading to cerebral embolism., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

β-Carotene is an orange fat-soluble compound, which has been widely used in fields such as food, medicine and cosmetics owing to its anticancer, antioxidant and cardiovascular disease prevention properties. Currently, natural β-carotene is mainly extracted from plants and algae, which cannot meet the growing market demand, while chemical synthesis of β-carotene cannot satisfy the pursuit for natural products of consumers. The β-carotene production through microbial fermentation has become a promising alternative owing to its high efficiency and environmental friendliness. With the rapid development of synthetic biology and in-depth study on the synthesis pathway of β-carotene, microbial fermentation has shown promising applications in the β-carotene synthesis. Accordingly, this review aims to summarize the research progress and strategies of natural carotenoid producing strain and metabolic engineering strategies in the heterologous synthesis of β-carotene by engineered microorganisms. Moreover, it also summarizes the adoption of inexpensive carbon sources to synthesize β-carotene as well as proposes new strategies that can further improve the β-carotene production., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Abnormal expression of protein tyrosine kinase 6 (PTK6) has been proven to be involved in the development of gynecological tumors. However, its immune-related carcinogenic mechanism in other tumors remains unclear., Objective: The aim of this study was to identify PTK6 as a novel prognostic biomarker in pan-cancer, especially in lung adenocarcinoma (LUAD), which is correlated with immune infiltration, and to clarify its clinicopathological and prognostic significance., Methods: The prognostic value and immune relevance of PTK6 were investigated by using bio-informatics in this study. PTK6 expression was validated in vitro experiments (lung cancer cell lines PC9, NCI-H1975, and HCC827; human normal lung epithelial cells BEAS-2B). Western blot (WB) revealed the PTK6 protein expression in lung cancer cell lines. PTK6 expression was inhibited by Tilfrinib. Colony formation and the Cell Counting Kit-8 (CCK-8) assay were used to detect cell proliferation. The wound healing and trans-well were performed to analyze the cell migration capacity. Then flow cytometry was conducted to evaluate the cell apoptosis. Eventually, the relationship between PTK6 and immune checkpoints was examined. WB was used to estimate the PD-L1 expression at different Tilfrinib doses., Results: PTK6 was an independent predictive factor for LUAD and was substantially expressed in LUAD. Pathological stage was significantly correlated with increased PTK6 expression. In accordance with survival analysis, poor survival rate in LUAD was associated with a high expression level of PTK6. Functional enrichment of the cell cycle and TGF-β signaling pathway was demonstrated by KEGG and GSEA analysis. Moreover, PTK6 expression considerably associated with immune infiltration in LUAD, as determined by immune analysis. Thus, the result of vitro experiments indicated that cell proliferation and migration were inhibited by the elimination of PTK6. Additionally, PTK6 suppression induced cell apoptosis. Obviously, PD-L1 protein expression level up-regulated while PTK6 was suppressed., Conclusion: PTK6 has predictive value for LUAD prognosis, and could up regulated PD-L1., (© 2024. The Author(s).)

Genome-editing technologies have revolutionized research in plant biology, with major implications for agriculture and worldwide food security, particularly in the face of challenges such as climate change and increasing human populations. Among these technologies, clustered regularly interspaced short palindromic repeats [CRISPR]-CRISPR-associated protein [Cas] systems are now widely used for editing crop plant genomes. In this review, we provide an overview of CRISPR-Cas technology and its most significant applications for improving crop sustainability. We also review current and potential technological advances that will aid in the future breeding of crops to enhance food security worldwide. Finally, we discuss the obstacles and challenges that must be overcome to realize the maximum potential of genome-editing technologies for future crop and food production., (© 2024. The Author(s).)

Background: Gan-song Yin (GSY) is originated from the scripture "Gan-song Pills", a medical work of the Ningxia ethnic minorities, and its treatment of kidney diseases has good results. Its method of treating Renal clear cell carcinoma (KIRC) is still unknown, nevertheless., Methods: Firstly, utilizing a network pharmacology strategy to screen GSY for active components and targets and looking up KIRC-related targets in GeneCards and GEO databases. Secondly, protein interaction networks were constructed and analyzed for GO and KEGG enrichment. Molecular docking was then performed and clinical and other correlations of the network pharmacology results were analyzed using bioinformatic analysis methods. Finally, we performed in vitro cellular experiments with 786-O cells and ACHN cells to validate the results of network pharmacology and bioinformatic analysis., Results: With the help of network pharmacological analysis, six hub targets were eliminated. Bioinformatics study revealed that the hub targets has clinically significant clinical guiding importance. The results showed that GSY inhibited the proliferation of 786-O cells and ACHN cells, induced cell apoptosis, blocked cell cycle, and reduced cell colony formation ability. qRT-PCR results showed that GSY promoted the expression of ALB and CASP3 genes, and inhibited the expression of EGFR, JUN, MYC and VEGFA genes. Western blot results showed that GSY could promote the expression of ALB and CASP3 protein, and inhibit the expression of EGFR, JUN, MYC and VEGFA protein., Conclusions: Network pharmacology and bioinformatics analysis showed that GSY could act on multiple targets through a variety of components to achieve the effect of treating KIRC. In this study, we confirmed that GSY inhibits KIRC by regulating the expression of core targets through in vitro cellular experiments, thus providing a reference for subsequent related studies., (© 2024. The Author(s).)

Objective: This study aimed to evaluate the potential alleviation of quadriceps spasticity in children diagnosed with spastic cerebral palsy (CP) following selective dorsal rhizotomy (SDR)., Methods: A retrospective study was conducted on children suffering from spastic CP who underwent SDR at the Department of Neurosurgery, Shanghai Children's Hospital, from July 2018 to September 2020. Inclusion criteria comprised children exhibiting quadriceps spasticity exceeding modified Ashworth Scale grade 2. Muscle tone and motor function were assessed before the operation, at short-term follow-up and at the last follow-up after SDR. Additionally, intraoperative neurophysiological monitoring data were reviewed., Results: The study comprised 20 eligible cases, where, prior to surgery, 35 quadriceps muscles exhibited spasticity exceeding modified Ashworth Scale grade 2. Following short-term and mid-term follow-up, specifically an average duration of 11 ± 2 days and 1511 ± 210 days after SDR, it was observed that muscle tension in adductors, hamstrings, gastrocnemius, and soleus decreased significantly. This reduction was accompanied by a decrease in quadriceps muscle tone in 24 out of 35 muscles (68.6%). Furthermore, the study found that intraoperative electrophysiological parameters can predict postoperative spasticity relief in the quadriceps. The triggered electromyographic (EMG) output of the transected sensory root/rootlets after single-pulse stimulation revealed that the higher the EMG amplitudes in quadriceps, the greater the likelihood of postoperative decrease in quadriceps muscle tension., Conclusions: SDR demonstrates the potential to reduce muscle spasticity in lower extremities in children diagnosed with CP, including a notable impact on quadriceps spasticity even they are not targeted in SDR. The utilization of intraoperative neurophysiological monitoring data enhances the predictability of quadriceps spasticity reduction following SDR., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Purpose: Interleukin-10 receptor (IL-10R) deficiency can result in life-threatening very early-onset inflammatory bowel disease (VEO-IBD). Umbilical cord blood transplantation (UCBT) is a curative therapy for patients with IL-10R deficiency. This study aimed to investigate the efficacy of UCBT in treating IL-10R deficiency and develop a predictive model based on pre-transplant factors., Methods: Eighty patients with IL-10R deficiency who underwent UCBT between July 2015 and April 2023 were retrospectively analyzed. Cox proportional hazards regression and random survival forest were used to develop a predictive model., Results: Median age at transplant was 13.0 months (interquartile range [IQR], 8.8-25.3 months). With a median follow-up time of 29.4 months (IQR, 3.2-57.1 months), the overall survival (OS) rate was 65.0% (95% confidence interval [CI], 55.3%-76.3%). The engraftment rate was 85% (95% CI, 77%-93%). The cumulative incidences of acute and chronic graft-versus-host disease were 48.2% (95% CI, 37.1%-59.4%) and 12.2% (95% CI, 4.7%-19.8%), respectively. VEO-IBD-associated clinical symptoms were resolved in all survivors. The multivariate analysis showed that IL-6 and stool occult blood were independent prognostic risk factors. The multivariate Cox proportional hazards regression model with stool occult blood, length- or height-for-age Z-score, medical history of sepsis, and cord blood total nucleated cells showed good discrimination ability, with a bootstrap concordance index of 0.767-0.775 in predicting OS., Conclusion: Better inflammation control before transplantation and higher cord blood total nucleated cell levels can improve patient prognosis. The nomogram can successfully predict OS in patients with IL-10R deficiency undergoing UCBT., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

D-glucuronic acid is a kind of glucose derivative, which has excellent properties such as anti-oxidation, treatment of liver disease and hyperlipidemia, and has been widely used in medicine, cosmetics, food and other fields. The traditional production methods of D-glucuronic acid mainly include natural extraction and chemical synthesis, which can no longer meet the growing market demand. The production of D-glucuronic acid by biocatalysis has become a promising alternative method because of its high efficiency and environmental friendliness. This review describes different production methods of D-glucuronic acid, including single enzyme catalysis, multi-enzyme cascade, whole cell catalysis and co-culture, as well as the intervention of some special catalysts. In addition, some feasible enzyme engineering strategies are provided, including the application of enzyme immobilized scaffold, enzyme mutation and high-throughput screening, which provide good ideas for the research of D-glucuronic acid biocatalysis., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Heart failure (HF) caused by structural or functional cardiac abnormalities is a significant cause of morbidity and mortality worldwide. While HF with reduced ejection fraction (HErEF) is well understood, more than half of patients have HF with preserved ejection fraction (HFpEF). Currently, the treatment for HFpEF primarily focuses on symptom alleviation, lacking specific drugs. The stressed heart undergoes metabolic switches in substrate preference, which is a compensatory process involved in cardiac pathological remodeling. Although metabolic reprogramming in HF has gained attention in recent years, its role in HFpEF still requires further elucidation. In this review, we present a summary of cardiac mitochondrial dysfunction and cardiac metabolic reprogramming in HFpEF. Additionally, we emphasize potential therapeutic approaches that target metabolic reprogramming for the treatment of HFpEF., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Sex differences in cancer incidence and survival are constant and pronounced globally, across all races and all age groups of cancer types. In 2016, after the National Institutes of Health proposed a policy of utilizing sex as a biological variable, researchers started paying more attention to the molecular mechanisms behind gender variations in cancer. Historically, most previous studies investigating sex differences have been centered on gonadal sex hormones. Nevertheless, sex differences also involve genetic and molecular pathways that run throughout the entire process of cancer cell proliferation, metastasis, and treatment response, in addition to sex hormones. In particular, there is significant gender dimorphism in the efficacy and toxicity of oncology treatments, including conventional radiotherapy and chemotherapy, as well as the emerging targeted therapies and immunotherapy. To be clear, not all mechanisms will exhibit gender bias, and not all gender bias will affect cancer risk. Our goal in this review is to discuss some of the significant sex-related changes in fundamental cancer pathways. To this purpose, we summarize the differential impact of gender on cancer development in three dimensions: sex hormones, genetics, and epigenetics, and focus on current hot subjects including tumor suppressor function, immunology, stem cell renewal, and non-coding RNAs. Clarifying the essential mechanisms of gender differences will help guide the clinical treatment of both sexes in tumor radiation and chemotherapy, medication therapy with various targets, immunotherapy, and even drug development. We anticipate that sex-differentiated research will help advance sex-based cancer personalized medicine models and encourage future basic scientific and clinical research to take sex into account., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Six aroylhydrazone di-m-chlorobenzyltin complexes {[X-C 6 H 4 (O)C=N-N=C(Me)COO](MeOH)(m-Cl-C 6 H 4 CH 2 ) 2 Sn} 2 (X = p-Me- (1), p-MeO- (2), p-t-Bu- (3), p-NO 2 - (4), p-OH- (5) or o-OH- (6)) were synthesized and characterized by HRMS (high-resolution mass spectrometry), NMR (nuclear magnetic resonance spectroscopy), IR (Fourier transform infrared spectroscopy), and TGA (thermogravimetric analysis) techniques. The molecular structure of complexes 1-6 was confirmed by single-crystal X-ray crystallography. The structure of complexes showed a distorted pentagonal bipyramidal configuration around the tin atom center, and the ligands adopted a tridentate chelating mode. Fascinatingly, either one-dimensional infinite chain structures or two-dimensional network structures were observed in the complexes through hydrogen bonds. Complex 2 has the strongest inhibitory effect on MCF7 and HepG2 cell proliferation, its effect was superior to that of the positive control drug cisplatin. The interaction of ct-DNA (calf-thymus DNA) with complex 2 was explored using UV absorption (ultraviolet absorption) and fluorescence spectroscopy. Complex 2 exhibited a moderate affinity for ct-DNA through intercalation modes. The interaction of complex 2 with ct-DNA has also been supported by molecular docking studies., (© 2023. The Author(s), under exclusive licence to Society for Biological Inorganic Chemistry (SBIC).)

Background: People with autoimmune diseases are prone to cancer, and there is a close relationship between rheumatoid arthritis (RA) and acute myeloid leukemia (AML). The bone marrow (BM) is affected throughout the course of RA, with a variety of hematologic involvement. Hopes are pinned on rheumatoid arthritis research to obtain BM biomarkers for AML., Methods: Synovial transcriptome sequencing data for RA and osteoarthritis (OA), and single-cell sequencing data for RA and controls were obtained from the GEO database.Bone marrow sequencing data for AML patients and normal subjects were obtained from the UCSC Xena database. The final immune heterogeneity characteristics of RA were determined through ssGSEA analysis, gene differential expression analysis, fuzzy c-means clustering algorithm, and XGboost algorithm. Random Ferns classifiers (RFs) are used to identify new bone marrow markers for AML., Results: SELL, PTPRC, IL7R, CCR7, and KLRB1 were able to distinguish leukemia cells from normal cells well, with AUC values higher than 0.970., Conclusion: Genes characterizing the immune heterogeneity of RA are associated with AML, and KLRBA may be a potential target for AML treatment., (© 2023. The Author(s).)

Industrial co-agglomeration (IC) plays a pivotal role in the development of local and adjacent green energy efficiency across 284 Chinese cities, encompassing both resource-based and non-resource-based urban centers. Based on the panel data of 284 cities in China from 2005 to 2020, this study employs spatial econometric methods to empirically assess the influence of IC and its spillover effects on green energy efficiency, employing a spatial Durbin model. Additionally, the study categorizes the 284 Chinese cities into resource-based and non-resource-based categories, utilizing spatial econometric methods to delve into the heterogeneity of their effects and spillover impacts. The key findings are as follows: (1) The average green energy efficiency across the 284 Chinese cities from 2005 to 2020 stands at 0.5834. The trend in IC indicates growth and concentration towards the central areas, increasing from 2.7396 in 2005 to 2.7658 in 2020. (2) The IC, with a coefficient of 0.0918, promotes the local green energy efficiency. (3) There are spillover effects of local IC on the green energy efficiency in adjacent areas with a coefficient of 0.2550 and an Indirect Effect of 0.4567. (4) In resource-based cities, IC positively impacts local green energy efficiency with a coefficient of 0.1056 but negatively affects green energy efficiency in adjacent areas with a coefficient of -0.1368. In non-resource-based cities, IC enhances green energy efficiency in adjacent cities with a coefficient of 0.1335. Consequently, the study offers pertinent policy recommendations aimed at improving energy efficiency in light of these findings., (© 2023. The Author(s).)

The Lancang River flows through the alpine canyon region of southwest China, an area that has experienced frequent geological disasters over the years. Early monitoring of geological hazards is essential for disaster prevention and mitigation. However, traditional ground monitoring techniques are limited by the complex terrain conditions in high-altitude valley regions. In contrast, interferometric synthetic aperture radar (InSAR) technology can provide a high-precision, wide-range monitoring of slow rock-slope deformation, making it an effective tool for studying geological hazards. Within the study area, multiple synthetic aperture radar (SAR) images from the Sentinel-1A satellite were collected, and surface deformation was obtained using the small baseline subset InSAR (SBAS-InSAR). The results demonstrate that combining ascending and descending orbit images can be successfully applied to landslide monitoring in complex mountainous areas. Over 30 potential landslides were identified by combining InSAR results with optical images. The Line-Of-Sight (LOS) direction deformation features and their relationship with precipitation were analyzed based on two typical landslides, and two-dimensional/three-dimensional (2D/3D) deformation decomposition was carried out to reveal its motion characteristics. It was found that the cumulative deformation fluctuation amplitude was higher during the rainy season, and the main movement direction of the landslide was east-west. In addition, based on the spatial distribution and statistical analysis of deformation points along with meteorological data, geological elements, human activities, and topographic conditions, it is inferred that factors such as low vegetation coverage, tectonic movements, human activities, and high-altitude glacier thawing may contribute to the occurrence of disasters. And it was found that areas with high vegetation cover, high rainfall, and snow cover exhibit lower coherence coefficients. This study offers valuable insights for investigating large-scale geological in alpine canyon regions., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Few studies were performed on the impact of exposure to gaseous pollutants on the risk of knee osteoarthritis (KOA). We conducted this study to analyze the association between short-term exposure to gaseous pollutants and the risk of hospitalizations for KOA. A total of 2952 KOA hospitalizations derived from two hospitals in Hefei, and the relationship between gaseous pollutants and KOA hospitalizations was analyzed by a distributed lag non-linear model combined with a generalized linear model. We found that the decreased risk of hospitalizations for KOA were both related to exposure to NO 2 (RR = 0.993, lag19 day) and O 3 (RR = 0.984, lag0 day), while exposure to CO could increase the risk of hospitalizations for KOA (RR = 1.076, lag2 day). Stratified analyses suggested that the KOA patients < 65 years were more susceptible to O 3 exposure, and the female, male, patients ≥ 65 years, and patients < 65 years were both more sensitive to CO exposure. Our findings demonstrated that exposure to NO 2 , O 3 resulted in a decreased risk for KOA hospitalizations, and CO exposure might increase the risk of KOA hospitalizations., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Two-dimensional (2D) transition metal chalcogenides (TMCs) hold great promise as novel microwave absorption materials owing to their interlayer interactions and unique magnetoelectric properties. However, overcoming the impedance mismatch at the low loading is still a challenge for TMCs due to the restricted loss pathways caused by their high-density characteristic. Here, an interface engineering based on the heterostructure of 2D Cr 5 Te 8 and graphite is in situ constructed via a one-step chemical vapor deposit to modulate impedance matching and introduce multiple attenuation mechanisms. Intriguingly, the Cr 5 Te 8 @EG (ECT) heterostructure exhibits a minimum reflection loss of up to - 57.6 dB at 15.4 GHz with a thin thickness of only 1.4 mm under a low filling rate of 10%. The density functional theory calculations confirm that the splendid performance of ECT heterostructure primarily derives from charge redistribution at the abundant intimate interfaces, thereby reinforcing interfacial polarization loss. Furthermore, the ECT coating displays a remarkable radar cross section reduction of 31.9 dB m 2 , demonstrating a great radar microwave scattering ability. This work sheds light on the interfacial coupled stimulus response mechanism of TMC-based heterogeneous structures and provides a feasible strategy to manipulate high-quality TMCs for excellent microwave absorbers., (© 2023. The Author(s).)