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Abstract Colorectal cancer (CRC) ranks as the third most prevalent cancer globally. It’s recognized that the molecular subtype of CRC, characterized by mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H), plays a critical role in determining appropriate treatment strategies. This review examines the current molecular classifications, focusing on dMMR/MSI-H CRC and its subtypes: Lynch syndrome (LS), Lynch-like syndrome (LLS), and sporadic cases. Despite advances in understanding of these genetic backgrounds, clinical trials have not conclusively differentiated the efficacy of immune checkpoint inhibitors among these subgroups. Therefore, while this review details the molecular characteristics and their general implications for treatment and prognosis, it also highlights the limitations and the need for more refined clinical studies to ascertain tailored therapeutic strategies for each subtype. Furthermore, this review summarizes completed and ongoing clinical studies, emphasizing the importance of developing treatments aligned more closely with molecular profiles. By discussing these aspects, the review seeks to provide a comprehensive analysis of oncological characteristics, presenting a detailed understanding of their implications for treatment and prognosis in dMMR/MSI-H CRC.

Abstract Radar observation variables reflect the precipitation amount of strong convective precipitation processes, which accurate forecast is an important difficulty in weather forecasting. Current forecasting methods are mostly based on radar echo extrapolation, which has the insufficiency of input information and the ineffectiveness of model architecture. This paper presents a Bidirectional Long Short-Term Memory forecasting method for strong convective precipitation based on the attention mechanism and residual neural network (ResNet-Attention-BiLSTM). First, this paper uses ResNet to effectively extract the key information of extreme weather and solves the problem of regression to the mean of the prediction model by learning the residuals of the radar observation data. Second, this paper uses the attention mechanism to adaptively weight the fusion of the features to enhance the extraction of the important features of the precipitation image data. On this basis, this paper presents a novel spatio-temporal reasoning method for radar observations and establishes a precipitation forecasting model, which captures the past and future time-order relationship of the sequence data. Finally, this paper conducts experiments based on the real collected data of a strong convective precipitation process and compares its performance with the existing models, the mean absolute percentage error of this model was reduced by 15.94% (1 km), 18.72% (3 km), and 14.91% (7 km), and the coefficient of determination ( $$R^{2}$$ R 2 ) was increased by 10.89% (1 km), 9.61% (3 km), and 9.29% (7 km), which proves the state of the art and effectiveness of this forecasting model.

Abstract Background Usage of immune checkpoint inhibitors (ICIs) has prolonged the overall survival (OS) of patients with extensive‐stage small‐cell lung cancer (ES‐SCLC). In clinical trials, males accounted for a large proportion, leading to the uncertainty of its efficacy in female patients. We therefore conducted this study to explore the efficacy and safety of using ICIs in female patients with ES‐SCLC. Methods We retrospectively enrolled female SCLC patients and subdivided them into two groups. Group A (n = 40) was defined as ES‐SCLC patients who received first‐line standard chemotherapy with or without ICIs. Group B (n = 47) included relapsed SCLC patients who were administered with second‐line therapies. Kaplan–Meier methodology was used to calculate survival analysis. Chi‐squared tests were used to analyze the incidence of adverse events (AEs). Results Median progression‐free survival (PFS) and median OS favored the ICI‐contained cohorts (Group A PFS: 8.3 vs. 6.1 months; OS: not reached vs. 11.3 months; Group B PFS: 15.1 vs. 3.3 months; OS: 35.3 vs. 8.3 months), especially in those patients who received second‐line immunotherapies. Patients who received immunotherapy had a slightly higher incidence rate of grade ≥3 AEs (Group A: 71.4% vs. 46.2%; Group B: 44.5% vs. 13.2%). Those who developed grade ≥3 AEs in first‐line ICIs cohort had a more favorable survival (PFS: 8.3 vs. 3.2 months; OS: not reached vs. 5.1 months). Conclusions Our study suggested that female ES‐SCLC patients treated with immunotherapy tended to achieve a relatively longer survival. The incidence of AEs (grade ≥3) was higher in women patients receiving ICIs, which requires monitoring more closely.

Abstract Background Molecularly targeted therapies have recently become a hotspot in the treatment of LUAD, with ongoing efforts to identify new effective targets due to individual variability. Among these potential targets, the mitochondrial transcription elongation factor (TEFM) stands out as a crucial molecule involved in mitochondrial synthetic transcriptional processing. Dysregulation of TEFM has been implicated in the development of various diseases; however, its specific role in LUAD remains unclear. Methods We conducted a comprehensive analysis of TEFM expression in LUAD, leveraging data from the TCGA database. Subsequently, we validated these findings using clinical specimens obtained from the First Affiliated Hospital of Soochow University, employing western blotting and qRT-PCR techniques. Further experimental validation was performed through the transfection of cells with TEFM overexpression, knockdown, and knockout lentiviruses. The effects of TEFM on LUAD were evaluated both in vitro and in vivo using a range of assays, including CCK-8, colony formation, EdU incorporation, Transwell migration, Tunel assay, flow cytometry, JC-1 staining, and xenograft tumour models. Results Our investigation uncovered that TEFM exhibited elevated expression levels in LUAD and exhibited co-localization with mitochondria. Overexpression of TEFM facilitated malignant processes in LUAD cells, whereas its silencing notably curbed these behaviors and induced mitochondrial depolarization, along with ROS production, culminating in apoptosis. Moreover, the absence of TEFM substantially influenced the expression of mitochondrial transcripts and respiratory chain complexes. Results from nude mouse xenograft tumors further validated that inhibiting TEFM expression markedly hindered tumor growth. Conclusion TEFM promotes LUAD malignant progression through the EMT pathway and determines apoptosis by affecting the expression of mitochondrial transcripts and respiratory chain complexes, providing a new therapeutic direction for LUAD-targeted therapy. Graphical Abstract

Abstract BUB1 mitotic checkpoint serine/threonine kinase B (BUB1b) has been unequivocally identified as an oncogene in various cancers. However, the potential mechanism by which BUB1b orchestrates the progression of lung adenocarcinoma (LUAD) remains unclear. Here we found that both the transcript and protein levels of BUB1b were dramatically upregulated in tumor tissues and contributed to the dismal prognosis of LUAD patients. Moreover, gain- and loss-of-function assays, conducted both in vitro and in vivo, confirmed that BUB1b enhanced the viability of LUAD cells. Mechanistically, BUB1b forms a complex with OTUD3 and NRF2 and stabilizes the downstream NRF2 signaling pathway to facilitate insensitivity to ferroptosis and chemotherapy. In BALB/c nude mice bearing subcutaneous tumors that overexpress BUB1b, a combined strategy of ML385 targeting and chemotherapy achieved synergistic effects, inhibiting tumor growth and obviously improving survival. Taken together our study uncovered the underlying mechanism by which BUB1b promotes the progression of LUAD and proposed a novel strategy to enhance the efficacy of chemotherapy.

Abstract Artificial wrinkles, especially those with responsive erasure/regeneration behaviors have gained extensive interest due to their potential in smart applications. However, current wrinkle modulation methods primarily rely on network rearrangement, causing bottlenecks in in situ wrinkle regeneration. Herein, we report a dually cross-linked network wherein [2]rotaxane cross-link can dissipate stress within the wrinkles through its sliding motion without disrupting the network, and quadruple H-bonding cross-link comparatively highlight the advantages of [2]rotaxane modulation. Acid stimulation dissociates quadruple H-bonding and destructs network, swiftly eliminating the wrinkles. However, the regeneration process necessitates network rearrangement, making in situ recovery unfeasible. By contrast, alkaline stimulation disrupts host–guest recognition, and subsequent intramolecular motion of [2]rotaxane dissipate energy to eliminate wrinkles gradually. The always intact network allows for the in situ recovery of surface microstructures. The responsive behaviors of quadruple H-bonding and mechanical bond are orthogonal, and their combination leads to wrinkles with multiple but accurate responsiveness.

Background: Currently, awareness about platelet count (PC) and its consequences for perinatal outcome have increased, but there is little reliable evidence on fecundability. Methods: Based on the National Free Pre-conception Check-up Projects supported by the Chinese government, 5,524,886 couples met the inclusion criteria and were included in this cohort study. Cox regression models were adopted to estimate fecundability ratios (FRs) and their 95% confidence intervals (CIs) for pre-pregnancy PC quintiles. Restricted cubic splines were used to flexibly model and visualize the relationship of PC with FRs. Microsoft SQL server and R software were used for data management and analysis. Results: The median of pre-pregnancy PC among women was 221.00 × 109/L. The first (223.06 × 109/L) were associated with the risk of reduced female fecundability (P for non-linearity < 0.01). Conclusion: PC is associated with female fecundability. Further classification of PC levels may deepen our understanding of the early warnings and significance of female fecundability.

Regulated cell death is a pivotal regulatory mechanism governing the development and homeostasis of multicellular organisms. A comprehensive understanding of RCD's regulatory mechanisms is crucial for developing novel therapeutic strategies against diseases associated with cell death, such as cancer and neurodegenerative diseases. However, existing data repositories support limited types of cell death data and lack comprehensive annotation and analytical functionalities. Thus, establishing an extensive cell death database is an urgent imperative. To address this gap, we developed the Regulated Cell Death Database (RCDdb, chenyclab.com/RCDdb), the first comprehensively manually annotated database designed to support annotations and analytical capabilities across all RCD types. We compiled 3090 marker gene annotations associated with 15 RCD types from 2180 relevant articles. The RCDdb includes annotation data on these marker genes concerning diseases, drugs, pathways, proteins, and gene expressions. Furthermore, it provides 49 diverse visualization methods to present this information. More importantly, the RCDdb features three online analysis tools for identifying and analyzing RCD-related features within user-submitted data. Furthermore, the RCDdb offers a user-friendly interface for querying, browsing, analysis, and visualization of detailed information associated with each RCD category. This resource promises to significantly aid researchers in better understanding the mechanisms of cell death, thereby accelerating progress in research and therapeutic strategies aimed at combating RCD-related diseases.

Abstract Background Pleural solitary fibrous tumors (pSFTs) are rare mesenchymal pleural tumors with rich vascularity. Surgical resection is the cornerstone of pSFTs treatment, requiring careful preoperative imaging to delineate lesion extent and vascular supply including contrast-enhanced computed tomography and other examinations depending on its size and characteristics. Case presentation The patient was a 34-year-old female with a mass measuring approximately 67 × 42 × 65 mm in the left posterior mediastinum. Intraoperatively, the mass demonstrated rich vascularity. Two veins originating from the abdominal cavity entered the lower pole, one converged from the superior pole, draining into the brachiocephalic vein. Additionally, two arteries arose directly from the descending aorta, while several veins drained into the intercostal veins. In response to unexpected intraoperative vascular findings, vascular clips and silk threads were used to ligate them. Subsequently, the tumor was successfully dissected, with approximately 600 ml of blood loss recorded during the 4-hour surgery. The patient exhibited a satisfactory postoperative recovery, and follow-up spanning over six months revealed no indications of recurrence or metastasis. Conclusions We firstly present a case of successful resection of a pSFT in a 34-year-old woman with a distinct feeding vessel arising from the descending aorta and describe the related surgical procedures. This case highlights preoperative evaluation of mass vascularity based on contrast-enhanced computed tomography. When blood supply is challenging to clarify, angiography can offer additional details, especially for giant pSFTs. Despite this, thorough intraoperative exploration remains essential to detect unexpected vessels. Appropriate interventions should be customized based on the vascular origins and the surrounding anatomical structures.

Abstract The whole-cell inorganic-biohybrid systems show special functions and wide potential in biomedical application owing to the exceptional interactions between microbes and inorganic materials. However, the hybrid systems are still in stage of proof of concept. Here, we report a whole-cell inorganic-biohybrid system composed of Spirulina platensis and gold nanoclusters (SP-Au), which can enhance the cancer radiotherapy through multiple pathways, including cascade photocatalysis. Such systems can first produce oxygen under light irradiation, then convert some of the oxygen to superoxide anion (•O2 −), and further oxidize the glutathione (GSH) in tumor cells. With the combination of hypoxic regulation, •O2 − production, GSH oxidation, and the radiotherapy sensitization of gold nanoclusters, the final radiation is effectively enhanced, which show the best antitumor efficacy than other groups in both 4T1 and A549 tumor models. Moreover, in vivo distribution experiments show that the SP-Au can accumulate in the tumor and be rapidly metabolized through biodegradation, further indicating its application potential as a new multiway enhanced radiotherapy sensitizer.

Abstract The immunoprotective components control COVID-19 disease severity, as well as long-term adaptive immunity maintenance and subsequent reinfection risk discrepancies across initial COVID-19 severity, remain unclarified. Here, we longitudinally analyzed SARS-CoV-2-specific immune effectors during the acute infection and convalescent phases of 165 patients with COVID-19 categorized by severity. We found that early and robust SARS-CoV-2-specific CD4+ and CD8+ T cell responses ameliorate disease progression and shortened hospital stay, while delayed and attenuated virus-specific CD8+ T cell responses are prominent severe COVID-19 features. Delayed antiviral antibody generation rather than titer level associates with severe outcomes. Conversely, initial COVID-19 severity imprints the long-term maintenance of SARS-CoV-2-specific adaptive immunity, demonstrating that severe convalescents exhibited more sustained virus-specific antibodies and memory T cell responses compared to mild/moderate counterparts. Moreover, initial COVID-19 severity inversely correlates with SARS-CoV-2 reinfection risk. Overall, our study unravels the complicated interaction between temporal characteristics of virus-specific T cell responses and COVID-19 severity to guide future SARS-CoV-2 wave management.

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 While accurate mapping of strain distribution is crucial for assessing stress concentration and estimating fatigue life in engineering applications, conventional strain sensor arrays face a great challenge in balancing sensitivity and sensing density for effective strain mapping. In this study, we present a Fowler-Nordheim tunneling effect of monodispersed spiky carbon nanosphere array on polydimethylsiloxane as strain sensor arrays to achieve a sensitivity up to 70,000, a sensing density of 100 pixel cm−2, and logarithmic linearity over 99% within a wide strain range of 0% to 60%. The highly ordered assembly of spiky carbon nanospheres in each unit also ensures high inter-unit consistency (standard deviation ≤3.82%). Furthermore, this sensor array can conformally cover diverse surfaces, enabling accurate acquisition of strain distributions. The sensing array offers a convenient approach for mapping strain fields in various applications such as flexible electronics, soft robotics, biomechanics, and structure health monitoring.

The estuarine delta is a densely populated and economically developed region, and its land use change research is of great significance for regional economic and social development. In this paper, the remote sensing images from 1987 to 2019 are classified, and the digital coastline system is used to analyze the change rate of coastline, and then explore the relationship between the two and the influencing factors. The results indicate that: From 1987 to 2019, the area of construction land, wetlands, and aquaculture ponds increased, with the area of construction land increasing by 57.34 km2, while the area of cultivated land, terrestrial vegetation, and water bodies decreased. From 1987 to 2019, the annual average rate of shoreline advancement was 33.90 m/a, and the direction of shoreline development was seaward extension, indicating that the shoreline was in a state of growth. The change of coastline is strongly associated with the change of land use type. This study provides reference for the protection and utilization of natural resources in the Qin River Delta.

B4C–TiB2 is an advanced electrically conductive ceramic with excellent mechanical and electrical discharge machinable properties. It is challenging and rewarding to achieve highly conductive and hard B4C–TiB2 composites at a minimum content of conductive TiB2 that has inferior hardness but double specific gravity of the B4C matrix. A novel strategy was used to construct conductive networks in B4C‒15 vol% TiB2 composite ceramics with B4C, TiC, and amorphous B as raw materials by a two-step spark plasma sintering method. The influences of particle size matching between B4C and TiC on the conducting of the strategy and the microstructure were discussed based on the selective matrix grain growth mechanism. The mechanical and electrical properties were also systematically investigated. The B4C–15 vol% TiB2 composite ceramic prepared from 10.29 µm B4C and 0.05 µm TiC powders exhibited a perfect three-dimensional interconnected conductive network with a maximum electrical conductivity of 4.25×104 S/m, together with excellent mechanical properties including flexural strength, Vickers hardness, and fracture toughness of 691±58 MPa, 30.30±0.61 GPa, and 5.75±0.32 MPa·m1/2, respectively, while the composite obtained from 3.12 µm B4C and 0.8 µm TiC powders had the best mechanical properties including flexural strength, Vickers hardness, and fracture toughness of 827±35 MPa, 32.01±0.51 GPa, and 6.45±0.22 MPa·m1/2, together with a decent electrical conductivity of 0.65×104 S/m.

Abstract Background The ectopic superior parathyroid in the tracheoesophageal groove and paraesophageal region is rare. Hyperparathyroidism results when these glands become hyperfunctioning. That may necessitate surgical intervention in the form of parathyroidectomy, which requires a transsternal or transthoracic approach due to a deeply seated mediastinal parathyroid gland. Minimally invasive strategies have emerged recently as an alternative approach with less morbidity. Case presentation We present a case of the paraesophageal ectopic parathyroid gland in the superior posterior mediastinum, which was successfully treated with thoracoscopic resection. Conclusion The current imaging tools improve the thoracoscopic management of mediastinal parathyroid glands. Video-assisted thoracoscopic surgery (VATS) can provide access and exposure to ectopic parathyroid adenoma with low morbidity and financial burden.

Abstract Background The initial phase II stuty (NCT03215693) demonstrated that ensartinib has shown clinical activity in patients with advanced crizotinib‐refractory, anaplastic lymphoma kinase (ALK)‐positive non‐small cell lung cancer (NSCLC). Herein, we reported the updated data on overall survival (OS) and molecular profiling from the initial phase II study. Methods In this study, 180 patients received 225 mg of ensartinib orally once daily until disease progression, death or withdrawal. OS was estimated by Kaplan‒Meier methods with two‐sided 95% confidence intervals (CIs). Next‐generation sequencing was employed to explore prognostic biomarkers based on plasma samples collected at baseline and after initiating ensartinib. Circulating tumor DNA (ctDNA) was detected to dynamically monitor the genomic alternations during treatment and indicate the existence of molecular residual disease, facilitating improvement of clinical management. Results At the data cut‐off date (August 31, 2022), with a median follow‐up time of 53.2 months, 97 of 180 (53.9%) patients had died. The median OS was 42.8 months (95% CI: 29.3‐53.2 months). A total of 333 plasma samples from 168 patients were included for ctDNA analysis. An inferior OS correlated significantly with baseline ALK or tumor protein 53 (TP53) mutation. In addition, patients with concurrent TP53 mutations had shorter OS than those without concurrent TP53 mutations. High ctDNA levels evaluated by variant allele frequency (VAF) and haploid genome equivalents per milliliter of plasma (hGE/mL) at baseline were associated with poor OS. Additionally, patients with ctDNA clearance at 6 weeks and slow ascent growth had dramatically longer OS than those with ctDNA residual and fast ascent growth, respectively. Furthermore, patients who had a lower tumor burden, as evaluated by the diameter of target lesions, had a longer OS. Multivariate Cox regression analysis further uncovered the independent prognostic values of bone metastases, higher hGE, and elevated ALK mutation abundance at 6 weeks. Conclusion Ensartinib led to a favorable OS in patients with advanced, crizotinib‐resistant, and ALK‐positive NSCLC. Quantification of ctDNA levels also provided valuable prognostic information for risk stratification.

Abstract Pancreatic ductal adenocarcinoma (PDAC) develops through step-wise genetic and molecular alterations including Kras mutation and inactivation of various apoptotic pathways. Here, we find that development of apoptotic resistance and metastasis of Kras G12D -driven PDAC in mice is accelerated by deleting Plk3, explaining the often-reduced Plk3 expression in human PDAC. Importantly, a 41-kDa Plk3 (p41Plk3) that contains the entire kinase domain at the N-terminus (1-353 aa) is activated by scission of the precursor p72Plk3 at Arg354 by metalloendopeptidase nardilysin (NRDC), and the resulting p32Plk3 C-terminal Polo-box domain (PBD) is removed by proteasome degradation, preventing the inhibition of p41Plk3 by PBD. We find that p41Plk3 is the activated form of Plk3 that regulates a feed-forward mechanism to promote apoptosis and suppress PDAC and metastasis. p41Plk3 phosphorylates c-Fos on Thr164, which in turn induces expression of Plk3 and pro-apoptotic genes. These findings uncover an NRDC-regulated post-translational mechanism that activates Plk3, establishing a prototypic regulation by scission mechanism.

Abstract Purpose In VATS surgery, precise preoperative localization is particularly crucial when dealing with small-diameter pulmonary nodules located deep within the lung parenchyma. The purpose of this study was to compare the efficacy and safety of laser guidance and freehand hook-wire for CT-guided preoperative localization of pulmonary nodules. Methods This retrospective study was conducted on 164 patients who received either laser guidance or freehand hook-wire localization prior to Uni-port VATS from September 1st, 2022 to September 30th, 2023 at The First Affiliated Hospital of Soochow University. Patients were divided into laser guidance group and freehand group based on which technology was used. Preoperative localization data from all patients were compiled. The localization success and complication rates associated with the two groups were compared. The risk factors for common complications were analyzed. Results The average time of the localization duration in the laser guidance group was shorter than the freehand group (p

Abstract Background The association of genital Mollicutes infection transition with adverse pregnancy outcomes was insignificant among general pregnant women, but there remains a paucity of evidence linking this relationship in gestational diabetes mellitus (GDM) women. The aim was to investigate the association between genital Mollicutes infection and transition and adverse pregnancy outcomes in GDM women, and to explore whether this association still exist when Mollicutes load varied. Methods We involved pregnant women who attended antenatal care in Chongqing, China. After inclusion and exclusion criteria, we conducted a single-center cohort study of 432 GDM women with pregnancy outcomes from January 1, 2018 to December 31, 2021. The main outcome was adverse pregnancy outcomes, including premature rupture of membrane (PROM), fetal distress, macrosomia and others. The exposure was Mollicutes infection, including Ureaplasma urealyticum (Uu) and Mycoplasma hominis (Mh) collected in both the second and the third trimesters, and testing with polymerase chain reaction method. The logistic regression models were used to estimate the relationship between Mollicutes infection and adverse pregnancy outcomes. Results Among 432 GDM women, 241 (55.79%) were infected with genital Mollicutes in either the second or third trimester of pregnancy. At the end of the pregnancy follow-up, 158 (36.57%) participants had adverse pregnancy outcomes, in which PROM, fetal distress and macrosomia were the most commonly observed adverse outcomes. Compared with the uninfected group, the Mollicutes (+/-) group showed no statistical significant increase in PROM (OR = 1.05, 95% CI:0.51 ∼ 2.08) and fetal distress (OR = 1.21, 95% CI: 0.31 ∼ 3.91). Among the 77 participants who were both Uu positive in the second and third trimesters, 38 participants presented a declined Uu load and 39 presented an increased Uu load. The Uu increased group had a 2.95 odds ratio (95% CI: 1.10~8.44) for adverse pregnancy outcomes. Conclusion Mollicutes infection and transition during trimesters were not statistically associated with adverse pregnancy outcomes in GDM women. However, among those consistent infections, women with increasing Uu loads showed increased risks of adverse pregnancy outcomes. For GDM women with certain Mollicutes infection and colonization status, quantitative screening for vaginal infection at different weeks of pregnancy was recommended to provide personalized fertility treatment.

Introduction: Rheumatoid arthritis (RA) is a systemic autoimmune disease with limited treatment success, characterized by chronic inflammation and progressive cartilage and bone destruction. Accumulating evidence has shown that neutrophil extracellular traps (NETs) released by activated neutrophils are important for initiating and perpetuating synovial inflammation and thereby could be a promising therapeutic target for RA. K/B × N serum transfer-induced arthritis (STIA) is a rapidly developed joint inflammatory model that somehow mimics the inflammatory response in patients with RA. Human gingival-derived mesenchymal stem cells (GMSCs) have been previously shown to possess immunosuppressive effects in arthritis and humanized animal models. However, it is unknown whether GMSCs can manage neutrophils in autoimmune arthritis. Objectives: To evaluate whether infusion of GMSCs can alleviate RA by regulating neutrophils and NETs formation. If this is so, we will explore the underlying mechanism(s) in an animal model of inflammatory arthritis. Methods: The effects of GMSCs on RA were assessed by comparing the symptoms of the K/B × N serum transfer-induced arthritis (STIA) model administered either with GMSCs or with control cells. Phenotypes examined included clinical scores, rear ankle thickness, paw swelling, inflammation, synovial cell proliferation, and immune cell frequency. The regulation of GMSCs on NETs was examined through immunofluorescence and immunoblotting in GMSCs-infused STIA mice and in an in vitro co-culture system of neutrophils with GMSCs. The molecular mechanism(s) by which GMSCs regulate NETs was explored both in vitro and in vivo by silencing experiments. Results: We found in this study that adoptive transfer of GMSCs into STIA mice significantly ameliorated experimental arthritis and reduced neutrophil infiltration and NET formation. In vitro studies also showed that GMSCs inhibited the generation of NETs in neutrophils. Subsequent investigations revealed that GMSCs secreted prostaglandin E2 (PGE2) to activate protein kinase A (PKA), which ultimately inhibited the downstream extracellular signal-regulated kinase (ERK) pathway that is essential for NET formation. Conclusion: Our results demonstrate that infusion of GMSCs can ameliorate inflammatory arthritis mainly by suppressing NET formation via the PGE2-PKA-ERK signaling pathway. These findings further support the notion that the manipulation of GMSCs is a promising stem cell-based therapy for patients with RA and other autoimmune and inflammatory diseases.

This paper reports on a qualitative research study that explored the practical and emotional experiences of young people aged 13–17 using algorithmically-mediated online platforms. It demonstrates an RI-based methodology for responsible two-way dialogue with the public, through listening to young people's needs and responding to their concerns. Participants discussed in detail how online algorithms work, enabling the young people to reflect, question, and develop their own critiques on issues related to the use of internet technologies. The paper closes with action areas from the young people for a fairer, usefully transparent and more responsible online environment. These actions include a desire to be informed about what data (both personal and situational) is collected and how, and who uses it and why, and policy recommendations for meaningful algorithmic transparency and accountability. Finally, participants claimed that whilst transparency is an important first principle, they also need more control over how platforms use the information they collect from users, including more regulation to ensure transparency is both meaningful and sustained.

IntroductionIn the course of immune development, HIV-exposed uninfected (HEU) infants exhibit abnormal immune function and increased infectious morbidity compared to HIV-unexposed uninfected (HUU) infants. Yet the specific functional phenotypes and regulatory mechanisms associated with in-utero HIV and/or ART exposure remain largely obscure.MethodsWe utilized flow cytometry and RNA-seq technologies to conduct the immunological and transcriptomic profiling in cord blood from 9 HEU mother-infant pairs and 24 HUU pairs. On top of that, we compared the cord blood dataset with the maternal venous blood dataset to characterize unique effects induced by in-utero HIV and/or ART exposure.ResultsFlow cytometry immunophenotyping revealed that the level of B lymphocyte subsets was significantly decreased in HEU cord blood as compared to HUU (P < 0.001). Expression profiling-based cell abundance assessment, includes CIBERSORT and ssGSEA algorithm, showed a significantly reduced abundance of naive B cells in HEU cord blood (both P < 0.05), supporting the altered composition of B lymphocyte subsets in HEU. Functional enrichment analysis demonstrated suppressed innate immune responses and impaired immune regulatory function of B cells in HEU cord blood. Furthermore, through differential expression analysis, co-expression network analysis using WGCNA, and feature selection analysis using LASSO, we identified a 4-gene signature associated with HEU status. This signature effectively assesses B cell levels in cord blood, enabling discrimination between HEU and HUU infants.DiscussionOur study provides the first comprehensive immunological and transcriptomic characterization of HEU cord blood. Additionally, we establish a 4-gene-based classifier that holds potential for predict immunological abnormalities in HEU infants.

The catalytic fast pyrolysis process is a promising method for converting biomass waste into bio-oil, where the catalyst plays a crucial role in determining the yield and quality of the products. In this study, ultrafine iron nanoparticles were incorporated onto a montmorillonite substrate through the pyrolyzing coordinated polymer method to enhance liquid fuel production via catalytic pyrolysis of biomass waste. The catalyst showed a uniform distribution of iron on the montmorillonite surface, indicating that the incorporation was successful. Catalytic pyrolysis led to an increase in liquid yields and a decrease in gas product yields compared to direct pyrolysis. The highest bio-oil yield obtained was 56.9% during the catalytic pyrolysis of corncob, which was found to be particularly well-suited for the production of bio-oil. Furthermore, the proposed reaction pathway was based on identifying the composition of the bio-oil, which was further supported by quantum chemical calculations of chemical bond strength and the likelihood of free radical attacks. These findings demonstrate the potential of using montmorillonite-supported ultrafine iron nanoparticles to enhance bio-oil yield and quality in biomass pyrolysis processes.

Microplastics (MPs) have been detected in various human tissues. However, whether MPs can accumulate within tumors and how they affect the tumor immune microenvironment (TIME) and therapeutic responses remains unclear. This study aimed to determine the presence of MPs in tumors and their potential effects on the TIME. Sixty-one tumor samples were collected for analysis. The presence of MPs in tumors was qualitatively and quantitatively assessed using pyrolysis-gas chromatography-mass spectrometry. MPs were detected in 26 of the samples examined. Three types of MPs were identified: polystyrene, polyvinyl chloride, and polyethylene. In lung, gastric, colorectal, and cervical tumors, the MP detection rates were 80 %, 40 %, 50 %, and 17 % (7.1–545.9 ng/g), respectively. MPs were detected in 70 % of pancreatic tumors (18.4–427.1 ng/g) but not detected in esophageal tumors. In pancreatic cancer, the MP-infiltrated TIME exhibited a reduction in CD8+ T, natural killer, and dendritic cell counts, accompanied by substantial neutrophil infiltration. This study illustrates the potential presence of MPs in diverse tumors; varying adhesive affinities were observed among different tumor types. MPs may lead to a more adverse TIME in pancreatic tumors. Further investigations are warranted to assess whether MPs promote tumor progression and affect the efficacy of immunotherapy

Potato Verticillium wilt (PVW) caused by Verticillium dahliae is a vascular disease, that seriously affects potato (Solanum tuberosum L.) yield and quality worldwide. V. dahliae occupies the vascular bundle and therefore it cannot efficiently be treated with fungicides. Further, the application of these pesticides causes serious environmental problems. Therefore, it is of great importance to find environmentally friendly biological control methods. In this study, bacterial strains were isolated from agricultural lands on which potato had been cultured for 5 years. Five strains with a broad-spectrum antagonistic activity were selected. Among these five strains, Bacillus velezensis XS142 showed the highest antagonistic activity. To study the mechanism of XS142, by which this strain might confer tolerance to V. dahliae in potato, the genome of strain XS142 was sequenced. This showed that its genome has a high level of sequence identity with the model strain B. velezensis FZB42 as the OrthoANI (Average Nucleotide Identity by Orthology) value is 98%. The fungal suppressing mechanisms of this model strain are well studied. Based on the genome comparison it can be predicted that XS142 has the potential to suppress the growth of V. dahliae by production of bacillomycin D, fengycin, and chitinase. Further, the transcriptomes of potatoes treated with XS142 were analyzed and this showed that XS142 does not induce ISR, but the expression of genes encoding peptides with antifungal activity. Here we showed that XS142 is an endophyte. Further, it is isolated from a field where potato had been cultured for several years. These properties give it a high potential to be used, in the future, as a biocontrol agent of PVW in agriculture.

Anti-programmed cell death protein 1 (PD-1) therapy has demonstrated notable efficacy in treating patients with deficient mismatch repair/high microsatellite instability (dMMR/MSI-H) metastatic colorectal cancer (mCRC). However, its clinical application is fraught with challenges and can lead to significant immune-related adverse events (ir-AEs). In this report, we present a complicated case of an mCRC patient with MSI-H and mutations in β2M and LRP1B proteins, complicated by concurrent bacteremia and liver fluke infection, who received first-line anti-PD1 therapy. The patient exhibited a positive response to anti-PD1 treatment, even in the presence of concomitant antibiotic and anti-parasitic interventions. Additionally, the patient experienced immunotherapy-related autoimmune hemolytic anemia (ir-AIHA), a rare hematological ir-AE, which was effectively treated later on. Immunotherapy represents a pivotal and highly effective approach to tumor treatment. Baseline assessment of the MMR and MSI status is a crucial step before initiating immunotherapy, and regular ongoing assessments during the treatment course can facilitate early recognition of any secondary complications, enabling prompt intervention and ensuring optimal therapeutic outcomes. Overall, a multidisciplinary diagnostic and therapeutic algorithm can help maximize the therapeutic benefits of immunotherapy.

BackgroundThe present study aimed to evaluate the association between body fat ratio (BFR), visceral fat area (VFA), body mass index (BMI) and visceral fat density (VFD) and assess their reliability in assessing risk of postoperative complications and survival status in patients with rectal cancer (RC).Materials and methodsThe present study retrospectively included 460 patients who underwent surgical treatment for RC at the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College, Wuhu, China) between September 2018 and July 2021. BFR, VFA, BMI, and VFD were measured and basic information, clinical data, complications and survival were recorded.ResultsStatistical analysis was performed to determine optimal BFR cut-off and evaluate group differences. BFR demonstrated a significant positive correlation with VFA (R = 0.739) and BMI (R = 0.783) and significant negative correlation with VFD (R = −0.773). The areas under the receiver operating characteristic curve of BFR, VFA, BMI, and VFD in predicting postoperative complications in RC were all >0.7 and the optimal cut-off value of BFR was 24.3. Patients in the BFR-low group had fewer postoperative complications, lower intraoperative indices, shorter hospitalization times and lower costs than those in the BFR-high group. BFR predicted complications with high diagnostic significance and was validated by multiple models. Furthermore, patients in the BFR-high group had a longer overall survival compared with patients in the BFR-low group.ConclusionBFR was associated with BMI, VFA, and VFD. A BFR threshold of 24.3 was correlated with decreased complications and enhanced long-term survival.

Background: Tumor necrosis (TN) is a common feature in lung squamous cell carcinoma (LSCC), which could provide useful predictive and prognostic information. Objectives: This study aimed to investigate the effect of pretreatment pulmonary TN (PTN) on the prognosis of first-line anti-programmed cell death 1 (PD-1)/PD ligand 1 (PD-L1) inhibitor in advanced LSCC. Design: We conducted a retrospective study to analyze the association between the presence of PTN and clinical outcomes in advanced LSCC patients treated with anti-PD-1/PD-L1 inhibitors. Methods: Data from 240 eligible patients were collected from 27 hospitals across China between 2016 and 2020. The presence of PTN was assessed using contrast-enhanced chest computed tomography (CT) imaging at baseline. We utilized the Cox proportional-hazards regression model to analyze the association between PTN and clinical outcomes. In addition, to account for potential confounding factors and ensure comparability between groups, we employed propensity score-matching (PSM) analysis. Results: In the overall patient cohort, the presence of PTN was 39.6%. The median follow-up duration was 20.3 months. The positive PTN group exhibited a notably inferior median progression-free survival (PFS; 6.5 months vs 8.6 months, p = 0.012) compared to the negative PTN group. Within the Cox proportional-hazards regression model, PTN emerged as an independent predictor of unfavorable PFS (hazard ratio (HR) = 1.354, 95% confidence interval (CI): 1.002–1.830, p = 0.049). After PSM, the median PFS for the positive PTN group (6.5 months vs 8.0 months, p = 0.027) remained worse than that of the negative PTN group. Multivariate analyses also further underscored that the presence of PTN independently posed a risk for shorter PFS (HR = 1.494, 95% CI: 1.056–2.112, p = 0.023). However, no statistically significant difference in overall survival was observed between the two groups. Conclusion: Our study suggests that the presence of PTN on baseline contrast-enhanced chest CT is a potential negative prognostic imaging biomarker for the outcome of anti-PD-1/PD-L1 inhibitor therapy in advanced LSCC. Further studies are warranted to validate these findings and explore the underlying mechanisms.

Background: This study aimed to evaluate the efficacy of ranibizumab for the treatment of macular edema secondary to branch retinal vein occlusion (BRVO-ME), changes in retinal volume and central retinal thickness (CRT) before and after therapy, and the connection between visual prognosis and changes in retinal volume. Methods: The 120 patients(121 eyes) of BRVO-ME were recruited from July 2020 to October 2022 at the Affiliated Hospital of Weifang Medical University. The clinical data of patients were retrospectively examined for changes in best-corrected visual acuity (BCVA), retinal volume, and CRT at 1 day, 1 week, 1 month, 3 months, 6 months and 1year after treatment. Findings: Visual acuity improved gradually and became steady approximately 1 months after treatment, whereas retinal volume decreased gradually in both the outer and full layers and stabilized around 6 month after treatment. The decline in retinal volume and CRT was more visible in the deeper layers than in the inner levels. A higher correlation was observed between retinal volume and BCVA than between CRT and BCVA. BCVA after one year of treatment had a high correlation with baseline outer retinal volume. Interpretation: Treatment of BRVO-ME with ranibizumab is highly effective, and the recovery of visual function was depends more on early treatment. The outer retina is the major site of edema. Changes in retinal volume may serve as a better predictor of visual prognosis than changes in CRT. Baseline ourter retinal volume is correlated with long-term visual prognosis.

There is a lack of a systematic understanding of the specific mechanism of action of DL0410 in AD treatment. In this study, the combination of RNA-seq and proteomics was firstly employed to uncover the mechanism of action of DL0410 in APP/PS1 transgenic mice. The results of behavioral tests showed that oral administration of DL0410 for 8 weeks improved memory and cognition of APP/PS1 mice. DL0410 significantly reduced β-amyloid deposition and resulted in significant upregulation of synaptophysin, PSD95 and NMDAR/ CaMKⅡ signaling pathway in the hippocampus and cortex, indicating that DL0410 improved synaptic plasticity in APP/PS1 mice, which agrees with the results of RNA-seq and proteomics. Furthermore, the enrichment results of differentially expressed genes identified by RNA-seq and proteomics demonstrate the potential protective effects of DL0410 against oxidative stress and mitochondrial dysfunction. As expected, DL0410 dose-dependently ameliorated oxidative damage and markedly increased the expression of PGC-1α, TFAM, SOD1 and SOD2. Mitochondrial high-resolution respirometry results revealed that mitochondrial respiratory function was significantly improved in APP/PS1 mice administered with DL0410. In addition, DL0410 treatment reduced oxidative damage, strengthened antioxidant system and improved mitochondrial function in Aβ-induced HT22 cells. Altogether, our findings suggest the potential of DL0410 as a novel candidate for AD treatment.

ABSTRACT: Interferon-induced protein with tetratricopeptide repeats (IFITs), a family of proteins strongly induced by type I interferon (IFN-I), are deeply involved in many cellular and viral processes. IFIT5, the sole protein in this family found in birds, also plays a crucial role in regulating virus infection. In this study, goose IFIT5 (gIFIT5) was first cloned from peripheral blood lymphocyte (PBL) and phylogenetic analysis showed that it was highly homologous with duck IFIT5 (dIFIT5), sharing 94.6% identity in amino acid sequence. Subsequently, the expression kinetics of gIFIT5 during goose astrovirus (GAstV) infection and the regulatory effect of gIFIT5 on GAstV proliferation were evaluated. Results showed that the mRNA and protein expression level of gIFIT5 was greatly induced by GAstV infection, especially at 12 hpi. Importantly, gIFIT5 could conversely promote GAstV replication in GEF cells. Virus titers in gIFIT5 overexpression group were significantly higher than those in control group at 12 and 24 hpi. Western blot and quantitative real-time PCR (qRT-PCR) further demonstrated that the production of viral cap protein was significantly facilitated in gIFIT5-transfected group. Collectively, GAstV facilitates self-replication via promoting gIFIT5 expression.

Data heterogeneity, particularly noted in fields such as genetics, has been identified as a key feature of big data, posing significant challenges to innovation in knowledge and information. This paper focuses on characterizing and understanding the so-called ''curse of heterogeneity'' in gene identification for low infant birth weight from a statistical learning perspective. Owing to the computational and analytical advantages of expectile regression in handling heterogeneity, this paper proposes a flexible, regularized, partially linear additive expectile regression model for high-dimensional heterogeneous data. Unlike most existing works that assume Gaussian or sub-Gaussian error distributions, we adopt a more realistic, less stringent assumption that the errors have only finite moments. Additionally, we derive a two-step algorithm to address the reduced optimization problem and demonstrate that our method, with a probability approaching one, achieves optimal estimation accuracy. Furthermore, we demonstrate that the proposed algorithm converges at least linearly, ensuring the practical applicability of our method. Monte Carlo simulations reveal that our method's resulting estimator performs well in terms of estimation accuracy, model selection, and heterogeneity identification. Empirical analysis in gene trait expression further underscores the potential for guiding public health interventions.

IntroductionGansu Province is situated in the northwest region of China, characterized by diverse and complex topography and a rich diversity of ethnic groups. This study aims to explore the prevalence and risk factors of adolescent suspected scoliosis in Gansu Province through a cross-sectional population study.MethodsFrom April 2022 to July 2022, a prospective cross-sectional study was conducted in Baiyin City, Jinchang City, Lanzhou City, Linxia Hui Autonomous Prefecture, and Gannan Tibetan Autonomous Prefecture in Gansu Province. The screening covered 3,118 middle and high school students across 24 institutions, including middle and high schools. Diagnosis of suspected scoliosis was established through visual inspection, the Adams forward bend test, and measurement of trunk rotation angle. Employing a custom-designed questionnaire, demographic data were collected, and the prevalence of suspected scoliosis was calculated. Univariate and multivariate logistic regression analyses were employed to assess factors associated with suspected scoliosis.ResultsA total of 3,044 participants were ultimately included in the analysis. The overall prevalence of suspected scoliosis was 5.68% in Gansu Province. The peak prevalence for boy is at 14 years (6.70%), while for girl, it is at 15 years (8.75%). Lanzhou City exhibits the highest prevalence rates (boy, 9.82%; girl, 10.16). The results of univariate logistic regression analysis presented that BMI (OR = 0.92, 95% CI: 0.88–0.96), altitude of habitation (1,600 m-2000 m) (OR = 0.50, 95% CI: 0.34–0.73), altitude of habitation (2000 m-3321 m) (OR = 0.58, 95% CI: 0.40–0.83), family medical history (OR = 1.56, 95% CI: 1.02–2.31), and shoulders of unequal height (OR = 1.49, 95% CI: 1.09–2.03) were significantly correlated with suspected scoliosis. The multivariate logistic regression analysis indicated that BMI (OR = 0.91, 95% CI: 0.86–0.95), altitude of habitation (1,600 m-2000 m) (OR = 0.35, 95% CI: 0.23–0.54), altitude of habitation (2000 m-3321 m) (OR = 0.39, 95% CI: 0.24–0.60), family medical history (OR = 1.66, 95% CI:1.08–2.49), and shoulders of unequal height (OR = 1.45, 95% CI:1.06–1.99) were independently associated with suspected scoliosis.ConclusionLow BMI, residence at an altitude of 1,600 m-3321 m, family medical history, and shoulders of unequal height were independently associated with an increased prevalence of suspected scoliosis. It is recommended to promptly screen high-risk adolescents for suspected scoliosis, provide effective preventive and intervention measures.

Abstract The photocatalytic reduction of CO2 represents an environmentally friendly and sustainable approach for generating valuable chemicals. In this study, a thiophene‐modified highly conjugated asymmetric covalent triazine framework (As‐CTF‐S) is developed for this purpose. Significantly, single‐component intramolecular energy transfer can enhance the photogenerated charge separation, leading to the efficient conversion of CO2 to CO during photocatalysis. As a result, without the need for additional photosensitizers or organic sacrificial agents, As‐CTF‐S demonstrates the highest photocatalytic ability of 353.2 µmol g−1 and achieves a selectivity of ≈99.95% within a 4 h period under visible light irradiation. This study provides molecular insights into the rational control of charge transfer pathways for high‐efficiency CO2 photoreduction using single‐component organic semiconductor catalysts.

IntroductionTransient receptor potential (TRP) channels function as cellular sensors with a broad impact, and their dysregulation is linked to numerous cancers. The influence of TRP channel-related long noncoding RNAs (TCRLs) on uveal melanoma (UM) remains poorly understood.MethodsWe employed bioinformatics to examine the RNA-seq data and relevant clinical information of UM in the TCGA databases. By implementing coexpression analysis, we identified differentially expressed TCRLs. Using univariate Cox regression analysis, selection operator (LASSO) algorithm and stepwise regression, five key prognostic biomarkers were chosen. The high- and low-risk groups were divided based on the risk scores. Afterwards, the prediction performance of the signature was evaluated by receiver operating characteristic (ROC) curve and Kaplan-Meier (K-M) survival analysis. The functional enrichment analysis of TCRLs was also investigated. Following that, we examined immune cell infiltration, immune checkpoint expression, and tumor immune microenvironment between patients in high and low risk groups. TCRLs were validated using Random forests and multifactor Cox analysis. Candidate biomarkers were identified and screened. Finally, the effects of the candidate biomarkers on the proliferation, migration and invasion of UM cells were detected by CCK-8 assay, migration assay and perforation invasion assay.ResultsThe risk score generated by five TCRLs demonstrated robust predictive power. The high-risk group exhibited a poorer prognosis, increased immune cell infiltration, and an active tumor immune microenvironment compared to the low-risk group. Furthermore, two TCRLs of risk score, AC092535.4 and LINC01637, were screened to multiplex modelling. The in vitro experiments demonstrated that UM cells were suppressed following AC092535.4 or LINC01637 knockdown.DiscussionTwo TCRLs, AC092535.4 and LINC01637, serve as novel prognostic biomarkers for uveal melanoma and may present potential therapeutic targets.

AimDelirium poses a major challenge to global health care, yet there is currently a dearth of single effective interventions or medications. Particularly, addressing delirium induced by critical illness is a complex process. Occupational therapy is considered to have a high potential for use in the prevention of delirium, as it involves both cognitive training and training in ADL. To comprehensively analyze the effect of occupational therapy on delirium prevention, we evaluated the effects of occupational therapy vs. standard non-pharmacological prevention on incidence and duration of delirium, clinical outcomes and rehabilitation outcomes in critically ill patients.MethodsThe data sources, including PubMed/Medline, Web of Science, EMBASE, and Cochrane Library, were comprehensively searched from their inception until 15 October 2023. Following the PICOS principle, a systematic screening of literature was conducted to identify relevant studies. Subsequently, the quality assessment was performed to evaluate the risk of bias in the included literature. Finally, outcome measures from each study were extracted and comprehensive analysis was conducted using Review Manager 5.4.ResultsA total of four clinical trials met the selection criteria. The pooled analysis indicated no significant difference in the incidence and duration of delirium between the OT group and standard non-pharmacological interventions. A comprehensive analysis of clinical outcomes revealed that OT did not significantly reduce the length of hospital stay or ICU stay. Meanwhile, there was no significant difference in mortality rates between the two groups. It is noteworthy that although grip strength levels did not exhibit significant improvement following OT intervention, there were obvious enhancements observed in ADL and MMSE scores.ConclusionAlthough occupational therapy may not be the most effective in preventing delirium, it has been shown to significantly improve ADL and cognitive function among critically ill patients. Therefore, we contend that occupational therapy is a valuable component of a comprehensive multidisciplinary approach to managing delirium. In the future, high-quality researches are warranted to optimize the implementation of occupational therapy interventions for delirium prevention and further enhance their benefits for patients.

Background Tumor deposits (TD) was a significant risk factor impacting the prognosis of patients diagnosed with gastric cancer (GC), yet it was not currently incorporated into TNM staging systems. The objective of this research was to develop a predictive model for assessing the prognosis of patients with TD-positive GC. Methods Retrospective analysis was performed on the data of 4,972 patients treated for GC with D2 radical gastrectomy at Wannan Medical College’s Yijishan Hospital between January 2012 and December 2021. The patients were categorized based on the number of TD (L1: 1, L2: 2–3, L3: ≥4) and the anatomical location of TD (Q1: single area, Q2: multiple areas). In a 3:1 ratio, patients were randomly assigned to one of two groups: training or validation. Results The study included a total of 575 patients who were divided into the training group (n = 432) and validation group (n = 143). Survival analysis showed that the number and anatomical location of TD had a significant impact on the prognosis of patients with TD-positive GC. Univariate analysis of the training group data revealed that tumor size, T-stage, N-stage, histological grade, number and distribution of TD, neural invasion, and postoperative chemotherapy were associated with prognosis. Multivariate Cox regression analysis identified poor histological grade, T4 stage, N3 stage, number of TD, neural invasion, and postoperative chemotherapy as independent prognostic factors for GC patients with TD. A nomogram was developed using these variables, demonstrating well predictive ability for 1, 3, and 5-year overall survival (OS) in the validation set. The DCA curve shows that the constructed model shows a large positive net gain compared to the eighth edition Tumour, Node, Metastasis (TNM) staging system. Conclusion The prognostic model developed for patients with TD-positive GC has a higher clinical utility compared to the eighth edition of TNM staging.

Defecation care for disabled patients is a major challenge in health management. Traditional post-defecation treatment will bring physical injury and negative emotions to patients, while existing pre-defecation forecasting care methods are physically intrusive. On the basis of exploring the mechanism of defecation intention generation, and based on the characteristic analysis and clinical application of bowel sounds, it is found that the generation of desire to defecate and bowel sounds are correlated to a certain extent. Therefore, a deep learning-based bowel sound recognition method is proposed for human defecation prediction. The wavelet domain based Wiener filter is used to filter the bowel sound data to reduce other noise. Statistical analysis, fast Fourier transform and wavelet packet transform are used to extract the integrated features of bowel sound in time, frequency and time-frequency domain. In particular, an audio signal expansion data algorithm based on the Informer model is proposed to solve the problem of poor generalization of the training model caused by the difficulty of collecting bowel sound in reality. An improved one-dimensional residual network model (1D-IResNet) for defecation classification prediction is designed based on multi-domain features. The experimental results show that the proposed bowel sound augmentation strategy can effectively improve the data sample size and increase the sample diversity. Under the augmented dataset, the training speed of the 1D-IResNet model is accelerated, and the classification accuracy reaches 90.54 %, the F1 score reaches 83.88 %, which achieves a relatively good classification stability while maintaining a high classification index.

Objective: To examine the clinical features and synovial pathologies in rheumatoid arthritis (RA) patients across varying titers of circulating anti-citrullinated protein antibodies (ACPA). Methodology: We devised a negative pressure suction and rebound synovial biopsy tool to enhance the yield of synovial biopsies, noted for its ease and safety of use. This research involved a retrospective examination of 60 active RA patients who underwent synovial biopsies with this tool from June to November 2013 at our institution. A range of disease activity markers were collected, including DAS28-CRP, ESR, CRP, count of swollen and tender joints, VAS pain scale, and so forth. Synovial tissue underwent HE staining and immunohistochemistry, including synovitis grading (GSS) and counting of B cells (CD20), T cells (CD3), macrophages (CD68), and plasma cells (CD138). Participants: were categorized into three groups as per ACPA titers: ACPA-negative (0–5U/mL), low-titer (5–20U/mL), and high-titer (above 20U/mL). The study compared the clinical features and synovial pathologies across these groups. Results: Of the 60 RA patients, they were segregated into three groups based on ACPA titers: 20 in ACPA-negative, 9 in the low-titer group, and 31 in the high-titer group. No significant differences were observed in GSS scores, synovial cell proliferation and loss, matrix activation, inflammatory infiltration, and neovascularization among these groups (P > 0.05). The high-titer ACPA group demonstrated significantly increased counts of CD3+ T cells, CD20+ B cells, and CD68+ macrophages in synovial tissues compared to the ACPA-negative and low-titer groups (p

Abstract Maternal anaemia is a major public health problem. Developing maternal anaemia prevention and control policies is an important prerequisite for carrying out evidence‐based interventions. This article reviews maternal anaemia prevention and control policies in China, identifies gaps, and provides references for other countries. We examined policies concerning maternal nutrition and other related literature in China, identified through key databases and government websites, and conducted a narrative review of the relevant documentations guided by the Smith Policy‐Implementing‐Process framework. A total of 65 articles and documents were identified for analysis. We found that Chinese government has committed to reducing maternal anaemia at the policy level, with established objectives and a clear time frame. However, most of policies were not accompanied by operational guidelines, standardized interventions, and vigorous monitoring and evaluation mechanisms, and 85% of the policies don't have quantifiable objectives on anaemia. Maternal anaemia prevention and control services offered in clinical settings were primarily nutrition education and anaemia screening. Population‐based interventions such as iron fortification have yet to be scaled up. Furthermore, medical insurance schemes in some regions do not cover anaemia prevention and treatment, and in other regions that offer coverage, the reimbursement rate is low. The number and capacity of health professionals is also limited. Policy changes should focus on the integration of evidence‐based interventions into routine antenatal care services and public health service packages, standardization of dosages and provision of iron supplementation, streamline of reimbursement for outpatient expenses, and capacity building of health professionals.

The aim of this paper is to study the flexural behavior of reinforced concrete (RC) beams reinforced by engineered cementitious composite (ECC). The reinforcement effect of ECC on RC beam is studied by experiments, numerical simulation and theoretical analysis, considering the secondary load. Five beams were tested under static load, including two beams with ECC layers at the top and bottom (TBEB), two beams with ECC layers at the bottom (BEB) and one unreinforced beam. Different parameters in the test include reinforcement ratio, whether the top is equipped with ECC layer, and the thickness of the top ECC layer. The test data were used to validate the finite element model developed to simulate the bending response of the ECC layer reinforced beam. Then, a series of parameter studies were carried out to evaluate the effects of ECC layer thickness, reinforcement ratio and ECC elastic modulus on the reinforced beam. The experimental and numerical simulation results show that compared with other reinforced beams, TBEB equipped with 50 mm ECC layer at the top and bottom has better performance. Compared with the control beams, the ultimate bearing capacity is increased by 82.6 %, ductility and deformation capacity are increased by 2.38 times and 2.11 times, respectively. Finally, a calculation model for predicting the flexural capacity of TBEB is presented. The predicted flexural capacity is in good agreement with the experimental results.

The integration of high-temperature resistant geopolymer concrete, reinforced with basalt fiber reinforced polymer (BFRP), addresses several challenges encountered by conventional reinforced concrete structures, such as elevated energy consumption, substantial carbon emissions, and susceptibility to steel corrosion. To investigate the impact of geopolymer concrete cover on the mechanical performance of BFRP bars after high temperature treatment, this study conducted mechanical tests on a total 406 tensile specimens and 406 transverse shear specimens, spanning a temperature range from ambient temperature to 700 °C. The BFRP bars with diameters of 6 mm, 12 mm, and 16 mm underwent heat treatment durations of 0 h, 1 h, 2 h, and 3 h. Subsequently, they were examined for mass loss rat, residual tensile properties, and residual shear strength following natural cooling. Notably, this study also compared the impact of different geopolymer concrete cover thickness (30 mm, 40 mm, and 50 mm) on these performance parameters. The test results revealed that with an increase in heating temperature, the resin of BFRP experienced decomposition, leading to alterations in surface morphology, as well as changes in tensile and shear failure modes. In the temperature range of 400 °C to 700 °C, bare BFRP bars exhibited a significant decrease in both tensile and transverse shear strengths, with strength loss rates ranging from 50% to 90%. Moreover, the degradation in shear strength was comparatively slower than that in tensile strength. The presence of geopolymer concrete cover effectively mitigated the strength degradation of BFRP bars following high temperature treatment, and this protective effect improved with an increase in the concrete cover thickness. Additionally, scanning electron microscope (SEM) analysis was employed to elucidate the damage mechanisms for both bare and geopolymer concrete-covered BFRP bars. SEM results indicated that the deterioration induced by high temperature treatment gradually propagated radially from the edge to the core area of the bar. Finally, a simplified calculation model was adopted to evaluate the residual tensile strengths of BFRP bars wrapped in geopolymer concrete after high temperature treatment.

The catalytic conversion of biomass into high-value chemicals, such as furan derivatives, from 5-hydroxymethylfurfural (HMF) holds significant importance. In this study, a bifunctional catalyst prepared from phosphomolybdic acid (PMA) and chitosan was developed for the one-pot synthesis of 2,5-diformylfuran (DFF) from fructose. This approach offered the advantage of bypassing the solvent consumption and cost associated with HMF separation and purification for DFF production. The catalytic activity of the prepared catalyst primarily originated from the loaded PMA. Under optimized reaction conditions, the catalyst achieved a DFF yield of approximately 60% after a 6-h reaction at 150 °C or a 1-h reaction at 170 °C. Moreover, the catalyst exhibited good stability and reusability. These results highlight the potential of the bifunctional catalyst for efficient and cost-effective conversion of fructose into DFF, enabling practical applications in the production of valuable chemicals from bioresources.

For the problem of retaining gangue bending and skewing in the process of hard roof cutting roadway, this paper takes the 11# coal 1105 working face haulage roadway of Qiuji Coal Mine as the object of study and builds the mechanical model of gangue retaining in the whole process. Then the stress and deformation of the retaining gangue structure under the impact and extrusion of gangue are simulated with the numerical calculation software ABAQUS, respectively. The results show that the hard roof caving gangue has obvious punching characteristics, which can easily lead to the lateral bending of the retaining gangue, especially the upper part of the I-steel in retaining gangue, and can effectively reduce the deformation of the I-steel by imposing a lateral constraint on the top of the I-steel. The metal mesh will deform and produce large tensile stress on the adjacent I-steel under the extrusion of gangue, which is easy to cause overall instability. The deformation of the steel mesh will be significantly reduced when the spacing between I-steels is 800 mm. A new gangue retaining support scheme is proposed. According to field monitoring, the deformation of the waste rock slope under the new scheme has been reduced by about 49 %, which is in line with production safety requirements.

ABSTRACT: Mechanically interlocked polymers (MIPs) are promising candidates for the construction of elastomeric materials with desirable mechanical performance on account of their abilities to undergo inherent rotational and translational mechanical movements at the molecular level. However, the investigations on their mechanical properties are lagging far behind their structural fabrication, especially for linear polyrotaxanes in bulk. Herein, we report stretchable poly[2]rotaxane elastomers (PREs) which integrate numerous mechanical bonds in the polymeric backbone to boost macroscopic mechanical properties. Specifically, we have synthesized a hydroxy-functionalized [2]rotaxane that subsequently participates in the condensation polymerization with diisocyanate to form PREs. Benefitting from the peculiar structural and dynamic characteristics of the poly[2]rotaxane, the representative PRE exhibits favorable mechanical performance in terms of stretchability (∼1200%), Young's modulus (24.6 MPa), and toughness (49.5 MJ/m3). Moreover, we present our poly[2]rotaxanes as model systems to understand the relationship between mechanical bonds and macroscopic mechanical properties. It is concluded that the mechanical properties of our PREs are mainly determined by the unique topological architectures which possess a consecutive energy dissipation pathway including the dissociation of host−guest interaction and consequential sliding motion of the wheel along the axle in the [2]rotaxane motif.

Abstract Background This study examined the association between chest muscles and chronic obstructive pulmonary disease (COPD) and the relationship between chest muscle areas and acute exacerbations of COPD (AECOPD). Methods There were 168 subjects in the non-COPD group and 101 patients in the COPD group. The respiratory and accessory respiratory muscle areas were obtained using 3D Slicer software to analysis the imaging of computed tomography (CT). Univariate and multivariate Poisson regressions were used to analyze the number of AECOPD cases during the preceding year. The cutoff value was obtained using a receiver operating characteristic (ROC) curve. Results We scanned 6342 subjects records, 269 of which were included in this study. We then measured the following muscle areas (non-COPD group vs. COPD group): pectoralis major (19.06 ± 5.36 cm2 vs. 13.25 ± 3.71 cm2, P

Abstract Deep shale gas development has great potential, but the frequent occurrence of shale gas well casing change problems triggered by geological factors seriously restricts deep shale gas development. In order to investigate the influence of geological factors on the casing stress of the cemented casing in the sleeve, a model of formation-cement sheath-double casing assemblage was established, and the influence of three-way geostress and fault slip on the casing stress of the casing-in-casing cementing was investigated by using finite element analysis. The results show the following: the smaller the difference between the vertical geostress and the maximum horizontal geostress is, the lower the equivalent force on the casing is, and when the difference gradually decreases from 20 to 7 MPa, the maximum equivalent force of the inner casing under fracturing condition decreases by 9.4%; the increase of the minimum horizontal geostress leads to the increase of the equivalent force of the inner and outer casing. When the minimum horizontal stress gradually increases from 80 to 90 MPa, the maximum equivalent force of the inner casing under fracturing condition increases by 5.9%. The larger the fault slip and the fault angle, the larger the equivalent force generated on the casing. The shear resistance of the double-layer casing is significantly greater than that of the single-layer casing, with an average increase in fault slip distance that can be withstood of about 45.25% and 40.2% in the no internal pressure and fracturing conditions. The larger the casing steel grade and the thicker the wall thickness, the higher the shear resistance. It is recommended to reduce placing of wells in areas where the difference between the vertical and maximum horizontal ground stresses is large, and at locations where the fault slip angle is large, and to use both higher steel grades and larger wall thicknesses of casing. This research result demonstrates the feasibility of “milling + casing-in-casing” technology in severe casing change wells and also provides useful guidance for the application of this technology in the field.

AIM: To identify disease-causative mutations in families with congenital cataract. METHODS: Two Chinese families with autosomal-dominant congenital cataract (ADCC) were recruited and underwent comprehensive eye examinations. Gene panel next-generation sequencing of common pathogenic genes of congenital cataract was performed in the proband of each family. Sanger sequencing was used to valid the candidate gene mutations and sequence the other family members for co-segregation analysis. The effect of sequence changes on protein structure and function was predicted through bioinformatics analysis. Major intrinsic protein (MIP)-wildtype and MIP-G29R plasmids were constructed and microinjected into zebrafish single-cell stage embryos. Zebrafish embryonic lens phenotypes were screened using confocal microscopy. RESULTS: A novel heterozygous mutation (c.85G>A; p.G29R) in the MIP gene was identified in the proband of one family. A known heterozygous mutation (c.97C>T; p.R33C; rs864309693) in MIP was found in the proband of another family. In-silico prediction indicated that the novel mutation might affect the MIP protein function. Zebrafish embryonic lens was uniformly transparent in both wild-type PCS2+MIP and mutant PCS2+MIP. CONCLUSION: Two missense mutations in the MIP gene in Chinese cataract families are identified, and one of which is novel. These findings expand the genetic spectrum of MIP mutations associated with cataracts. The functional studies suggest that the novel MIP mutation might not be a gain-of-function but a loss-of-function mutation.

Binderless tungsten carbide possesses superior wear/oxidation/corrosion resistance, high-temperature performance and polishing characteristics in comparison with traditional WC-Co cemented carbide. However, the poor sinterability coupled with intrinsic brittleness has become the twin problem restricting the development of binderless tungsten carbide especially for application specifically at the harsh conditions. Herein, we systemically investigated the effects of hybrid carbide and oxide ceramic binder, SiC whisker and graphene on the densification, microstructure evolution and mechanical properties of tungsten carbide prepared through two-step spark plasma sintering. These results demonstrate that ceramic binder together with SiC whisker performed effectively on improving the densification of WC, while graphene was the optimum reinforcement for WC-SiCw based nanocomposites. Excellent mechanical properties were achieved for SG0.15 samples with a hardness of 23.21 GPa, a flexural strength of 1207.2 MPa as well as a SENB fracture toughness of 10.66 MPa m1/2. This study could provide reference to develop high-performance binderless tungsten carbide matrix composites, further advancing the application of binderless tungsten carbide.