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Abstract Background The emergence of plasmid-mediated mobile colistin resistance (mcr) gene poses a great challenge to the clinical application of polymyxins. To date, mcr-1 to mcr-10 have been found in animals, humans, and the environment. Among them, mcr-8 was first identified in Klebsiella pneumoniae (K. pneumoniae) of swine origin, and then mcr-8.1 to mcr-8.5 were successively identified. Notably, K. pneumoniae is the major host of the mcr-8 gene in both animals and humans. This study aims to explore the characteristics of K. pneumoniae strains carrying the mcr-8 gene and tmexCD1-toprJ1 gene cluster and investigate the correlation between these two antibiotic resistance genes. Methods The isolates from the poultry farms and the surrounding villages were identified by mass spectrometer, and the strains positive for mcr-1 to mcr-10 were screened by polymerase chain reaction (PCR). The size of the plasmid and the antimicrobial resistance genes carried were confirmed by S1-nuclease pulsed-field gel electrophoresis (S1-PFGE) and Southern hybridization, and the transferability of the plasmid was verified by conjugation experiments. Antimicrobial susceptibility testing (AST) and whole genome sequencing (WGS) were used to characterize the strains. Results Two K. pneumoniae isolates (KP26 and KP29) displaying polymyxin resistance were identified as mcr-8 gene carriers. Besides that, tigecycline-resistant gene cluster tmexCD1-toprJ1 was also found on the other plasmid which conferred strain resistance to tigecycline. Through epidemiological analysis, we found that the mcr-8 gene has dispersed globally, circulating in the human, animals, and the environment. Furthermore, our analysis suggests that the coexistence of mcr-8 and tmexCD1-toprJ1 on a single plasmid might evolved through plasmid recombination. Conclusions Although the mcr-8 and tmexCD1-toprJ1 gene clusters in the two strains of K. pneumoniae in this study were on two different plasmids, they still pose a potential threat to public health, requiring close monitoring and further study.

Gastric cancer (GC) is a major cause of cancer-related mortality worldwide. GC is determined by multiple (epi)genetic and environmental factors; can occur at distinct anatomic positions of the stomach; and displays high heterogeneity, with different cellular origins and diverse histological and molecular features. This heterogeneity has hindered efforts to fully understand the pathology of GC and develop efficient therapeutics. In the past decade, great progress has been made in the study of GC, particularly in molecular subtyping, investigation of the immune microenvironment, and defining the evolutionary path and dynamics. Preclinical mouse models, particularly immunocompetent models that mimic the cellular and molecular features of human GC, in combination with organoid culture and clinical studies, have provided powerful tools for elucidating the molecular and cellular mechanisms underlying GC pathology and immune evasion, and the development of novel therapeutic strategies. Herein, we first briefly introduce current progress and challenges in GC study and subsequently summarize immunocompetent GC mouse models, emphasizing the potential application of genetically engineered mouse models in antitumor immunity and immunotherapy studies.

Abstract As the prevalence of Type 2 Diabetes Mellitus (T2DM) and Glioblastoma (GBM) rises globally, the relationship between T2DM and GBM remains controversial. This study aims to investigate whether genetically predicted T2DM is causally associated with GBM. We performed bidirectional Mendelian randomization (MR) analysis using data from genome-wide studies on T2DM (N = 62,892) and GBM (N = 218,792) in European populations. The results of the inverse-variance weighted (IVW) approach served as the primary outcomes. We applied Cochran’s Q test and MR-Egger regression for heterogeneity assessment. Leave-one-out analysis was used to evaluate whether any single SNP significantly influenced the observed effect. Our findings reveal a significant causal association between T2DM and an increased risk of GBM (OR [95% CI] 1.70 [1.09, 2.65], P = 0.019). Conversely, the reverse association between T2DM and GBM was insignificant (OR [95% CI] 1.00 [0.99, 1.01], P = 0.408) (P > 0.40). Furthermore, the results from Cochran’s Q-test and funnel plots in the MR-Egger method indicated no evidence of pleiotropy between the SNPs and GBM. Additionally, we mapped causal SNPs to genes and identified 10 genes, including MACF1, C1orf185, PTGFRN, NOTCH2, ABCB10, GCKR, THADA, RBMS1, SPHKAP, and PPARG, located on chromosomes 1, 2, and 3. These genes are involved in key biological processes such as the BMP signaling pathway and various metabolic pathways relevant to both conditions. This study provides robust evidence of a significant causal relationship between T2DM and an increased risk of GBM. The identified SNP-mapped genes highlight potential biological mechanisms underlying this association.

Abstract Background Delayed spinal epidural hematoma (SEH) following central neuraxial block (CNB) is a rare but serious complication. The underlying causes of SEH associated with neuraxial anesthesia are still unclear. Furthermore, the decision between surgical intervention and conservative management for SEH remains a complex and unresolved issue. Case Presentation We report a case of delayed SEH in a 73-year-old woman who underwent vaginal hysterectomy under combined spinal-epidural anesthesia, with the administration of postoperative anticoagulants to prevent deep vein thrombosis on the 1st postoperative day (POD). She experienced symptoms 56 h after CNB. Magnetic resonance imaging (MRI) revealed a dorsal SEH at the L1-L4 level with compression of the thecal sac. On conservative treatment, full recovery was achieved after six months. Conclusions This case reminds anesthesiologists should be alert to the possible occurrence of a delayed SEH following CNB, particularly with the administration of anticoagulants. Immediate neurological evaluation of neurological deficit and MRI are advised. Conservative treatment combined with close and dynamic neurological function monitoring may be feasible for patients with mild or nonprogressive symptoms even spontaneous recovery.

Abstract At present, the multi‐object tracking method based on transformer generally uses its powerful self‐attention mechanism and global modelling ability to improve the accuracy of object tracking. However, most existing methods excessively rely on hardware devices, leading to an inconsistency between accuracy and speed in practical applications. Therefore, a lightweight transformer joint position awareness algorithm is proposed to solve the above problems. Firstly, a joint attention module to enhance the ShuffleNet V2 network is proposed. This module comprises the spatio‐temporal pyramid module and the convolutional block attention module. The spatio‐temporal pyramid module fuses multi‐scale features to capture information on different spatial and temporal scales. The convolutional block attention module aggregates channel and spatial dimension information to enhance the representation ability of the model. Then, a position encoding generator module and a dynamic template update strategy are proposed to solve the occlusion. Group convolution is adopted in the input sequence through position encoding generator module, with each convolution group responsible for handling the relative positional relationships of a specific range. In order to improve the reliability of the template, dynamic template update strategy is used to update the template at the appropriate time. The effectiveness of the approach is validated on the MOT16, MOT17, and MOT20 datasets.

Abstract Patients with multiple myeloma (MM) experience relapse and drug resistance; therefore, novel treatments are essential. Clotrimazole (CTZ) is a wide-spectrum antifungal drug with antitumor activity. However, CTZ’s effects on MM are unclear. We investigated CTZ’s effect on MM cell proliferation and apoptosis induction mechanisms. CTZ’s effects on MM.1S, NCI- H929, KMS-11, and U266 cell growth were investigated using Cell Counting Kit-8 (CCK-8) assay. The apoptotic cell percentage was quantified with annexin V-fluorescein isothiocyanate/7-amino actinomycin D staining. Mitochondrial membrane potential (MMP) and cell cycle progression were evaluated. Reactive oxygen species (ROS) levels were measured via fluorescence microscopy. Expression of apoptosis-related and nuclear factor (NF)-κB signaling proteins was analyzed using western blotting. The CCK-8 assay indicated that CTZ inhibited cell proliferation based on both dose and exposure time. Flow cytometry revealed that CTZ decreased apoptosis and MMP and induced G0/G1 arrest. Immunofluorescence demonstrated that CTZ dose-dependently elevated in both total and mitochondrial ROS production. Western blotting showed that CTZ enhanced Bax and cleaved poly ADP-ribose polymerase and caspase-3 while decreasing Bcl-2, p-p65, and p-IκBα. Therefore, CTZ inhibits MM cell proliferation by promoting ROS-mediated mitochondrial apoptosis, inducing G0/G1 arrest, inhibiting the NF-κB pathway, and has the potential for treating MM.

Abstract Drug resistance remains a significant challenge in the treatment of pancreatic cancer. The development of drug-resistant cell lines is crucial to understanding the underlying mechanisms of resistance and developing novel drugs to improve clinical outcomes. Here, a novel pancreatic cancer cell line, PDAC-X1, derived from Chinese patients has been established. PDAC-X1 was characterized by the immune phenotype, biology, genetics, molecular characteristics, and tumorigenicity. In vitro analysis revealed that PDAC-X1 cells exhibited epithelial morphology and cell markers (CK7 and CK19), expressed cancer-associated markers (E-cadherin, Vimentin, Ki-67, CEA, CA19-9), and produced pancreatic cancer-like organs in suspension culture. In vivo analysis showed that PDAC-X1 cells maintained tumorigenicity with a 100% tumor formation rate. This cell line exhibited a complex karyotype, dominated by subtriploid karyotypes. In addition, PDAC-X1 cells exhibited intrinsic multidrug resistance to multiple drugs, including gemcitabine, paclitaxel, 5-fluorouracil, and oxaliplatin. In conclusion, the PDAC-X1 cell line has been established and characterized, representing a useful and valuable preclinical model to study the underlying mechanisms of drug resistance and develop novel drug therapeutics to improve patient outcomes.

Abstract Background Elevation of carpal tunnel pressure is known to be associated with carpal tunnel syndrome. This study aimed to correlate the shear wave elastography in the transverse carpal ligament (TCL) with carpal tunnel pressures using a cadaveric model. Methods Eight human cadaveric hands were dissected to evacuate the tunnels. A medical balloon was inserted into each tunnel and connected to a pressure regulator to simulate tunnel pressure in the range of 0-210 mmHg with an increment of 30 mmHg. Shear wave velocity and modulus was measure in the middle of TCL. Results SWV and SWE were significantly dependent on the pressure levels (p

Abstract Background High doses of long-acting opioids were used to facilitate off-pump coronary artery bypass grafting procedure, which may result in opioid-related adverse events after surgery. Transcutaneous electrical acupoint stimulation (TEAS) had been reported to be effective in reducing intraoperative opioids consumption during surgery. The aim of this study is to assess whether TEAS with difference acupoints can reduce the doses of opioid analgesics. Methods This was a multicenter, randomized, controlled, double-blind trial. Patients underwent off-pump coronary artery bypass grafting under general anesthesia were enrolled. Eligible patients were randomly and equally grouped into sham acupuncture group (n = 105), regional acupoints combination group (n = 105), or distal–proximal acupoints combination group (n = 105) using a centralized computer-generated randomization system. Transcutaneous electrical acupoint stimulation was applied for 30 min before anesthesia induction. The primary outcome was the doses of sufentanil during anesthesia. Secondary outcomes included the highest postoperative vasoactive-inotropic scores within 24 h, intraoperative propofol consumption, length of mechanical ventilation, duration of cardiac care unit and postoperative hospital stay, incidence of postoperative complications, and mortality within 30 days after surgery. Results Of the 315 randomized patients, 313 completed the trial. In the modified intention-to-treat analysis, the doses of sufentanil were 303.9 (10.8) μg in the distal–proximal acupoints group, significantly lower than the sham group, and the mean difference was − 34.9 (− 64.9 to − 4.9) μg, p = 0.023. The consumption of sufentanil was lower in distal–proximal group than regional group (303.9 vs. 339.5), and mean difference was − 35.5 (− 65.6 to − 5.5) μg, p = 0.020. The distal–proximal group showed 10% reduction in opioids consumption comparing to both regional and sham groups. Secondary outcomes were comparable among three groups. Conclusion Transcutaneous electrical acupoint stimulation with distal–proximal acupoints combination, compared to regional acupoints combination and sham acupuncture, significantly reduced sufentanil consumption in patients who underwent off-pump coronary artery bypass grafting surgery.

Abstract Background Lung cancer is the second most common cancer with the highest mortality in the world. Calumenin as a molecular chaperone that not only binds various proteins within the endoplasmic reticulum but also plays crucial roles in diverse processes associated with tumor development. However, the regulatory mechanism of calumenin in lung adenocarcinoma remains elusive. Here, we studied the impact of calumenin on lung adenocarcinoma and explored possible mechanisms. Methods 5-ethynyl-2’-deoxyuridine assay, colony formation, transwell and wound healing assays were performed to explore the effects of calumenin on the proliferation and migration of lung adenocarcinoma cells. To gain insights into the underlying mechanisms through which calumenin knockdown inhibits the migration and proliferation of lung adenocarcinoma, we performed Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Gene Set Enrichment Analysis and Ingenuity Pathway Analysis based on transcriptomics by comparing calumenin knockdown with normal A549 cells. Results The mRNA and protein levels of calumenin in lung adenocarcinoma are highly expressed and they are related to an unfavorable prognosis in this disease. Calumenin enhances the proliferation and migration of A549 and H1299 cells. Gene Set Enrichment Analysis revealed that knockdown of calumenin in A549 cells significantly inhibited MYC and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog signaling pathways while activating interferon signals, inflammatory signals, and p53 pathways. Ingenuity pathway analysis provided additional insights, indicating that the interferon and inflammatory pathways were prominently activated upon calumenin knockdown in A549 cells. Conclusions The anti-cancer mechanism of calumenin knockdown might be related to the inhibition of MYC and KRAS signals but the activation of interferon signals, inflammatory signals and p53 pathways.

Abstract Objective The Center for Neurologic Study Bulbar Function Scale (CNS-BFS) was specifically designed as a self-reported measure of bulbar function. The purpose of this research was to validate the Chinese translation of the CNS-BFSC as an effective measurement for the Chinese population with ALS. Methods A total of 111 ALS patients were included in this study. The CNS-BFSC score, three bulbar function items from the ALSFRS-R, and visual analog scale (VAS) score for speech, swallowing and salivation were assessed in the present study. Forty-six ALS patients were retested on the same scale 5–10 days after the first evaluation. Results The CNS-BFSC sialorrhea, speech and swallowing subscores were separately correlated with the VAS subscores (p 0.05). The Cronbach’s α of the CNS-BFSC was 0.972. Conclusion The Chinese version of the CNS-BFSC has acceptable efficacy and reliability for the assessment of bulbar dysfunction in ALS patients.

Enhancing the economic resilience of agriculture is essential for promoting sustainable and high-quality agricultural development. The emergence of digital technology has created new opportunities in this field. However, existing research predominantly focuses on traditional agricultural factors and technologies. Therefore, the impact of digital technology on agricultural economic resilience within the broader context of the “production–operation–industry” system in agriculture has not been comprehensively explored. To bridge this gap, this study analyzes panel data from 30 Chinese provinces from 2011 to 2020. It employs the static Van Dorn’s law and a dynamic spatial panel model to examine how digital technology empowers agricultural resilience. The findings indicate a continuous strengthening of digital technology development in China, albeit with significant polarization and spatial imbalances. Moreover, the resilience of the agricultural economy undergoes notable fluctuations, initially narrowing and subsequently displaying an upward trend. Digital technology clearly plays a pivotal role in empowering resilience through agricultural scale operation, industrial transformation, and technological progress. Its impact, particularly on the promotion of resilience in the eastern region and non-grain-producing areas and on high-level agricultural economies, also shows regional and technological variations.

To address data scarcity on long-term glacial discharge and inadequacies in simulating and predicting hydrological processes in the Tien Shan, this study analysed the observed discharge at multiple timescales over 1980s–2017 and projected changes within a representative glacierized high-mountain region: eastern Tien Shan, Central Asia. Hydrological processes were simulated to predict changes under four future scenarios (SSP1, SSP2, SSP3, and SSP5) using a classical hydrological model coupled with a glacier dynamics module. Discharge rates at annual, monthly (June, July, August) and daily timescales were obtained from two hydrological gauges: Urumqi Glacier No.1 hydrological station (UGH) and Zongkong station (ZK). Overall, annual and summer discharge increased significantly (p

Abstract Background Hepatocellular carcinoma (HCC) is a common gastrointestinal malignancy with a high incidence and poor prognosis. The subunits of the integrator complex (INTS1-14) play a crucial role in regulating genes dependent on RNA Polymerase II, which may be associated with cancer. However, the role of INTSs in HCC remains unclear. This study aims to comprehensively analyze the clinical value and potential role of INTS family genes in HCC through systematic bioinformatics analysis. Methods We employed various public databases, including UALCAN, HPA, Kaplan–Meier Plotter, GEPIA2, TNMplot, STRING, TIMER, and TISIDB, to investigate the expression levels, clinicopathological correlations, diagnostic and prognostic value, genetic alterations, co-expression network, molecular targets, and immune infiltration of INTSs in HCC. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were utilized to investigate the biological functions of genes associated with INTSs. Furthermore, Western blot, real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-qPCR), and immunohistochemistry techniques were employed to assess the expression of relevant proteins and genes. The proliferation of HCC cells was evaluated using the CCK8 assay. Results We found that in HCC, there was a significant upregulation of INTSs at the transcriptional level, particularly INTS1, INTS4, INTS7, and INTS8. Additionally, the protein levels of INTS1 and INTS8 were notably elevated. The overexpression of these INTSs was strongly correlated with tumor stages in HCC patients. INTS1, INTS4, INTS7, and INTS8 exhibited significant diagnostic and prognostic value in HCC. Moreover, their expression was associated with immune infiltrations and activated status, including B cells, CD8 + T cells, CD4 + T cells, NK cells, macrophages, and dendritic cells. Functional predictions indicated that INTS1, INTS4, INTS7, and INTS8 were involved in various cancer-related signaling pathways, such as TRAIL, IFN-gamma, mTOR, CDC42, Apoptosis, and the p53 pathway. Furthermore, we observed a significant upregulation of INTS1, INTS4, INTS7, and INTS8 expression in HCC cell lines compared to normal liver cell lines. The level of INTS1 protein was higher in cancerous tissues compared to adjacent non-cancerous tissues (n = 16), and the suppression of INTS1 resulted in a significant decrease in the proliferation of Huh7 cells. Conclusion These findings indicate the potential of INTS family genes as diagnostic biomarkers and therapeutic targets in HCC. Further research is needed to understand the underlying mechanisms and explore clinical applications.

Abstract The cottony cushion scale, Icerya purchasi, a polyphagous pest, poses a significant threat to the global citrus industry. The hermaphroditic self-fertilization observed in I. purchasi is an exceptionally rare reproductive mode among insects. In this study, we successfully assembled a chromosome-level genome sequence for I. purchasi using PacBio long-reads and the Hi-C technique, resulting in a total size of 1,103.38 Mb and a contig N50 of 12.81 Mb. The genome comprises 14,046 predicted protein-coding genes, with 462,722,633 bp occurrence of repetitive sequences. BUSCO analysis revealed a completeness score of 93.20%. The genome sequence of I. purchasi serves as a crucial resource for comprehending the reproductive modes in insects, with particular emphasis on hermaphroditic self-fertilization.

Abstract The etiology and pathophysiology of heart failure are still unknown. Increasing evidence suggests that abnormal microRNAs (miRNAs) and transcription factors (TFs) expression may be associated with the development of heart failure. Therefore, this study aims to explore key miRNAs, TFs, and related genes in heart failure to gain a greater understanding of the pathogenesis of heart failure. To search and download the dataset of mRNA chips related to heart failure from the GEO database (GSE59867, GSE9128, and GSE134766), we analyzed differential genes and screened the common differentially expressed genes on two chips using R language software. The binary interactions and circuits among miRNAs, TFs, and corresponding genes were determined by Pearson correlation coefficient. A regulatory network of miRNAs, TFs, and target genes was constructed based on bioinformatics. By comparing the sequences of patients with and without heart failure, five downregulated genes with hypermethylated mRNA and three upregulated genes with hypomethylated mRNA were identified. The miRNA-TF gene regulatory network consisted of 26 miRNAs, 22 TFs and six genes. GO and KEGG analysis results revealed that BP terms like cellular response to organic substance, cellular response to cytokine stimulus, and KEGG pathways like osteoclast differentiation, MAPK signaling pathway, and legionellosis were enriched of the DEGs. TMEM87A, PPP2R2A, DUSP1, and miR-92a have great potential as biomarkers for heart failure. The integrated analysis of the mRNA expression spectrum and microRNA-transcription factor-gene revealed the regulatory network of heart failure, which may provide clues to its alternative treatment.

Abstract. Background:. Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients' recovery. Methods:. This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group (n = 665) and fasting group (n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results:. The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P

Abstract Background The molecular mechanisms of osteosarcoma (OS) are complex. In this study, we focused on the functions of melanoma cell adhesion molecule (MCAM), methyltransferase 3 (METTL3) and insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) in OS development. Methods qRT-PCR assay and western blot assay were performed to determine mRNA and protein expression of MCAM, METTL3, IGF2BP1 and YY1. MTT assay and colony formation assay were conducted to assess cell proliferation. Cell apoptosis, invasion and migration were evaluated by flow cytometry analysis, transwell assay and wound-healing assay, respectively. Methylated RNA Immunoprecipitation (MeRIP), dual-luciferase reporter, Co-IP, RIP and ChIP assays were performed to analyze the relationships of MCAM, METTL3, IGF2BP1 and YY1. The functions of METTL3 and MCAM in tumor growth were explored through in vivo experiments. Results MCAM was upregulated in OS, and MCAM overexpression promoted OS cell growth, invasion and migration and inhibited apoptosis. METTL3 and IGF2BP1 were demonstrated to mediate the m6A methylation of MCAM. Functionally, METTL3 or IGF2BP1 silencing inhibited OS cell progression, while MCAM overexpression ameliorated the effects. Transcription factor YY1 promoted the transcription level of METTL3 and regulated METTL3 expression in OS cells. Additionally, METTL3 deficiency suppressed tumor growth in vivo, while MCAM overexpression abated the effect. Conclusion YY1/METTL3/IGF2BP1/MCAM axis aggravated OS development, which might provide novel therapy targets for OS.

Abstract With the development of digital technology, the proportion of time spent on digital informal learning in students’ daily lives is increasing. However, digital informal learning behaviors in sports field have not been fully justified and studied. This article aims to investigate the current situation and influencing factors of digital informal learning of sports knowledge (DIL-S) of Chinese undergraduates. As a cross-sectional study, 401 non-sports undergraduate students from six Chinese universities completed the DIL-S measurement questionnaire. The partial least squares structural equation modeling (PLS-SEM) was constructed to explore association among DIL-S, technology expectancy (TE) and digital competence (DC). Results show that (1) Male students’ cognitive learning (CL) was significantly better than that of females; Senior students’ metacognitive learning (MCL) was significantly better than that of junior students; Sports university students’ cognitive learning, metacognitive learning, and social and motivation learning (SML) were significantly better than that of non-sports university students. (2) Digital competence has a significant positive impact on technology expectancy and digital informal learning of sport knowledge, while technology expectancy has a significant negative impact on digital informal learning of sport knowledge. Based on the results, following conclusions can be made (1) Undergraduates have a strong competence to use digital technology and have a high interest in using digital technology to participate in learning. However, they have a low investment in digital informal learning of sports knowledge fields. (2) Males’ sports knowledge learning consciousness and actual performance are better than girls; Compared with freshmen, senior students have stronger monitoring and planning ability for personal sports knowledge learning; The behavior of digital informal learning of sports knowledge in sports university students is better than that of non-sports university students. (3) Digital competence and technological expectancy are key factors influencing digital informal learning of sport knowledge, with digital competence having the most significant impact. These findings underscore the need to enhance the promotion of digital informal learning among undergraduates and to develop assessments that improve their understanding and knowledge of sports.

AIM: To investigate ocular surface disorders and tear function changes in patients with acne vulgaris and explore the potential relationship between acne vulgaris and dry eye. METHODS: This cross-sectional study included right eyes of 53 patients with acne vulgaris and 54 healthy controls. The participants completed the Ocular Surface Disease Index (OSDI) questionnaire. The following ocular surface-related parameters were measured: tear meniscus height (TMH), noninvasive tear breakup time (NIBUT), Schirmer I test (SIT), lipid layer thickness (LLT) score of the tear film, meibum score, meibomian gland orifice obstruction score, the ratio of meibomian gland loss, conjunctival hyperemia score, and corneal fluorescein staining (CFS) score. RESULTS: The stability of the tear film decreased in acne vulgaris patients. In the acne group, the TMH and NIBUT were lower, whereas the OSDI, meibum score, meibomian gland orifice obstruction score, ratio of meibomian gland loss, and conjunctival hyperemia score were higher compared with controls (P0.05). In two dry eye groups, the TMH, NIBUT, and LLT score were lower in the acne with dry eye (acne-DE) group, and the meibum score, meibomian gland orifice obstruction score, ratio of meibomian gland loss and conjunctival hyperemia score in the acne-DE group were higher (P0.05). CONCLUSION: Patients with moderate-to-severe acne vulgaris are more likely to experience dry eye than those without acne vulgaris. Reduced tear film stability and meibomian gland structure dysfunction are more pronounced in patients with moderate-to-severe acne and dry eye.

Objectives: The aim of this study was to investigate the molecular mechanism underlying odontoblast damage repair in dentin hypersensitivity (DH) and the role of Yes-associated protein (YAP) in this process. Methods: The DH model was constructed in Sprague-Dawley (SD) rats, and the in vivo expression of Piezo1, Integrin αvβ3, YAP, and dentin sialophosphoprotein (DSPP) was detected by immunohistochemistry. COMSOL Multiphysics software was used to simulate the dentinal tubule fluid flow velocity and corresponding fluid shear stress (FSS) on the odontoblast processes. MDPC-23 cells were cultured in vitro and loaded with a peristaltic pump for 1 hour at FSS values of 0.1, 0.3, 0.5, and 0.7 dyne/cm2. The expression of Piezo1, Integrin αvβ3, and YAP was detected by immunofluorescence. Verteporfin (a YAP-specific inhibitor) was utilised to confirm the effect of YAP on the expression of dentineogenesis-related protein under FSS. Results: The level and duration of external mechanical stimuli have an effect on the functional expression of odontoblasts. In DH, the harder the food that is chewed, the faster the flow of the dentinal tubule fluid and the greater the FSS on the odontoblast processes. The expression of Piezo1, Integrin αvβ3, and YAP can be promoted when the FSS is less than 0.3 dyne/cm2. After YAP inhibition, the DSPP protein expression level was reduced at 0.3 dyne/cm2 FSS. Conclusions: These results suggest that appropriate FSS can enhance the expression of odontoblast-related factors in odontoblasts via the Piezo1–Integrin αvβ3–YAP mechanotransduction pathway and the YAP appears to play an essential role in the response of odontoblasts to external mechanical stimuli.

Abstract Studies have suggested that endoplasmic reticulum stress (ERS) is involved in neurological dysfunction and that electroacupuncture (EA) attenuates neuropathic pain (NP) via undefined pathways. However, the role of ERS in the anterior cingulate cortex (ACC) in NP and the effect of EA on ERS in the ACC have not yet been investigated. In this study, an NP model was established by chronic constriction injury (CCI) of the left sciatic nerve in rats, and mechanical and cold tests were used to evaluate behavioral hyperalgesia. The protein expression and distribution were evaluated using western blotting and immunofluorescence. The results showed that glucose-regulated protein 78 (BIP) and inositol-requiring enzyme 1α (IRE-1α) were co-localized in neurons in the ACC. After CCI, BIP, IRE-1α, and phosphorylation of IRE-1α were upregulated in the ACC. Intra-ACC administration of 4-PBA and Kira-6 attenuated pain hypersensitivity and downregulated phosphorylation of IRE-1α, while intraperitoneal injection of 4-PBA attenuated hyperalgesia and inhibited the activation of P38 and JNK in ACC. In contrast, ERS activation by intraperitoneal injection of tunicamycin induced behavioral hyperalgesia in naive rats. Furthermore, EA attenuated pain hypersensitivity and inhibited the CCI-induced overexpression of BIP and pIRE-1α. Taken together, these results demonstrate that EA attenuates NP by suppressing BIP- and IRE-1α-mediated ERS in the ACC. Our study presents novel evidence that ERS in the ACC is implicated in the development of NP and provides insights into the molecular mechanisms involved in the analgesic effect of EA.

Abstract Background The implementation of antibiotic intravenous-to-oral switch (IVOS) therapy in hospitals can slow down the development of drug resistance, reduce the occurrence of adverse reactions, and bring significant economic benefits. The aim of this study is to investigate the understanding of physicians at the Second Affiliated Hospital of Soochow University in Suzhou, China towards the antibiotic IVOS therapy. Methods 15 physicians working in 9 different departments of the Second Affiliated Hospital of Soochow University participated in this study. A semi-structured face-to-face interview was conducted to collect interview information about the antibiotic IVOS therapy. NVivo12 software was used to organize the entire interview content, and the interview data was analyzed and summarized using the Colaizzi seven step method. Results 60% of participants were not familiar with antibiotic IVOS therapy. Barriers of antibiotic IVOS therapy were included by three key issues: (i) Physicians’ potential cognition: ‘Iv is always better than oral’; (ii) Subjective infusion intention of patients; and (iii) Limitations of drug selection. 60% of participants expressed welcome for pharmacists to help them perform antibiotic IVOS treatment. And electronic recognition technology may be a feasible method for prompting IVOS conversion that recognized by all participants in the interview. Participants also provided some suggestions for pharmacists and IVOS computer reminders. Conclusion Physicians’ in China still have insufficient understanding of antibiotic IVOS therapy. The promotion of antibiotic IVOS therapy in China faces many challenges and obstacles. Strategies such as IVOS therapy computer reminders and clinical pharmacists’ medication guidance were worth studying to help physicians develop antibiotic IVOS treatment.

Abstract Sleep is a pillar of human health and wellbeing. In high- and middle-income countries, there is a great reliance on heating, ventilation, and air conditioning systems (HVAC) to control the interior thermal environment in the bedroom. However, these systems are expensive to buy, maintain, and operate while being energy and environmentally intensive—problems that may increase due to climate change. Easily-accessible passive and low-energy strategies, such as fans and electrical heated blankets, address these challenges but their comparative effectiveness for providing comfort in sleep environments has not been studied. We used a thermal manikin to experimentally show that many passive and low-energy strategies are highly effective in supplementing or replacing HVAC systems during sleep. Using passive strategies in combination with low-energy strategies that elevate air movement like ceiling or pedestal fans enhances the cooling effect by three times compared to using fans alone. We extrapolated our experimental findings to estimate heating and cooling effects in two historical case studies: the 2015 Pakistan heat wave and the 2021 Texas power crisis. Passive and low-energy strategies reduced sleep-time heat or cold exposure by 69–91%. The low-energy strategies we tested require one to two orders of magnitude less energy than HVAC systems, and the passive strategies require no energy input. These strategies can also help reduce peak load surges and total energy demand in extreme temperature events. This reduces the need for utility load shedding, which can put individuals at risk of hazardous heat or cold exposure. Our results may serve as a starting point for evidence-based public health guidelines on how individuals can sleep better during heat waves and cold snaps without relying on HVAC.

Heterogeneous asymmetric catalysis is an important strategy for the industrial production of chiral compounds. Herein, we reported a polymer-bound Xu-Phos-derived palladium catalyst that shows good performance in heterogeneous asymmetric reductive Heck reaction of allyl aryl ethers. This heterogeneous catalyst was easily prepared by efficient immobilization of the sulfonamide phosphine ligand (Xu-Phos) in the cross-linked polystyrene via copolymerization, and exhibits similar catalytic activity and enantioselectivity to that of the homogeneous catalyst. Moreover, the heterogeneous catalyst system is proved to be easily recovered and reused several times without losing catalytic activity obviously.

Abstract Backgrounds Intraplacental choriocarcinoma (IC) is an extremely rare subtype of gestational choriocarcinoma. The long-term follow-up and reproductive outcomes of IC patients remain unclear. Here, we report a series of 14 cases and conduct a literature review to assess the fertility and recurrence results of this rare disease. Results Fourteen patients with pathologically confirmed IC treated in Peking Union Medical College Hospital between January 2002 and July 2022 were included in this study. Half of them had metastatic IC and were treated by chemotherapy with or without surgery. Only 1 patient had chemoresistant disease, but she achieved complete remission after immunotherapy. The median follow-up time was 45.5 months (range 4-192), and no recurrence occurred. One metastatic IC patient who achieved remission after chemotherapy had a full-term delivery. Among the 5 patients with fertility demands, 3 abandoned their pursuit of pregnancy because of “fear and worry about choriocarcinoma recurrence”. We reviewed a total of 89 cases of IC in English and Chinese literature from 1963 to 2022, and only 5 cases with subsequent pregnancy were reported, all of them were nonmetastatic IC cases. Conclusions IC is sensitive to chemotherapy and has good long-term remission and a low recurrence rate. Patients with metastatic or nonmetastatic IC can have good pregnancy results after treatment. Doctors should pay more attention to the psychology of these patients. Clinical trial registration N/A.

Abstract Background To establish a method to induce Campylobacter jejuni colonization in the intestines of C57BL/6 mice through antibiotic-induced microbiome depletion. Results Fifty-four female C57BL/6 mice were divided into the normal, control, and experimental groups. The experimental group was administered intragastric cefoperazone sodium and sulbactam sodium (50 mg/mL) for 2 days; then, the experimental and control mice were intragastrically administered 200 µL C. jejuni, which was repeated once more after 2 days. Animal feces were collected, and the HipO gene of C. jejuni was detected using TaqMan qPCR from day 1 to day 14 after modeling completion. Immunofluorescence was used to detect intestinal C. jejuni colonization on day 14, and pathological changes were observed using hematoxylin and eosin staining. Additionally, 16S rDNA analyses of the intestinal contents were conducted on day 14. In the experimental group, C. jejuni was detected in the feces from days 1 to 14 on TaqMan qPCR, and immunofluorescence-labeled C. jejuni were visibly discernable in the intestinal lumen. The intestinal mucosa was generally intact and showed no significant inflammatory-cell infiltration. Diversity analysis of the colonic microbiota showed significant inter-group differences. In the experimental group, the composition of the colonic microbiota differed from that in the other 2 groups at the phylum level, and was characterized by a higher proportion of Bacteroidetes and a lower proportion of Firmicutes. Conclusions Microbiome depletion induced by cefoperazone sodium and sulbactam sodium could promote long-term colonization of C. jejuni in the intestines of mice.

Abstract This study developed a kind of PEG-crosslinked O-carboxymethyl chitosan (O-CMC–PEG) with various PEG content for food packaging. The crosslinking agent of isocyanate-terminated PEG was firstly synthesized by a simple condensation reaction between PEG and excess diisocyanate, then the crosslink between O-carboxymethyl chitosan (O-CMC) and crosslinking agent occurred under mild conditions to produce O-CMC–PEG with a crosslinked structure linked by urea bonds. FT-IR and 1H NMR techniques were utilized to confirm the chemical structures of the crosslinking agent and O-CMC–PEGs. Extensive research was conducted to investigate the impact of the PEG content (or crosslinking degree) on the physicochemical characteristics of the casted O-CMC–PEG films. The results illuminated that crosslinking and components compatibility could improve their tensile features and water vapor barrier performance, while high PEG content played the inverse effects due to the microphase separation between PEG and O-CMC segments. The in vitro degradation rate and water sensitivity primarily depended on the crosslinking degree in comparison with the PEG content. Furthermore, caused by the remaining –NH2 groups of O-CMC, the films demonstrated antibacterial activity against Escherichia coli and Staphylococcus aureus. When the PEG content was 6% (medium crosslinking degree), the prepared O-CMC–PEG−6% film possessed optimal tensile features, high water resistance, appropriate degradation rate, low water vapor transmission rate and fine broad-spectrum antibacterial capacity, manifesting a great potential for application in food packaging to extend the shelf life.

Abstract The knee joint has long been considered a closed system. The pathological effects of joint diseases on distant organs have not been investigated. Herein, our clinical data showed that post-traumatic joint damage, combined with joint bleeding (hemarthrosis), exhibits a worse liver function compared with healthy control. With mouse model, hemarthrosis induces both cartilage degeneration and remote liver damage. Next, we found that hemarthrosis induces the upregulation in ratio and differentiation towards Th17 cells of CD4+ T cells in peripheral blood and spleen. Deletion of CD4+ T cells reverses hemarthrosis-induced liver damage. Degeneration of cartilage matrix induced by hemarthrosis upregulates serological type II collagen (COL II), which activates CD4+ T cells. Systemic application of a COL II antibody blocks the activation. Furthermore, bulk RNAseq and single-cell qPCR analysis revealed that the cartilage Akt pathway is inhibited by blood treatment. Intra-articular application of Akt activator blocks the cartilage degeneration and thus protects against the liver impairment in mouse and pig models. Taken together, our study revealed a pathological joint–liver axis mediated by matrikine-activated CD4+ T cells, which refreshes the organ-crosstalk axis and provides a new treatment target for hemarthrosis-related disease. Intra-articular bleeding induces cartilage degradation through down-reulation of cartilage Akt pathway. During this process, the soluble COL II released from the damaged cartilage can activate peripheral CD4+ T cells, differention into Th17 cells and secretion of IL-17, which consequently induces liver impairment. Intra-articular application of sc79 (inhibitor of Akt pathway) can prevent the cartilage damage as well as its peripheral influences.

Decay levels of wooden components in the Yang former residence were classified using polarized light and fluorescence methods. Analysis of the decay cause was conducted based on external conditions and wood species characteristics. The polarization and fluorescence effects revealed that there were varying degrees of decay in larch (Larix potaninii var. australis), spruce (Picea brachytyla), lace-bark pine (Pinus bungeana), Masson pine (Pinus massoniana), Chinese Douglas fir (Pseudotsuga sinensis), Chinese fir (Cunninghamia lanceolata), poplar (Populus tomentosa), and elm (Ulmus pumila). The primary factors contributing to decay included the inherent low natural durability of the wood species and adverse external conditions, such as damaged roofs, missing dripping water and tiles causing water leakage, uneven indoor and outdoor ground levels, contemporary tile paving indoors, and inadequate ventilation. This study aims to establish a scientific basis for subsequent conservation strategies.

In order to explore the research and development of oyster in the field of medicine and food homology, response surface methodology was used to optimize the preparation process of oyster protease-depeptidase, and its effects on testosterone secretion and oxidative stress in mouse leydig cells were studied. Based on the investigation of hydrolysis degree as the evaluation index, a biomimetic enzymatic hydrolysis method was employed to optimize the preparation process of oyster protein enzymolysis peptides using response surface analysis, building upon the foundation of single-factor experiments. Simultaneously, a hydrogen peroxide (H2O2)-induced oxidative damage model was established using mouse testicular interstitial cells (TM3), and the effects of oyster protein enzymolysis peptides on testosterone (T) secretion and oxidative stress were investigated through assessments of cell viability, DAPI staining, testosterone secretion level, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) content in TM3 cells. The results showed that the optimal enzymatic hydrolysis conditions for oyster protein enzymolysis peptides were as follows: Substrate-to-solvent ratio of 1:10 g/mL, gastric protease concentration of 1.1%, hydrolysis time of 1.0 h, pancreatic protease concentration of 2.1%, and hydrolysis time of 3.1 h. Under these conditions, the degree of hydrolysis was determined to be 39.43%±0.42%. Oyster protein enzymolysis peptides exhibited varying degrees of proliferative activity on H2O2-induced TM3 cells, significantly (P

The purpose of this study was to conduct a screening and comparative analysis of proteolytic peptides with anti-inflammatory properties derived from three different ginseng concoctions: Sundried ginseng, red ginseng and black ginseng. Ginseng proteins were extracted from three different types of ginseng products using a low-temperature leaching method. Subsequently, the extracted proteins underwent enzymatic digestion using alkaline protease, neutral protease, and pepsin through a stepwise enzyme digestion method. This process yielded three distinct enzyme digestion products, namely BGP (black ginseng proteolytic peptide), RGP (red ginseng proteolytic peptide), and SGP (sundried ginseng proteolytic peptide). The samples were subjected to separation using ultrafiltration membranes, resulting in the acquisition of ultrafiltration fractions with distinct molecular weights. Subsequently, the ultrafiltration fractions were further separated utilizing ultrafiltration membranes to obtain fractions with varying molecular weights. The fraction exhibiting the most potent anti-inflammatory activity was determined through the application of a lipopolysaccharide (LPS)-induced RAW264.7 inflammation model. The impact of the active fractions on the secretion of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β ((IL-1β), and interleukin-6 (IL-6) by RAW264.7 cells was assessed using enzyme immunoassay. The amino acid composition and content of the three proteolytic peptides were examined. Multivariate statistical analysis was employed to identify the distinct amino acids in the three ginseng concoctions and investigate their correlation with the inhibition of cytokine secretion by RAW264.7 cells. The findings of the study indicated that the proteolytic peptide fraction with a molecular weight of less than 1 kDa in the three ginseng products exhibited the most pronounced impact on the proliferation of RAW264.7 cells compared to the other fractions. Additionally, this fraction significantly suppressed the secretion of NO, TNF-α, IL-6, and IL-1β at concentrations ranging from 50~200 μg/mL (P

MgAl2O4 ceramics possess outstanding mechanical properties, making them promising for use as reinforcing or interfacial modulating phase in Al-based metal composites. The challenge lies in the insufficient interatomic potential parameters to accurately characterize the MgAl2O4/Al interfacial interactions, which hampers a detailed understanding of the interfacial strengthening mechanisms at the atomic level. Since the pair potential satisfies the requirements for computational efficiency and accuracy, it has been widely used for investigating the interfacial properties of composite materials. In this study, the interatomic potential parameters for Al–Mg and Al–Al bonds were derived from Buckingham potential, while those for Al–O bonds were obtained from Morse potential via first principles calculations. The uniaxial tensile mechanical properties and interface-dislocation strengthening mechanisms of MgAl2O4/Al interface configuration were explored through molecular dynamics simulations. The analyses reveal that the strength enhancement of the MgAl2O4/Al interface is due to the generation of a large number of immovable 1/6 stair-rod dislocations therein. The thickness of MgAl2O4 layer significantly influences the mechanical properties. Below a thickness of 20 Å, the presence of movable dislocations reduces the strengthening effect. Conversely, increasing the thickness of MgAl2O4 encourages the emergence of immovable dislocations and increases the flow stress, while the corresponding yield strain decreases. These insights open up new prospects in the development of aluminum metal matrix composites with enhanced performance.

The Yangtze River is the mother river of China. To promote the aquatic ecosystem protection of the great river, the Project of Yangtze Fisheries Resources and Environment Investigation (2017–2021) supported by the Ministry of Agriculture and Rural Affairs, P. R. China carried out by 24 institutes and universities that located in the Yangtze River basin surveys the status of (1) fish species composition and spatial distribution, (2) current fish abundance, (3) endangered fishes, (4) Yangtze finless porpoise, (5) aquatic eco-environments, (6) water-level fluctuation areas, (7) capture fisheries and recreational fisheries of the Yangtze River mainstream and 10 of its main tributaries, including Yalong River, Heng River, Min River (including Dadu River), Chishui River, Tuo River, Jialing River, Wu River, Han River, Dongting Lake and Poyang Lake. The results showed that there were 443 fish species (belonging to 163 genus, 37 families, and 18 orders) before 2017, but only 323 fish species (including 15 new recorded exotic species) were recorded in the project of 2017–2021. Among them, Cyprinus carpio, Carassius auratus, Hypophthalmichthys molitrix, Pelteobagrus fulvidraco, Coilia brachygnathus, Silurus asotus, Saurogobio dabryi, Ctenopharyngodon idellus, Pelteobagrus nitidus, Hemiculter leucisculus, Siniperca chuatsi, Coreius heterodon, Culter alburnus, Parabramis pekinensis, and Aristichthys nobilis were the dominant species across the whole Yangtze River system. It is estimated that there were 886 million individuals weighing 124.8 million kg, merely equivalent to 27.3% of the resources in 1950s, 30.9% of the resources in 1960s, or 58.7% of the resources in 1980s. In the new list of protected fishes that recorded in the Yangtze River system, only 15 of 29 were collected in this project of 2017–2021. Psephurus gladius has been affirmed to be Extinct by International Union for Conservation of Nature (IUCN). The wild individuals of Tenualosa reevesii and Luciobrama macrocephalus have disappeared for many years and maybe have been extinct already. Acipenser dabryanus has been affirmed to be Extinct in the Wild by IUCN. The natural propagations of A. sinensis, Myxocyprinus asiaticus and Trachidermus fasciatus have been interrupted for many years. The populations of Yangtze finless porpoise in the Yangtze River mainstream, Dongting Lake and Poyang Lake have steadily rising sizes and expanding distributions in 2017–2021. Parts of them migrate from one region to another with the seasons, which would result in the fluctuation of Yangtze finless porpoise population within some regions. The conventional indicators of water quality in the Yangtze River system were good and conformed to the water quality criteria of fishery in 2017–2021. In the last 40 years, the maximum surface water area in the Yangtze River basin extended to approximately 63,360 km2, the minimum surface water area covered approximately 26,396 km2, and the seasonal water-level fluctuation areas occupied approximately 36,964 km2. Compared with 1984–2000 period, the 2001–2020 period witnessed an overall decreasing trend in the frequency of surface water occurrence within about 25,869 km2 of aquatic areas. From 1984 to 2000 period to 2001–2020 period, permanent surface water has decreased by nearly 8,750 km2. In 2017, the fishermen were mainly 40–60 years old and their educational levels were mainly lower than junior high school. In 2017, most anglers were older than 40 and used hand rod and/or sea rod. Their average catch of each time was mainly less than 1 kg. Results suggested that the fishing ban in key waters of the Yangtze River basin is not only an ecological project of aquatic ecosystem conservation, but also a livelihood project for the fisherman to embrace industrial transformation and improve their living conditions. After the implementation of the fishing ban, the fisheries resources would gradually recover, and the Yangtze finless porpoise population size would also see a steady increase. However, the endangered species would remain threatened for a long time. The degraded waterbodies and water-level fluctuation areas would be the key restrictive factors for future aquatic ecosystem recovery in the Yangtze River basin. Since this survey was carried out before the fishing ban, the current results could provide a baseline for future evaluation of the effect of the Yangtze River fishing ban.

This study proposes an image-based visual servoing (IBVS) method based on a velocity observer for an unmanned aerial vehicle (UAV) for tracking a dynamic target in Global Positioning System (GPS)-denied environments. The proposed method derives the simplified and decoupled image dynamics of underactuated UAVs using a constructed virtual camera and then considers the uncertainties caused by the unpredictable rotations and velocities of the dynamic target. A novel image depth model that extends the IBVS method to track a rotating target with arbitrary orientations is proposed. The depth model ensures image feature accuracy and image trajectory smoothness in rotating target tracking. The relative velocities of the UAV and the dynamic target are estimated using the proposed velocity observer. Thanks to the velocity observer, translational velocity measurements are not required, and the control chatter caused by noise-containing measurements is mitigated. An integral-based filter is proposed to compensate for unpredictable environmental disturbances in order to improve the anti-disturbance ability. The stability of the velocity observer and IBVS controller is analyzed using the Lyapunov method. Comparative simulations and multistage experiments are conducted to illustrate the tracking stability, anti-disturbance ability, and tracking robustness of the proposed method with a dynamic rotating target.

Abstract Introduction Pseudobulbar palsy is a common symptom in patients with amyotrophic lateral sclerosis (ALS), but it is often underdiagnosed or misdiagnosed as other diseases. The Center for Neurologic Study Lability Scale (CNS-LS) is a self-report scale consisting of seven questions designed for evaluating pseudobulbar affect (PBA). The current study aimed to validate a Chinese version of the CNS-LS. Methods The Chinese version of the CNS-LS was obtained through a standardized forward–backward translation and cultural adaptation. A total of 105 patients with ALS were recruited from the ALS database of Peking University Third Hospital in Beijing, China, to complete the CNS-LS. The reliability of the Chinese version was determined by the test–retest method, and receiver operating characteristic (ROC) analysis was performed for criterion validity. Results Of 105 patients with ALS, 37 had symptoms of PBA and were diagnosed with that condition by neurologists. Forty-two patients completed the CNS-LS twice, and there was no statistically significant difference between the scores (Z = -0.896, p = 0.37). The Spearman correlation coefficient between the test and retest scores was 0.940 (p

ABSTRACTYB2C2 is a novel ultra-high temperature ceramic material with high damage tolerance. In this work, the synthesis mechanism, crystal structure, electronic structure, elastic properties and thermal shock resistance of YB2C2 were systematically investigated through experiments and calculations. It was determined by differential scanning calorimetry with the heating rate of 10°C/min that YB2C2 was formed by the reaction of YB2C and C at about 1202°C, and became the main phase at 1450°C. The space group of YB2C2 was determined to be P4/mbm by X-ray diffraction, transmission electron microscopy, Rietveld refinement and first-principles calculations for the first time. The lattice constants are a = b = 0.5351 nm and c = 0.3561 nm. The atom positions are as follows: Y is located at 2a (0, 0, 0), B is located 4 h (0.133, 0.633, 0.5) and C is located at 4 h (0.662, 0.162, 0.5). The chemical bonding of YB2C2 displayed sharp anisotropy, with strong B-C bond within the B2C2 nets, and weak Y-B/Y-C bond between Y atom layers and B2C2 nets. Additionally, YB2C2 exhibited abnormal thermal shock resistance when the thermal shock temperature exceeded 800°C, with the residual flexural strength at 1300°C being more than 70% of the strength at room temperature.

Abstract Numerous plant parasitic nematodes (PPNs) have the potential to inflict considerable damage on agricultural crops. Through a comprehensive survey aimed at identifying PPNs affecting crops, cyst nematodes were isolated from the rhizosphere soil of buckwheat (Fagopyrum esculentum). Employing both molecular and morphological techniques, this cyst nematode was conclusively identified as Heterodera ripae. Notably, this represents the first documented occurrence of this particular cyst nematode species within the rhizosphere soil of F. esculentum.

Abstract Near-surface atmospheric moisture is a key environmental and hydro-climatic variable that has significant implications for the natural and human systems. However, high-resolution moisture data are severely lacking for fine-scale studies. Here, we develop the first 1 km high spatial resolution dataset of monthly moisture index collection in China (HiMIC-Monthly) over a long period of 2003~2020. HiMIC-Monthly is generated by the light gradient boosting machine algorithm (LightGBM) based on observations at 2,419 weather stations and multiple covariates, including land surface temperature, vapor pressure, land cover, impervious surface proportion, population density, and topography. This collection includes six commonly used moisture indices, enabling fine-scale assessment of moisture conditions from different perspectives. Results show that the HiMIC-Monthly dataset has a good performance, with R2 values for all six moisture indices exceeding 0.96 and root mean square error and mean absolute error values within a reasonable range. The dataset exhibits high consistency with in situ observations over various spatial and temporal regimes, demonstrating broad applicability and strong reliability.

Abstract Syndecan-binding protein (SDCBP) was reported to stimulate the advancement of esophageal squamous cell carcinoma (ESCC) and could potentially be a target for ESCC treatment. There is a growing corpus of research on the anti-tumor effects of iron chelators; however, very few studies have addressed the involvement of dexrazoxane in cancer. In this study, structure-based virtual screening was employed to select drugs targeting SDCBP from the Food and Drug Administration (FDA)-approved drug databases. The sepharose 4B beads pull-down assay revealed that dexrazoxane targeted SDCBP by interacting with its PDZ1 domain. Additionally, dexrazoxane inhibited ESCC cell proliferation and anchorage-independent colony formation via SDCBP. ESCC cell apoptosis and G2 phase arrest were induced as measured by the flow cytometry assay. Subsequent research revealed that dexrazoxane attenuated the binding ability between SDCBP and EGFR in an immunoprecipitation assay. Furthermore, dexrazoxane impaired EGFR membrane localization and inactivated the EGFR/PI3K/Akt pathway. In vivo, xenograft mouse experiments indicated that dexrazoxane suppressed ESCC tumor growth. These data indicate that dexrazoxane might be established as a potential anti-cancer agent in ESCC by targeting SDCBP.

Abstract Chemotherapy resistance poses clinical challenges in pancreatic cancer treatment. Developing cell lines resistant to chemotherapy is crucial for investigating drug resistance mechanisms and identifying alternative treatment pathways. The genetic and biological attributes of pancreatic cancer depend on its aetiology, racial demographics and anatomical origin, underscoring the need for models that comprehensively represent these characteristics. Here, we introduce PDAC-X2, a pancreatic cancer cell line derived from Chinese patients. We conducted a comprehensive analysis encompassing the immune phenotype, biology, genetics, molecular characteristics and tumorigenicity of the cell line. PDAC-X2 cells displayed epithelial morphology and expressed cell markers (CK7 and CK19) alongside other markers (E-cadherin, Vimentin, Ki-67, CEA and CA19-9). The population doubling time averaged around 69 h. In vivo, PDAC-X2 cells consistently maintained their tumorigenicity, achieving a 100% tumour formation rate. Characterised by a predominantly tetraploid karyotype, this cell line exhibited a complex genetic markup. Notably, PDAC-X2 cells demonstrated resistance to multiple drugs, including gemcitabine, paclitaxel, 5-fluorouracil and oxaliplatin. In conclusion, PDAC-X2 presents an invaluable preclinical model. Its utility lies in facilitating the study of drug resistance mechanisms and the exploration of alternative therapeutic approaches aimed at enhancing the prognosis of this tumour type.

Abstract Mutations in isocitrate dehydrogenases (IDH) are oncogenic events due to the generation of oncogenic metabolite 2-hydroxyglutarate. However, the role of wild-type IDH in cancer development remains elusive. Here we show that wild-type IDH2 is highly expressed in triple negative breast cancer (TNBC) cells and promotes their proliferation in vitro and tumor growth in vivo. Genetic silencing or pharmacological inhibition of wt-IDH2 causes a significant increase in α-ketoglutarate (α-KG), indicating a suppression of reductive tricarboxylic acid (TCA) cycle. The aberrant accumulation of α-KG due to IDH2 abrogation inhibits mitochondrial ATP synthesis and promotes HIF-1α degradation, leading to suppression of glycolysis. Such metabolic double-hit results in ATP depletion and suppression of tumor growth, and renders TNBC cells more sensitive to doxorubicin treatment. Our study reveals a metabolic property of TNBC cells with active utilization of glutamine via reductive TCA metabolism, and suggests that wild-type IDH2 plays an important role in this metabolic process and could be a potential therapeutic target for TNBC.

Abstract Background The main cause of anesthesia-related deaths is the failure to manage difficult airways. Difficult laryngoscopic exposure is a major cause of unsuccessful management of difficult airways. Inadequate preoperative airway assessment hinders the clinical management of difficult airways cases, emphasizing the critical need for accurate identification of difficult airways. Currently, no definitive and reliable indicators are available to predict a difficult airway. Our study aims to predict laryngoscope exposure risk factors by combining ultrasonically measured upper airway anatomic parameters with physical examination indicators. Methods Patients aged 18 to 75 years, classified as American Standards Association (ASA) I-III, and scheduled for elective general anesthesia with endotracheal intubation were included. All patients received the upper airway and ultrasonographic measurements. After anesthesia induction, laryngoscope exposure was analyzed using the Cormack-Lehane grading system, with Grades III and IV as indicative of difficult laryngoscopy. Univariate and multivariate logistic regression analyses were performed to identify reliable indicators for predicting difficult laryngoscopy. Receiver Operating Characteristic (ROC) curve analysis was utilized to assess the predictive performance of each indicator. Results A total of 1120 patients finished the study, with 710 cases found in Grade I laryngoscopic exposure group, 360 cases in Grade II group, and 50 cases in Grade III group. There was no case observed in Grade IV group, thereby resulting in an incidence of difficult laryngoscopy of 4.46%. Univariate logistic regression analysis revealed that several parameters including age, Body Mass Index (BMI), neck circumference, neck mobility, snoring intensity, as well as ultrasound measurements of the pre-epiglottic space and thyromental distance were identified as significant risk factors for difficult laryngoscopy (P

Abstract Background Overactive bladder is a common chronic urological disorder in children, liable to impact normal social activities, disrupt sleep and even impair self-esteem. We aimed to evaluate the efficacy and safety of solifenacin combined with biofeedback for paediatric overactive bladder. Method Forty-five children with overactive bladder were enrolled and divided into three groups: 15 patients in Group A were treated with solifenacin, 15 cases in Group B with biofeedback, and the other 15 patients in Group C with the combination of solifenacin plus biofeedback. Each group was subdivided into the non-urge incontinence (non-UI) and urge incontinence (UI) groups. The remission rates were compared among the three groups at 2, 4, 8 and 12 weeks from the beginning of treatment. The side effects of solifenacin were recorded and followed up. Result After 2 weeks since initial treatment, the complete response rates were 33.3% (5/15), 20.0% (3/15), and 53.3% (8/15) in the three groups. At 4 weeks, the complete remission rates were 46.7% (7/15), 33.3% (5/15), and 60.0% (9/15) respectively. Moreover, the complete remission rates of the UI groups were higher than the non-UI groups (p

Abstracts Purpose Preoperative anemia increases postoperative morbidity, mortality, and the risk of allogeneic transfusion. However, the incidence of preoperative anemia in patients undergoing total hip arthroplasty and total knee arthroplasty (TKA) and its relationship to postoperative outcomes has not been previously reported. Methods We conducted a comprehensive literature search through PubMed, Cochrane Library, Web of Sincien, and Embase from inception to July 2023 to investigate the prevalence of preoperative anemia in patients undergoing Total Joint Arthroplasty, comorbidities between anemic and non-anemicpatients before surgery, and postoperative outcomes. postoperative outcomes were analyzed. Overall prevalence was calculated using a random-effects model, and heterogeneity between studies was examined by Cochran's Q test and quantified by the I 2 statistic. Subgroup analyses and meta-regression analyses were performed to identify sources of heterogeneity. Publication bias was assessed by funnel plots and validated by Egger's test. Results A total of 21 studies with 369,101 samples were included, all of which were retrospective cohort studies. 3 studies were of high quality and 18 studies were of moderate quality. The results showed that the prevalence of preoperative anemia was 22% in patients awaiting arthroplasty; subgroup analyses revealed that the prevalence of preoperative anemia was highest in patients awaiting revision of total knee arthroplasty; the highest prevalence of preoperative anemia was found in the Americas; preoperative anemia was more prevalent in the female than in the male population; and preoperative anemia with a history of preoperative anemia was more common in the female than in the male population. patients with a history of preoperative anemia; patients with joint replacement who had a history of preoperative anemia had an increased risk of infection, postoperative blood transfusion rate, postoperative blood transfusion, Deep vein thrombosis of the lower limbs, days in hospital, readmission within three months, and mortality compared with patients who did not have preoperative anemia. Conclusion The prevalence of preoperative anemia in patients awaiting total joint arthroplasty is 22%, and is higher in TKA and female patients undergoing revision, while preoperative anemia is detrimental to the patient's postoperative recovery and will increase the risk of postoperative complications, transfusion rates, days in the hospital, readmission rates, and mortality.

Abstract Objective Branchio-oto-renal syndrome (BOR, OMIM#113,650) is a rare autosomal dominant disorder that presents with a variety of symptoms, including hearing loss (sensorineural, conductive, or mixed), structural abnormalities affecting the outer, middle, and inner ear, branchial fistulas or cysts, as well as renal abnormalities.This study aims to identify the pathogenic variants by performing genetic testing on a family with Branchio-oto-renal /Branchio-otic (BO, OMIM#602,588) syndrome using whole-exome sequencing, and to explore possible pathogenic mechanisms. Methods The family spans 4 generations and consists of 9 individuals, including 4 affected by the BOR/BO syndrome. Phenotypic information, including ear malformation and branchial cleft, was collected from family members. Audiological, temporal bone imaging, and renal ultrasound examinations were also performed. Whole-exome sequencing was conducted to identify candidate pathogenic variants and explore the underlying molecular etiology of BOR/BO syndrome by minigene experiments. Results Intra-familial variability was observed in the clinical phenotypes of BOR/BO syndrome in this family. The severity and nature of hearing loss varied in family members, with mixed or sensorineural hearing loss. The proband, in particular, had profound sensorineural hearing loss on the left and moderate conductive hearing loss on the right. Additionally, the proband exhibited developmental delay, and her mother experienced renal failure during pregnancy and terminated the pregnancy prematurely. Genetic testing revealed a novel heterozygous variant NM_000503.6: c.639 + 3 A > C in the EYA1 gene in affected family members. In vitro minigene experiments demonstrated its effect on splicing. According to the American College of Medical Genetics (ACMG) guidelines, this variant was classified as likely pathogenic. Conclusion This study highlights the phenotypic heterogeneity within the same family, reports the occurrence of renal failure and adverse pregnancy outcomes in a female patient at reproductive age with BOR syndrome, and enriches the mutational spectrum of pathogenic variants in the EYA1 gene.

Abstract Background There are a few studies on the effectiveness and safety of intravenous administration of tranexamic acid(TXA) in patients who underwent foot and ankle surgery, especially for preoperative hidden blood loss in patients with freshfoot and ankle fractures. Thus, the aim of this study was to investigate whether intravenous administration of different doses of TXA can effectively reduce perioperative blood loss and blood loss before surgery and to determine its safety. Methods A total of 150 patients with fresh closed foot and ankle fractures from July 2021 to July 2023 were randomly divided into a control group (placebo controlled [PC]), standard-dose group (low-dose group [LD], 1 g/24 h; medium-dose group [MD], 2 g/24 h), and high-dose group (HD, 3 g/24 h; ultrahigh-dose group [UD], 4 g/24 h). After admission, all patients completed hematological examinations as soon as possible and at multiple other time points postsurgery. Results There was a significant difference in the incidence of hidden blood loss before the operation between the TXA group and the control group, and the effect was greater in the overdose groups than in the standard-dose groups. There were significant differences in surgical blood loss (intraoperative and postoperative), postoperative HGB changes, and hidden blood loss among the groups. The TXA groups showed a significant decrease in blood loss compared to that of the control group, and the overdose groups had a more significant effect than the standard-dose groups. A total of 9 patients in the control group had early wound infection or poor healing, while only 1 patient in the other groups had this complication, and the difference among the groups was significant. No patients in any group suffered from late deep wound infection, cardiovascular or cerebrovascular events or symptomatic VTE. Conclusion This is the first study on whether TXA can reduce preoperative hidden blood loss in patients with freshfoot and ankle fractures. In our study, on the one hand, intravenous application of TXA after foot and ankle fractures as soon as possible can reduce preoperative blood loss and postoperative blood loss. On the other hand, TXA can also lower wound complications, and over-doses of TXA are more effective than standard doses. Moreover, overdoses of TXA do not increase the incidence of DVT.

Abstract Disc cutters are essential for full-section hard-rock tunnel boring machines. The performance of these devices directly affects tunnel engineering costs and duration. This paper proposes a sinusoidal variable cross-section (VCS) cutter ring and design method and establishes a digital model. Rock-like materials are simulated with a finite element model, and the model validity is verified via rock simulation mechanics tests. A disc cutter rolling rock simulation model for a linear cutting machine is also established, and simulation tests are performed for single- and three-cutter rolling using sinusoidal VCSs and constant cross-section (CCS) cutter models, respectively. The stress and energy changes for the cutters and rock-like material damage area were compared via simulation, confirming that some sinusoidal VCS cutter rings do less work on rock-like materials and cause larger crushing areas under the same engineering parameters; therefore, these cutter rings have smaller specific energies. The sinusoidal VCS cutter ring performance is 7% greater than that of CCS on average under single-cutter simulation, and the intermediate cutter performance of the intermediate cutter is 9% greater than that of CCS on average under three-cutter simulation. Thus, sinusoidal VCS cutter rings offer improved rock damage performance, and further research and application of this technology will improve the working efficiency of tunnel boring machines.