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Abstract Background Targeting the STAT3 signaling pathway is a promising therapeutic approach for cancer patients. However, the association between STAT3 expression, the tumor immune microenvironment, and genetic variation remains unclear across human cancers, especially prostate cancer. Methods We used R software and other tools to analyze pan-cancer and mutation data from publicly available databases statistically. A comprehensive investigation was performed to assess the genetic heterogeneity and clinical relevance of STAT3 in various malignancies, with a specific focus on its role in the immune landscape and prognostic significance in prostate cancer. The findings were validated through immunohistochemistry (IHC) and multiplex immunofluorescence (mIF). Results STAT3 expression is abnormal in the majority of cancer tissues, which is strongly correlated with these patients' prognosis. Eight measures of tumor heterogeneity and six measures of tumor stemness of multiple tumor types showed a strong correlation with STAT3 expression. Furthermore, in individuals with prostate cancer, STAT3 expression indicated the degree of immune cell infiltration and the advancement of the disease. IHC analysis revealed that STAT3 was down-regulated in prostate tumor tissues, while mIF analysis demonstrated that STAT3 signaling (p-STAT3) was extensively active in tumor tissues and positive lymph node tissues. Conclusion STAT3 may serve as a valuable prognostic biomarker and therapeutic target across various cancers, with particular relevance to prostate cancer.

Abstract Recent advances in neuroscience have transformed our understanding of the meninges, the layers surrounding the central nervous system (CNS). Two key findings have advanced our understanding: researchers identified cranial bone marrow as a reservoir for meningeal immune cells, and rediscovered a brain lymphatic system. Once viewed merely as a protective barrier, the meninges are now recognized as a dynamic interface crucial for neuroimmune interactions. This shift in perspective highlights their unique role in maintaining CNS balance, shaping brain development, and regulating responses to injury and disease. This review synthesizes the latest insights into meningeal anatomy and function, with a focus on newly identified structures such as dural-associated lymphoid tissues (DALT) and arachnoid cuff exit (ACE) points. We also examine the diverse immune cell populations within the meninges and their interactions with the CNS, underscoring the emerging view of the meninges as active participants in brain immunity. Finally, we outline critical unanswered questions about meningeal immunity, proposing directions for future research. By addressing these knowledge gaps, we aim to deepen our understanding of the meninges’ role in brain health and disease, potentially paving the way for novel therapeutic approaches.

Abstract Background SARS-CoV-2, a highly contagious coronavirus, is responsible for the global pandemic of COVID-19 in 2019. Currently, it remains uncertain whether SARS-CoV-2 possesses oncogenic or oncolytic potential in influencing tumor progression. Therefore, it is important to evaluate the clinical and functional role of SARS-CoV-2 on tumor progression. Methods Here, we integrated bioinformatic analysis of COVID-19 RNA-seq data from the GEO database and performed functional studies to explore the regulatory role of SARS-CoV-2 in solid tumor progression, including lung, colon, kidney and liver cancer. Results Our results demonstrate that infection with SARS-CoV-2 is associated with a decreased expression of genes associated with cancer proliferation and metastasis in lung tissues from patients diagnosed with COVID-19. Several cancer proliferation or metastasis related genes were frequently downregulated in SARS-CoV-2 infected intestinal organoids and human colon carcinoma cells. In vivo and in vitro studies revealed that SARS-CoV-2 nucleocapsid (N) protein inhibits colon and kidney tumor growth and metastasis through the N-terminal (NTD) and the C-terminal domain (CTD). The molecular mechanism indicates that the N protein of SARS-CoV-2 interacts with YBX1, resulting in the recruitment of PKM mRNA into stress granules mediated by G3BP1. This process ultimately destabilizes PKM expression and suppresses glycolysis. Conclusion Our study reveals a new function of SARS-CoV-2 nucleocapsid protein on tumor progression.

Abstract Background Incorporating backfill cohorts in phase I oncology trials is a recently developed strategy for dose optimization. However, the efficacy assessment window is long in general, causing a lag in identifying ineffective doses and more patients being backfilled to those doses. There is necessity to investigate how to use patient-reported outcomes (PRO) to determine doses for backfill cohorts. Methods We propose a unified Bayesian design framework, called ‘Backfill-QoL’, to utilize patient-reported quality of life (QoL) data into phase I oncology trials with backfill cohorts, including methods for trial monitoring, algorithm for dose-finding, and criteria for dose selection. Simulation studies and sensitivity analyses are conducted to evaluate the proposed Backfill-QoL design. Results The simulation studies demonstrate that the Backfill-QoL design is more efficient than traditional dose-expansion strategy, and fewer patients would be allocated to doses with unacceptable QoL profiles. A user-friendly Windows desktop application is developed and freely available for implementing the proposed design. Conclusions The Backfill-QoL design enables continuous monitoring of safety, efficacy and QoL outcomes, and the recommended phase II dose (RP2D) can be identified in a more patient-centered perspective.

Abstract We demonstrate an all-fiber oscillator with high optical-to-optical efficiency using laser diodes working at 915nm as the pump sources to reduce the demand for thermal management. When the output power of the bidirectional pumped oscillator is 1.16kW, the optical-to-optical efficiency is as high as 75.4%. In this working state, the output characteristics of the oscillator are observed. The Raman suppression ratio is 41.23dB and the beam quality factor Mx 2 = 1.14, My 2 = 1.29. Analyzing the time trajectory of the highest power output, there are no significant characteristic peaks in the time domain signal and the frequency domain signal, which indicates that the oscillator has good stability.Improving the output characteristics of the 915nm pumping lasers has a positive significance for the application of non-strict ambient temperature control.

Abstract Background Although extant literature has investigated the impacts of social sites on employees’ job performance in different sectors, scholars have given little attention to teachers’ job performance (TJoP) in higher educational institutes. Purpose We aimed to investigate the direct and mediating impact of social media use (SMU) on TJoP. Based on social cognitive theory, this study proposed a model that consists of six hypotheses. Methodology : To empirically test the model, we develop a survey link to collect data from respondents working in universities in Jiangsu province, China. Partial least square structural equation modeling (PLS–SEM) using SmartPLS 4 has been used for analyzing 454 respondents. Results Research findings demonstrate the significant effects of SMU on TJoP, well-being, and social media addiction (SMAdd). In addition, teachers’ well-being and SMAdd have a positive and negative significant effect, respectively, on TJoP. Moreover, this research evidenced a significant partial mediation of teachers’ well-being and SMAdd. Conclusion This study points out the key role of SMU in the direct and indirect influences of TJoP through well-being and SMAdd. Further, it brings into view the urgency of higher education to prudently consider the implications of SMU on performance and general well-being among its faculty.

This paper proposes a novel vibration fatigue testing methodology of thin-walled specimens in the very high cycle fatigue (VHCF) regime, with the lifetime up to 109 cycles. A series of novel thin-walled specimens for the single crystal superalloy DD6 are designed, considering the thickness range from 0.5 to 1.5 mm. And the influences of the wall thickness on the S–N relations are obtained at RT and 760 °C, respectively. Subsequently, the thickness debit effect of the superalloy in terms of VHCF is presented and the relevant mechanism is discussed finally. The results show the proposed fatigue testing methodology is feasible and efficient for the thin-walled specimens. It is revealed the thickness debit effect of the superalloy at 760 °C, which shows the fatigue strengths of the 0.5 mm specimens are remarkably lower than those of other thicker specimens, especially in the VHCF regime. The thickness debit effect is mainly attributed to the fatigue crack initiation assisted by oxide penetration.

Abstract Constructing a LiF-rich solid electrolyte interphase (SEI) is a feasible strategy for inhibiting lithium (Li) dendrites of Li metal anodes (LMAs). However, selecting appropriate F-containing additives with efficient LiF contribution is still under active research. Herein, a series of fluorinated additives with diverse F/C molar ratios are investigated, and we demonstrate that the hexafluoroglutaric anhydride (F6−0) holds the best capability to derive the LiF-rich SEI in regular carbonate electrolytes (RCEs). To ameliorate the decomposition kinetics of the F6−0, LiNO3 (LNO) as an adjuvant is further introduced in the system. As a result, the reduction efficiency of F6−0 is increased to 91% under the F6−0/LNO synergistic effect, enabling the LMA with a uniform LiF-rich SEI in the RCE with merely 4 vol. % F6−0/LNO (F6L) addition. The LiNi0.8Co0.1Mn0.1O2||Li-20μm full-cell with the F6L also showcases better cycling and rate performances than the cases with other F-containing additives.

Abstract The traditional diagnostic markers for mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are synaptophysin (SYP), chromogranin A (CHGA) and CD56. However, there is still a lack of a large series of article focused on the expression of insulinoma-associated protein 1 (INSM1) in gastrointestinal and pancreatic MiNENs. This study compared the expression of INSM1 and traditional neuroendocrine markers in MiNENs. In this study, we collected 46 cases of gastrointestinal and pancreatic MiNENs and performed immunohistochemical staining for INSM1, SYP, CHGA, and CD56. Histologically, the neuroendocrine components of MiNENs were all neuroendocrine carcinomas, with small cell neuroendocrine carcinomas accounting for 15.2% (7/46) and large cell neuroendocrine carcinomas accounting for 84.8% (39/46). With respect to immunohistochemical expression, the overall sensitivity of INSM1 was 80.4% (37/46), which was lower than that of SYP (100%, 46/46), but comparable to that of CHGA (67.4%, 31/46) or CD56 (73.9%, 34/46). The overall specificity of INSM1 was 91.3% (42/46), which was greater than that of SYP (63.0%, 29/46) and CD56 (69.6, 32/46), but was not significantly different from that of CHGA (82.6%, 38/46). The proportion of 3 + staining for SYP (100%, 46/46) was greater than that of INSM1 (71.7, 33/46), while the proportion of 3 + staining for CHGA (10.9, 5/46) or CD56 (21.7, 10/46) was lower than that of INSM1. In conclusion, INSM1 exhibited high sensitivity and specificity in the diagnosis of gastrointestinal and pancreatic MiNENs.

Abstract It is generally believed that Carbapenem-resistant Enterobacterales (CRE) colonization is primarily responsible for systemic infection in humans. However, there is no consensus on whether decolonization should be recommended in clinical practice. In China, the specific situation of CRE colonization and consequent systemic infection in hospitalized patients necessitates further exploration. We conducted a cohort study and analyzed various clinical characteristics of inpatients with intestinal CRE colonization. A risk prediction model for consequent CRE infection was established and externally validated. Our prediction model is freely available online at https://creinfection.shinyapps.io/dynnomapp/ . 839 intestinal CRE colonization samples from inpatients were included. 317 cases of intestinal CRE colonization were enrolled, 25.9% of whom developed systemic infections. The consequent CRE infection rates of Klebsiella pneumoniae and Escherichia coli were 27.0% and 32.3%. The departments at high risk for subsequent CRE infection were respiratory medicine, hematology, and intensive care unit. Secondary infection after intestinal CRE colonization in inpatients can significantly prolong the length of hospital stay (26 days vs. 33 days, P < 0.001), increase the total medical cost (144735.34￥ vs. 281852.34￥, P < 0.001), and has poor (85.11% vs. 52.44%, P < 0.001) efficacy and high mortality (5.96% vs. 18.29%, P = 0.001). Our study makes a significant contribution to comprehensively specify CRE infection, because these results can facilitate early identification of high-risk hospitalized patients, timely implementation to decolonize treatment interventions, ultimately achieve the goal of CRE nosocomial infection prevention and control.

Abstract Objectives The Functional Clear Aligner (FCA) is a novel orthodontic appliance designed for the treatment of Class II malocclusion with mandibular retrognathia in adolescents. The aim of this study was to investigate the biomechanical characteristics of the masticatory muscles, jawbone, and temporomandibular joint (TMJ) during mandibular advancement using either FCA or Class II elastics combined with clear aligner (Class II elastics) through finite element analysis. Materials and methods A 3D finite element model of the ‘muscle-jawbone-TMJ-appliance’ system was constructed based on CBCT and MRI images of a boy with skeletal Class II malocclusion. Masticatory muscles included masseter, temporal, medial pterygoid, and lateral pterygoid muscles. The TMJ consists of the temporal bone’s glenoid fossa, disc, and mandibular condyle. To observe the biomechanical characteristics of the muscles and TMJ during orthodontic appliance wearing and the retention phase, two different protocols were used: Model 1: The mandibular advancement using FCA; Model 2: The mandibular advancement using Class II elastics. Results The FCA group produced greater and more coordinated masticatory muscle forces compared to the Class II elastics group. Temporal and masseter muscles exhibited the most pronounced variation in muscle strength during mandibular advancement. The FCA group exhibited greater TMJ region stress compared to the Class II elastics group. Interestingly, the stress on the articular discs in both models decreased over time. Tensile stresses were observed in both the condyle and the posterior region of the articular fossa. Conclusion During skeletal Class II malocclusion treatment, masticatory muscle forces and stress on the TMJ were higher in the FCA group compared to the Class II elastics group. In both models, stress cushioning was provided by the articular disc.

Abstract Background Hand, foot and mouth disease (HFMD) is a common infectious disease caused by viral infection by a variety of enteroviruses, with coxsackievirus A 10 (CA10) having become more prevalent in recent years. Methods In this study, models of CA10 infection were established in 7‐day‐old Institute of Cancer Research (ICR) mice by intraperitoneal injection to analyze the pathogenicity of the virus. RNA sequencing analysis was used to screen the differentially expressed genes (DEGs) after CA10 infection. Coxsackievirus A 16 (CA16) and enterovirus 71 (EV71) infections were also compared with CA10. Results After CA10 virus infection, the mice showed paralysis of the hind limbs at 3 days post infection and weight loss at 5 days post infection. We observed viral replication in various tissues and severe inflammatory cell infiltration in skeletal muscle. The RNA‐sequencing analysis showed that the DEGs in blood, muscle, thymus and spleen showed heterogeneity after CA10 infection and the most up‐regulated DEGs in muscle were enriched in immune‐related pathways. Compared with CA16 and EV71 infection, CA10 may have an inhibitory effect on T helper (Th) cell differentiation and cell growth. Additionally, the common DEGs in the three viruses were most enriched in the immune system response, including the Toll‐like receptor pathway and the nucleotide‐binding and oligomerization domain (NOD)‐like pathway. Conclusions Our findings revealed a group of genes that coordinate in response to CA10 infection, which increases our understanding of the pathological mechanism of HFMD.

As the cornerstone for evaluating the storage capacity of shale reservoirs and assessing the viability of shale gas exploitation, shale pores play a very important role in shale reservoirs. Based on drilling well and test data, deep learning, and artificial intelligence for image analysis, the types, characteristics, structures, and vertical heterogeneity of shale pores were studied. Additionally, we conducted a comprehensive investigation into the sedimentary environment characteristics and their influence on the heterogeneity of shale reservoir pores in the Longmaxi Formation using associated geochemical analyses. The results revealed that the sedimentary environment underwent significant changes in the Longmaxi Formation, characterized by a sea level fall, accelerated sedimentation rates, weakened reducing conditions, decreased palaeoproductivity, and increased terrigenous influx, which led to a decrease in the frequency of organic matter (OM) pores, paralleled by a gradual increase in inorganic pores. In the S1l11−1, S1l11−2, S1l11−3 sections of the Long11 sub-member, OM pores constitute the primary pore type. Conversely, in the S1l11−4 section and the Long12 sub-member, inorganic pores prevail as the primary pore type. Furthermore, the strongly anoxic sections are also pay zones that are not only enriched in OM but also concentrated with OM pores. The S1l11−1 and S1l11−2 sections are characterized by anoxic conditions, with total organic carbon (TOC) content exceeding 4% and abundant biogenic silica. Notably, an increased terrigenous influx adversely impacts the development and preservation of pores in the Long11 sub-member while exerting a dual effect in the Long12 sub-member. The increased terrigenous influx dilutes the OM and decreases the probability of intergranular pores and intragranular pores filled by OM. Moreover, more brittle mineral particles were deposited, which promotes the development and preservation of intergranular and intragranular pores.

Abstract Background Coronary artery calcification (CAC) is a common risk factor of cardiovascular disease. Although triglyceride glucose (TYG) index and high-density lipoprotein cholesterol (HDL-c) are both associated with CAC, no study has evaluated the correlation between the TYG/HDL-c ratio and CAC. In the present study, we investigated the relationships between CAC and the TYG index and the TYG/HDL-c ratio. Methods A total of 9585 participants who underwent computed tomography (CT) screening for lung cancer from 2018 to 2020 were included in this cross-sectional study. Demographic data, laboratory test data and medical history data were collected from medical records. TYG = Ln[fasting glucose (mg/dL)×fasting TG (mg/dL/2]. The triglyceride glucose-HDL-c ratio was calculated as TYG/HDL-c. CAC was evaluated on chest CT images. Multivariate logistic regression analysis and restricted cubic splines were used to determine the relationships among the TYG index, TYG/HDL-c ratio and risk of CAC. The receiver operating characteristic (ROC) curve was used to evaluate the performance of the TYG index and TYG/HDL-c ratio in identifying CACs in individuals aged 60 years and above. Results CAC was detected in 2515 of 9585 participants (mean age 51.8 ± 15.5 years, 61.2% men). The prevalence of CAC was significantly greater in participants with a high TYG/HDL-c ratio (32.6% in the fourth quartile vs. 19.1% in the first quartile, p

Abstract Background Overconsumption of retinoic acid (RA) or its analogues/derivatives has been linked to severe craniomaxillofacial malformations, such as cleft palate and midface hypoplasia. It has been noted that RA disturbed the proliferation and migration of embryonic palatal mesenchymal (EPM) cells in these malformations, yet the exact mechanisms underlying these disruptions remained unclear. Methods A model of retinoic acid (RA)-induced cleft palate in fetal mice was successfully established. Histological alterations in the palate were evaluated using Hematoxylin and Eosin (H&E) staining and RNA in situ hybridization (RNAscope). Cellular proliferation levels were quantified via the Cell Counting Kit-8 (CCK-8) assay and EdU incorporation assay, while cell migration capabilities were investigated using wound healing and Transwell assays. Mitochondrial functions were assessed through Mito-Tracker fluorescence, mitochondrial reactive oxygen species (ROS) measurement, ATP level quantification, and mitochondrial DNA (mtDNA) copy number analysis. Differential gene expression and associated signaling pathways were identified through bioinformatics analysis. Alterations in the transcriptional and translational levels of Lhx6 and genes associated with mitophagy were quantified using quantitative PCR (qPCR) and Western blot analysis, respectively. Mitochondrial morphology and the mitochondrial autophagosomes within cells were examined through transmission electron microscopy (TEM). Results Abnormal palatal development in mice, along with impaired proliferation and migration of human embryonic palatal mesenchymal (HEPM) cells, was associated with RA affecting mitochondrial function and concomitant downregulation of Lhx6. Knockdown of Lhx6 in HEPM cells resulted in altered cell proliferation, migration, and mitochondrial function. Conversely, the aberrant mitochondrial function, proliferation, and migration observed in RA-induced HEPM cells were ameliorated by overexpression of Lhx6. Subsequent research demonstrated that Lhx6 ameliorated RA-induced dysfunction in HEPM cells by modulating PINK1/Parkin-mediated mitophagy, thereby activating the MAPK signaling pathways. Conclusion Lhx6 is essential for mitochondrial homeostasis via tuning PINK1/Parkin-mediated mitophagy and MAPK signaling pathways. Downregulation of Lhx6 by RA transcriptionally disturbs the mitochondrial homeostasis, which in turn leads to the proliferation and migration defect in HEPM cells, ultimately causing the cleft palate. Graphical abstract

Abstract The therapeutic approach to thymic cysts remains a subject of controversy. Predicted biomarkers for identifying thymic cysts and thymoma (THYM) are crucial. In this research, patients diagnosed with thymic cysts (MTC, n = 6) and thymoma (B1, n = 6; B3, n = 6) were enrolled. Proteins of superior quality were subjected to TMT labeling and UPLC-MS, and differentially expressed proteins (DEPs) were identified. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interactive network analyses were applied to the DEPs. Some key differentially expressed genes(DEGs) were corroborated through GEPIA 32. The pan-cancer expression levels of key DEGs remarkably linked with prognosis were determined utilizing The University of ALabama at Birmingham CANcer data analysis Portal (UALCAN). Eventually, 49 DEPs were identified in the B1 vs. MTC comparison (17 upregulated and 32 downregulated), 27 in the B3 vs. MTC comparison (8 upregulated and 19 downregulated), and 38 in the B3 vs. B1 comparison (9 upregulated and 29 downregulated). IL13RA1 (down), galectin-3 binding protein (LGALS3BP)(up), PRCSH (down), C3 (down), MXRA5 (down), TNN (down), CFHR1 (down), SUN3 (down) were jointly altered in both B1 vs. NZ and B3 vs. NZ. GEPIA validated that LGALS3BP was significantly upregulated in thymoma patients. In conclusion, LGALS3BP might be an essential biomarker to identify thymoma from the thymic cyst.

Abstract Background We aimed to develop multiple machine learning models to predict the risk of early intracranial aneurysms (IAs) rupture, evaluate and compare the performance of predictive models. Methods Information related to patients diagnosed with IA by CT angiography and clinicians in Central hospital of Dalian University of Technology from January 2010 to June 2022 was collected, including clinical characteristics, blood indicators and IA morphological parameters. IA with rupture or maximum growth ≥ 0.5 mm within 1 month of first diagnosis was considered unstable. The relevant factors affecting IA stability were screened and predictive models were developed based on the above three levels, including random forest (RF), support vector machine (SVM), and artificial neural network (ANN). Sensitivity, specificity, accuracy and area under curve (AUC) value were used to evaluate the predictive models. Results A total of 989 IA patients were included in the study, including 561 stable patients and 428 unstable patients. For RF models, the training set showed that sensitivity, specificity, accuracy and the AUC values were 72.8–83.7%, 76.9–86.9%, 75.1–84.1% and 0.748 (0.719–0.778)–0.839 (0.814–0.864), respectively; after test set validation, the results were 71.9–78.8%, 75.0–84.0%, 73.6–81.1% and 0.734 (0.688–0.781)–0.809 (0.768–0.850), respectively. For SVM models, the training set were 66.0–80.2%, 76.5–85.5%, 71.7–82.3%, 0.712 (0.682–0.743)–0.913 (0.884–0.924), respectively; the test set were 44.2–78.3%, 63.4–84.4%, 57.9–80.9%, 0.699 (0.651–0.747)–0.806 (0.765–0.848), respectively. For ANN models, the training set were 66.8–83.0%, 75.3–82.3%, 71.6–82.1%, 0.783 (0.757–0.808)–0.897 (0.879–0.914); the test set were 63.1–76.3%, 65.5–84.0%, 64.4–80.6%, 0.680 (0.593–0.694)–0.860 (0.821–0.899). The results of variable importance showed that age, white blood cell count (WBC) and uric acid (UA) played an important role in predicting the stability of IA. Conclusions The predictive stability models of IA based on three artificial intelligence methods shows good clinical application. Age, WBC and UA played an important role in predicting the IA stability, and were potentially important predictors.

Abstract The triglyceride glucose (TyG) related index, a metric used to evaluate assessing insulin resistance (IR), has received limited attention in its association with sarcopenia. Our study aims to explore the predictive potential of the TyG index for sarcopenia. This study utilized data from the China Health and Retirement Longitudinal Study, a nationally representative, community-based cohort study, including a sample size of 10,537 participants aged 45 years and older. Associations between TyG related index and sacopenia was explored using multivariate logistic regression. Analysis of the predictive value of TyG related index for sarcopenia using receiver-operating characteristic curve (ROC). We evaluated the correlation between the TyG related index and the risk of sarcopenia using Cox proportional hazards models. Additionally, we utilized restricted cubic spline (RCS) regression analyses to explore the connections between the TyG-related index and sarcopenia. Logistic regression analysis showed an association between TyG (OR 0.961[0.955,0.968], P

Abstract In order to improve the bioavailability of baicalin, this article prepared for α-zein loaded with baicalin composites (α-zein@BA) by pH driven method and they were characterized using scanning electron microscopy, infrared spectroscopy, and measurement of particle size distribution in water solution phase techniques. The digestive behavior and antioxidant activity of composites before and after simulating gastrointestinal fluid in vitro were studied as well. At the same time, molecular dynamics simulation techniques were used to reveal the molecular mechanism behind the formation of the composite between the two. The results indicated that the composites of α-zein@BA were observed to be approximately spherical under a scanning electron microscope, and their particle size was mainly distributed in the range of 94.55-145.10 μm in aqueous solution, whose encapsulation efficiency of baicalin was (86.61 ± 0.71) %. Infrared spectroscopy analysis indicated that α-zein and baicalin mainly formed complexes through hydrogen bonding, electrostatic and hydrophobic interactions. The measurement results of baicalin residue in simulated digestion of gastric and intestinal fluids in vitro are as follows: α-zein@BA > Baicalin, while both significantly increased in the gastric digestion stage (P

Abstract The design of the reactant gas flow field structure in bipolar plates significantly influences the performance of proton exchange membrane fuel cells (PEMFCs). In this study, we introduced four innovative U-shaped flow field designs, namely: In-Out Multi-U, Out-In Multi-U, Distro In-Out Multi-U, and Distro Out-In Multi-U. To investigate the impact of these various flow fields on PEMFC performance, we conducted computational fluid dynamics (CFD) numerical simulations, validated through model experiments. Our results indicate that the Distro Out-In Multi-U flow field offers notable advantages compared to the conventional parallel flow field (CPFF) and conventional serpentine flow field (CSFF). These benefits include reduced inlet and outlet pressures, lower liquid water content, more uniform liquid water distribution, and a more even current density distribution. Furthermore, the Distro Out-In Multi-U design demonstrates improved efficiency, consuming less H2 (91.9%) than the CSFF while achieving a higher net power density output (10.1%). As a result, for the same power output, the Distro Out-In Multi-U utilizes only 83.5% of the H2 consumed by the CSFF. In summary, the U-shaped structured flow field exhibits superior output performance, enhanced energy efficiency, and improved resistance to flooding. These findings suggest that the U-shaped flow field design holds significant potential as a reactive flow field for PEMFCs.

Sorbus tapashana (Rosaceae) from Taibai Shan, Qinling, China, has been treated as a synonym of S. tianschanica. Both species belong to a distinctive group characterized by white tomentose buds, relatively large flowers, and red fruits. However, these two species do not cluster together in the plastome-based phylogenetic analysis. Morphologically, S. tapashana differs from S. tianschanica by its persistent white tomentose on the peduncle, pedicels, rachis, both sides of the midrib on abaxial surface, its leaflets with 31–51 teeth on each side and much smaller corymbs and fruits. Therefore, S. tapashana is reinstated as a distinct species here.

Abstract Background Vegetable soybean is rich in nutrients and has a unique flavor. It is highly preferred by people because of its pharmacological activities, including those that regulate the intestines and lower blood pressure. The pod color of vegetable soybeans is an important quality that indicates their freshness and has a significant impact on their commercialization. Results In this study, pod color was evaluated in 301 vegetable soybean accessions collected from various regions. Genome-wide association analysis was carried out using the Mixed linear model (MLM), a total of 18 quantitative trait loci including 117 SNPs were detected. Two significant QTLs located on chromosomes 6 (qGPCL4 /qGPCa1/qGPCb2) and 18 (qGPCL10/qGPCb3) were consistently detected across different variables. Based on gene functional annotation, 30 candidate genes were identified in these two candidate intervals. Combined with transcriptome analysis, Glyma.18g241700 has been identified as a candidate gene for regulating pod color in vegetable soybeans. Glyma.18g241700 encodes a chlorophyll photosystem I subunit XI. which localizes to the chloroplast named GmPsaL, qRT-PCR analysis showed that GmPsaL was specifically highly expressed in developing pods. Furthermore, overexpression of GmPsaL in transgenetic Arabidopsis plants produced dark green pods. Conclusions These findings may be useful for clarifying the genetic basis of the pod color of vegetable soybeans. The identified candidate genes may be useful for the genetic improvement of the appearance quality of vegetable soybeans.

Abstract Glycolytic metabolic reprogramming in cancer is regulated by both cancer intrinsic variations like isocitrate dehydrogenase 1 (IDH1) status and non-cancerous microenvironment components like tumor associated macrophages (TAMs). However, the detailed mechanism remains elusive. Here, we identify hexosaminidase B (HEXB) as a key regulator for glycolysis in glioblastoma (GBM). HEXB intercellularly manipulates TAMs to promote glycolysis in GBM cells, while intrinsically enhancing cancer cell glycolysis. Mechanistically, HEXB elevation augments tumor HIF1α protein stability through activating ITGB1/ILK/YAP1; Subsequently, HIF1α promotes HEXB and multiple glycolytic gene transcription in GBM cells. Genetic ablation and pharmacological inhibition of HEXB elicits substantial therapeutic effects in preclinical GBM models, while targeting HEXB doesn’t induce significant reduction in IDH1 mutant glioma and inhibiting IDH1 mutation-derived 2-hydroxyglutaric acid (2-HG) significantly restores HEXB expression in glioma cells. Our work highlights a HEXB driven TAMs-associated glycolysis-promoting network in GBM and provides clues for developing more effective therapies against it.

Abstract Retinoic acid-inducible gene I (RIG-I) is a pattern recognition receptor involved in innate immunity, but its role in adaptive immunity, specifically in the context of CD8+ T-cell antitumour immunity, remains unclear. Here, we demonstrate that RIG-I is upregulated in tumour-infiltrating CD8+ T cells, where it functions as an intracellular checkpoint to negatively regulate CD8+ T-cell function and limit antitumour immunity. Mechanistically, the upregulation of RIG-I in CD8+ T cells is induced by activated T cells, and directly inhibits the AKT/glycolysis signalling pathway. In addition, knocking out RIG-I enhances the efficacy of adoptively transferred T cells against solid tumours, and inhibiting RIG-I enhances the response to PD-1 blockade. Overall, our study identifies RIG-I as an intracellular checkpoint and a potential target for alleviating inhibitory constraints on T cells in cancer immunotherapy, either alone or in combination with an immune checkpoint inhibitor.

Abstract We investigated the clinical characteristics of primary aldosteronism (PA) screened from patients with hypertension in China. The participants were hypertensive patients who were suspected of PA and registered in the China Primary Aldosteronism Prospective Study. Plasma aldosterone‐to‐renin ratio (ARR) was used as the screening test. In patients screened positive for PA, that is, an ARR exceeding the thresholds and plasma aldosterone concentration (PAC) > 100 pg/mL, a confirmatory test was performed for diagnosis. Patients with PA underwent a CT scan and adrenal venous sampling for subtyping. Of the 1497 screened patients, 754 (50.4%) had an ARR exceeding the diagnostic threshold and 637 (84.5% of those eligible) were registered. These registered hypertensive patients with suspected PA had a mean (standard deviation) age of 52.6 ± 12.1 years, and included 442 (58.6%) women. In multiple stepwise logistic regression, the significant odds ratios for the presence of diagnosed (n = 490) versus suspected and non‐diagnosed PA (n = 147) were 4.54 (95% CI: 2.78‐7.39) for a history of hypokalemia, 0.79 (95% CI: 0.64‐0.98) for a 0.9 mmol/l higher serum total cholesterol, and 2.25 (95% CI: 1.63‐3.10) for a doubling of PAC in the supine or standing/sitting position. In multiple stepwise logistic regression, the significant odds ratios for the presence of unilateral (n = 135) versus bilateral PA (n = 53) were 3.04 (95% CI: 1.90‐4.87) for a 0.4 mmol/l lower minimum serum potassium concentration and 1.86 (95% CI: 1.20‐2.86) for a 0.3 mmol/l higher serum high‐density lipoprotein cholesterol. PA might be a biochemical continuum in the adrenal hypersecretion of aldosterone as well as hypokalemia.

Abstract Background The potential effects of global warming on soil fungal communities and their functions remain uncertain. To address this issue, we investigated the effects of 3-year simulated field warming on the community and function of fungi in a temperate steppe of Inner Mongolia, northern China. Methods The diversity and structure of the fungal community were measured by high-throughput sequencing. The functionality of fungal communities was identified by comparison with the ITS reference database. Results Our results showed that warming did not affect the diversity of fungi, but significantly increased the complexity of the fungal community, with fungal taxa more closely associating with each other. We observed that plant pathogens and arbuscular mycorrhizal fungi were the most abundant functional groups. Meanwhile, warming significantly decreased the relative abundance of animal pathogens. Conclusions Warming significantly increased the complexity of the fungal community, with soil pH being the main factor affecting soil fungal function. Our findings emphasize that the response of the fungal community and its functional groups to warming has significant implications for ecosystem biogeochemical cycling.

Abstract Allosteric drugs offer a new avenue for modern drug design. However, the identification of cryptic allosteric sites presents a formidable challenge. Following the allostery nature of residue-driven conformation transition, we propose a state-of-the-art computational pipeline by developing a residue-intuitive hybrid machine learning (RHML) model coupled with molecular dynamics (MD) simulation, through which we can efficiently identify the allosteric site and allosteric modulator as well as reveal their regulation mechanism. For the clinical target β2-adrenoceptor (β2AR), we discover an additional allosteric site located around residues D792.50, F2826.44, N3187.45 and S3197.46 and one putative allosteric modulator ZINC5042. Using Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) and protein structure network (PSN), the allosteric potency and regulation mechanism are probed to further improve identification accuracy. Benefiting from sufficient computational evidence, the experimental assays then validate our predicted allosteric site, negative allosteric potency and regulation pathway, showcasing the effectiveness of the identification pipeline in practice. We expect that it will be applicable to other target proteins.

Abstract Boron-doped biochar (B-BC) was synthesized by pyrolysis using solid waste of sorghum straw as raw material. The specific surface area of B-BC increased significantly by 2.38 times compared to that of pure BC. This enhancement allowed B-BC (0.3 g L−1) to achieve complete adsorption of 10 mg L−1 tartrazine (TTZ) within 40 min. Moreover, acidic conditions were more favorable for TTZ adsorption, achieving complete removal of TTZ in only 15 min at a pH of 3.0. Interestingly, the adsorption rate of TTZ by B-BC in the presence of 0.05 M Cl− was approximately 2.12 times higher than that in the absence of Cl−. When other background electrolytes were present, excluding PO4 3−, complete adsorption of TTZ could also be achieved within 60 min. Thermodynamic analysis and DFT calculations described the parameters of B-BC for TTZ adsorption, including $$\Delta {\text{G}}^{\Theta }$$ Δ G Θ (

Abstract Despite recent advances, severe acute pancreatitis (SAP) remains a lethal inflammation with limited treatment options. Here, we provide compelling evidence of GV-971 (sodium oligomannate), an anti-Alzheimer’s medication, as being a protective agent in various male mouse SAP models. Microbiome sequencing, along with intestinal microbiota transplantation and mass cytometry technology, unveil that GV-971 reshapes the gut microbiota, increasing Faecalibacterium populations and modulating both peripheral and intestinal immune systems. A metabolomics analysis of cecal contents from GV-971–treated SAP mice further identifies short-chain fatty acids, including propionate and butyrate, as key metabolites in inhibiting macrophage M1 polarization and subsequent lethal inflammation by blocking the MAPK pathway. These findings suggest GV-971 as a promising therapeutic for SAP by targeting the microbiota metabolic immune axis.

Highlights Comprehensively reviewed the progress in research on graphene electrode-based triboelectric nanogenerators (TENGs) from two dimensions, including precision processing methods of graphene electrodes and applications of TENGs. Discussed the various applications of graphene electrode-based TENGs in different scenarios, as well as the ways in which graphene electrodes enhance the performance of TENGs. Offered a prospective discussion on the future development of graphene electrode-based TENGs, with the aim of promoting continuous advancements in this field.

Abstract Background This single-blind randomized controlled trial was aimed to evaluate the microbiological and clinical effects of Zeger therapy on gingival health. Methods Twenty-four adults with gingivitis were recruited and monitored micro-biologically and clinically at baseline (Day 0), 4 weeks (Day 29) after therapy. All volunteers received one-stage full-mouth supragingival scaling as basic oral health care for baseline, and then randomly divided into experimental (koumiss, n = 12) or control (none, n = 12) group. The koumiss was used once a day for 4 weeks. Results The microbial diversity of the experimental group increased significantly after drinking koumiss (p 0.05). However, there was no significant difference between the two groups in the clinical parameters (p > 0.05). Conclusions Zeger therapy promotes the diversity of supragingival microbiome in adults with gingivitis and increases the abundance of some beneficial flora while decreasing some harmful without clinical parameters marked changing, which holds promise for improving of gingivitis and may be a valuable oral health care approach in the future. Trial registration The clinical trial was approved by the Medical Ethics Committee of West China Hospital of Stomatology, Sichuan University, batch No. WCHSIRB-D-2021-428. Before patient registration began, the prospective clinical trial was registered in www.clinicaltrials.gov public repository in China under the registration number ChiCTR2200060555 on 04/06/2022.

Abstract Background Dentatorubral-pallidoluysian atrophy is a rare autosomal dominant neurodegenerative disease. It is a rare disease in the world. Therefore, sharing clinical encounters of this case can deepen global awareness and understanding of the disease. Case presentation The patient was a 34-year-old male of Han nationality who was unmarried. The patient was admitted owing to weakness of the left lower limb with walking instability for 2 months and aggravation for 1 month. There was no dizziness, headache, numbness of limbs, convulsions, nausea, vomiting, abdominal pain, ataxia, nausea, vomiting, or abdominal pain. No nausea, vomiting, diarrhea, abdominal distension, tinnitus, hearing loss, fever, cough, expectoration. Personal history: worked in Cambodia 5 years ago, worked in Dubai 3 years ago, engaged in computer work, smoking or drinking habits. The patient was unmarried. Family history: the mother had symptoms similar to walking unsteadily (undiagnosed). Positive signs include a wide-base gait with a rotatory nystagmus that jumps upward in both eyes. Bilateral finger-nose instability test was quasi-positive, rapid alternating test was negative, and eye closure tolerance test was positive. Tendon reflexes were active in both upper limbs and hyperreflexia in both lower limbs. Stability of the heel, knee, and tibia. Genetic testing showed that the number of repeats in the dentatorubral-pallidoluysian atrophy ATN1 gene was 18 and 62, and the (CAG)n repeat sequence in the ATN1 gene was abnormal, with a repeat number of 62, and the patient was a pathogenic variant. The patient was diagnosed with dentatorubral-pallidoluysian atrophy. Dentatorubral-pallidoluysian atrophy remains a progressive neurodegenerative disease with no effective treatment. At present, the proband is taking 5 mg of buspirone three times a day, which has been reported to improve the symptoms. The patient was followed up for 6 months after taking buspirone, and there was no significant improvement in the temporary symptoms. At present, there are few cases of dentatorubral-pallidoluysian atrophy, and the characteristics of nystagmus in this disease have not been proposed in the past. This case reported the unusual presentation of nystagmus. Conclusion Dentatorubral-pallidoluygur atrophy is a rare neurodegenerative disease with autosomal dominant inheritance. To the best of our knowledge, our present case report is the first case report of dentatorubral-pallidoluygur atrophy with specific nystagmus. We describe the special eye shake and its positive signs to increase dentatorubral-pallidoluysian atrophy clinical positive signs.

Abstract Background Intrahepatic cholangiocarcinoma (iCCA) is a lethal primary liver tumor characterized by clinical aggressiveness, poor prognosis, and scarce therapeutic possibilities. Therefore, new treatments are urgently needed to render this disease curable. Since cumulating evidence supports the oncogenic properties of the Heat Shock Factor 1 (HSF1) transcription factor in various cancer types, we investigated its pathogenetic and therapeutic relevance in iCCA. Methods Levels of HSF1 were evaluated in a vast collection of iCCA specimens. The effects of HSF1 inactivation on iCCA development in vivo were investigated using three established oncogene-driven iCCA mouse models. In addition, the impact of HSF1 suppression on tumor cells and tumor stroma was assessed in iCCA cell lines, human iCCA cancer-associated fibroblasts (hCAFs), and patient-derived organoids. Results Human preinvasive, invasive, and metastatic iCCAs displayed widespread HSF1 upregulation, which was associated with a dismal prognosis of the patients. In addition, hydrodynamic injection of a dominant-negative form of HSF1 (HSF1dn), which suppresses HSF1 activity, significantly delayed cholangiocarcinogenesis in AKT/NICD, AKT/YAP, and AKT/TAZ mice. In iCCA cell lines, iCCA hCAFs, and patient-derived organoids, administration of the HSF1 inhibitor KRIBB-11 significantly reduced proliferation and induced apoptosis. Cell death was profoundly augmented by concomitant administration of the Bcl-xL/Bcl2/Bcl-w inhibitor ABT-263. Furthermore, KRIBB-11 reduced mitochondrial bioenergetics and glycolysis of iCCA cells. Conclusions The present data underscore the critical pathogenetic, prognostic, and therapeutic role of HSF1 in cholangiocarcinogenesis.

The sulfate process for bamboo pulp production encounters silicon interference during the pulping stage, necessitating desilication before the alkali recovery section. This study investigated the desilication of bamboo pulping black liquor (BPBL), demonstrating that silicon was removed effectively by adding Mg/Al compound desilication agent to the BPBL via burning at high temperature. The desilication extent can reach 84% when the desilication agent is added in the proportion of Mg/Al (magnesium sulfate and sodium metaluminate) in the ratio 1.25:0.75. Subsequently, less-silicon white mud (LSWM) can be prepared after black liquor (BL) combustion desilication. LSWM was compared with normal WM as a blank sample, and the morphology and physicochemical properties of two kinds of WM were characterized. X-ray diffractometry revealed that both types of WM are primarily composed of calcite crystalline CaCO3 and hydrated CaSiO3. Scanning electron microscopy, X-ray photoelectron spectroscopy, and particle size analysis demonstrated the reduced content of CaSiO3 generated in the LSWM. This result indicated that the Mg/Al compound desilication agent removed the silicon from the green liquor (GL), thereby reducing the residual silicon in WM. This reduction is beneficial to the calcination recovery and comprehensive utilization of WM.

During the survey of potential pathogens in the Tian-e-zhou National Reserve for Lipotes vexillifer in Shishou, China, isolate SS20210504 was isolated from the diseased prey fish-Pelteobagrus fulvidraco and was identified as Aerococcus viridans through 16S rRNA gene, morphological observation, and physiological and biochemical analysis. Artificial infection trials with fish through different methods were conducted. Results indicated that the isolate of SS2021504 caused mortality in fish with the LD50 of 1.0 × 106.2 CFU/mL, 1.0 × 107.9 CFU/mL and 1.0 × 106.8 CFU/mL with the infection method of intraperitoneal injection, co-immersion, and scratch immersion, respectively. Challenged fish exhibited hemorrhages signs similar to naturally diseased fish. Histology analysis showed that the liver and kidney were the principal target organs of isolate SS2021504 in fish, and obvious vacuolation and karyopyknosis occurred in the above organs. To evaluate the pathogenicity of isolate SS20210504 in mice, healthy mice and immunosuppressed mice were further experimentally infected with bacteria, respectively. No death was observed either in healthy mice or in immunocompromised mice. However, the immunocompromised mice inoculated with bacteria showed obvious clinical symptoms and severe damage to multiple organs. The inflammatory signaling pathways were significantly activated with upregulated levels of Myd88, TNFα, AP-1, IL-1β, IL-6, and IFN-γ gene in the spleen from the immunocompromised mice after infected with isolate SS20210504. These findings imply that isolate SS20210504 has the potential risk to YFPs and residents. Continued surveillance of A. viridans and other pathogens in the TZO reserve is suggested to prevent outbreaks in prey fish, YFPs, and residents as well.

Histopathology image classification is crucial in pathological diagnosis workflow for early detection and treatment. The integration of deep learning technology has greatly improved diagnostic accuracy and efficiency. However, there are limitations when morphological features are not obvious in pathological sections, leading to difficulties in identifying deep cells and an increased risk of misdiagnosis. To address this issue, this study introduces a new hybrid network model, termed ICDNET, designed to fuse global and local features without destroying the integrity of the feature data, thus enhancing the accuracy of medical image classification. The ICDNET model consists of two main features: (i) a serial hierarchical structure composed of global and local feature blocks; and (ii) an Internal Communication Hierarchical Fusion Block (ICHF) and an Efficient Dual Self-Attention (EDA) mechanism. This network structure solves internal communication issues and enriches contextual semantic information, extracting local features and global representations from different internal spaces. To evaluate the performance of the ICDNET network model, experiments were conducted on four major public datasets with the addition of Gaussian noise. The experimental results demonstrate excellent accuracy and the ability to handle limited training samples, highlighting the potential of the ICDNET model to assist pathologists in pathological diagnosis.

Altered cell-cell communication is a hallmark of aging, but its impact on bone marrow aging remains poorly understood. Based on a common and effective pipeline and single-cell transcriptome sequencing, we detected 384,124 interactions including 2575 ligand-receptor pairs and 16 non-adherent bone marrow cell types in old and young mouse and identified a total of 5560 significantly different interactions, which were then verified by flow cytometry and quantitative real-time PCR. These differential ligand-receptor interactions exhibited enrichment for the senescence-associated secretory phenotypes. Further validation demonstrated supplementing specific extracellular ligands could modify the senescent signs of hematopoietic stem cells derived from old mouse. Our work provides an effective procedure to detect the ligand-receptor interactions based on single-cell sequencing, which contributes to understand mechanisms and provides a potential strategy for intervention of bone marrow aging.

Abstract Aims To explore rare and difficult cases of undifferentiated embryonal sarcoma of the liver (UESL) in children in a single centre, summarize the diagnosis and treatment experience and analyse the role of a computer-assisted surgery system (Hisense CAS), thus providing a new global vision and three-dimensional perspective. Methods We retrospectively collected the clinical data including the diagnoses and treatment processes, of children with UESL confirmed by histopathological examination in our hospital from January 2009 to December 2020. The relationship between the tumour volume and important blood vessels and between the liver volume and tumour volume, as well as other three-dimensional characteristics in the reconstructed three-dimensional model were analysed using Hisense CAS. The findings from this analysis can be used to aid in surgical decision-making and preoperative planning. Results Four children—3 girls and 1 boy—with UESL were included in the study. The age at onset ranged from 6 to 8 years. All four children presented with symptoms of abdominal discomfort, and abdominal masses were detected during physical examination. Owing to the wishes of their parents and the possibility that the disease was benign, all four children underwent one-stage radical surgery. For patient 1, a three-dimensional reconstruction was created during the initial diagnosis, which made accurate evaluation and planning of the preoperative procedure challenging. In patient 2, the tumour was located in the middle lobe of the liver and involved the first and second hepatic hilum. For patient 3, the pathological diagnosis of the tumour after surgery was challenging, but eventually, the diagnosis was confirmed through histochemistry and consultation with higher-level hospitals. Patient 4 had a giant tumour, which had a preoperative simulated future liver remnant volume (FLV) that was 21.0% of the total volume of the liver and tumour (TLTV). According to the standard liver volume (SLV) for children, the FLV was 77.0% of the SLV, making surgery feasible. All four children underwent complete resection, and only patient 4 experienced recurrence below the diaphragm 19 months after surgery. Currently, the 3-year overall survival rate is 100%, and the 3-year event-free survival rate is 75%. Conclusion UESL in children is rare, and the key to diagnosis and treatment is complete surgical resection. Through individualized three-dimensional surgical planning, accurate and complete resection of difficult and complex UESL in children can be achieved, leading to a favourable prognosis.

Abstract Activated Wnt/β-catenin pathway is a key genetic event in liver cancer development. Solute carrier (SLC) transporters are promising drug targets. Here, we identify SLC13A3 as a drug-targetable effector downstream of β-catenin in liver cancer. SLC13A3 expression is elevated in human liver cancer samples with gain of function (GOF) mutant CTNNB1, the gene encoding β-catenin. Activation of β-catenin up-regulates SLC13A3, leading to intracellular accumulation of endogenous SLC13A3 substrates. SLC13A3 is identified as a low-affinity transporter for glutathione (GSH). Silencing of SLC13A3 downregulates the leucine transporter SLC7A5 via c-MYC signaling, leading to leucine depletion and mTOR inactivation. Furthermore, silencing of SLC13A3 depletes GSH and induces autophagic ferroptosis in β-catenin-activated liver cancer cells. Importantly, both genetic inhibition of SLC13A3 and a small molecule SLC13A3 inhibitor suppress β-catenin-driven hepatocarcinogenesis in mice. Altogether, our study suggests that SLC13A3 could be a promising therapeutic target for treating human liver cancers with GOF CTNNB1 mutations.

Abstract Background Non-tuberculous mycobacteria (NTM) are present widely in the natural environment and can invade the human body through the respiratory tract, gastrointestinal tract, and skin. Immunocompromised patients are particularly prone to infection, which primarily affects multiple organs, including the lungs, lymph nodes, and skin. However, cases of NTM bloodstream infections are rare. Here, we report a rare case of Mycobacterium marseillense bloodstream infection with concurrent skin fungal infection in a patient after kidney transplantation. Related literature was reviewed to enhance the understanding of this rare condition. Case presentation A 58-year-old male with a history of long-term steroid and immunosuppressant use after kidney transplantation presented with limb swelling that worsened over the past two months. Physical examination revealed redness and swelling of the skin in all four limbs, with a non-healing wound on the lower left limb. Skin tissue analysis by metagenomic next-generation sequencing (mNGS) and fungal culture indicated infection with Trichophyton rubrum. Blood culture results suggested infection with Mycobacterium marseillense. After receiving anti-NTM treatment, the patient’s symptoms significantly improved, and he is currently undergoing treatment. Conclusion Mycobacterium marseillense is a NTM. Gram staining suffered from misdetection, and the acid-fast staining result was positive. This bacterium was identified by mass spectrometry and mNGS analyses. Antimicrobial susceptibility tests for NTM were performed using the broth microdilution method. The results of the susceptibility test showed that Mycobacterium marseillense was sensitive to clarithromycin, an intermediary between moxifloxacin and linezolid. Bacterial clearance requires a combination of drugs and an adequate course of treatment. NTM bloodstream infections are relatively rare, and early identification and proactive intervention are key to their successful management.

Abstract The optimal timing and type of hematopoietic stem cell transplantation (HSCT) for treating peripheral T-cell lymphoma (PTCL) remain controversial. This retrospective real-world study investigated the application pattern and outcomes of HSCT in China. The analysis encompassed 408 PTCL patients with a median age of 45.5 years, all of whom received initial adequate therapy at five hospitals. Among patients with nodal PTCL who responded effectively to first-line therapy (the “responders”, n = 127) and subsequently underwent HSCT consolidation (n = 47, 37.0%), 93.6% received auto-HSCT, while 6.4% underwent allo-HSCT. Front-line auto-HSCT showed potential for long-term disease control in nodal PTCL responders. Among non-nodal PTCL responders (n = 80) with HSCT (n = 26, 32.5%), 46.2% underwent allo-HSCT and 53.8% received auto-HSCT. Upfront allo-HSCT provides longer progression-free survival (PFS) for non-nodal PTCL responders, with lower 3-year cumulative incidence of relapse (CIR) (16.7% vs. 56.0%) and comparable non-relapse mortality (NRM) (10.4% vs. 11.0%) compared to auto-HSCT. For patients who achieved remission with second-line salvage regimens, allo-HSCT was the primary choice (82.4%) for non-nodal PTCL, while auto-HSCT was more common (82.4%) in nodal PTCL. Nodal PTCL patients underwent auto-HSCT after ≥ 3 lines of treatment had a higher 3-year CIR (81.0%) compared to those treated in the first (26.0%) or second line (26.0%). Non-nodal PTCL patients underwent allo-HSCT after ≥ 3 lines had a higher 3-year NRM (37.5%) compared to after first (10.4%) or second line treatment (8.5%). These findings highlight distinct HSCT application patterns for PTCL in China, emphasizing the impact of early disease control and upfront consolidative HSCT.

Abstract Background With the development of Internet information technology, especially the impact of the sudden outbreak of the novel coronavirus disease 2019 epidemic, along with the call for “classes suspended but learning continues,” a large number of medical educators have learned and experienced online teaching. They have understood the shortcomings of traditional teaching methods. Not only the blended BOPPPS teaching mode combines the advantages of the BOPPPS teaching mode but also the online teaching platform breaks through the limitation of time and space. However, a general consensus on the effectiveness of the blended BOPPPS teaching strategy in China is lacking, and few studies use quantitative synthesis to evaluate the effectiveness of this teaching strategy. Hence, this study aimed to assess the overall effectiveness of online and offline blended BOPPPS teaching strategies in higher medical education in China compared with the lecture-based learning (LBL) teaching model. Methods Studies that blended learning with the BOPPPS model in China from January 2000 to October 2023 were searched in the Chinese and English-language online databases. We analyzed the objective and subjective scores of students and performed subgroup analysis for specialties and online teaching platforms. The data were analyzed using the Stata version 14.0 software. The quality assessment was performed using the Jadad scoring scale. Results Forty-four studies were included in this meta-analysis. Compared with the LBL mode, the blended the BOPPPS teaching mode was more effective in terms of the overall capacity [standardized mean difference (SMD) = 1.193, 95% confidence interval (CI): 0.813–1.572], mastery of medical theory knowledge (SMD = 1.090, 95% CI: 0.730–1.450), and practical skills (SMD = 1.246, 95% CI: 0.799–1.693). The analyzed questionnaire surveys indicated the positive effects of the blended BOPPPS teaching mode on classroom satisfaction, autonomous learning ability, learning interest, teamwork ability, interpersonal skills, ability to analyze and solve problems, group interaction, learning engagement, and learning strategies. Conclusions The study underscored that the blended BOPPPS teaching mode could effectively improve the comprehensive quality of students. The subjective scores also indicated that students generally preferred this novel teaching mode.

Abstract Background To retrospectively analyze the risk factors of liver metastases in patients with gastric cancer in a single center, and to establish a Nomogram prediction model to predict the occurrence of liver metastases. Methods A total of 96 patients with gastric cancer who were also diagnosed with liver metastasis (GCLM) and treated in our center from January 1, 2010 to December 31, 2020 were included. The clinical data of 1095 patients with gastric cancer who were diagnosed without liver metastases (GC) in our hospital from January 1, 2014 to December 31, 2017 were retrospectively compared by univariate and multivariate logistic regression. 309 patients diagnosed with gastric cancer in another medical center from January 1, 2014 to December 31, 2018 were introduced as external validation cohorts. Results Based on the training cohort, multivariate analysis revealed that tumor site (OR = 0.55, P = 0.046), N stage (OR = 4.95, P = 0.004), gender (OR = 0.04, P = 0.001), OPNI (OR = 0.95, P = 0.041), CEA (OR = 1.01, P = 0.018), CA724 (OR = 1.01, P = 0.006), CA242 (OR = 1.01, P = 0.006), WBC (OR = 1.13, P = 0.024), Hb (OR = 0.98, P

Abstract FOXO transcription factors modulate aging-related pathways and influence longevity in multiple species, but the transcriptional targets that mediate these effects remain largely unknown. Here, we identify an evolutionarily conserved FOXO target gene, Oxidative stress-responsive serine-rich protein 1 (OSER1), whose overexpression extends lifespan in silkworms, nematodes, and flies, while its depletion correspondingly shortens lifespan. In flies, overexpression of OSER1 increases resistance to oxidative stress, starvation, and heat shock, while OSER1-depleted flies are more vulnerable to these stressors. In silkworms, hydrogen peroxide both induces and is scavenged by OSER1 in vitro and in vivo. Knockdown of OSER1 in Caenorhabditis elegans leads to increased ROS production and shorter lifespan, mitochondrial fragmentation, decreased ATP production, and altered transcription of mitochondrial genes. Human proteomic analysis suggests that OSER1 plays roles in oxidative stress response, cellular senescence, and reproduction, which is consistent with the data and suggests that OSER1 could play a role in fertility in silkworms and nematodes. Human studies demonstrate that polymorphic variants in OSER1 are associated with human longevity. In summary, OSER1 is an evolutionarily conserved FOXO-regulated protein that improves resistance to oxidative stress, maintains mitochondrial functional integrity, and increases lifespan in multiple species. Additional studies will clarify the role of OSER1 as a critical effector of healthy aging.

Abstract There is a need for high-throughput, scale-relevant, and direct electrochemical analysis to understand the corrosion behavior and sensitivity of nuclear materials that are exposed to extreme (high pressure, temperature, and radiation exposure) environments. We demonstrate the multi-scale, multi-modal application of scanning electrochemical cell microscopy (SECCM) to electrochemically profile corrosion alterations in nuclear alloys in a microstructurally resolved manner. Particularly, we identify that both mechanically deformed and irradiated microstructures show reduced charge-transfer resistance that leads to accelerated oxidation. We highlight that the effects of mechanical deformation and irradiation are synergistic, and may in fact, superimpose each other, with implications including general-, galvanic-, and/or irradiation-activated stress-corrosion cracking. Taken together, we highlight the ability of non-destructive, electrochemical interrogations to ascertain how microstructural alterations result in changes in the corrosion tendency of a nuclear alloy: knowledge which has implications to rank, qualify and examine alloys for use in nuclear construction applications.

Abstract Chromodomain helicase DNA-binding protein (CHD) gene family, an ATP (adenosine triphosphate) -dependent chromatin remodeler family, is involved in multiple developmental process and tumor development. However, there have been none pan-cancer analyses of this family. The expression levels, survival profiles, mutation profiles and immune infiltration of the CHD family genes from TCGA and TARGET database were analyzed using online tools or R packages. Interestingly, all types of CHD gene expressions were associated with the prognosis of Neuroblastoma, Acute lymphoblastic leukemia-Phase 3 and Acute Myeloid Leukemia (All P

Abstract Background Acute respiratory distress syndrome (ARDS) after cardiac surgery is a severe respiratory complication with high mortality and morbidity. Traditional clinical approaches may lead to under recognition of this heterogeneous syndrome, potentially resulting in diagnosis delay. This study aims to develop and external validate seven machine learning (ML) models, trained on electronic health records data, for predicting ARDS after cardiac surgery. Methods This multicenter, observational cohort study included patients who underwent cardiac surgery in the training and testing cohorts (data from Nanjing First Hospital), as well as those patients who had cardiac surgery in a validation cohort (data from Shanghai General Hospital). The number of important features was determined using the sliding windows sequential forward feature selection method (SWSFS). We developed a set of tree-based ML models, including Decision Tree, GBDT, AdaBoost, XGBoost, LightGBM, Random Forest, and Deep Forest. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and Brier score. The SHapley Additive exPlanation (SHAP) techinque was employed to interpret the ML model. Furthermore, a comparison was made between the ML models and traditional scoring systems. ARDS is defined according to the Berlin definition. Results A total of 1996 patients who had cardiac surgery were included in the study. The top five important features identified by the SWSFS were chronic obstructive pulmonary disease, preoperative albumin, central venous pressure_T4, cardiopulmonary bypass time, and left ventricular ejection fraction. Among the seven ML models, Deep Forest demonstrated the best performance, with an AUC of 0.882 and a Brier score of 0.809 in the validation cohort. Notably, the SHAP values effectively illustrated the contribution of the 13 features attributed to the model output and the individual feature's effect on model prediction. In addition, the ensemble ML models demonstrated better performance than the other six traditional scoring systems. Conclusions Our study identified 13 important features and provided multiple ML models to enhance the risk stratification for ARDS after cardiac surgery. Using these predictors and ML models might provide a basis for early diagnostic and preventive strategies in the perioperative management of ARDS patients.

Abstract Background Community-Acquired Pneumonia (CAP) remains a significant global health concern, with a subset of cases progressing to Severe Community-Acquired Pneumonia (SCAP). This study aims to develop and validate a CT-based radiomics model for the early detection of SCAP to enable timely intervention and improve patient outcomes. Methods A retrospective study was conducted on 115 CAP and SCAP patients at Southern Medical University Shunde Hospital from January to December 2021. Using the Pyradiomics package, 107 radiomic features were extracted from CT scans, refined via intra-class and inter-class correlation coefficients, and narrowed down using the Least Absolute Shrinkage and Selection Operator (LASSO) regression model. The predictive performance of the radiomics-based model was assessed through receiver operating characteristic (ROC) analysis, employing machine learning classifiers such as k-Nearest Neighbors (KNN), Support Vector Machine (SVM), Logistic Regression (LR), and Random Forest (RF), trained and validated on datasets split 7:3, with a training set (n = 80) and a validation set (n = 35). Results The radiomics model exhibited robust predictive performance, with the RF classifier achieving superior precision and accuracy compared to LR, SVM, and KNN classifiers. Specifically, the RF classifier demonstrated a precision of 0.977 (training set) and 0.833 (validation set), as well as an accuracy of 0.925 (training set) and 0.857 (validation set), suggesting its superior performance in both metrics. Decision Curve Analysis (DCA) was utilized to evaluate the clinical efficacy of the RF classifier, demonstrating a favorable net benefit within the threshold ranges of 0.1 to 0.8 for the training set and 0.2 to 0.7 for the validation set. Conclusions The radiomics model developed in this study shows promise for early SCAP detection and can improve clinical decision-making.