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Abstract Tuberculous meningitis (TBM) is a fatal tuberculosis caused by a large number of Mycobacterium tuberculosis (M. tuberculosis) spread by blood flow, with a case fatality rate of more than 50%. It is one of the most serious complications of miliary tuberculosis (MT), whose incidence is closely related to MT. If doctors can provide early diagnosis and active treatment for TBM, the case fatality rate will be significantly reduced. At present, there is a lack of methods to predict the progression of MT to TBM in clinic. To explore whether MT cases will experience TBM, we propose an early screening model of miliary tuberculosis with tuberculous meningitis (MT-TBM) based on few-shot learning with multiple windows and feature granularities (MWFG). This model aims to screen potential TBM cases through chest computerized tomography (CT) images of MT cases. Chest CT is a routine examination for MT cases. The MWFG module can extract more comprehensive features from a set of CT images of each MT case. The softmax classifier with adaptive regularization is trained on the cooperation of support set and query set, which can effectively prevent overfitting. Experiments on a dataset of 40 MT cases with chest CT images established by the medical records demonstrate that our proposed model achieves state-of-the-art performance in the early screening of MT-TBM. It can establish the connection between MT and MT-TBM through chest CT images of MT cases. The early screening model of MT-TBM based on few-shot learning with MWFG fills the research gap in computer-aided predicting TBM and has certain clinical effects. This research can provide some reference for clinicians in early diagnosis of MT-TBM and help clinicians in the early prevention and treatment of TBM for MT patients.

Abstract Background This study explored the significance of consolidation maintenance chemotherapy after concurrent chemoradiotherapy with different regimens in patients with esophageal squamous cell carcinoma. Method A prospective randomized controlled phase III clinical trial was designed and registered in the China Clinical Trials Registry (Registration number: ChiCTR‐TRC‐12002719). Survival data were analyzed in terms of intention‐to‐treat (ITT) and per‐protocol (PP) sets for patients undergoing cisplatin and 5‐fluorouracil (PF) (group A), or cisplatin and paclitaxel (TP) (group B). Results The incidence risk of grade III–IV leukopenia in group B was higher than in group A (49.2% vs. 25.5%, p = 0.012). The survival rates at 1, 2, 3, and 5 years were 83.8%, 62.6%, 53.1%, and 41.3%, respectively. Consolidation chemotherapy after concurrent chemoradiation therapy had no benefit on median progression‐free survival (PFS) (p = 0.95) and overall survival (OS) (p = 0.809). According to the ITT analysis, the median PFS in group A and group B was 28.6 months and 30.3 months (X2 = 0.242, p = 0.623), while the median OS was 31.0 months and 50.3 months (X2 = 1.25，p = 0.263). For the PP analysis, the median PFS in group A and group B were 28.6 months and 30.3 months (p = 0.584), while the median OS was 31.0 months and 50.3 months (p = 0.259), respectively. Patients receiving consolidation chemotherapy did not show significant OS benefits (46.9 months vs. 38.3 months; X2 = 0.059, p = 0.866). Conclusion Similar PFS and OS were found between PF and TP regimens with concurrent chemoradiotherapy. Consolidation chemotherapy did not show any significant OS benefits.

Abstract Immune-mediated liver injury is a common characteristic of various liver diseases, including autoimmune and viral hepatitis. Here, we investigated the role of DEAD-box helicase 3, X-linked (DDX3X) in immune-mediated liver injury. Liver injury was induced in C57BL/6J mice via concanavalin A (Con A). DDX3X hepatocyte-specific knockout (DDX3XΔHep) mice and control (DDX3Xfl/fl) mice were utilized to investigate the role of DDX3X in liver injury. Primary hepatocytes were treated with tunicamycin (TM) to induce ER stress in vitro. The expression of DDX3X in patients with various liver diseases was evaluated. Hepatic DDX3X expression increased, and DDX3X translocated from the cytoplasm to the nucleus during Con A-induced liver injury. DDX3X deficiency ameliorated mouse liver injury and reduced ER stress in liver tissue. The inhibition of ER stress with 4-PBA significantly attenuated liver injury while decreasing DDX3X levels in liver tissue. However, the upregulation of hepatic DDX3X expression reversed Con A-induced liver injury and negated the protective effect of 4-PBA. Mechanistically, the nuclear translocation of DDX3X promoted ER stress-induced apoptosis through the transcriptional induction of CHOP. Moreover, DDX3X was elevated and translocated into the nucleus in patients with HBV-LF and AIH. Additionally, serum DDX3X levels markedly increased in patients with HBV-LF, and a consistent decrease in DDX3X was associated with a good prognosis. The cytoplasmic-to-nuclear translocation of DDX3X promotes ER stress-induced apoptosis, which is an obligatory step that drives hepatic necrosis and tissue damage. Notably, DDX3X is a potential therapeutic target for immune-mediated liver injury.

Abstract Currently, even the most effective anti-cancer therapies are often limited by the development of drug resistance and tumor relapse, which is a major challenge facing current cancer research. A deep understanding of the molecular and biochemical bases of drug efficacy that can help predict the clinical drug resistance, coupled with the evolution of systematic genomic and proteomic technologies, have facilitated studies identifying and elucidating the underlying mechanisms. In this review, we focus on several important issues on cancer drug resistance and provide a framework for understanding the common ways by which cancers develop resistance to therapeutic agents. With the increasing arsenal of novel anticancer agents and techniques, there are now unprecedented opportunities to understand and overcome drug resistance. The proteolysis targeting chimera (PROTAC) technology, immunotherapy, nanomedicine, and real-time monitoring of drug response all provide effective approaches for combating drug resistance. In addition to the advancement of therapeutic technologies, the revolution of treatment concept is also of great importance. We can take advantage of the interplay between drug sensitive and resistant subclones for combating cancer. However, there remains a long way to go in the protracted war against cancer drug resistance.

Abstract Background N6-Methyladenosine (m6A) methylation, a common form of RNA modification, play an important role in the pathogenesis of various diseases and in the ontogeny of organisms. Nevertheless, the precise function of m6A methylation in photoaging remains unknown. Objectives This study aims to investigate the biological role and underlying mechanism of m6A methylation in photoaging. Methods m6A dot blot, Real-time quantitative PCR (RT-qPCR), western blot and immunohistochemical (IHC) assays were employed to detect the m6A level and specific m6A methylase in ultraviolet ray (UVR)-induced photoaging tissue. The profile of m6A-tagged mRNA was identified by methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq analysis. Finally, we investigated the regulatory mechanism of KIAA1429 by MeRIP-qPCR, RNA knockdown and immunofluorescence assay. Results m6A levels were increased in photoaging and were closely associated with the upregulation of KIAA1429 expression. 1331 differentially m6A methylated genes were identified in the UVR group compared with the control group, of which 1192 (90%) were hypermethylated. Gene ontology analysis showed that genes with m6A hypermethylation and mRNA downregulation were mainly involved in extracellular matrix metabolism and collagen metabolism-related processes. Furthermore, KIAA1429 knockdown abolished the downregulation of TGF-bRII and upregulation of MMP1 in UVR-irradiated human dermal fibroblasts (HDFs). Mechanically, we identified MFAP4 as a target of KIAA1429-mediated m6A modification and KIAA1429 might suppress collagen synthesis through an m6A-MFAP4-mediated process. Conclusions The increased expression of KIAA1429 hinders collagen synthesis during UVR-induced photoaging, suggesting that KIAA1429 represents a potential candidate for targeted therapy to mitigate UVR-driven photoaging.

Abstract Abscisic acid (ABA) is the primary preventing factor of seed germination, which is crucial to plant survival and propagation. ABA-induced seed germination inhibition is mainly mediated by the dimeric PYR/PYL/RCAR (PYLs) family members. However, little is known about the relevance between dimeric stability of PYLs and seed germination. Here, we reveal that stabilization of PYL dimer can relieve ABA-induced inhibition of seed germination using chemical genetic approaches. Di-nitrobensulfamide (DBSA), a computationally designed chemical probe, yields around ten-fold improvement in receptor affinity relative to ABA. DBSA reverses ABA-induced inhibition of seed germination mainly through dimeric receptors and recovers the expression of ABA-responsive genes. DBSA maintains PYR1 in dimeric state during protein oligomeric state experiment. X-ray crystallography shows that DBSA targets a pocket in PYL dimer interface and may stabilize PYL dimer by forming hydrogen networks. Our results illustrate the potential of PYL dimer stabilization in preventing ABA-induced seed germination inhibition.

Integrated pest management is a pest control strategy that combines biological and chemical methods to reduce environmental pollution and protect biodiversity. Recent research indicated that the fear caused by predators had a significant effect on the growth, development, and reproductive processes of prey. Therefore, we have proposed a pest-natrual enemy system, which is a nonlinear state-dependent feedback control model that incorporated the fear effect in the predator-prey relationship. We discussed impulsive sets and phase sets of the model and derived an expression for the Poincaré map. Furthermore, we analyzed the existence and stability of order-$ 1 $ periodic solutions and explored the existence of order-$ k $ $ (k\ge2) $ periodic solutions. Finally, numerical simulations were conducted to validate our theoretical results and reveal their biological implications.

Abstract Background The prognosis nutritional index (PNI) and the systemic inflammatory immunological index (SII) are characteristic indicators of the nutritional state and the systemic inflammatory response, respectively. However, there is an unknown combined effect of these indicators in the clinic. Therefore, the practicality of using the SII-PNI score to predict prognosis and tumor response of locally advanced gastric cancer (LAGC) following chemotherapy was the main focus of this investigation. Methods We retrospectively analyzed 181 patients with LAGC who underwent curative resection after neoadjuvant chemotherapy in a prospective study (NCT01516944). We divided these patients into tumour regression grade(TRG) 3 and non-TRG3 groups based on tumor response (AJCC/CAP guidelines). The SII and PNI were assessed and confirmed the cut-off values before treatment. The SII-PNI values varied from 0 to 2, with 2 being the high SII (≥ 471.5) as well as low PNI (≤ 48.6), a high SII or low PNI is represented by a 1 and neither is represented by a 0, respectively. Results 51 and 130 samples had TRG3 and non-TRG3 tumor responses respectively. Patients with TRG3 had substantially higher SII-PNI scores than those without TRG3 (p

Abstract Background In cardiac surgical procedures, patients carrying high-risk profiles are prone to encompass complicated cardiopulmonary bypass (CPB) separation. Intraoperative transesophageal echocardiography (TEE), a readily available tool, is utilized to detect cardiac structural and functional pathologies as well as to facilitate clinical management of CPB separation, especially in the episodes of hemodynamic compromise. However, the conventional TEE examination, always performed in a liberal fashion without any restriction of view acquisition, is relatively time-consuming; there appear its flaws in the context of critically severe status. We therefore developed the perioperative rescue transesophageal echocardiography (PReTEE), a simplified three-view TEE protocol consisting of midesophageal four chamber, midesophageal left ventricular long axis, and transgastric short axis. Methods This is a single-center and randomized controlled trial which will be implemented in Peking Union Medical College Hospital, Beijing, China. A total of 46 TEE scans are schemed to be performed by 6 operators participating in and randomly assigned to either the PReTEE or the conventional TEE group. This study is purposed to investigate whether the efficiency of discriminating leading causes of difficult CPB wean-off can be significantly improved via an abbreviated sequence of TEE views. The primary outcome of interest is the difference between the groups of PReTEE and the conventional TEE in the successful discrimination of etiologies in specified 120 s. Cox proportional hazards model will be further employed to calculate the outcome difference. Discussion The estimated results of this trial are oriented at verifying whether a simplified TEE exam sequence can improve the efficiency of etiologies discrimination during CPB separation in cardiac surgery. Trial registration ClinicalTrials.gov NCT05960552. Registered on 6 July 2023.

Abstract In August 2023, Xiaomi unveiled the Redmi K60 Ultra, the first multi-frequency smartphone integrated with BeiDou-3 Navigation Satellite System Precise Point Positioning (PPP-B2b) services and employing PPP technology as the primary positioning method. The positioning enhancement service is provided by the Assisted Global Navigation Satellite System (A-GNSS) location platform developed by the China Academy of Information and Communications Technology. The signaling interaction between the server and the users strictly adheres to the Third Generation of Mobile Communications Technology Partnership Project Long-Term Evolution Positioning Protocol and the Open Mobile Alliance Secure User Plane Location framework. To comprehensively evaluate the Redmi K60 Ultra’s capabilities, this study designed six distinct experimental scenarios and conducted comprehensive research on multi-frequency and multi-GNSS observation noise, Time to First Fix (TTFF), as well as the performance of both GNSS-based and network-based positioning. Experimental results indicate that the GNSS chipset within the Redmi K60 Ultra has achieved a leading position in the consumer market concerning supported satellite constellations, frequencies, and observation accuracy, and is comparable to some low-cost GNSS receivers. A-GNSS positioning can reduce the TTFF from 30 to under 5 s, representing an improvement of over 85% in the cold start speed compared to a standalone GNSS mode. The positioning results show that the A-GNSS PPP-B2b service can achieve positioning performance with RMS errors of less than 1.5 m, 2.5 m, and 4 m in open-sky, realistic, and challenging urban environments. Compared to GNSS-based positioning, cellular network-based Observed Time Difference of Arrival (OTDOA) positioning achieves an accuracy ranging from tens to hundreds of meters in various experimental scenarios and currently functions primarily as coarse location determination. Additionally, this study explores the potential of the Three-Dimensional Mapping-Aided (3DMA) GNSS algorithm in detecting Non-Line-of-Sight signals and enhancing positioning performance. The results indicate that 3DMA PPP, as compared to conventional PPP, can significantly accelerate PPP convergence and improve positioning accuracy by over 30%. Consequently, 3D city models can be utilized as future assistance data for the A-GNSS location platform.

A reliable suspension-based platform for scaling engineered cardiac tissue (ECT) production from human induced pluripotent stem cells (hiPSCs) is crucial for regenerative therapies. Here, we compared the production and functionality of ECTs formed using our scaffold-based, engineered tissue microsphere differentiation approach with those formed using the prevalent scaffold-free aggregate platform. We utilized a microfluidic system for the rapid (1 million cells/min), high density (30, 40, 60 million cells/ml) encapsulation of hiPSCs within PEG-fibrinogen hydrogel microspheres. HiPSC-laden microspheres and aggregates underwent suspension-based cardiac differentiation in chemically defined media. In comparison to aggregates, microspheres maintained consistent size and shape initially, over time, and within and between batches. Initial size and shape coefficients of variation for microspheres were eight and three times lower, respectively, compared to aggregates. On day 10, microsphere cardiomyocyte (CM) content was 27 % higher and the number of CMs per initial hiPSC was 250 % higher than in aggregates. Contraction and relaxation velocities of microspheres were four and nine times higher than those of aggregates, respectively. Microsphere contractile functionality also improved with culture time, whereas aggregate functionality remained unchanged. Additionally, microspheres displayed improved β-adrenergic signaling responsiveness and uniform calcium transient propagation. Transcriptomic analysis revealed that while both microspheres and aggregates demonstrated similar gene regulation patterns associated with cardiomyocyte differentiation, heart development, cardiac muscle contraction, and sarcomere organization, the microspheres exhibited more pronounced transcriptional changes over time. Taken together, these results highlight the capability of the microsphere platform for scaling up biomanufacturing of ECTs in a suspension-based culture platform.

Abstract Alternative splicing is a crucial process in multicellular eukaryote, facilitated by the assembly of spliceosomal complexes comprising numerous small ribonucleoproteins. At an early stage, U1C is thought to be required for 5′ splice site recognition and base pairing. However, a systematic analysis of the U1C gene family in response to developmental cues and stress conditions has not yet been conducted in plants. This study identified 114 U1C genes in 72 plant species using basic bioinformatics analyses. Phylogenetic analysis was used to compare gene and protein structures, promoter motifs, and tissue- and stress-specific expression levels, revealing their functional commonalities or diversity in response to developmental cues, such as embryonic expression, or stress treatments, including drought and heat. Fluorescence quantitative expression analysis showed that U1C gene expression changed under salt, low temperature, drought, and Cd stress in rice seedlings. However, gene expression in shoots and roots was not consistent under different stress conditions, suggesting a complex regulatory mechanism. This research provides foundational insights into the U1C gene family's role in plant development and stress responses, highlighting potential targets for future studies.

Codonopsis pilosula (known as dangshen) is experiencing a serious replant disease caused by continuous monoculture in its main and endemic cultivation region in Dingxi, China. In this study, changes in physicochemical properties, fungal microbiomes, and isolated strains were investigated in the rhizosphere soil of 1-, 2-, 3-, and 5-year continuous monoculture natural fields. It was observed that wilted seedlings and a variety of root rot diseases occurred after the third year of continuous monoculture in the field. The soil-available potassium content and the pH value decreased significantly in the 3- and 5-year fields. Using Illumina sequencing, it was demonstrated that the 3- and 5-year fields had a higher diversity of fungal communities compared with the 1- and 2-year fields. At the genus level, abundance of some potentially pathogenic fungal taxa also increased. A total of 33 isolated strains belonging to the Fusarium species complexes Plectosphaerella cucumerina, Paraphoma ledniceana, Alternaria alstroemeriae, Mucor hiemalis, and Clonostachys rosea were obtained from the roots in 3- and 5-year fields. The correlation analysis revealed that the abundance of the fungal community at the genus level was positively correlated with the available phosphorus, total nitrogen, and soil organic matter. The results revealed that continuous monoculture has a negative impact on the fungal community and enriches potential pathogenic fungi in the rhizosphere of C. pilosula.

Abstract Background Higher mammographic density (MD), a radiological measure of the proportion of fibroglandular tissue in the breast, and lower terminal duct lobular unit (TDLU) involution, a histological measure of the amount of epithelial tissue in the breast, are independent breast cancer risk factors. Previous studies among predominantly white women have associated reduced TDLU involution with higher MD. Methods In this cohort of 611 invasive breast cancer patients (ages 23–91 years [58.4% ≥ 50 years]) from China, where breast cancer incidence rates are lower and the prevalence of dense breasts is higher compared with Western countries, we examined the associations between TDLU involution assessed in tumor-adjacent normal breast tissue and quantitative MD assessed in the contralateral breast obtained from the VolparaDensity software. Associations were estimated using generalized linear models with MD measures as the outcome variables (log-transformed), TDLU measures as explanatory variables (categorized into quartiles or tertiles), and adjusted for age, body mass index, parity, age at menarche and breast cancer subtype. Results We found that, among all women, percent dense volume (PDV) was positively associated with TDLU count (highest tertile vs. zero: Expbeta = 1.28, 95% confidence interval [CI] 1.08–1.51, ptrend =

Abstract Background Diabetes mellitus (DM)-induced testicular damage is associated with sexual dysfunction and male infertility in DM patients. However, the pathogenesis of DM-induced testicular damage remains largely undefined. Methods A streptozotocin (STZ)-induced diabetic model and high glucose (HG)-treated in vitro diabetic model were established. The histological changes of testes were assessed by H&E staining. Serum testosterone, iron, MDA and GSH levels were detected using commercial kits. Cell viability and lipid peroxidation was monitored by MTT assay and BODIPY 581/591 C11 staining, respectively. qRT-PCR, immunohistochemistry (IHC) or Western blotting were employed to detect the levels of BRD7, Clusterin, EZH2 and AMPK signaling molecules. The associations among BRD7, EZH2 and DNMT3a were detected by co-IP, and the transcriptional regulation of Clusterin was monitored by methylation-specific PCR (MSP) and ChIP assay. Results Ferroptosis was associated with DM-induced testicular damage in STZ mice and HG-treated GC-1spg cells, and this was accompanied with the upregulation of BRD7. Knockdown of BRD7 suppressed HG-induced ferroptosis, as well as HG-induced Clusterin promoter methylation and HG-inactivated AMPK signaling in GC-1spg cells. Mechanistical studies revealed that BRD7 directly bound to EZH2 and regulated Clusterin promoter methylation via recruiting DNMT3a. Knockdown of Clusterin or inactivation of AMPK signaling reverses BRD7 silencing-suppressed ferroptosis in GC-1spg cells. In vivo findings showed that lack of BRD7 protected against diabetes-induced testicular damage and ferroptosis via increasing Clusterin expression and activating AMPK signaling. Conclusion BRD7 suppressed Clusterin expression via modulating Clusterin promoter hypermethylation in an EZH2 dependent manner, thereby suppressing AMPK signaling to facilitate ferroptosis and induce diabetes-associated testicular damage.

Abstract Background Irinotecan (CPT-11) is a first-line treatment for advanced colorectal cancer (CRC). Four components (baicalin, baicalein, wogonin, and glycyrrhizic acid) derived from Huangqin Decoction (HQD) have been proven to enhance the anticancer activity of CPT-11 in our previous study. Objective This study aimed to determine the optimal combination of the four components for sensitizing CPT-11 as well as to explore the underlying mechanism. Methods The orthogonal design method was applied to obtain candidate combinations (Cmb1-9) of the four components. The influence of different combinations on the anticancer effect of CPT-11 was first evaluated in vitro by cell viability, wound healing ability, cloning formation, apoptosis, and cell cycle arrest. Then, a CRC xenograft mice model was constructed to evaluate the anticancer effect of the optimal combination in vivo. Potential mechanisms of the optimal combination exerting a sensitization effect combined with CPT-11 against CRC were analyzed by targeted metabolomics. Results In vitro experiments determined that Cmb8 comprised of baicalin, baicalein, wogonin, and glycyrrhizic acid at the concentrations of 17 μM, 47 μM, 46.5 μM and 9.8 μM respectively was the most effective combination. Importantly, the cell viability assay showed that Cmb8 exhibited synergistic anticancer activity in combination with CPT-11. In in vivo experiments, this combination (15 mg/kg of baicalin, 24 mg/kg of baicalein, 24 mg/kg of wogonin, and 15 mg/kg of glycyrrhizic acid) also showed a synergistic anticancer effect. Meanwhile, inflammatory factors and pathological examination of the colon showed that Cmb8 could alleviate the gastrointestinal damage induced by CPT-11. Metabolic profiling of the tumors suggested that the synergistic anticancer effect of Cmb8 might be related to the regulation of fatty acid metabolism. Conclusion The optimal combination of four components derived from HQD for the synergistic sensitization of CPT-11 against CRC was identified.

Abstract Background This study aimed to develop a novel six-gene expression biomarker panel to enhance the early detection and risk stratification of peritoneal recurrence and micrometastasis in locally advanced gastric cancer (LAGC). Methods We used genome-wide transcriptome profiling and rigorous bioinformatics to identify a six-gene expression biomarker panel. This panel was validated across multiple clinical cohorts using both tissue and liquid biopsy samples to predict peritoneal recurrence and micrometastasis in patients with LAGC. Results Through genome-wide expression profiling, we identified six mRNAs and developed a risk prediction model using 196 samples from a surgical specimen training cohort. This model, incorporating a 6-mRNA panel with clinical features, demonstrated high predictive accuracy for peritoneal recurrence in gastric cancer patients, with an AUC of 0.966 (95% CI: 0.944–0.988). Transitioning from invasive surgical or endoscopic biopsy to noninvasive liquid biopsy, the model retained its predictive efficacy (AUC = 0.963; 95% CI: 0.926–1.000). Additionally, the 6-mRNA panel effectively differentiated patients with or without peritoneal metastasis in 95 peripheral blood specimens (AUC = 0.970; 95% CI: 0.936–1.000) and identified peritoneal micrometastases with a high efficiency (AUC = 0.941; 95% CI: 0.874–1.000). Conclusions Our study provides a novel gene expression biomarker panel that significantly enhances early detection of peritoneal recurrence and micrometastasis in patients with LAGC. The RSA model's predictive capability offers a promising tool for tailored treatment strategies, underscoring the importance of integrating molecular biomarkers with clinical parameters in precision oncology.

Abstract Objective This study aimed to systematically review epidemiological evidence on associations between screen time exposure and myopia in children and adolescents, and to quantitatively evaluate summary effect estimates from existing literature. Method There were three online databases including PubMed, Embase, and Web of Science, for epidemiological studies on screen time exposure and myopia published before June 1, 2023. The risk of bias was assessed by the Newcastle Ottawa Scale (NOS) checklist. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the correlation between screen time exposure and myopia using random or fixed-effect models by exposure type (categorical/continuous). We also performed subgroup analysis by screen device type, study quality, geographic region, and research period. Results We searched 7,571 records from three databases and identified 19 eligible studies, including 14 high-quality studies and 5 moderate-quality studies. Meta-analyses suggested that there was a statistically significant correlation between screen time (high vs. low) and myopia. The pooled ORs with 95%CIs were respectively 2.24 (1.47–3.42) for cross-sectional studies, and 2.39 (2.07–2.76) for cohort studies. We also found a significant association between continuous exposure to screen time (per 1 h/d increase) and myopia in cohort studies. The pooled ORs with 95%CIs were 1.07 (1.01–1.13). In subgroup analysis stratified by screen device type in cross-sectional studies, screen time exposures from computers (categorical: OR = 8.19, 95%CI: 4.78–14.04; continuous: OR = 1.22, 95%CI: 1.10–1.35) and televisions (categorical: OR = 1.46, 95%CI: 1.02–2.10) were associated with myopia, while smartphones were not. Although publication bias was detected, the pooled results did not show significant changes after adjustment using the trim and fill method. Conclusion Our findings support that screen time exposure was significantly associated with myopia in children and adolescents. Notably, screen time exposure from computers may have the most significant impact on myopia.

Construction of disaster-resilient cities has attracted considerable attention. However, traditional methods of studying urban disaster resilience through experimental approaches are often constrained by various limitations, such as testing sites, costs and ethical considerations. To address these constraints, this paper proposes incorporating digital twin concepts into urban disaster resilience research. By establishing a connection between the physical realm of the city and its virtual counterpart, this approach utilizes digital simulations to overcome the limitations of experimental methods and enables dynamic deduction and control of the disaster process. This paper delves into three key aspects encompassing the acquisition of data from reality to the virtual space, disaster simulation within the virtual space, and translation of virtual insights into effective disaster prevention strategies in reality. It provides a comprehensive summary of relevant research endeavors from the authors’ research group and showcases the effectiveness and potential of the proposed techniques. These findings serve as references for pre-disaster planning, real-time emergency assessments, post-disaster rescue operations, and accident investigations for buildings and cities.

Abstract Molecular computing is an emerging paradigm that plays an essential role in data storage, bio-computation, and clinical diagnosis with the future trends of more efficient computing scheme, higher modularity with scaled-up circuity and stronger tolerance of corrupted inputs in a complex environment. Towards these goals, we construct a spatially localized, DNA integrated circuits-based classifier (DNA IC-CLA) that can perform neuromorphic architecture-based computation at a molecular level for medical diagnosis. The DNA-based classifier employs a two-dimensional DNA origami as the framework and localized processing modules as the in-frame computing core to execute arithmetic operations (e.g. multiplication, addition, subtraction) for efficient linear classification of complex patterns of miRNA inputs. We demonstrate that the DNA IC-CLA enables accurate cancer diagnosis in a faster (about 3 h) and more effective manner in synthetic and clinical samples compared to those of the traditional freely diffusible DNA circuits. We believe that this all-in-one DNA-based classifier can exhibit more applications in biocomputing in cells and medical diagnostics.

Abstract Variations in chromosome number are occasionally observed among oomycetes, a group that includes many plant pathogens, but the emergence of such variations and their effects on genome and virulence evolution remain ambiguous. We generated complete telomere-to-telomere genome assemblies for Phytophthora sojae, Globisporangium ultimum, Pythium oligandrum, and G. spinosum. Reconstructing the karyotype of the most recent common ancestor in Peronosporales revealed that frequent chromosome fusion and fission drove changes in chromosome number. Centromeres enriched with Copia-like transposons may contribute to chromosome fusion and fission events. Chromosome fusion facilitated the emergence of pathogenicity genes and their adaptive evolution. Effectors tended to duplicate in the sub-telomere regions of fused chromosomes, which exhibited evolutionary features distinct to the non-fused chromosomes. By integrating ancestral genomic dynamics and structural predictions, we have identified secreted Ankyrin repeat-containing proteins (ANKs) as a novel class of effectors in P. sojae. Phylogenetic analysis and experiments further revealed that ANK is a specifically expanded effector family in oomycetes. These results revealed chromosome dynamics in oomycete plant pathogens, and provided novel insights into karyotype and effector evolution.

Abstract Formaldehyde (HCHO) is a serious hazardous air pollutant and crucial precursor of PM2.5 and ozone compound pollution. There has been a dearth of HCHO research in Tibet where pressing need to protect the unique ecosystem. Therefore, this study aims to investigate the spatial-temporal distribution of HCHO from 2013 to 2021 and identify its influencing factors using satellite observations. Our findings reveal a noteworthy annual growth rate of 2.25% yr−1 in HCHO vertical column density (VCD) in Tibet. This rate is comparable to that in India and even surpasses levels observed in many other regions worldwide, including eastern China. Furthermore, unlike other areas, the eastern region of Tibet exhibits no discernible seasonal pattern in HCHO VCD. The anomalous variation in HCHO concentrations in Tibet can primarily be attributed to long-distance transnational transport originating from incomplete combustion in India Assam. Our research underscores the urgent need for enhanced atmospheric environmental management in Tibet.

Abstract Background Surgical staplers have been widely used to facilitate surgeries, and this study aimed to examine the real-world effectiveness of a new powered stapling system with Gripping Surface Technology (GST) on intraoperative outcomes of gastrectomy for gastric cancer. Method The data were extracted from the Fourth Hospital of Hebei Medical University’s (FHHMU) medical records system. Participants (N = 121 patients) were classified into the GST (n = 59) or non-GST group (n = 62), based on the use of the GST system. The intraoperative outcomes such as bleeding were assessed by reviewing video records. T-tests, Chi-square tests, and Mann–Whitney-U tests were used to compare the baseline characteristics between groups. Multivariate logistic regression was conducted for adjusting outcomes to study the effect of variables. Results Compared with the non-GST group, the GST group had significantly lower risks for intraoperative bleeding, intraoperative anastomosis intervention rate, intraoperative suture, and intraoperative pression (aORs: 0.0853 (p

Abstract Cholangiocarcinoma (CCA) is a highly malignant biliary tract cancer with currently suboptimal diagnostic and prognostic approaches. We present a novel system to monitor CCA using exosomal circular RNA (circRNA) via serum and biliary liquid biopsies. A pilot cohort consisting of patients with CCA-induced biliary obstruction (CCA-BO, n = 5) and benign biliary obstruction (BBO, n = 5) was used to identify CCA-derived exosomal circRNAs through microarray analysis. This was followed by a discovery cohort (n = 20) to further reveal a CCA-specific circRNA complex (hsa-circ-0000367, hsa-circ-0021647, and hsa-circ-0000288) in both bile and serum exosomes. In vitro and in vivo studies revealed the three circRNAs as promoters of CCA invasiveness. Diagnostic and prognostic models were established and verified by two independent cohorts (training cohort, n = 184; validation cohort, n = 105). An interpreter-free diagnostic model disclosed the diagnostic power of biliary exosomal circRNA signature (Bile-DS, AUROC = 0.947, RR = 6.05) and serum exosomal circRNA signature (Serum-DS, AUROC = 0.861, RR = 4.04) compared with conventional CA19-9 (AUROC = 0.759, RR = 2.08). A prognostic model of CCA undergoing curative-intent surgery was established by calculating early recurrence score, verified with bile samples (Bile-ERS, C-index=0.783) and serum samples (Serum-ERS, C-index = 0.782). These models, combined with other prognostic factors revealed by COX-PH model, enabled the establishment of nomograms for recurrence monitoring of CCA. Our study demonstrates that the exosomal triple-circRNA panel identified in both bile and serum samples serves as a novel diagnostic and prognostic tool for the clinical management of CCA.

IntroductionVisual impairment, encompassing low visual acuity and visual field loss, significantly impacts the older adult population worldwide, leading to increased disability and mortality risks. Recent studies suggest a strong association between visual impairment and anxiety, particularly among older adults. This study aims to explore the relationship between visual impairment and anxiety symptoms in older adult individuals in China, and to investigate potential mediating factors.MethodsData for this study were derived from the 2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS), including 11,702 participants aged 65 and older. Visual impairment was assessed through self-reported visual function, while anxiety symptoms were measured using the 7-item Generalized Anxiety Disorder scale (GAD-7). Additional assessments included sleep quality and duration, exercise status, and dietary diversity. Logistic regression models and mediation analysis were employed to explore associations and mediating effects.ResultsThe findings indicate that visual impairment is significantly associated with increased anxiety symptoms among the older adult (OR = 1.51, 95% CI: 1.32–1.72, p

ABSTRACT Purpose To compare the efficacy of first‐line regimens based on programmed cell death (or ligand) [PD‐(L)1] blockade in extensive‐stage small‐cell lung cancer (ES‐SCLC) patients with or without liver metastases (LM), and to identify optimal treatment strategies. Methods Network meta‐analysis of randomized controlled trials (RCTs) comparing chemo‐immunotherapy (CIT) and chemotherapy (CT) in ES‐SCLC patients stratified by LM. Overall survival (OS) and progression‐free survival (PFS) were evaluated using hazard ratios (HRs) and 95% confidence intervals (CIs). Results Seven RCTs involving 3658 ES‐SCLC patients (1243 with LM, 2415 without LM) were analyzed. For patients with LM, the combination therapies of anti‐PD‐1 + CT (HR, 0.67; 95% CI, 0.54%–0.82%; p

Enhancing rural teacher job satisfaction, which is a pivotal aspect in elevating the overall quality of rural education, serves as a crucial means to promote balanced educational development and to foster societal equity and cohesion. The objective of the study was to explore the factors that influence job satisfaction of rural teachers teaching in China's Heartland. 15 rural primary school teachers were meticulously chosen for in-depth interviews, utilizing a qualitative research paradigm and purposive sampling technique, spanning from March 2021 to July 2021. With reference to Hoppock's view of job satisfaction, this study designed an interview outline based on specificities of rural workplaces. Through in-depth interviews, a wealth of first-hand text materials was collected about rural teacher job satisfaction. Then these textual materials were processed with a rigorous tertiary coding based on grounded theory. This study found that rural teacher job satisfaction was influenced by various factors, encompassing both external and internal factors. External factors included national policies, campus culture, and rural environment. Internal factors included growth experience and self-cognition. Further, strong external support was strongly associated with improvement of rural teacher job satisfaction. Intra-individual characteristics of rural teachers were the most implicit influencing factors.

Background: Sorafenib is approved for the targeted therapy of cancers such as liver cancer and renal cancer. Given its widespread use, drug-related adverse events have received attention, and the post-marketing regulatory link is crucial. Objective: By using the FAERS database to mine the adverse events (AEs) related to sorafenib, comparing the association intensity of key AEs, and exploring potential drug-related AEs, it provides a reference for clinical medication. Methods: Collect ADE data related to sorafenib in the FAERS database from 2006 to 2023. Standardize the data, and map adverse events to system organ classes and preferred terms. Analyze using various signal quantification techniques such as ROR, PRR, BCPNN, and MGPS. Results: Among 18,520 adverse event reports (AERs) where sorafenib was the primary suspected drug, a total of 390 preferred terms (PTs) of adverse reactions were identified, covering 24 different system organ classes (SOCs). Specifically, the adverse events of sorafenib mainly involve the digestive system, skin and subcutaneous tissue, as well as non-specific physical discomfort including infection and injury. Among them, digestive system symptoms and skin toxicity are typical adverse reactions of sorafenib. We also observed uncommon but clearly strong AE signals, such as chloracne (n = 3, ROR 1756.39, PRR 1756.32, IC 8.78, EBGM 439.83), low-differentiated thyroid cancer (n = 4, ROR 585.47, PRR 585.44, IC 8.2, EBGM 293.22). It is worth noting that palmar-plantar erythrodysaesthesia syndrome (n = 2109, ROR 73.98, PRR 72.03, IC 6.01, EBGM 64.25) and hepatic encephalopathy (n = 457, ROR 37.44, PRR 37.23, IC 5.13, EBGM 35.07) have a higher incidence and signal intensity. In addition, we also observed some adverse events not mentioned in the official drug instructions, such as vitamin K deficiency or increased protein induced by antagonist II (PIVKA-II), abnormal alpha-fetoprotein, tumor metastasis, and splenic atrophy. Conclusion: Sorafenib carries the risk of various adverse reactions while providing therapeutic effects. In clinical applications, physicians should closely monitor the occurrence of digestive system reactions, skin lesions, endocrine system lesions, as well as injuries, infections, and other events.

The excessive presence of heavy metals (HMs) in soil poses a significant threat to both ecosystems and human health. Consequently, there is a compelling need for quantitative analysis of HMs concentration in soil and the prediction of potential contamination. In this study, 58 surface soil samples were systematically collected from 11 different townships in Luolong County. Using ArcGIS 10.7, the fishing net interpolation resampling was performed to obtain model data. The GeoDetector model was employed to determine the key driving factors and their interrelationships affecting soil composition. Subsequently, influential driving factors with higher explanatory power and employed a Random Forest (RF) model to generate a contamination prediction map. The results revealed that arsenic (As), cadmium (Cd) and lead (Pb) exceeded the risk screening values by 8.62%, 10.34%, and 10.34%, respectively. The GeoDetector model identified factors such as elevation, annual average precipitation, distance to the nearest river, geomorphic type in natural sources, geological type in geological sources, distance from roads, proximity to mining sites, per capita income of inhabitants, total potassium content and organic matter content in anthropogenic sources significantly influencing the spatial distribution of HMs concentration in the soil. The interactions among the primary driving factors increased their explanatory capacity. By using RF model to predict the spatial distribution of the main influencing factors of HMs, it was found that areas with a high probability of As contamination were mainly concentrated in the northern, central and southeast regions of Luolong County. Regions with Cd concentration exceeding the risk screening value were primarily concentrated in the east, northeast and a few northern areas of Luolong County, while the likelihood of Pb contamination was higher in the northern and southwestern regions of Luolong County. This study integrates spatial stratified heterogeneity with the random forest model to mitigate overfitting in the prediction of soil HM contamination, a common issue in traditional machine learning methods. This approach is essential for elucidating the environmental drivers of soil HM pollution, predicting high-risk areas in regions with complex environmental conditions and limited data, and ensuring the safety and stability of agricultural production as well as the well-being of local residents.

BackgroundKeloid is a fibroproliferative disease with unsatisfactory therapeutic effects and a high recurrence rate. exosomes produced by adipose-derived mesenchymal stem cells (ADSC-Exos) have attracted significant interest due to their ability to treat fibrosis. However, the molecular mechanisms of ADSC-Exos in keloids remain inconclusive.ObjectiveOur study revealed the relationship between ferroptosis and fibrosis in keloids. Subsequently, this study aimed to explore further the anti-fibrotic effect of ADSC-Exos on keloids through ferroptosis and the potential underlying mechanisms.MethodsTo investigate the impact of ferroptosis on keloid fibrosis, Erastin and ferrostatin-1 (fer-1) were utilized to treat keloid fibroblast. Keloid keloids treated with Erastin and fer-1 were cocultured with ADSC-Exos to validate the impact of ferroptosis on the effect of ADSC-Exos on keloid anti-ferrotic protein, peroxidase 4 (GPX4) and anti-fibrotic effects in vivo and in vitro by Western blot, as well as variations in iron metabolite expression, malondialdehyde (MDA), liposomal peroxidation (LPO) and glutathione (GSH) were analyzed. The effect of solute carrier family 7-member 11 (SLC7A11) silencing on ADSC-Exo-treated keloid fibroblast was investigated.ResultsIron metabolite dysregulation was validated in keloids. Fibrosis progression is enhanced by Erastin-induced ferroptosis. The anti-fibrotic effects of ADSC-Exos and fer-1 are related to their ability to prevent iron metabolism. ADSC-Exos effectively suppressed keloid fibrosis progression and increased GSH and GPX4 gene expression. Additionally, the use of Erastin limits the effect of ADSC-Exos in keloids. Furthermore, the effect of ADSC-Exos on keloids was associated with SLC7A11-GPX4 signaling pathway.ConclusionWe demonstrated a new potential mechanism by which anti-ferroptosis inhibits the progression of keloid fibrosis and identified an ADSC-Exo-based keloid therapeutic strategy. Resisting the occurrence of ferroptosis and the existence of the SLC7A11-GPX4 signaling pathway might serve as a target for ADSC-Exos.

ObjectiveTo assess the effect of intravenous immunoglobulin (IVIG) therapy on unexplained recurrent spontaneous abortion (URSA).MethodsWe retrieved all randomized controlled trials (RCTs) related to the effect of IVIG therapy on URSA in the following databases: PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials before April 30, 2023, according to the PRISMA statement. The therapeutic effect of IVIG was measured by live birth rates. Quality assessment was conducted independently by two reviewers, based on the Newcastle‐Ottawa scale. For the meta-analysis, we used odds ratios (random effects model and fixed effects model). The between-study heterogeneity was assessed by the Q test. Publication bias was assessed by funnel plots.ResultsA total of 12 studies with 751 participants were included in this meta-analysis. There was no statistical significance [OR = 1.07, 95%CI (0.65, 1.75), P=0.80] between the IVIG group and the non-IVIG group, including low molecular weight heparin (LMWH) plus low-dose aspirin (LDA), intralipid, multivitamins, albumin, and normal saline. A subgroup analysis was conducted according to the different treatment regimens of the non-IVIG group. Compared to the placebo group, including multivitamins, albumin, and saline, the live birth rate of the IVIG group is superior, but there was no statistical significance [OR =1.43, 95%CI (0.99, 2.07), P=0.05]. Another subgroup analysis was performed according to URSA with positive for antiphospholipid antibodies (aPLs). Results showed the live birth rate of IVIG on URSA with positive for aPLs is inferior to that of LMWH plus LDA [OR = 0.25, 95%CI (0.11, 0.55), P=0.0007].ConclusionsIVIG didn’t increase the live birth rate of URSA compared to placebo. Conversely, compared with the IVIG, the LMWH plus LDA treatment schedule can increase the live birth rate of URSA with positive for aPLs.

ObjectiveStudies on the baseline vitamin D levels in osteogenesis imperfecta (OI) patients before medication are scarce. This study assessed the vitamin D status of a population with OI at both the overall level and within different age groups. It correlated baseline 25-hydroxyvitamin D (25(OH)D) levels with other bone-related factors, biochemical markers, and bone density.Patients and methodsWe collected 25(OH)D levels from 95 OI patients in East China (59 under 18 years old and 36 over 18 years old). Postmenopausal women and men over 50 years old are excluded. Measurements included body indicators, biochemical markers, and bone mineral density (BMD) assessed by Dual-energy X-ray absorptiometry (DXA). Data analysis was performed using SPSS 26.0.ResultsIn the overall population, among those under 18 years old, and among those over 18 years old, 87.4, 83.1, and 94.4%, respectively, were vitamin D deficient (30 ng/mL) showed a negative correlation with BMI. In OI patients under 18 years old, serum 25(OH)D was negatively correlated with serum β-CTX levels. In adult male OI population, 25(OH)D levels were negatively correlated with OI severity (Type I, IV, III). No statistically significant correlation was found between 25(OH)D levels and BMD Z-scores.ConclusionThis study on OI in East China reveals significant vitamin D insufficiency and deficiency in baseline levels among pediatric, adolescent and adult OI patients. It assesses the correlation of 25(OH)D levels with various influencing factors, providing crucial insights into understanding the impact of OI on vitamin D status across different age groups and aiding in better clinical management of OI patients.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors in the contemporary era, representing a significant global health concern. Early HCC patients have mild symptoms or are asymptomatic, which promotes the onset and progression of the disease. Moreover, advanced HCC is insensitive to chemotherapy, making traditional clinical treatment unable to block cancer development. Sorafenib (SFB) is a first-line targeted drug for advanced HCC patients with anti-angiogenesis and anti-tumor cell proliferation effects. However, the efficacy of SFB is constrained by its off-target distribution, rapid metabolism, and multi-drug resistance. In recent years, nanoparticles based on a variety of materials have been demonstrated to enhance the targeting and therapeutic efficacy of SFB against HCC. Concurrently, the advent of joint drug delivery systems has furnished crucial empirical evidence for reversing SFB resistance. This review will summarize the application of nanotechnology in the field of HCC treatment over the past five years. It will focus on the research progress of SFB delivery systems combined with multiple therapeutic modalities in HCC treatment.

Due to the complex structures associated with neutron resonance cross sections, their accurate evaluation has received considerable attention in the field of nuclear data research. The traditional R-matrix method still faces some difficulties in evaluating the neutron resonance data, especially in briefly reproducing the high-frequency oscillating cross sections. Recently, the applications of machine learning methods in nuclear physics have been expanding. In this paper, a novel Phase Shift Deep Neural Network (PSDNN) method, which not only overcomes the limitations of other machine learning methods in fitting the high-frequency oscillating data, but also is more concise than the R-matrix method, is developed to reproduce the neutron resonance cross sections. The results show that PSDNN method can simultaneously reproduce the low and high-frequency oscillating cross sections for the 235U(n,f) reaction with high accuracy and efficiency. Moreover, from an algorithmic point of view, the PSDNN method lays a solid foundation for further fine-grained processing of experimental data and extraction of critical neutron resonance parameters, opening up new possibilities for practical applications in nuclear data research.

Abstract Astragalus mongholicus is a medicinal plant that is known to decrease in quality in response to continuous cropping. However, the differences in the root-associated microbiome and root exudates in the rhizosphere soil that may lead to these decreases are barely under studies. We investigated the plant biomass production, root-associated microbiota, and root exudates of A. mongholicus grown in two different fields: virgin soil (Field I) and in a long-term continuous cropping field (Field II). Virgin soil is soil that has never been cultivated for A. mongholicus. Plant physiological measurements showed reduced fresh and dry weight of A. mongholicus under continuous cropping conditions (i.e. Field II). High-throughput sequencing of the fungal and bacterial communities revealed differences in fungal diversity between samples from the two fields, including enrichment of potentially pathogenic fungi in the roots of A. mongholicus grown in Field II. Metabolomic analysis yielded 20 compounds in A. mongholicus root exudates that differed in relative abundance between rhizosphere samples from the two fields. Four of these metabolites (2-aminophenol, quinic acid, tartaric acid, and maleamate) inhibited the growth of A. mongholicus, the soil-borne pathogen Fusarium oxysporum, or both. This comprehensive analysis enhances our understanding of the A. mongholicus microbiome, root exudates, and interactions between the two in response to continuous cropping. These results offer new information for future design of effective, economical approaches to achieving food security.

Abstract. Background:. Somatic copy number variations (SCNVs) in the CDKN2A gene are among the most frequent events in the dysplasia-carcinoma sequence of esophageal squamous cell carcinoma. However, whether CDKN2A SCNVs are useful biomarkers for the risk stratification and management of patients with esophageal squamous cell dysplasia (ESCdys) is unknown. This study aimed to investigate the characteristics and prognostic value of CDKN2A SCNVs in patients with mild or moderate (m/M) ESCdys. Methods:. This study conducted a prospective multicenter study of 205 patients with a baseline diagnosis of m/M ESCdys in five high-risk regions of China (Ci County, Hebei Province; Yanting, Sichuan Province; Linzhou, Henan Province; Yangzhong, Jiangsu Province; and Feicheng, Shandong Province) from 2005 to 2019. Genomic DNA was extracted from paraffin biopsy samples and paired peripheral white blood cells from patients, and a quantitative polymerase chain reaction assay, P16-Light, was used to detect CDKN2A copy number. The cumulative regression and progression rates of ESCdys were evaluated using competing risk models. Results:. A total of 205 patients with baseline m/M ESCdys were enrolled. The proportion of ESCdys regression was significantly lower in the CDKN2A deletion cohort than in the diploid and amplification cohorts (18.8% [13/69] vs. 35.0% [28/80] vs. 51.8% [29/56], P

Abstract Abnormal uterine bleeding (AUB) during the menopausal transition results in reproductive endocrine disorders and both physiological and pathological changes, substantially impacting women’s health. This study aimed to investigate the factors influencing AUB in perimenopausal women. Between April 2021 and June 2022, 120 perimenopausal women with AUB in the menopausal transition, diagnosed and treated at the Gynaecology Department of Kunming Tongren Hospital, were included in the case group. Concurrently, women undergoing routine health examinations at the same hospital were randomly selected as the control group. Univariate and multivariate logistic regression analyses identified factors related to AUB. The univariate analysis revealed significant associations (P

Abstract The role of circular RNA (circRNAs) in hepatocellular carcinoma (HCC) has been extensively studied. Previous research has highlighted the regulatory role of circSNX6 in HCC cells and tissues. However, the precise mechanism underlying HCC progression still requires comprehensive investigation. The study initially utilized quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to assess circSNX6 expression levels in HCC cell lines and tissues. Subsequently, the stability of circRNA was evaluated through Ribonuclease R and actinomycin D treatment assays. The impact of circSNX6 knockdown on proliferation, migration, invasion, and angiogenesis abilities was determined using various assays including colony formation, Transwell culture system, tube formation assay, and cell counting kit (CCK)-8 assays. Additionally, RNA immunoprecipitation chip and dual-luciferase reporter assays were employed to investigate the interactions between circSNX6 and miR-383-5p. Finally, an HCC xenograft tumor model in mice was established to assess the in vivo expression of circSNX6 and its functional role in HCC. Our findings revealed an elevated circSNX6 expression in HCC tissues, which was correlated with poor patient prognosis. Knockdown of circSNX6 suppressed HCC cell growth, invasion, metastasis, and angiogenesis. The downregulation of miR-383-5p, a target of circSNX6, significantly attenuated the tumor-suppressive effects induced by circSNX6 knockdown. Moreover, circSNX6 was found to modulate VEGFA expression by targeting miR-383-5p. The inhibition of HCC cell proliferation by miR-383-5p could be partially reversed by overexpressing VEGFA. Silencing circSNX6 also suppressed tumor formation and the metastasis of HCC cells in a mouse model. In summary, our findings suggest that circSNX6 promotes cell proliferation, metastasis, and angiogenesis in HCC by regulating the miR-383-5p/VEGFA pathway.

Abstract Background Colorectal cancer (CRC) is the 3rd most common malignancy with the liver being the most common site of metastases. The recurrence rate of colorectal liver metastases (CRLM) after liver resection (LR) is notably high, with an estimated 40% of patients experiencing recurrence within 6 months. In this context, we conducted a meta-analysis to synthesize and evaluate the reliability of evidence pertaining to prognostic factors associated with early recurrence (ER) in CRLM following LR. Methods Systematic searches were conducted from the inception of databases to July 14, 2023, to identify studies reporting prognostic factors associated with ER. The Quality in Prognostic Factor Studies (QUIPS) tool was employed to assess risk-of-bias for included studies. Meta-analysis was then performed on these prognostic factors, summarized by forest plots. The grading of evidence was based on sample size, heterogeneity, and Egger’s P value. Results The study included 24 investigations, comprising 12705 individuals, during an accrual period that extended from 2007 to 2023. In the evaluation of risk-of-bias, 22 studies were rated as low/moderate risk, while two studies were excluded because of high risk. Most of the studies used a postoperative interval of 6 months to define ER, with 30.2% (95% confidence interval [CI], 24.1–36.4%) of the patients experiencing ER following LR. 21 studies were pooled for meta-analysis. High-quality evidence showed that poor differentiation of CRC, larger and bilobar-distributed liver metastases, major hepatectomy, positive surgical margins, and postoperative complications were associated with an elevated risk of ER. Additionally, moderate-quality evidence suggested that elevated levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19–9 (CA199), lymph node metastases (LNM) of CRC, and a higher number of liver metastases were risk factors for ER. Conclusion This review has the potential to enhance the efficacy of surveillance strategies, refine prognostic assessments, and guide judicious treatment decisions for CRLM patients with high risk of ER. Additionally, it is essential to undertake well-designed prospective investigations to examine additional prognostic factors and develop salvage therapeutic approaches for ER of CRLM.

Abstract Background The efficacy and safety of low-pressure balloon pre-dilatation before intracoronary pro-urokinase (pro-UK) in preventing no-reflow during percutaneous coronary intervention (PCI) remains unknown. This study aimed to evaluate the clinical outcomes of intracoronary pro-UK combined with low-pressure balloon pre-dilatation in patients with anterior ST-segment-elevation myocardial infarction (STEMI). Methods This was a randomized, single-blind, investigator-initiated trial that included 179 patients diagnosed with acute anterior STEMI. All patients were eligible for PCI and were randomized into two groups: intracoronary pro-UK combined with (ICPpD group, n = 90) or without (ICP group, n = 89) low-pressure balloon pre-dilatation. The main efficacy endpoint was complete epicardial and myocardial reperfusion. The safety endpoints were major adverse cardiovascular events (MACEs), which were analyzed at 12 months follow-up. Results Patients in the ICPpD group presented significantly higher TIMI myocardial perfusion grade 3 (TMPG3) compared to those in the ICP group (77.78% versus 68.54%, P = 0.013), and STR ≥ 70% after PCI 30 min (34.44% versus 26.97%, P = 0.047) or after PCI 90 min (40.0% versus 31.46%, P = 0.044). MACEs occurred in 23 patients (25.56%) in the ICPpD group and in 32 patients (35.96%) in the ICP group. There was no difference in hemorrhagic complications during hospitalization between the groups. Conclusion Patients with acute anterior STEMI presented more complete epicardial and myocardial reperfusion with adjunctive low-pressure balloon pre-dilatation before intracoronary pro-UK during PCI. Trial registration 2019xkj213.

Abstract Perovskite photovoltaics, typically based on a solution-processed perovskite layer with a film thickness of a few hundred nanometres, have emerged as a leading thin-film photovoltaic technology. Nevertheless, many critical issues pose challenges to its commercialization progress, including industrial compatibility, stability, scalability and reliability. A thicker perovskite film on a scale of micrometres could mitigate these issues. However, the efficiencies of thick-film perovskite cells lag behind those with nanometre film thickness. With the mechanism remaining elusive, the community has long been under the impression that the limiting factor lies in the short carrier lifetime as a result of defects. Here, by constructing a perovskite system with extraordinarily long carrier lifetime, we rule out the restrictions of carrier lifetime on the device performance. Through this, we unveil the critical role of the ignored lattice strain in thick films. Our results provide insights into the factors limiting the performance of thick-film perovskite devices.

Abstract Accelerating the discovery of advanced materials is crucial for modern industries, aerospace, biomedicine, and energy. Nevertheless, only a small fraction of materials are currently under experimental investigation within the vast chemical space. Materials scientists are plagued by time-consuming and labor-intensive experiments due to lacking efficient material discovery strategies. Artificial intelligence (AI) has emerged as a promising instrument to bridge this gap. Although numerous AI toolkits or platforms for material science have been developed, they suffer from many shortcomings. These include primarily focusing on material property prediction and being unfriendly to material scientists lacking programming experience, especially performing poorly with limited data. Here, we developed MLMD, an AI platform for materials design. It is capable of effectively discovering novel materials with high-potential advanced properties end-to-end, utilizing model inference, surrogate optimization, and even working in situations of data scarcity based on active learning. Additionally, it integrates data analysis, descriptor refactoring, hyper-parameters auto-optimizing, and properties prediction. It also provides a web-based friendly interface without need programming and can be used anywhere, anytime. MLMD is dedicated to the integration of material experiment/computation and design, and accelerate the new material discovery with desired one or multiple properties. It demonstrates the strong power to direct experiments on various materials (perovskites, steel, high-entropy alloy, etc). MLMD will be an essential tool for materials scientists and facilitate the advancement of materials informatics.

Abstract Background Magnetic resonance (MR)‐guided ultra‐hypofractionated radiotherapy with whole‐pelvic irradiation (UHF‐WPRT) is a novel approach to radiotherapy for patients with high‐risk (HR) and very high‐risk (VHR) prostate cancer (PCa). However, the inherent complexity of adaptive UHF‐WPRT might inevitably result in longer on‐couch time. We aimed to estimate the delivered dose, study the feasibility and safety of adaptive UHF‐WPRT on a 1.5‐Tesla MR‐Linac. Methods Ten patients with clinical stage T3a‐4N0‐1M0‐1c PCa, who consecutively received UHF‐WPRT, were enrolled prospectively. The contours of the target and organ‐at‐risks on the position verification‐MR (PV‐MR), beam‐on 3D‐MR(Bn‐MR), and post‐MR (after radiotherapy delivery) were derived from the pre‐MR data by deformable image registration. The physician then manually adjusted them, and dose recalculation was performed accordingly. GraphPad Prism 9 (GraphPad Prism Software Inc.) was utilized for conducting statistical analyses. Results In total, we collected 188 MR scans (50 pre‐MR, 50 PV‐MR, 44 Bn‐MR, and 44 post‐MR scans). With median 59 min, the mean prostate clinical target volume (CTV)‐V100% was 98.59% ± 2.74%, and the mean pelvic CTVp‐V100% relative percentages of all scans was 99.60% ± 1.18%. The median V29 Gy change in the rectal wall was −2% (−18% to 20%). With a median follow‐up of 9 months, no patient had acute Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or more severe genitourinary (GU) or gastrointestinal (GI) toxicities (0%). Conclusion UHF‐RT to the prostate and the whole pelvis with concomitant boost to positive nodes using an Adapt‐To‐Shape (ATS) workflow was technically feasible for patients with HR and VHR PCa, presenting only mild GU and GI toxicities. The estimated target dose during the beam‐on phase was clinically acceptable based on the 3D‐MR–based dosimetry analysis. Clinical trial registration Chinese Clinical Trial Registry ChiCTR2000033382.

Carbon materials (graphite or C/C composites) are widely used in aerospace applications due to their unique performance advantages, including low density, high specific strength and low coefficients of thermal expansion. However, carbon materials are highly susceptible to destructive oxidation in high-temperature oxygen-containing environments, limiting their application scope and service life. Coating technology is an effective approach for solving the above problem, and ceramic coatings are the most widely used protective system. In this review, the latest research progress regarding different types of silicon carbide-based antioxidation and anti-ablation ceramic coatings on the surfaces of carbon materials is described, and the protective properties and mechanism analysis of the SiC and modified SiC coatings by ultrahigh-temperature ceramic borides, carbides, silicides and other reinforcements are elucidated. In addition, the current main challenges of ceramic coatings are carefully analysed, and the perspectives for the future development of ceramic protection coatings are also discussed.

G protein-coupled receptor 35 (GPR35) has gained increasing attention as a promising target in treating inflammatory and gastrointestinal tract conditions, cardiovascular diseases, and cancer. Metabolites including kynurenic acid, lysophosphatidic acids, chemokine 17, and 5-hydroxyindole acetic acid have been suggested to be endogenous ligands of GPR35. However, little is known regarding the downstream metabolic characteristics upon GPR35 regulation. Herein, four GPR35 interventions in cell models, comprising GPR35 knock-down, over-expression, activation, or inhibition, were established through lentiviral transduction, or the use of a potent agonist (pamoic acid) or antagonist (ML194). Targeted metabolomics and pseudotargeted lipidomics were performed on these cell models to capture GPR35-associated metabolites and lipids. Levels of 75 metabolites and 204 lipids were significantly altered in response to one or more GPR35 interventions. Levels of metabolites involved in fatty acid β-oxidation and phosphatidylethanolamine metabolism were notably altered. This study reports the first exploration of the metabolic characteristics of GPR35, and may aid in understanding of the potential mechanisms and functions of GPR35 in various physiological and pathological conditions.

Abstract Predicting and elucidating the impacts of materials on human health and the environment is an unending task that has taken on special significance in the context of nanomaterials research over the last two decades. The properties of materials in environmental and physiological media are dynamic, reflecting the complex interactions between materials and these media. This dynamic behavior requires special consideration in the design of databases and data curation that allow for subsequent comparability and interrogation of the data from potentially diverse sources. We present two data processing methods that can be integrated into the experimental process to encourage pre-mediated interoperability of disparate material data: Knowledge Mapping and Instance Mapping. Originally developed as a framework for the NanoInformatics Knowledge Commons (NIKC) database, this architecture and associated methods can be used independently of the NIKC and applied across multiple subfields of nanotechnology and material science.

Abstract Aims To estimate the effects of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) on proteinuria and oxidative stress expression in type 2 diabetes patients. Materials and methods 68 patients with type 2 diabetes mellitus (T2DM) were divided into three groups according urinary albumin-to-creatinine ratio (UACR), including T2DM with non-albuminuria group (UACR 300 mg/g). They all received SGLT2 inhibitors (SGLT2i) treatment for 12 weeks. The expression of advanced glycation end products (AGEs) in plasma and 8-hydroxy-2-deoxyguanosine (8-OHdG) in urine were measured as indications of oxidative stress. The 24-hour urine samples were collected to measure the concentration of proteinuria and 8-OHdG before and after 12 weeks SGLT2i treatment. Plasma renin activity (PRA), angiotensin II (Ang II) and Aldosterone (ALD) were measured to evaluate renin angiotensin aldosterone system (RASS) levels. Results After 12 weeks SGLT2 inhibitors treatment, the median values of 24-hour proteinuria decreased in macroalbuminuria compared to baseline (970 vs. 821 mg/d, P = 0.006). The median values of AGEs and 8-OHdG decreased in microalbuminuria and macroalbuminuria groups when compared to baseline, AGEs (777 vs. 136 ug/ml, P = 0.003) and (755 vs. 210 ug/ml, P = 0.001), 8-OHdG (8.00 vs. 1.88 ng/ml, P = 0.001) and (11.18 vs. 1.90 ng/ml, P

Background/Purpose: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is capable of causing serious community and hospital-acquired infections. However, currently, the identification of CRKP is complex and inefficient. Hence, this study aimed to develop methods for the early and effective identification of CRKP to allow reasonable antimicrobial therapy in a timely manner. Methods: K. pneumoniae (KP)-, K. pneumoniae carbapenemase (KPC)- and New Delhi metallo-β-lactamase (NDM)- specific CRISPR RNAs (crRNAs), polymerase chain reaction (PCR) primers and recombinase-aided amplification (RAA) primers were designed and screened in conserved sequence regions. We established fluorescence and lateral flow strip assays based on CRISPR/Cas13a combined with PCR and RAA, respectively, to assist in the detection of CRKP. Sixty-one clinical strains (including 51 CRKP strains and 10 carbapenem-sensitive strains) were collected for clinical validation. Results: Using the PCR-CRISPR assay, the limit of detection (LOD) for KP and the blaKPC and blaNDM genes reached 1 copy/μL with the fluorescence signal readout. Using the RAA-CRISPR assay, the LOD could reach 101 copies/μL with both the fluorescence signal readout and the lateral flow strip readout. Additionally, the positivity rates of CRKP-positive samples detected by the PCR/RAA-CRISPR fluorescence and RAA-CRISPR lateral flow strip methods was 92.16% (47/51). The sensitivity and specificity reached 100% for KP and blaKPC and blaNDM gene detection. For detection in a simulated environmental sample, 1 CFU/cm2 KP could be detected. Conclusion: We established PCR/RAA-CRISPR assays for the detection of blaKPC and blaNDM carbapenemase genes, as well as KP, to facilitate the detection of CRKP.

Objectives To explore the effects and mechanisms of bilirubin on mitochondrial function and type of macrophage cell death after exposure to cigarette smoke extract (CSE).Methods RAW264.7 macrophages were treated with different concentrations of CSE and bilirubin solutions and divided into four groups: control, CSE, bilirubin, and bilirubin + CSE groups. The necrotic and apoptotic states of the macrophages were determined using an Annexin V-fluorescein 5-isothiocyanate/propidium iodide (FITC/PI) staining kit. Cytoplasmic NOD-like receptor family, pyrin domain containing 3 (NLRP3) expression in macrophages was detected by immunofluorescence and the levels of IL-1β and IL-18 in the supernatants of culture medium were detected by enzyme linked immunosorbent assay (ELISA) test. A JC-1 mitochondrial membrane potential detection kit was used to assess mitochondrial membrane damage and the adenosine triphosphate (ATP) assay kit was used to determine intracellular ATP levels. After the macrophages were stained with reactive oxygen species (ROS) specific dye, 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA), the fluorescence intensity and proportion of ROS-positive macrophages were measured using flow cytometry.Results We observed that compared with those of 0 μM (control group), concentrations of 5, 10, or 20 μΜ bilirubin significantly decreased cell viability, which was increased by bilirubin exposure below 1 μM. The effect of CSE on macrophage viability was concentration- and time-dependent. Bilirubin of 0.2 μM could alleviate the inhibition of macrophage viability caused by 5% CSE. In addition, bilirubin intervention could reduce the occurrence of necrosis and pyroptosis to a certain extent.Conclusions CSE could cause mitochondrial dysfunction in macrophages, as demonstrated by a decrease in mitochondrial membrane potential and intracellular ATP levels and an increase in ROS production, while bilirubin could relieve mitochondrial dysfunction caused by CSE.

More than 99 % of precancerous cervical lesions are associated with human papillomavirus (HPV) infection, with HPV types 16 and 18 (especially type 16) found in over 70 % of cervical cancer cases globally. The growth of HPV-positive cervical cancer depends on the sustained expression of the viral oncogenes E6 and E7, which are key factors in maintaining the malignant phenotype of HPV-positive tumor cells. E6 and E7 oncoproteins can cause the degradation of the tumor suppressor gene p53 and the inactivation of pRb, respectively, thereby inducing carcinogenesis. However, the inhibition of p53 and pRb cannot fully explain the oncogenic mechanism of cervical cancer. Although the development of the HPV vaccine has controlled the incidence of HPV infection, its application and widespread adoption remain limited. In addition, many developing countries cannot afford the cost of vaccines. More importantly, the vaccine only prevents HPV infection and does not provide an effective treatment for patients who are already infected or have cervical cancer. Therefore, HPV-related diseases, especially cervical cancer, remain a serious challenge. This article reviews the role of glucose metabolism changes and key molecular events in HPV-induced cervical cancer, summarizes potential targets for the treatment of cervical cancer, and provides strategies for future clinical treatment. It also offers a theoretical basis for research into cervical cancer and other HPV-related tumors. Furthermore, we discuss potential treatments for HPV-associated cervical cancer through targeted metabolic pathways and analyze the risks and challenges of current targeted glucose metabolism therapies for cervical cancer.