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Abstract Chronic alcohol consumption can lead to alcohol live disease (ALD). Steatosis is a critical hallmark of ALD, making it an important stage for therapeutic intervention. Saikosaponin A (SSa), a compound found in Radix Bupleuri, has previously shown promising hepatoprotective, anti-inflammatory, and antioxidant properties. However, its role in ALD remains understudied. We employ cell-based screening models and a chronic-plus-binge ethanol-fed mouse model to investigate the protective mechanisms of SSa and its metabolite Saikogenin A (SGA), against ethanol-induced hepatocyte injury. Our RNA-seq analysis in mice unveils that SSa primarily acts through the mTOR and PPAR-α signaling pathways in the liver. Biophysical assays and loss of function experiments confirm SGA directly binds to and modulates the activity of SIRT1 protein, mitigating ethanol-induced cell injury via the SIRT1-mTOR-PPAR-α axis. Furthermore, SGA displays a survival prolonging advantage compared to resveratrol for treating ALD. This suggests SGA holds promise as a potential therapeutic agent for ALD.

In response to the unclear understanding of fracture propagation and intersection interference in zipper fracturing under the factory development model of deep shale gas wells, a coupled hydro-mechanical model for zipper fracturing considering the influence of natural fracture zones was established based on the finite element – discrete element method. The reliability of the model was verified using experimental data and field monitoring pressure increase data. Taking the deep shale gas reservoir in southern Sichuan as an example, the propagation and interference laws of fracturing fractures under the influence of natural fracture zones with different characteristics were studied. The results show that the large approaching angle fracture zone has a blocking effect on the forward propagation of fracturing fractures and the intersection of inter well fractures. During pump shutdown, hydraulic fractures exhibit continued expansion behavior under net pressure driving. Under high stress difference, as the approaching angle of the fracture zone increases, the response well pressure increase and the total length of the fractured fracture show a trend of first decreasing and then increasing, and first increasing and then decreasing, respectively. Compared to small approach angle fracture zones, natural fracture zones with large approach angles require longer time and have greater difficulty to intersect. The width of fractures and the length of natural fractures are negatively and positively correlated with the response well pressure increase, respectively, and positively and negatively correlated with the time required for intersection, the total length of hydraulic fractures, and fracturing efficiency, respectively. As the displacement distance of the well increases, the probability of fracture intersection decreases, but the regularity between displacement distance and the response well pressure increase and the total length of fractures is not obvious.

Abstract The expression and biological function of junctional adhesion molecule-like protein (JAML) in colorectal cancer (CRC) remain unclear. Paraffin tissue samples from 50 cases of CRC were collected to determine the expression of JAML. JAML was overexpressed or knock-down in CRC cells to evaluated the proliferation, migration and invasion in vitro and in vivo. Western-blot and others were applied to explore the mechanisms. The study showed that JAML was highly expressed within cancer tissues in 50% (25/50) of patients with CRC, and was correlated with higher TNM stage (p

Abstract Previous studies have reported that senolytic drugs can reverse obesity-mediated accumulation of senescent cells in the ovary and protect against cisplatin-induced ovarian injury by removing senescent cells. Early intervention with ABT-263 has been shown to mitigate ovarian aging. However, it remains unknown whether treatment with ABT-263 could rejuvenate the aged ovary in reproductively old females. Therefore, the current study was aimed to investigate whether advanced age intervention with ABT-263 could ameliorate age-related decline in ovarian function. Fourteen 16-month-old mice with a C57/BL6 background were treated with ABT-263 (N = 7) or vehicle (N = 7) for two weeks. Mice were initially treated with ABT-263 (60 mg/kg/d) or vehicle for 7 consecutive days. After a 7-day break, the treatment was repeated for another 7 consecutive days. Six 2-month-old mice with C57BL/6 were used as a young control. The hormonal levels, estrus cycles, ovarian reserve, ovarian cell proliferation and apoptosis, ovarian fibrosis, and steroidogenic gene expression of ovarian stromal cells were evaluated. ABT-263 treatment did not rescue abnormal estrus cycles and sex hormonal levels, or inhibit the formation of multinucleated giant cells and ovarian stromal cell apoptosis in aged ovaries. However, it reduced ovarian fibrosis and preserved the steroidogenic gene expression of ovarian stromal cells in aged ovaries. Importantly, ABT-263 treatment further depleted ovarian follicles in aged mice. In conclusion, ABT-263 treatment accelerated the depletion of ovarian follicles in aged mice, suggesting that senolytic drugs for reproductively old female may adversely affect female fertility.

Abstract Video Anomaly Detection (VAD) has been an active research field for several decades. However, most existing approaches merely extract a single type of feature from videos and define a single paradigm to indicate the extent of abnormalities. A coarse‐to‐fine three‐level prediction is built by integrating different levels of spatio‐temporal representations, better highlighting the difference between normal and abnormal behaviors. First, an object‐level trajectory prediction is proposed to model human historical position using a graph transformer network. Subsequently, skeleton‐level prediction is achieved by incorporating the positional information from the trajectory prediction. More importantly, based on the predicted skeleton, a skeleton‐guided pixel‐level region prediction is performed. A novel Skeleton Conditioned Generative Adversarial Network (SCGAN) is designed to explore the correlation between skeleton‐level and pixel‐level motion prediction. Benefiting from SCGAN, the prediction of human regions is contributed by both coarse‐grained and fine‐grained motion features. This three‐level prediction, namely Progressive Prediction Video Anomaly Detection (P3VAD), enlarges the prediction error on irregular motion patterns. Besides, a pixel‐level analysis method is proposed to achieve Background‐bias Elimination (BE) and denoise the predicted region. Experimental results validate the effectiveness of P3VAD on the four benchmark datasets (ShanghaiTech, CUHK Avenue, IITB‐Corridor, and ADOC).

The safety and clinical effectiveness of preimplantation genetic testing for aneuploidy (PGT-A) in improving pregnancy outcomes for sub-fertile patients remains controversial. Potential sex-based differences in the relationship between PGT-A and pregnancy complications have not been investigated, which could guide the appropriate clinical application of PGT-A. In this secondary analysis of data from a multicenter, randomized, controlled, non-inferiority trial (NCT03118141), 940 women who achieved singleton live birth during the trial were included to estimate the between-group differences in pregnancy complications following PGT-A versus conventional in vitro fertilization (IVF) vary with fetal sex. Logistic regression analysis was used to adjust for possible confounders, and subgroup analysis was also performed. Among male fetuses, the risk of maternal preeclampsia was significantly lower after PGT-A compared to conventional IVF treatment (3.37% vs. 7.88%; adjusted OR, 0.40; 95% CI, 0.17-0.92; P = 0.032). However, this protective effect was not observed in pregnancies with female fetuses (3.63% vs. 3.38%; adjusted OR, 1.04; 95% CI, 0.36-3.00; P = 0.937). In addition, no significant sex-dependent differences in the risks of other pregnancy complications or neonatal outcomes were detected between PGT-A and conventional IVF groups (P > 0.05). In summary, PGT-A was associated with a decreased risk of maternal preeclampsia in singleton pregnancies with male fetuses, highlighting its potential utility in preeclampsia prevention in addition to spontaneous abortion rate reduction.

ObjectiveTo summarize the general situation and focal points of research on the physical activity and mental health of older people over the past 15 years and provide references for future research.MethodsLiterature published between January 1, 2009, and December 31, 2023, was retrieved from the Web of Science core database. A bibliometric visualization analysis of countries/regions, institutions, authors, keywords, and references was conducted using CiteSpace6.1.R6.ResultsA total of 4,329 articles were included, and the annual number of articles published over the past 15 years showed an upward trend. The articles were primarily from 65 countries/regions and 626 institutions. The most represented country and institution were the USA and the University of Pittsburgh, respectively. Among the authors identified, Schuch and Callow were the most influential. The research focuses on four areas: the psychological effects of physical activity in older people; physical activity intervention approaches to the mental health of older people; physical activity and mental health assessment questionnaires; and the impact of physical activity on multidimensional aging. Research frontiers involve emerging topics such as the assessment and intervention of mental health in older people and the relationship between their physical activity and cognitive function.ConclusionThis study conducted a comprehensive, objective, and visual analysis of publications and revealed the status of relevant studies, trending topics, and trends concerning the physical activity and mental health of older people from 2009 to 2023. We hope that this work will help researchers identify new perspectives on potential collaborators, important topics, and research frontiers.

Background Retrospective analysis to identify the risk factors for air embolism following computed tomography (CT)-guided percutaneous transthoracic needle biopsy (TNB). Methods A retrospective analysis of patients who underwent CT-TNB at The First Affiliated Hospital of Zhengzhou University and Xuzhou Cancer Hospital from January 2017 to December 2021 was performed. A total of 21 factors relevant to air embolisms were collected. Risk factors associated with air embolisms were determined by the least absolute shrinkage and selection operator (LASSO). The receiver-operator characteristic (ROC) was used to assess the ability of these factors to identify air embolisms. Results Of these 32,748 patients, 28 experienced air embolisms (19 at The First Affiliated Hospital of Zhengzhou University (incidence, 1.46%) and nine at Xuzhou Cancer Hospital (incidence, 0.69%); total incidence, 2.16%). Only seven patients exhibited symptoms (symptom rate, 25.00%). A total of 21 patients were asymptomatic at the time of swept-source CT. No deaths occurred. We found through univariate and multivariate analysis that eight out of these 21 factors are associated with the occurrence of air embolism. The area under the ROC curve was 0.721, indicating good predictive power (P

ObjectiveThis study examines the epidemiology of Mycoplasma pneumoniae (M. pneumoniae) infections among children in Suzhou, China, during various pandemic phases. The goal is to discern evolving epidemic trends and to furnish robust evidence for clinical diagnosis and treatment.MethodsFrom January 1, 2016, to December 31, 2023, 113,625 consecutive patients with respiratory infections from three hospitals in Suzhou, China (Children’s Hospital of Soochow University, Children’s Hospital of Wujiang District, and Affiliated Suzhou Hospital of Nanjing University Medical School), were retrospectively enrolled in a surveillance study. Additionally, in 2023, children hospitalized with M. pneumoniae pneumonia at the Children’s Hospital of Soochow University were tested for genotype (P1 gene typing, SNP genotyping) and macrolide resistance in their bronchoalveolar lavage fluid.ResultsFrom 2016 to 2023, the M. pneumoniae positive detection rate among pediatric respiratory infections fell from a pre-pandemic 21.1% to pandemic lows, then surged to 45.3% post-pandemic. Before the pandemic, peak M. pneumoniae infection rates occurred in summer, followed by autumn. Post-pandemic, the highest peak rates were in autumn. Peak M. pneumoniae detection rates occurred in 2019 and 2023, with a notable increase in children aged 6 and older in 2023. In this study, 200 M. pneumoniae-positive bronchoalveolar lavage fluid (BALF) cases in 2023 were randomly selected and analyzed for P1 genotype and SNP genotype. Among 156 cases, 81.4% were P1 genotype and 18.6% were P2 genotype. The proportion of severe M. pneumoniae pneumonia with the P1 type was significantly higher than that with the P2 type (p

Anthocyanins in maize (Zea mays L.) kernels determine the plant’s color and can enhance its resistance. Selenium (Se) significantly impacts plant growth, development, and secondary metabolic regulation. However, the molecular mechanisms by which Se regulates anthocyanin synthesis in waxy corn remain unclear. This study employed integrated transcriptomic and metabolomic analyses to investigate the mechanisms through which selenium influences anthocyanin synthesis in yellow and purple waxy corn. The results showed that maize varieties with higher anthocyanin content had higher selenium enrichment capacity in their kernels. Under selenium stress, HN2025 exhibited 1,904 more differentially expressed genes (DEGs) and 140 more differential metabolites compared to HN5. The expression levels of anthocyanin synthesis-related genes and transcription factors such as phenylalanine ammonia-lyase, flavonoid 3-hydroxylase (F3H), dihydroflavonol reductase (DFR), chalcone synthase (CHS), cinnamate-4-hydroxylase (C4H), anthocyanin 5,3-O-glucosyltransferases, and anthocyanidin reductase, MYB, and bHLH were strongly induced in HN2025. Metabolomic analysis revealed significant enrichment in anthocyanin biosynthesis, flavonoid and flavonol biosynthesis, glutathione metabolism, phenylalanine biosynthesis, and phenylalanine metabolism under selenium treatment. Three up-regulated PAL genes and one C4H gene were significantly enriched with DAMs in phenylalanine metabolism, phenylpropanoid biosynthesis, flavonoid biosynthesis, and anthocyanin biosynthesis, resulting in significant differences between HN5 and HN2025 in selenium-induced anthocyanin metabolism-related pathways. These findings provide a theoretical basis for understanding the effects of selenium on the molecular regulatory mechanisms of anthocyanin biosynthesis in maize kernels.

IntroductionCytokine release syndrome (CRS) is one of the leading causes of mortality in patients with COVID-19 caused by the SARS-CoV-2 coronavirus. However, the mechanism of CRS induced by SARS-CoV-2 is vague.MethodsUsing spike protein combined with IL-2, IFN-γ, and TNF-α to stimulate human peripheral blood mononuclear cells (PBMCs) to secrete CRS-related cytokines, the content of cytokines in the supernatant was detected, and the effects of NK, T, and monocytes were analyzed.ResultsThis study shows that dendritic cells loaded with spike protein of SARS-CoV-2 stimulate T cells to release much more interleukin-2 (IL-2,) which subsequently cooperates with spike protein to facilitate PBMCs to release IL-1β, IL-6, and IL-8. These effects are achieved via IL-2 stimulation of NK cells to release tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), as well as T cells to release IFN-γ Mechanistically, IFN-γ and TNF-α enhance the transcription of CD40, and the interaction of CD40 and its ligand stabilizes the membrane expression of toll-like receptor 4 (TLR4) that serves as a receptor of spike protein on the surface of monocytes. As a result, there is a constant interaction between spike protein and TLR4, leading to continuous activation of nuclear factor-κ-gene binding (NF-κB). Furthermore, TNF-α also activates NF-κB signaling in monocytes, which further cooperates with IFN-γ and spike protein to modulate NF-κB–dependent transcription of CRS-related inflammatory cytokines.DiscussionTargeting TNF-α/IFN-γ in combination with TLR4 may represent a promising therapeutic approach for alleviating CRS in individuals with COVID-19.

Oxytocin (OT) is a posterior pituitary hormone that, in addition to its role in regulating childbirth and lactation, also exerts direct regulatory effects on the skeleton through peripheral OT and oxytocin receptor (OTR). Bone marrow mesenchymal stem cells (BMSCs), osteoblasts (OB), osteoclasts (OC), chondrocytes, and adipocytes all express OT and OTR. OT upregulates RUNX2, BMP2, ALP, and OCN, thereby enhancing the activity of BMSCs and promoting their differentiation towards OB rather than adipocytes. OT also directly regulates OPG/RANKL to inhibit adipocyte generation, increase the expression of SOX9 and COMP, and enhance chondrocyte differentiation. OB can secrete OT, exerting influence on the surrounding environment through autocrine and paracrine mechanisms. OT directly increases OC formation through the NκB/MAP kinase signaling pathway, inhibits osteoclast proliferation by triggering cytoplasmic Ca2+ release and nitric oxide synthesis, and has a dual regulatory effect on OCs. Under the stimulation of estrogen, OB synthesizes OT, amplifying the biological effects of estrogen and OT. Mediated by estrogen, the OT/OTR forms a feedforward loop with OB. Apart from estrogen, OT also interacts with arginine vasopressin (AVP), prostaglandins (PGE2), leptin, and adiponectin to regulate bone metabolism. This review summarizes recent research on the regulation of bone metabolism by OT and OTR, aiming to provide insights into their clinical applications and further research.

In the process of high-speed additive manufacturing, machining defects such as low surface accuracy, high surface roughness, residual stresses and micro-cracks have a serious impact on the performance and life of the product. These machining defects need to be removed by post-treatment in order to promote the use of additive manufactured parts in industrial production. This article provides a systematic review of existing post-treatment technologies for additive manufactured parts, divided into surface post-treatment technologies and overall post-treatment technologies. The processing cost expenditure of the most common post-processing methods is analyzed. The core values and key metrics of post-processing are explored. The prospects for post-processing technology for additive manufactured parts in six key development directions are discussed. The present review systematically discusses the process capabilities and research developments of post-processing technologies for high-speed additive manufacturing, taking into account knowledge from both basic and applied research areas.

Abstract Cerebral ischemic stroke (CIS) has the characteristics of a high incidence, disability, and mortality rate. Here, we aimed to explore the potential pathogenic mechanisms of ferroptosis-related genes (FRGs) in CIS. Three microarray datasets from the Gene Expression Omnibus (GEO) database were utilized to analyze differentially expressed genes (DEGs) between CIS and normal controls. FRGs were obtained from a literature report and the FerrDb database. Weighted gene co-expression network analysis (WGCNA) and protein–protein interaction (PPI) network were used to screen hub genes. The receiver operating characteristic (ROC) curve was adopted to evaluate the diagnostic value of key genes in CIS, followed by analysis of immune microenvironment, transcription factor (TF) regulatory network, drug prediction, and molecular docking. In total, 128 CIS samples were divided into 2 subgroups after clustering analysis. Compared with cluster A, 1560 DEGs were identified in cluster B. After the construction of the WGCNA and PPI network, 5 hub genes, including MAPK3, WAS, DNAJC5, PRKCD, and GRB2, were identified for CIS. Interestingly, MAPK3 was a FRG that differentially expressed between cluster A and cluster B. The expression levels of 5 hub genes were all specifically highly in cluster A subtype. It is noted that neutrophils were the most positively correlated with all 5 real hub genes. PRKCD was one of the target genes of FASUDIL. In conclusion, five real hub genes were identified as potential diagnostic markers, which can distinguish the two subtypes well.

Abstract Background The Quick Delay Questionnaire (QDQ) is a short questionnaire designed to assess delay-related difficulties in adults. This study aimed to examine the reliability and validity of the Chinese version of the QDQ (C-QDQ) in Chinese adults, and explore the ecological characteristics of delay-related impulsivity in Chinese adults with attention-deficit/hyperactivity disorder (ADHD). Methods Data was collected from 302 adults, including ADHD (n = 209) and healthy controls (HCs) (n = 93). All participants completed the C-QDQ. The convergent validity, internal consistency, retest reliability and confirmatory factor analysis (CFA) of the C-QDQ were analyzed. The correlations between C-QDQ and two laboratory measures of delay-related difficulties and Barratt Impulsiveness Scale-11 (BIS-11), the comparison of C-QDQ scores between ADHD subgroups and HCs were also analyzed. Results The Cronbach’s α of C-QDQ was between 0.83 and 0.89. The intraclass correlation coefficient of C-QDQ was between 0.80 and 0.83. The results of CFA of C-QDQ favoured the original two-factor model (delay aversion and delay discounting). Significant positive associations were found between C-QDQ scores and BIS-11 total score and performance on the laboratory measure of delay-related difficulties. Participants with ADHD had higher C-QDQ scores than HCs, and female ADHD reported higher scores on delay discounting subscale than male. ADHD-combined type (ADHD-C) reported higher scores on delay aversion subscale than ADHD-inattention type (ADHD-I). Conclusion The C-QDQ is a valid and reliable tool to measure delay-related responses that appears to have clinical utility. It can present the delay-related impulsivity of patients with ADHD. Compared to HCs, the level of reward-delay impulsivity was higher in ADHD.

Abstract Background Visual-motor integration (VMI) is an essential skill in daily life. The present study aimed to use functional near-infrared spectroscopy (fNIRS) technology to explore the effective connectivity (EC) changes among brain regions during VMI activities of varying difficulty levels. Methods A total of 17 healthy participants were recruited for the study. Continuous Performance Test (CPT), Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A), and Beery VMI test were used to evaluate attention performance, executive function, and VMI performance. Granger causality analysis was performed for the VMI task data to obtain the EC matrix for all participants. One-way ANOVA analysis was used to identify VMI load-dependent EC values among different task difficulty levels from brain network and channel perspectives, and partial correlation analysis was used to explore the relationship between VMI load-dependent EC values and behavioral performance. Results We found that the EC values of dorsal attention network (DAN) → default mode network (DMN), DAN → ventral attention network (VAN), DAN → frontoparietal network (FPN), and DAN → somatomotor network (SMN) in the complex condition were higher than those in the simple and moderate conditions. Further channel analyses indicated that the EC values of the right superior parietal lobule (SPL) → right superior frontal gyrus (SFG), right middle occipital gyrus (MOG) → left SFG, and right MOG → right postcentral gyrus (PCG) in the complex condition were higher than those in the simple and moderate conditions. Subsequent partial correlation analysis revealed that the EC values from DAN to DMN, VAN, and SMN were positively correlated with executive function and VMI performance. Furthermore, the EC values of right MOG → left SFG and right MOG → right PCG were positively correlated with attention performance. Conclusions The DAN is actively involved during the VMI task and thus may play a critical role in VMI processes, in which two key brain regions (right SPL, right MOG) may contribute to the EC changes in response to increasing VMI load. Meanwhile, bilateral SFG and right PCG may also be closely related to the VMI performance.

Objectives Accurate epidemiological data are crucial for effective disease prevention and treatment. We conducted a large-scale survey to explore the thalassaemia prevalence and spectrum among the two major ethnic groups in Hainan Province.Methods A total of 399,053 childbearing-age individuals of Li (n = 77,563) and Han(n = 321,490) ethnic groups were recruited from 18 cities and counties in Hainan, and their thalassemia genotypes were systematically screened and statistically analysed.Results This study revealed a significantly higher thalassaemia carrier rate in the Li (55.39%) than that in the Han (13.13%). Specifically, the carrier rate of α-thalassaemia was 46.39% in the Li and 10.02% in the Han. The predominant α-thalassaemia mutations were – α3.7 and – α42. in Li, whereas the main mutation were – SEA and – α4.2 in Han. For β-thalassaemia, the carrier rates were 1.68% in Li and 2.38% in Han, with CD41-42(-CTTT) the most prevalent mutation in both groups. The carrier rates of β-/α-compound thalassaemia were 7.32% in Li and 0.73% in Han. Additionally, there were regional differences in the distribution of thalassemia among the Li and Han within Hainan Province.Conclusion Epidemiological characteristics and molecular spectrum of thalassaemia among the Li and Han ethnic groups in Hainan were revealed in this study. These findings can provide a scientific basis to develop and implement prevention strategies for thalassaemia in Hainan.

Abstract Considerable progress has been made in the development of drug delivery systems for diabetic wounds. However, underlying drawbacks, such as low delivery efficiency and poor tissue permeability, have rarely been addressed. In this study, a multifunctional biohybrid nanorobot platform comprising an artificial unit and several biological components is constructed. The artificial unit is a magnetically driven nanorobot surface modified with antibacterial 2‐hydroxypropyltrimethyl ammonium chloride chitosan, which enables the entire platform to move and has excellent tissue penetration capacity. The biological components are two‐step engineered extracellular vesicles that are first loaded with mangiferin, a natural polyphenolic compound with antioxidant properties, and then glycoengineered on the surface to enhance cellular uptake efficiency. As expected, the platform is more easily absorbed by endothelial cells and fibroblasts and exhibits outstanding dermal penetration performance and antioxidant properties. Encouraging results are also observed in infected diabetic wound models, showing improved wound re‐epithelialization, collagen deposition, angiogenesis, and accelerated wound healing. Collectively, a biohybrid nanorobot platform that possesses the functionalities of both artificial units and biological components serves as an efficient delivery system to promote diabetic wound repair through dual‐enhanced cell and tissue penetration and multistep interventions.

BackgroundThe implementation of a zero-COVID policy for 3 years in China during the COVID-19 pandemic significantly impacted a broad spectrum of acute respiratory tract infections (ARTIs). The epidemiological characteristics of ARTI pathogens in children following the cessation of the zero-COVID policy remain unclear.MethodsEtiologically diagnostic data from 82,708 children with ARTIs at the Children’s Hospital of Soochow University during 2016–2023 were analyzed for 8 pathogens (human respiratory syncytial virus [HRSV], influenza A [FluA], FluB, human parainfluenza virus [HPIV], adenovirus [ADV], human rhinovirus [HRV], bocavirus [BoV], and mycoplasma pneumoniae [MP]). The changes in respiratory infections in Suzhou, China during the first year (2020, Phase I) and the second and third years of the pandemic (2021–2022, Phase II) and the first year after the end of zero-COVID policy (2023, Phase III) versus that in the pre-pandemic years (2016–2019) were compared.ResultsWhen compared with the average pre-pandemic levels, the pathogen-positive rate decreased by 19.27% in Phase I (OR: 0.70; 95% CI: 0.67–0.74), increased by 32.87% in Phase II (OR: 1.78; 95% CI: 1.72–1.84), and increased by 79.16% in Phase III (OR: 4.58; 95% CI: 4.37–4.79). In Phase I, the positive rates of HRSV, FluA, ADV, and MP decreased by 26.72, 58.97, 72.85, and 67.87%, respectively, and the positive rates of FluB, HPIV, HRV, and BoV increased by 86.84, 25, 32.37, and 16.94%, respectively. In Phase III, the positive rates of HRSV, FluA, FluB, HPIV, ADV, and HRV increased by 39.74, 1046.15, 118.42, 116.57, 131.13, and 146.40%, respectively, while the positive rate of BoV decreased by 56.12%. MP was inhibited during the epidemic, and MP showed a delayed outbreak after the ending of the zero-COVID policy. Compared with the average pre-pandemic levels, the MP-positive rate in Phase III increased by 116.7% (OR: 2.86; 95% CI: 2.74–2.99), with the highest increase in 0–1-year-old children.ConclusionThe strict and large-scale implementation of the zero-COVID policy in the early stages of the COVID-19 pandemic was the main driving factor for the sharp reduction in the rate of children’s respiratory pathogenic infections. The termination of this policy can cause a resurgence or escalation of pathogenic infections.

BackgroundCatheter-related thrombosis (CRT) is a common complication for patients who receive central venous catheter (CVC) placement. This study investigated the risk factors for CRT and developed a nomogram for CRT prediction among cancer patients.MethodsThis nested case-control study was conducted in the Third Affiliated Hospital of Kunming Medical University between January 2019 and February 2021. Univariable and multivariable logistic regression analyses were used to identify the risk factors for CRT. A nomogram was developed to predict CRT. Receiver operating curves (ROC), calibration curves, and decision curves were used to evaluate the performance of the nomogram in the training and validation sets.ResultsA total of 4,691 cancer patients were included in this study. Among them, 355 (7.57%) had CRT, and 70% of CRTs occurred in the first week of insertion. Among the 3,284 patients in the training set, the multivariable analysis showed that nine characteristics were independently associated with CRT, and a nomogram was constructed based on the multivariable analysis. The ROC analysis indicated good discrimination in the training set (area under the curve [AUC] = 0.832, 95% CI: 0.802–0.862) and the testing set (AUC = 0.827, 95% CI: 0.783–0.871) for the CRT nomogram. The calibration curves showed good calibration abilities, and the decision curves indicated the clinical usefulness of the prediction nomograms.ConclusionThe validated nomogram accurately predicts CRT occurrence in cancer patients. This model may assist clinicians in developing treatment plans for each patient.

ABSTRACT Objective: Tibial plateau fractures are common intra-articular fractures that pose classification and treatment challenges for orthopedic surgeons. Objective: This study examines the value of 3D printing for classifying and planning surgery for complex tibial plateau fractures. Methods: We reviewed 54 complex tibial plateau fractures treated at our hospital from January 2017 to January 2019. Patients underwent preoperative spiral CT scans, with DICOM data processed using Mimics software. 3D printing technology created accurate 1:1 scale models of the fractures. These models helped subdivide the fractures into seven types based on the tibial plateau's geometric planes. Surgical approaches and simulated operations, including fracture reduction and plate placement, were planned using these models. Results: The 3D models accurately depicted the direction and extent of fracture displacement and plateau collapse. They facilitated the preoperative planning, allowing for precise reconstruction strategies and matching intraoperative details with the pre-printed models. Post-surgery, the anatomical structure of the tibial plateau was significantly improved in all 54 cases. Conclusion: 3D printing effectively aids in the classification and preoperative planning of complex tibial plateau fractures, enhancing surgical outcomes and anatomical restoration. Level of Evidence IV, Prospective Study.

The monolithically integrated self-driven photoelectric detector (PD) with the light-emitting diode (LED) epitaxial structure completely relies on the built-in electric field in the multi-quantum wells region to separate the photogenerated carriers. Here, we propose a novel superlattices–electron barrier layer structure to expand the potential field region and enhance the detection capability of the integrated PD. The PD exhibits a record-breaking photo-to-dark current ratio of 5.14 × 107, responsivity of 110.3 A/W, and specific detectivity of 2.2 × 1013 Jones at 0 V bias, respectively. A clear open-eyed diagram of the monolithically integrated chip, including the PD, LED, and waveguide, is realized under a high-speed communication rate of 150 Mbps. The obtained transient response (rise/decay) time of 2.16/2.28 ns also illustrates the outstanding transient response capability of the integrated chip. The on-chip optical communication system is built to achieve the practical video signals transmission application, which is a formidable contender for the core module of future large-scale photonic integrated circuits.

Abstract Background The current study aims to explore the relationship between tumor necrosis factor‐α (TNF‐α) polymorphism and the risk of primary nephrotic syndrome (PNS). Methods A total of 250 PNS patients were selected for this study, as well as 300 volunteers serving as the control group. TNF‐α polymorphism were assessed using the polymerase chain reaction‐restriction fragment length polymorphism method. In addition, a meta‐analysis was conducted to analyze previously published literature on this topic. Results No significant differences were observed in the genotypes frequency or alleles frequency among the study populations. Meta‐analysis results revealed a positive association between TNF‐α rs1800629 polymorphism and allele contrast in African populations (p = 0), homozygote comparison (p = .007), heterozygote comparison (p = .026), recessive genetic model (p = .011), and dominant genetic model (p = .000). Conclusions TNF‐α rs1800629 polymorphism does not appear to confer any increased risk for PNS.

Abstract The properties of rockfalls, such as the volume and geometry of the detached rock mass as well as the number and diameter of rock fragments, greatly affect their propagated behavior, and different strategies are required to mitigate rockfall hazards. Landquakes generated by rockfalls are regarded as good proxies for those properties. To explore the free‐fall impact dynamics of rockfalls, a series of free‐fall experiments on granular masses were designed and conducted with the characteristics of the generated landquakes versus initial variables being analyzed. The results show that the particle diameter is a dominant factor affecting landquakes, with the most significant effect on the mean frequency. The impact area is another key factor, with which both the maximum seismic amplitude and radiated seismic energy have strong positive correlations, while the mean frequency of landquakes shows a weak negative correlation. The maximum seismic amplitude appears to have a poor correlation with the numbers of layers of the free‐falling granular masses, and it was proven that the maximum seismic amplitude is determined by only the lower part of the granular masses. Quantitative relationships between the number of particles and seismic signal characteristics indicate that disintegration needs to be accounted for when landquakes are used to investigate the characteristics of a rockfall. Moreover, the frequency of landquakes decreases with a decrease in the vertical velocity and increase in the horizontal velocity during granular mass collapse.

Under a full straw returning system, the relationship between soil bacterial community diversity and straw decomposition, yield, and the combined application of slow-release nitrogen and urea remains unclear. To evaluate these effects and provide an effective strategy for sustainable agricultural production, a 2-year field positioning trial was conducted using maize as the research object. Six experimental treatments were set up: straw returning + no nitrogen fertilizer (S1N0), straw returning + slow-release nitrogen fertilizer:urea = 0:100% (S1N1), straw returning + slow-release nitrogen fertilizer:urea = 30%:70% (S1N2), straw returning + slow-release nitrogen fertilizer:urea = 60%:40% (S1N3), straw returning + slow-release nitrogen fertilizer:urea = 90%:10% (S1N4), and straw removal + slow-release nitrogen fertilizer:urea = 30%:70% (S0N2). Significant differences (p

Abstract Background Professional misconduct has evolved into a worldwide concern, involving various forms and types of behaviours that contribute to unsafe practices. This study aimed to provide insights into the patterns characterising pharmacist misconduct and uncover underlying factors contributing to such instances in New Zealand. Methods This research examined all cases of pharmacist misconduct sourced from the Health Practitioners Disciplinary Tribunal (HPDT) database in New Zealand since 2004. Characteristics of the sampled pharmacists and cases were extracted, followed by a systematic coding of the observed misconduct issues. Identification of risk factors was accomplished through content analysis techniques, enabling an assessment of their prevalence across various forms of misconduct. Results The dataset of pharmacist misconduct cases comprised 58 disciplinary records involving 55 pharmacists. Seven types of misconduct were identified, with the most commonly observed being quality and safety issues related to drug, medication and care, as well as criminal conviction. A total of 13 risk factors were identified and systematically classified into three categories: (1) social, regulatory, and external environmental factors, (2) systematic, organisational, and practical considerations in the pharmacy, and (3) pharmacist individual factors. The most frequently mentioned and far-reaching factors include busyness, heavy workload or distraction; health impairment issues; and life stress or challenges. Conclusions The patterns of pharmacist misconduct are complicated, multifaceted, and involve complex interactions among risk factors. Collaborative efforts involving individual pharmacists, professional bodies, responsible authorities, policy-makers, health funders and planners in key areas such as pharmacist workload and well-being are expected to mitigate the occurrence of misconduct. Future research should seek to uncover the origins, manifestations, and underlying relationships of various contributing factors through empirical research with appropriate individuals.

Highlights A lamellar-structured fluorinated cellulose nanofiber aerogel film is prepared by filtration-induced delaminated gelation and ambient drying. The aerogel film demonstrates exceptional mechanical flexibility and resistance to complex deformations. The aerogel film displays low thermal conductivity, high visible-light transmittance and superior selective infrared emissivity, rendering it high solar-thermal regulatory cooling performance.

Based on the elastic theory of porous media, embedded discrete fracture model and finite volume method, and considering the micro-seepage mechanism of shale gas, a fully coupled seepage-geomechanical model suitable for fractured shale gas reservoirs is established, the optimization method of refracturing timing is proposed, and the influencing factors of refracturing timing are analyzed based on the data from shale gas well in Fuling of Sichuan Basin. The results show that due to the depletion of formation pressure, the percentage of the maximum horizontal principal stress reversal area in the total area increases and then decreases with time. The closer the area is to the hydraulic fracture, the shorter the time for the peak of the stress reversal area percentage curve to appear, and the shorter the time for the final zero return (to the initial state). The optimum time of refracturing is affected by matrix permeability, initial stress difference and natural fracture approach angle. The larger the matrix permeability and initial stress difference is, the shorter the time for stress reversal area percentage curve to reach peak and return to the initial state, and the earlier the time to take refracturing measures. The larger the natural fracture approach angle is, the more difficult it is for stress reversal to occur near the fracture, and the earlier the optimum refracturing time is. The more likely the stress reversal occurs at the far end of the artificial fracture, the later the optimal time of refracturing is. Reservoirs with low matrix permeability have a rapid decrease in single well productivity. To ensure economic efficiency, measures such as shut-in or gas injection can be taken to restore the stress, and refracturing can be implemented in advance.

The vehicle routing problem with time windows (VRPTW) is a well-known NP-Hard combinatorial optimization problem, which is frequently encountered in transportation and logistics scenarios. When traditional algorithms solve this problem, there are some problems, such as slow convergence speed. In this paper, a Self-competitive Particle Swarm Optimization (ScPSO) algorithm is proposed, which regulates the learning direction of the next generation of particles based on their degree of self-competition. When the particle’s self-competition degree is low, it is compelled to learn from the individual optimal solution using the self-competition selection probability, thereby achieving rapid convergence. ScPSO uses the nonlinear inertia weight adaptive strategy to adjust the search preference in the search process, and it can balance the relationship between exploration and exploitation. Meanwhile, Random greedy heuristic selection and variable neighborhood search strategies are used in initial solution construction and constraint restriction. Finally, ScPSO is tested on 56 Solomon 100-customers benchmark problems and compared with four state-of-the-art VRPTW algorithms and best-known solutions reported on Solomon’s webpage.The running results of the ScPSO algorithm are better than four state-of-the-art VRPTW algorithms and best-known solutions reported on Solomon’s webpage. The experimental results show that ScPSO can solve VRPTW problems efficiently.

Abstract Background During human early placentation, a proportion of extravillous trophoblasts (EVTs) migrate to the maternal decidua, differentiating into endovascular EVTs to remodel spiral arteries and ensure the establishment of blood circulation at the maternal-fetal interface. Inadequate EVT migration and endovascular differentiation are closely associated with adverse pregnancy outcomes such as miscarriage. Activin A and fibronectin are both secretory molecules abundantly expressed at the maternal-fetal interface. Activin A has been reported to regulate EVT biological functions. However, whether fibronectin mediates activin A-promoted EVT migration and acquisition of endothelial-like phenotype as well as the underlying molecular mechanisms remain unknown. Additionally, the role of fibronectin in pregnancy establishment and maintenance warrants further investigation. Methods Primary and immortalized (HTR8/SVneo) human EVTs were used as in vitro study models. Cultured human first-trimester chorionic villous explants were utilized for ex vivo validation. A local fibronectin knockdown model in ICR mouse uteri, achieved by nonviral in vivo transfection with small interfering RNA (siRNA) targeting fibronectin 1 (si-Fn1), was employed to explore the roles of fibronectin in the establishment and maintenance of early pregnancy. Results Our results showed that activin A treatment significantly induced fibronectin 1 (FN1) mRNA expression and fibronectin protein production, which is essential for human trophoblast migration and endothelial-like tube formation. Both basal and activin A-upregulated fibronectin expression were abolished by the TGF-β type I receptor inhibitor SB431542 or siRNA-mediated knockdown of activin receptor-like kinase (ALK4) or SMAD4. Moreover, activin A-increased trophoblast migration and endothelial-like tube formation were attenuated following the depletion of fibronectin. Fibronectin knockdown via intrauterine siRNA administration reduced CD31 and cytokeratin 8 (CK8) expression at the maternal-fetal interface, resulting in a decrease in the number of implantation sites and embryos. Conclusions Our study demonstrates that activin A promotes trophoblast cell migration and acquisition of endothelial-like phenotype via ALK4-SMAD2/3-SMAD4-mediated fibronectin upregulation. Furthermore, through a local fibronectin knockdown model in mouse uteri, we found that the absence of fibronectin at the maternal-fetal interface impedes endovascular migration of trophoblasts and decidual vascularization, thereby interfering with early embryo implantation and the maintenance of pregnancy. These findings provide novel insights into placental development during early pregnancy establishment and contribute to the advancement of therapeutic approaches for managing pregnancy complications related to trophoblast dysfunction.

Abstract Recent technological breakthroughs in single-particle cryo-electron microscopy (cryo-EM) enable rapid atomic structure determination of biological macromolecules. A major bottleneck in the current single particle cryo-EM pipeline is the preparation of good quality frozen cryo-EM grids, which is mostly a trial-and-error process. Among many issues, preferred particle orientation and sample damage by air–water interface (AWI) are common practical problems. Here we report a method of applying metallo-supramolecular branched polymer (MSBP) in the cryo-sample preparation for high-resolution single-particle cryo-EM. Our data shows that MSBP keeps a majority of particles away from air–water interface and mitigates preferred orientation as verified by the analyses of apoferritin, hemagglutinin) trimer and various sample proteins. The use of MSBP is a simple method to improve particle distribution for high-resolution structure determination in single-particle cryo-EM.

Background: Drug-resistant tuberculosis (TB), especially multidrug-resistant tuberculosis (MDR-TB), constitutes a major obstacle to fulfill end TB strategy globally. Although fluoroquinolones (FQs), linezolid (LZD) and bedaquiline (BDQ) were classified as Group A drugs for MDR-TB treatment, our knowledge of the prevalence of TB which were resistant to Group A drugs in China is quite limited. Methods: In this study, we conducted a prospective multicenter surveillance study in China to determine the proportion of TB patients that were resistant to Group A drugs. A total of 1877 TB patients were enrolled from 2022 at four TB specialized hospitals. The drug susceptibility of isolated strains was conducted using the MGIT 960 system and the molecular mechanisms conferring drug resistance were investigated by Sanger sequencing. Results: 12.9% of isolates were resistant to levofloxacin (LFX), 13.2% were resistant to moxifloxacin (MOX), 0.2% were resistant to bedaquiline (BDQ), and 0.8% were resistant to linezolid (LZD). Totally, 14.0% and 0.4% were classified as multidrug resistant- (MDR-) and extensively drug resistant- (XDR-) TB. The drug resistance was more common in retreated TB cases compared to new cases. In addition, 70.0% of fluoroquinolone (FQ)-resistant isolates harbored mutations in the gyrA and gyrB gene. By contrast, the common drug-resistant mutations were only found in 50% BDQ-resistant and 20% LZD-resistant isolates. Conclusions: Our data demonstrate that approximate half of MDR -TB patients are resistant to fluoroquinolones, with extremely low prevalence of initial BDQ and LZD resistance. Findings from this study provide important implications for the current management of MDR-TB patients.

Abstract Janus particles, which have an attractive patch on the otherwise repulsive surface, have been commonly employed for anisotropic colloidal assembly. While current methods of particle synthesis allow for control over the patch size, they are generally limited to producing dome-shaped patches with a high symmetry (C∞). Here, we report on the synthesis of Janus particles with patches of various tunable shapes, having reduced symmetries ranging from C2v to C3v and C4v. The Janus particles are synthesized by partial encapsulation of an octahedral metal-organic framework particle (UiO-66) in a polymer matrix. The extent of encapsulation is precisely regulated by a stepwise, asymmetric dewetting process that exposes selected facets of the UiO-66 particle. With depletion interaction, the Janus particles spontaneously assemble into colloidal clusters reflecting the particles’ shapes and patch symmetries. We observe the formation of chiral structures, whereby chirality emerges from achiral building blocks. With the ability to encode symmetry and directional bonding information, our strategy could give access to more complex colloidal superstructures through assembly.

Abstract Collecting ground truth labels for hyperspectral image classification is difficult and time-consuming. Without an adequate number of training samples, hyperspectral image (HSI) classification is a challenging problem. Using generative adversarial networks (GANs) is a promising technique for solving this problem because GANs can learn features from both labeled and unlabeled samples. The cost functions widely used in current GAN methods are suitable for 2D nature images. Compared with natural images, HSIs have a simpler one-dimensional structure that facilitates image generation. Motivated by the one-dimensional spectral features of HSIs, we propose a novel semisupervised algorithm for HSI classification by introducing spectral angle distance (SAD) as a loss function and employing multilayer feature fusion. Since the differences between spectra can be quickly calculated using the spectral angle distance, the convergence speed of the GAN can be improved, and the samples generated by the generator model in the GAN are closer to the real spectrum. Once the entire GAN model has been trained, the discriminator can extract multiscale features of labeled and unlabeled samples. The classifier is then trained for HSI classification using the multilayer features extracted from a few labeled samples by the discriminator. The proposed method was validated on four hyperspectral datasets: Pavia University, Indiana Pines, Salinas, and Tianshan. The experimental results show that the proposed model provides very promising results compared with other related state-of-the-art methods.

Abstract Background Karyotype, as a basic characteristic of species, provides valuable information for fundamental theoretical research and germplasm resource innovation. However, traditional karyotyping techniques, including fluorescence in situ hybridization (FISH), are challenging and low in efficiency, especially when karyotyping aneuploid and polyploid plants. The use of low coverage whole-genome resequencing (lcWGR) data for karyotyping was explored, but existing methods are complicated and require control samples. Results In this study, a new protocol for molecular karyotype analysis was provided, which proved to be a simpler, faster, and more accurate method, requiring no control. Notably, our method not only provided the copy number of each chromosome of an individual but also an accurate evaluation of the genomic contribution from its parents. Moreover, we verified the method through FISH and published resequencing data. Conclusions This method is of great significance for species evolution analysis, chromosome engineering, crop improvement, and breeding.

ABSTRACTLymphangiogenesis plays pivotal roles in diverse physiological and pathological conditions. Steady direct-current electric fields (DC EFs) induce vascular endothelial behaviors related to angiogenesis have been observed. This study investigated the effects of DC EFs on the lymphangiogenic response of lymphatic endothelial cells (LECs). We demonstrated that EFs stimulation induced directional migration, reorientation, and elongation of human LECs in culture. These lymphangiogenic responses required VEGF receptor 3 (VEGFR-3) activation and were mediated through the PI3K-Akt, Erk1/2, and p38 MAPK signaling pathways in relation to the reorganization of the actin cytoskeleton. Our results indicate that endogenous EFs may play a role in lymphangiogenesis in vivo, and VEGFR-3 signaling activation may be involved in the cellular function of LECs driven by EFs.

A modified loess/chitosan composite (ML@CS) was prepared via solution. The microstructure and physicochemical properties of ML@CS were characterised via scanning electron microscope (SEM), Zeta potential, X-ray diffraction (XRD), Fourier transform infrared spectrum (FT-IR), and thermogravimetric analysis (TGA). An aqueous solution of methyl orange (MO) was used as simulated wastewater from which the influence of the initial concentration and pH of MO, the dosage amount and regeneration performance of ML@CS, adsorption temperature, and time on the adsorption effect of MO were systematically investigated. The adsorption kinetics, isothermal adsorption, and adsorption mechanism were also analysed. The results indicate that ML@CS had a good adsorption effect on MO. When the initial concentration of MO was 200 mg/L, pH was 5.0, and ML@CS dosage was 1.0 g/L, the adsorption equilibrium could be reached within 180 min at room temperature, and the equilibrium adsorption capacity and removal rate reached 199.52 mg/g and 99.75%, respectively. After five adsorption–desorption cycles, the MO removal rate remained above 82%. The adsorption behaviour of ML@CS for MO conforms to the pseudo–second–order kinetic model and the Langmuir isotherm adsorption model. The spontaneous exothermic process was mainly controlled by monolayer chemical adsorption and the physical adsorption only played an auxiliary role. ML@CS efficiently adsorbed MO in water and can be used as a high-efficiency, low-cost adsorbent for printing and dyeing wastewater treatment.

Green total factor productivity (GTFP) is critical to both the economic and ecological objectives of pig breeding. This research utilizes the SBM-ML model to calculate the GTFP of pig breeding in 381 counties within the Yangtze River Basin from 2014 to 2021. Then the GTFP is further decomposed into technical efficiency (MLEC) and technical progress (MLTC) to conduct in-depth exploration. The regression results reveal that: (1) Environmental regulation (ER) has significant double-threshold effects on GTFP, MLEC, and MLTC. (2) MLTC is the main force of GTFP growth, and stronger ER does not always lead to better GTFP growth. (3) GTFP is boosted by mechanization enhancement and industrial agglomeration limitation. (4) Counties in non-provincial capital cities and those closer to the river exhibit greater ER threshold effects. (5) Both pig price and transportation efficiency play a moderating role. (6) Further analysis demonstrates that ER simultaneously reduces pig production capacity and carbon emissions, as well as improves the water quality. And the reduction of ER, although beneficial for capacity, has a significant negative impact on GTFP. Finally, this study concludes with policy recommendations to boost the new quality productivity in the pig industry.

Solanum nigrum is a cadmium (Cd) and zinc (Zn) accumulator with potential for phytoextraction of soil contaminated with heavy metals. However, how Zn affects Cd accumulation in S. nigrum remains unclear. In this study, S. nigrum seedlings were treated with 100 μmol·L−1 Zn (Zn100), 100 μmol·L−1 Cd (Cd100), and the Zn and Cd combination (Zn100+Cd100) for 10 days under hydroponic culture. Compared with Cd100, the Cd content in stems, leaves, and xylem saps was 1.8, 1.6, and 1.3 times more than that in Zn100+Cd100, respectively. In addition, the production of reactive oxygen species in leaves was significantly upregulated in Cd100 compared with the control, and it was downregulated in Zn100. Comparative analyses of transcriptomes and proteomes were conducted with S. nigrum leaves. Differentially expressed genes (DEGs) were involved in Cd uptake, transport, and sequestration, and the upregulation of some transporter genes of Zn transporters (ZIPs), a natural resistance associated macrophage protein (Nramp1), a metal–nicotianamine transporter (YSL2), ATP-binding cassette transporters (ABCs), oligopeptide transporters (OPTs), and metallothionein (MTs) and glutathione S-transferase (GSTs) genes was higher in Zn100+Cd100 than in Cd100. In addition, differentially expressed proteins (DEPs) involved in electron transport chain, ATP, and chlorophyll biosynthesis, such as malate dehydrogenases (MDHs), ATPases, and chlorophyll a/b binding proteins, were mostly upregulated in Zn100. The results indicate that Zn supplement increases Cd accumulation and tolerance in S. nigrum by upregulating ATP-dependent Cd transport and sequestration pathways.

The Middle Permian Qixia Formation in the Shuangyushi area, northwestern Sichuan Basin, develops shoal-facies dolomite reservoirs. To pinpoint promising reservoirs in the Qixia Formation, deep thin shoal-facies dolomite reservoirs were predicted using the techniques of pre-stack Kirchhoff-Q compensation for absorption, inverse Q filtering, low-to high-frequency compensation, forward modeling, and facies-controlled seismic meme inversion. The results are obtained in six aspects. First, the dolomite reservoirs mainly exist in the middle and lower parts of the second member of Qixia Formation (Qi2 Member), which coincide with the zones shoal cores are developed. Second, the forward modeling shows that the trough energy at the top and bottom of shoal core increases with increasing shoal-core thickness, and weak peak reflections are associated in the middle of shoal core. Third, five types of seismic waveform are identified through waveform analysis of seismic facies. Type-I and Type-II waveforms correspond to promising facies (shoal core microfacies). Fourth, vertically, two packages of thin dolomite reservoirs turn up in the sedimentary cycle of intraplatform shoal in the Qi2 Member, and the lower package is superior to the upper package in dolomite thickness, scale and lateral connectivity. Fifth, in plane, significantly controlled by sedimentary facies, dolomite reservoirs laterally distribute with consistent thickness in shoal cores at topographical highs and extend toward the break. Sixth, the promising prospects are the zones with thick dolomite reservoirs and superimposition of horst–graben structural traps.

Summary: Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator that mediates cellular adaptation to decreased oxygen availability. HIF-1 recruits chromatin-modifying enzymes leading to changes in histone acetylation, citrullination, and methylation at target genes. Here, we demonstrate that hypoxia-inducible gene expression in estrogen receptor (ER)-positive MCF7 and ER-negative SUM159 human breast cancer cells requires the histone H2A/H2B chaperone facilitates chromatin transcription (FACT) and the H2B ubiquitin ligase RING finger protein 20/40 (RNF20/40). Knockdown of FACT or RNF20/40 expression leads to decreased transcription initiation and elongation at HIF-1 target genes. Mechanistically, FACT and RNF20/40 are recruited to hypoxia response elements (HREs) by HIF-1 and stabilize binding of HIF-1 (and each other) at HREs. Hypoxia induces the monoubiquitination of histone H2B at lysine 120 at HIF-1 target genes in an HIF-1-dependent manner. Together, these findings delineate a cooperative molecular mechanism by which FACT and RNF20/40 stabilize multiprotein complex formation at HREs and mediate histone ubiquitination to facilitate HIF-1 transcriptional activity.

Background: Bariatric surgeries, including the sleeve gastrectomy, have been recognized as the most effectively treatment strategy for severe obesity. Magnetic devices have been successfully used in bariatric surgeries. Here, we intended to evaluate the safety and efficiency of magnetic anchoring device assisted-laparoscopic sleeve gastrectomy (MLSG), and to make a comparison of the short-term results between conventional laparoscopic sleeve gastrectomy (CLSG) and MLSG. Methods: The retrospective cohort study was carried out by analyzing and summarizing the data from a database of routinely collected data. The cohort included the patients who underwent either CLSG (n = 120) or MLSG (n = 115) at a single center between January 2018 and December 2020 with a two-year follow-up. The effects of these two surgeries on the weight loss, resolution of comorbidities and quality of life (QOL) were analyzed. Results: The two groups were similar in gender, age, body mass index, abdominal girth, as well as the type and proportion of comorbidities. And the cases in MLSG group had a markedly shorter time of operation (MLSG, 72.59 min vs. CLSG, 76.67 min; P = 0.003). Length of stay in hospital was significantly shorter in the MLSG group than that in the CLSG group (MLSG, 5.59 days vs. CLSG, 5.96 days; P = 0.016). Neither fatal event nor conversion to open surgery happened among all cases. There were no differences in terms of the postoperative complications between the two groups. Magnetic device-related mild hepatic lacerations occurred and were handled by hemostatic treatments in 3 cases. The QOL of patients in MLSG was better at 6-month after surgery, but there was no significant difference between the two groups at 1-year or 2-year after surgery. Conclusion: Both MLSG and CLSG prove safe and effective, and the patients underwent MLSG have a shorter length of stay in hospital, and a better QOL during 6 months after surgery.

Background/Aims: The accuracy of endosonographers in diagnosing gastric subepithelial lesions (SELs) using endoscopic ultrasonography (EUS) is influenced by experience and subjectivity. Artificial intelligence (AI) has achieved remarkable development in this field. This study aimed to develop an AI-based EUS diagnostic model for the diagnosis of SELs, and evaluated its efficacy with external validation. Methods: We developed the EUS-AI model with ResNeSt50 using EUS images from two hospitals to predict the histopathology of the gastric SELs originating from muscularis propria. The diagnostic performance of the model was also validated using EUS images obtained from four other hospitals. Results: A total of 2,057 images from 367 patients (375 SELs) were chosen to build the models, and 914 images from 106 patients (108 SELs) were chosen for external validation. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the model for differentiating gastrointestinal stromal tumors (GISTs) and non-GISTs in the external validation sets by images were 82.01%, 68.22%, 86.77%, 59.86%, and 78.12%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in the external validation set by tumors were 83.75%, 71.43%, 89.33%, 60.61%, and 80.56%, respectively. The EUS-AI model showed better performance (especially specificity) than some endosonographers. The model helped improve the sensitivity, specificity, and accuracy of certain endosonographers. Conclusions: We developed an EUS-AI model to classify gastric SELs originating from muscularis propria into GISTs and non-GISTs with good accuracy. The model may help improve the diagnostic performance of endosonographers. Further work is required to develop a multi-modal EUS-AI system.

Abstract Resistance training could counter hypertension and improve muscle quality (MQ), but current evidence about the correlation between MQ and hypertension is limited. The authors aimed to explore this correlation using the data of participants aged 20–59 from NHANES 2011–2014 via a cross‐sectional study. The MQ was quantified as handgrip strength (kg)/lean soft tissue mass (kg) of the dominant arm. Weighted multivariate logistic regression models were mainly utilized to investigate the MQ—hypertension association; linear trend tests and subgroup analysis were also conducted. Moreover, the authors employed weighted multivariate linear regression models to uncover the association between blood pressure (BP) and MQ. Four thousand four hundred and sixty‐nine individuals were enrolled, and 1167 were hypertensive. Hypertensive participants had a lower MQ than normotensive participants. In the totally adjusted model, each unit elevation in MQ was related to a 7% reduction in hypertension prevalence (p =.002). There was a decreasing trend in hypertension prevalence and in systolic BP as the MQ increased from the bottom to the top quartile across all three models (p for trend ≤.01), with a 28% difference (OR: 0.72, 95% CI: 0.54, 0.95) in hypertension prevalence and a 1.88 mm Hg (95% CI: −3.56, −0.20) difference in SBP between the top and bottom quartiles in the fully adjusted model. Subgroup analysis further confirmed the MQ—hypertension inverse association. In conclusions, the MQ was negatively associated with hypertension prevalence and systolic BP, which suggests the MQ may be a protective factor for hypertension and need to be improved.

AP2/ERF transcription factors play important roles in plant growth, development and response to abiotic stress. In order to explore the response of AvAP2/ERF genes in Aquilegia vulgaris to salt stress, based on the transcriptome data obtained under salt stress in previous experiments, the AP2/ERF gene family in A. vulgaris were screened by bioinformatic methods, and their physical and chemical properties, conserved motifs, phylogenetic relations and expression changes of these genes in leaves and roots under salt stress were analyzed, etc. The expression of candidate genes was verified by qRT-PCR. The results were as follows：(1) 86 AvAP2/ERF genes were identified which encoded 132-722 amino acids, with molecular weight of 14 763.30-79 069.47 Da and isoelectric point ranged from 4.49 to 9.68. Most of them were slightly acidic proteins and all of them were hydrophilic. Most of AvAP2/ERF were localized in nucleus. (2)The similarity of secondary structure was high, which was proportionally composed of random coil and α-helix. The members all contained AP2 domains, and two conserved motifs were predicted. (3) Under different stages of salt treatment, there were 71 AvAP2/ERF genes responded to salt stress. There were 18 and 19 differentially expressed genes in leaves and roots, respectively. There were 86 AP2/ERF genes of A. vulgaris were divided into five subfamilies clustering with A. thaliana; the AP2/ERF genes of A. vulgaris and Arabidopsis thaliana were clustered into five subfamilies and 15 subgroups. Through expression analysis and homology relationship, AvAP2/ERF-56, AvAP2/ERF-61 and AvAP2/ERF-80 of them might be involved in salt resistance, and the qRT-PCR results were consistent with sequencing expression trends. The results of this study provides a reliable reference for further research on the function and stress response mechanism of AP2/ERF gene in Aquilegia vulgaris.

Abstract. Background:. The age, biomarkers, and clinical history (ABC)-atrial fibrillation (AF)-Stroke score have been proposed to refine stroke risk stratification, beyond what clinical risk scores such as the CHA2DS2-VASc score can offer. This study aimed to identify risk factors associated with thromboembolism and evaluate the performance of the ABC-AF-Stroke score in predicting thromboembolism in non-anticoagulated AF patients following successful ablations. Methods:. A total of 2692 patients who underwent successful ablations with discontinued anticoagulation after a 3-month blanking period in the Chinese Atrial Fibrillation Registry (CAFR) between 2013 and 2019 were included. Cox regression analysis was conducted to present the association of risk factors with thromboembolism risk. The ABC-AF-Stroke score was evaluated in terms of discrimination, including concordance index (C-index), net reclassification improvement (NRI) and integrated discrimination improvement (IDI), clinical utilization by decision curve analysis (DCA), and calibration by comparing the predicted risk with the observed annualized event rate. Results:. After a median follow-up of 3.5 years, 64 patients experienced thromboembolism events. Age, prior history of stroke/transient ischemic attack (TIA), high-sensitivity cardiac troponin T (cTnT-hs), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were independently associated with thromboembolism risk. The ABC-AF-Stroke score performed statistically significantly better than the CHA2DS2-VASc score in terms of C-index (0.67, 95% confidence interval [CI]: 0.59-0.74 vs. 0.60, 95% CI: 0.52-0.67, P = 0.030) and reclassification capacity. The DCA implied that the ABC-AF-Stroke score could identify more thromboembolism events without increasing the false positive rate compared to the CHA2DS2-VASc score. The calibration curve showed that the ABC-AF-Stroke score was well calibrated in this population. Conclusions:. In this real-world study enrolling non-anticoagulated AF patients following successful ablations, age, prior history of stroke/TIA, level of NT-proBNP, and cTnT-hs were independently associated with an increased risk of thromboembolism. The ABC-AF-Stroke score was well-calibrated and statistically significantly outperformed the CHA2DS2-VASc score in predicting thromboembolism risk.

Abstract The poor efficacy of chimeric antigen receptor T-cell therapy (CAR T) for solid tumors is due to insufficient CAR T cell tumor infiltration, in vivo expansion, persistence, and effector function, as well as exhaustion, intrinsic target antigen heterogeneity or antigen loss of target cancer cells, and immunosuppressive tumor microenvironment (TME). Here we describe a broadly applicable nongenetic approach that simultaneously addresses the multiple challenges of CAR T as a therapy for solid tumors. The approach reprograms CAR T cells by exposing them to stressed target cancer cells which have been exposed to the cell stress inducer disulfiram (DSF) and copper (Cu)(DSF/Cu) plus ionizing irradiation (IR). The reprogrammed CAR T cells acquire early memory-like characteristics, potent cytotoxicity, enhanced in vivo expansion, persistence, and decreased exhaustion. Tumors stressed by DSF/Cu and IR also reprogram and reverse the immunosuppressive TME in humanized mice. The reprogrammed CAR T cells, derived from peripheral blood mononuclear cells of healthy donors or metastatic female breast cancer patients, induce robust, sustained memory and curative anti-solid tumor responses in multiple xenograft mouse models, establishing proof of concept for empowering CAR T by stressing tumor as a promising therapy for solid tumors.

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common and challenging cancers in the world. N6-methyladenosine (m6A) modification and long non-coding RNAs (lncRNAs) play critical roles in the progression of HCC. However, there are few reports on genome-wide screening and functional annotations of m6A-methylated lncRNAs in HCC. Methods The expression levels of m6A methyltransferase METTL3 and the association with the prognosis in HCC were determined by RT-qPCR, public dataset platforms. Then, RNA-seq, Pearson correlation analysis, MeRIP-qPCR, RNA half-life assay, gene site-directed mutation, RIP assay and RT-qPCR analysis were employed to determine the downstream target of METTL3 in HCC. Subsequently, the expression levels and roles of lncRNA glucosylceramidase beta pseudogene 1 (GBAP1) in HCC were determined by Kaplan–meier curves, RT-qPCR, in vitro functional experiments and in vivo tumorigenesis and lung metastasis models. Then, the downstream target and pathway of GBAP1 were explored by GO biological process, KEGG pathway enrichment, luciferase reporter assay, RIP assay and rescue experiments and so on. Results METTL3 was upregulated in HCC and closely related to HCC prognosis. And METTL3 induced GBAP1 expression by acting as the m6A writer of GBAP1 and IGF2BP2 worked as its m6A reader. Clinically, GBAP1 expression was significantly associated with tumor size, venous infiltration, TNM stage and prognosis of HCC, Functionally, GBAP1 promoted HCC metastasis and growth both in vitro and in vivo. Furthermore, GBAP1 acted as the molecular sponge for miR-22-3p to increase the expression of bone morphogenetic protein receptor type 1A (BMPR1A), which then activated BMP/SMAD pathway in HCC cells. Conclusions Our findings demonstrated that METTL3-induced GBAP1 promoted migration, invasion and proliferation of HCC cells via GBAP1/miR-22-3p/BMPR1A/SMAD axis. GBAP1 could be a potential prognosis indicator and therapeutic target for HCC.

Abstract Objective Working memory (WM) deficits have frequently been linked to attention deficit hyperactivity disorder (ADHD). Despite previous studies suggested its high heritability, its genetic basis, especially in ADHD, remains unclear. The current study aimed to comprehensively explore the genetic basis of visual-spatial working memory (VSWM) in ADHD using wide-ranging genetic analyses. Methods The current study recruited a cohort consisted of 802 ADHD individuals, all met DSM-IV ADHD diagnostic criteria. VSWM was assessed by Rey-Osterrieth complex figure test (RCFT), which is a widely used psychological test include four memory indexes: detail delayed (DD), structure delayed (SD), structure immediate (SI), detail immediate (DI). Genetic analyses were conducted at the single nucleotide polymorphism (SNP), gene, pathway, polygenic and protein network levels. Polygenic Risk Scores (PRS) were based on summary statistics of various psychiatric disorders, including ADHD, autism spectrum disorder (ASD), major depressive disorder (MDD), schizophrenia (SCZ), obsessive compulsive disorders (OCD), and substance use disorder (SUD). Results Analyses at the single-marker level did not yield significant results (5E−08). However, the potential signals with P values less than E−05 and their mapped genes suggested the regulation of VSWM involved both ocular and neural system related genes, moreover, ADHD-related genes were also involved. The gene-based analysis found RAB11FIP1, whose encoded protein modulates several neurodevelopment processes and visual system, as significantly associated with DD scores (P = 1.96E−06, Padj = 0.036). Candidate pathway enrichment analyses (N = 53) found that forebrain neuron fate commitment significantly enriched in DD (P = 4.78E−04, Padj = 0.025), and dopamine transport enriched in SD (P = 5.90E-04, Padj = 0.031). We also observed a significant negative relationship between DD scores and ADHD PRS scores (P = 0.0025, Empirical P = 0.048). Conclusions Our results emphasized the joint contribution of ocular and neural genes in regulating VSWM. The study reveals a shared genetic basis between ADHD and VSWM, with GWAS indicating the involvement of ADHD-related genes in VSWM. Additionally, the PRS analysis identifies a significant relationship between ADHD-PRS and DD scores. Overall, our findings shed light on the genetic basis of VSWM deficits in ADHD, and may have important implications for future research and clinical practice.