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Purpose Arthroscopic Bankart repair combined with remplissage and autologous scapular spine bone grafting have been described as a treatment for off‐track Hill–Sachs lesions with subcritical glenoid bone defects in the anterior shoulder instability. However, whether these two techniques can achieve satisfactory postoperative outcomes is unclear, and there are few comparative studies between them. Therefore, this study compared the postoperative efficacy of the two techniques for off‐track Hill–Sachs lesions with subcritical glenoid bone loss. Method Between June 2017 and December 2020, 62 patients with shoulder instability due to Off‐Track Hill–Sachs lesions with subcritical glenoid bone loss underwent surgical treatment and were included in this regression study. Thirty‐two patients underwent arthroscopic Bankart repair combined with remplissage (B + R group), and 30 patients underwent additional autologous scapular glenoid bone grafting (additional bone grafting group). The general information of the patients was recorded. The patient's activity before and after surgery was recorded. The DASH score and Constant–Murley (CM) score were used to assess the patient's functional status; the Rowe score was used to evaluate the patient's shoulder stability. The shoulder function and stability before and after surgery were analyzed and compared between the two groups. Results The final DASH scores of the B + R group and the additional bone grafting group were significantly lower than those before surgery, with a statistically significant difference (9.76 ± 4.32 vs. 27.89 ± 6.63, 8.50 ± 3.32 vs. 28.0 ± 4.27, p = 0.000); the final CM scores of the two groups were significantly higher than those before surgery (88.71 ± 3.74 vs. 73.68 ± 3.74, 87.16 ± 2.29 vs. 71.37 ± 2.68, p = 0.000). There was no statistical difference in the final DASH score and final CM score between the two groups (p > 0.05). In terms of postoperative stability, the final Rowe scores of the two groups were significantly higher than those before surgery, with a statistically significant difference (89.06 ± 9.19 vs. 41.71 ± 4.13; 93.16 ± 4.99 vs. 42.33 ± 2.53, p = 0.000). Compared with the control group, the additional bone graft group achieved higher final Rowe scores (93.16 ± 4.99 vs. 89.06 ± 9.19, p = 0.032). Conclusion For patients with anterior shoulder instability due to off‐track Hill–Sachs lesions with subcritical glenoid bone loss, although Bankart and remplissage can achieve satisfactory clinical results, additional autogenous scapular spine bone grafting can provide better stability of the shoulder, especially for patients with high sports demands.

As a promising material for marine engineering, the insufficient corrosion resistance of manganese aluminium bronze (MAB) alloy when exposed to the marine environment may limit its application. In the present work, micro-arc oxidation (MAO) of MAB alloy was conducted in an aluminate-based electrolyte with the influence of ultrasonic vibration (UV) examined. A porous ceramic film has been successfully produced on MAB via MAO, which exhibits dramatic increases in both film thickness and compactness after the introduction of UV. As a result, the ceramic film produced by ultrasound-assisted MAO (UMAO) exhibits an enhanced corrosion resistance relative to that via MAO, which also possesses a desired antifouling capability. Hence, the present work illustrates the influence of UV on the MAO behaviour of non-valve alloys and, more importantly, provides theoretical guidance for related surface modification strategies in marine engineering.

Abstract The global health crisis of antibacterial resistance (ABR) poses a particular threat in low-resource settings like East Africa. Interventions for ABR typically target antibiotic use, overlooking the wider set of factors which drive vulnerability and behaviours. In this cross-sectional study, we investigated the joint contribution of behavioural, environmental, socioeconomic, and demographic factors associated with higher risk of multi-drug resistant urinary tract infections (MDR UTIs) in Kenya, Tanzania, and Uganda. We sampled outpatients with UTI symptoms in healthcare facilities and linked their microbiology data with patient, household and community level data. Using bivariate statistics and Bayesian profile regression on a sample of 1610 individuals, we show that individuals with higher risk of MDR UTIs were more likely to have compound and interrelated social and environmental disadvantages: they were on average older, with lower education, had more chronic illness, lived in resource-deprived households, more likely to have contact with animals, and human or animal waste. This suggests that interventions to tackle ABR need to take account of intersectional socio-environmental disadvantage as a priority.

Abstract Ions and radicals serve as key intermediates in molecular transformation, with their chemical properties being essential for understanding and predicting reaction reactivity and selectivity. In this data descriptor, we report a quantum chemical dataset named QM9star, comprising cations, anions, and radicals. This dataset is derived from the molecular structures of the QM9 dataset, created by removing terminal hydrogens followed by optimization using B3LYP-D3(BJ)/6-311 + G(d,p) level of density functional theory. The QM9star dataset includes approximately 1.9 million cations, anions, and radicals, along with 120 kilo neutral molecules prior to hydrogen removal. Each entry encompasses both molecular and atomic information: representative global properties include orbital energies, vibrational frequencies, etc., while local properties cover aspects such as charges and spin densities at each atomic site. The QM9star dataset not only serves as a comprehensive source of quantum chemical information for intermediates but also offers insights into the principle of atomic property distribution. We anticipate that these data will aid in machine learning studies related to chemical intermediates and contribute to the molecular representation learning.

Abstract Defective renal excretion and increased production of uric acid engender hyperuricemia that predisposes to gout. However, molecular mechanisms underlying defective uric acid excretion remain largely unknown. Here, we report a rare genetic variant of gout-unprecedented NUMB gene within a hereditary human gout family, which was identified by an unbiased genome-wide sequencing approach. This dysfunctional missense variant within the conserved region of the NUMB gene (NUMBR630H) underwent intracellular redistribution and degradation through an autophagy-dependent mechanism. Mechanistically, we identified the uric acid transporter, ATP Binding Cassette Subfamily G Member 2 (ABCG2), as a novel NUMB-binding protein through its intracellular YxNxxF motif. In polarized renal tubular epithelial cells (RTECs), NUMB promoted ABCG2 trafficking towards the apical plasma membrane. Genetic loss-of-function of NUMB resulted in redistribution of ABCG2 in the basolateral domain and ultimately defective excretion of uric acid. To recapitulate the clinical situation in human gout patients, we generated a NUMBR630H knock-in mouse strain, which showed marked increases of serum urate and decreased uric acid excretion. The NUMBR630H knock-in mice exhibited clinically relevant hyperuricemia. In summary, we have uncovered a novel NUMB-mediated mechanism of uric acid excretion and a functional missense variant of NUMB in humans, which causes hyperuricemia and gout.

Abstract GWASs have linked the 3p21.1 locus, which is associated with the expression levels of NEK4, to bipolar disorder. Here, we use integrative analyses of GWAS statistics and eQTL annotations to establish that elevated NEK4 expression in the hippocampus is associated with an increased risk of bipolar disorder. To further study this association, we generate transgenic male mice that conditionally overexpress NEK4 in the pyramidal neurons of the adult forebrain, or use AAV to overexpress NEK4 in the dorsal hippocampus. Compared to the control mice, male mice of both strains exhibit a shift from a diurnal anxiety state to a nocturnal normal or anxiolytic-like state. Overexpression of NEK4 also affects the circadian fluctuations in dendritic spine morphology and synaptic structure. Furthermore, we show that treatment with lithium ameliorates the effects of NEK4 overexpression in male mice. We then perform phosphoproteomic analyses to demonstrate that the diurnal and nocturnal phosphoproteomic profiles of male control and NEK4 overexpressing mice are different. These results suggest that male mice with different NEK4 expression levels may recapitulate some of the core features observed in patients with bipolar disorder, indicating that interruption of the homeostatic dynamics of synapses may underlie the emotional swings in bipolar disorder.

Abstract Introduction Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has been established as an effective treatment for peritoneal cancer (PC). However, this kind of combination therapy is associated with a high lactate level. Moreover, studies have suggested that the rate of complications early after surgery directly increased with elevated lactate levels. Glucose-insulin-potassium (GIP), a potent cardioprotective intervention, has been demonstrated to adjust blood glucose (BG) levels and reduce lactate levels. However, the insulin-glucose ratio should be adjusted according to the surgery performed. Here, we aimed to evaluate the advantages of using modified GIP during CRS/HIPEC to reduce the lactate level at the end of surgery and further reduce the incidence of early postoperative complications. Methods and analysis The modified GIP versus conventional management during surgery study is a single-center, randomized, single-blinded outcome assessment clinical trial of 80 patients with PC who are between 18 and 64 years old and undergoing CRS/HIPEC. Participants will be randomly allocated to receive modified GIP or conventional treatment (1:1). The primary outcome will be the plasma lactate level at the end of surgery. The secondary outcomes will include the highest levels and fluctuation ranges of lactate and BG during surgery, extubation time, APACHE-II score 24 h after surgery, postoperative defecation and exhaust time, postoperative lactate clearance time, postoperative liver and kidney function, incidence of complications within 7 days after surgery, length of intensive care unit stay (LIS), length of hospital stay (LHS), and total cost of hospitalization. Ethics and dissemination The trial protocol was approved by the Scientific Research Ethics Committee of Beijing Shijitan Hospital Affiliated with Capital Medical University, approval number sjtky11-1x-2022(118). The results will be published in international peer-reviewed journals. Trial registration ChiCTR2200057258. Registered on March 5, 2022.

Programmed cell death ligand-1 (PD-L1) is a T cell inhibitory immune checkpoint molecule that interacts with programmed cell death-1 (PD-1) to promote immune escape of tumor cells. Compared with antibody therapies, small molecule drugs show better prospects due to their advantages such as higher bioavailability, better tissue penetration, and reduced risk of immunogenicity. Here, we found that the small molecule demethylzeylasteral (Dem) can significantly downregulate the expression of PD-L1 in colorectal cancer cells and enhance the killing effect of T cells on tumor cells. Mechanistically, Dem binds to the deubiquitinating enzyme USP22 and promotes its degradation, resulting in increased ubiquitination and degradation of PD-L1 through the proteasome pathway. In addition, Dem increased the activity of cytotoxic T cells and reduced the number of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in tumor-infiltrating lymphocytes (TILs), thereby activating the tumor immune microenvironment and inhibiting the growth of subcutaneous MC38 tumors in C57BL/6 mice. Moreover, we also found that the combination of Dem and CTLA4 antibodies can further improve the efficacy of antitumor therapy. Our study reveals the mechanism by which Dem promotes PD-L1 degradation and suggests that the combination of Dem and CTLA4 antibodies may improve the efficacy of immunotherapy.

Abstract Background The excavation and utilization of endophytic fungi from medicinal plants is highly important for the development of new drugs. The endophytic fungus Aspergillus tamarii TPD11, which was isolated and obtained by the authors in the previous stage, can produce a variety of polyphyllins with important potential applications in hemostasis, inflammation and antitumor activities; however, the genomic information of TPD11 is still unknown. Results In this study, we sequenced and assembled the whole genome of the endophytic fungus A. tamarii TPD11, resolved the genome evolutionary relationships of 24 Aspergillus strains, and phylogenetic analysis of the genomes of 16 strains revealed the evolutionary differences between Aspergillus and Penicillium and the mechanisms of genome expansion and contraction. CAZy annotation analysis revealed that TPD11 obtains nutrients mainly by ingesting starch from the host plant. TPD11 has a biosynthesis-related gene cluster for the synthesis of squalestatin S1, and the silencing of this biosynthesis-related gene cluster might increase the content of polyphyllin. Annotation of 11 UDP-glycosyltransferase genes helps to further reveal the biosynthetic pathway of polyphyllin. In addition, secondary metabolism gene cluster and CAZy analyses confirmed the potential probiotic, insecticidal and antimicrobial activities of TPD11 on host plants. Conclusions This study reveals the intrinsic mechanism by which endophytic fungi increase the content of polyphyllin, which provides a basis for the synthetic synthesis of the natural product polyphyllin.

Abstract Background For renal hilar angiomyolipoma, general surgical resection is often quite challenging. The aim of this study is to evaluate the safety and efficacy of an innovative robot-assisted laparoscopic strategy that combines tumor enucleation with tumor aspiration in the treatment of renal hilar angiomyolipoma. Methods The clinical data of 38 patients with renal hilar angiomyolipoma who went through robotic tumor enucleation combined with tumor aspiration in the Department of Urology, the Affiliated Hospital of Nanjing University Medical School, from December 2019 to December 2022 were retrospectively analyzed. The basic characteristics, the perioperative variables, intraoperative procedures, and postoperative complications were all recorded. Patients were followed up to evaluate the angiomyolipoma recurrence and the renal function by urologic CT or ultrasound and renal function tests. Results All surgeries were successfully completed without conversion to radical nephrectomy or open surgery. One patient developed urinary extravasation 10 days after surgery, and was readmitted to the hospital for transurethral ureteral stenting considering the injury of the renal collecting system. The median operative time was 181.5 (123.8-206.3) min, the warm ischemia time was 20.0 (17.3–24.0) min, the blood loss was 125 (100.0-262.5) ml, and no patients received blood transfusion during and after surgery. The median hospitalization time was 7.0 (6.0–9.0) days, and the duration of indwelling drainage tube was 2.0 (2.0–3.0) days. The serum creatinine (Scr) on the first day, 3 months, and 6 months after surgery were 55.5 (50.8–62.8) µmol/L, 55.5 (48.0–62.0) µmol/L and 54.0 (51.8–63.5) µmol/L, respectively, and there was no significant difference compared with the preoperative level 56.0 (47.8–60.3) µmol/L. All patients were followed up after surgery, and the urinary CT scan or renal color doppler ultrasound, and renal function were reexamined. The median follow-up time of all patients was 19.0 (14.75-33.0) months, and no local recurrence of angiomyolipoma was seen in all patients. Conclusions The surgical strategy of robot-assisted laparoscopic tumor enucleation combined with tumor aspiration is safe and effective in the treatment of renal hilar angiomyolipoma.

Abstract Purpose To evaluate 18F-FDG myocardial metabolism imaging (MMI) using a total-body PET/CT scanner and explore the feasible scan duration to guide the clinical practice. Methods A retrospective analysis was conducted on 41 patients who underwent myocardial perfusion-metabolism imaging to assess myocardial viability. The patients underwent 18F-FDG MMI with a total-body PET/CT scanner using a list-mode for 600 s. PET data were trimmed and reconstructed to simulate images of 600-s, 300-s, 120-s, 60-s, and 30-s acquisition time (G600-G30). Images among different groups were subjectively evaluated using a 5-point Likert scale. Semi-quantitative evaluation was performed using standardized uptake value (SUV), myocardial to background activity ratio (M/B), signal to noise ratio (SNR), contrast to noise ratio (CNR), contrast ratio (CR), and coefficient of variation (CV). Myocardial viability analysis included indexes of Mismatch and Scar. G600 served as the reference. Results Subjective visual evaluation indicated a decline in the scores of image quality with shortening scan duration. All the G600, G300, and G120 images were clinically acceptable (score ≥ 3), and their image quality scores were 4.9 ± 0.3, 4.8 ± 0.4, and 4.5 ± 0.8, respectively (P > 0.05). Moreover, as the scan duration reduced, the semi-quantitative parameters M/B, SNR, CNR, and CR decreased, while SUV and CV increased, and significant difference was observed in G300-G30 groups when comparing to G600 group (P

Abstract Background The engagement of preschool teachers in their work is pivotal for maintaining teaching quality, ensuring teacher well-being, and fostering children’s development. Despite its significance, there is limited knowledge regarding the daily fluctuations in work engagement and the underlying factors influencing it. This study, guided by the Job Demands-Resources model and Affect Event Theory, utilized an experience sampling methodology to investigate the impact of challenge and hindrance stressors on daily work engagement, as well as the mediating role of affect and the moderating effect of mindfulness. Methods Utilizing an experience sampling method, this study collected data from 220 preschool teachers in Shanghai over five consecutive workdays, conducting surveys once daily. Data analysis was performed using multilevel linear models. Results The results from multilevel regression indicated that: (1) daily challenge stressors were positively related to work engagement, (2) daily hindrance stressors were negatively related to work engagement, (3) daily positive affect mediated the relationship between challenge stressors and work engagement, (4) daily negative affect mediated the relationship between hindrance stressors and work engagement, and (5) daily mindfulness played a crucial moderating role by alleviating the adverse effects of hindrance stressors on daily negative affect. Conclusions This study provides valuable insights into the daily experiences of preschool teachers and the factors that influence their work engagement. Understanding the impact of stressors, affect, and mindfulness on work engagement can inform the development of interventions and strategies to improve teacher well-being and work engagement.

Abstract Background Diabetic nephropathy (DN) has been a major factor in the outbreak of end-stage renal disease for decades. As the underlying mechanisms of DN development remains unclear, there is no ideal methods for the diagnosis and therapy. Objective We aimed to explore the key genes and pathways that affect the rate progression of DN. Methods Nanopore-based full-length transcriptome sequencing was performed with serum samples from DN patients with slow progression (DNSP, n = 5) and rapid progression (DNRP, n = 6). Results Here, transcriptome proclaimed 22,682 novel transcripts and obtained 45,808 simple sequence repeats, 1,815 transcription factors, 5,993 complete open reading frames, and 1,050 novel lncRNA from the novel transcripts. Moreover, a total of 341 differentially expressed transcripts (DETs) and 456 differentially expressed genes (DEGs) between the DNSP and DNRP groups were identified. Functional analyses showed that DETs mainly involved in ferroptosis-related pathways such as oxidative phosphorylation, iron ion binding, and mitophagy. Moreover, Functional analyses revealed that DEGs mainly involved in oxidative phosphorylation, lipid metabolism, ferroptosis, autophagy/mitophagy, apoptosis/necroptosis pathway. Conclusion Collectively, our study provided a full-length transcriptome data source for the future DN research, and facilitate a deeper understanding of the molecular mechanisms underlying the differences in fast and slow progression of DN.

Abstract Background Diabetic kidney disease (DKD) is the major complication of diabetes concomitant with gut dysbiosis and glycometabolic disorder, which are strongly associated with bile acid (BA) metabolism. Yet studies investigating the BA metabolism involving in DKD pathogenesis are limited. This study aimed to explore the metabolomic profiling of BAs in DKD and analyze its association with DKD progression. Methods An ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established to quantify BAs in the plasma, fecal and urine samples of patients with DKD or T2DM and healthy individuals (n = 30 for each group). The key BAs associated with DKD were identified by orthogonal partial least-squares discriminant analysis (OPLS-DA) and receiver-operating characteristic (ROC) curve. Polynomial regression and Pearson’s correlation analyses were performed to assess the correlation between the key BAs and the clinical indicators reflecting DKD progression. Results Metabolomic profiling of 50 kinds of BAs presented the markedly step-wise alterations of BAs in plasma and feces as well as the little in urine of patients with DKD. Eight kinds of BAs in the plasma, eight kinds in the feces and three kinds in the urine were abnormally expressed, accompanying with the increased conjugated/unconjugated ratios of cholic acid, deoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid and hyocholic acid in the plasma, and of cholic acid, chenodeoxycholic acid and lithocholic acid in the feces. Moreover, the increased plasma level of glycochenodeoxycholic acid, and the increased fecal levels of glycolithocholic acid, 7-ketodeoxycholic acid and chenodeoxycholic acid-3-β-D-glucuronide are strongly correlated with the clinical indicators reflecting DKD progression, including eGFR, 24 h urinary protein and 24 h urinary microalbumin. Conclusions Our study for the first time disclosed the specific alterations of BA metabolism reflecting the step-wise progression of DKD, providing the basis for early identification and therapeutical strategies for DKD.

Abstract Background Infection of mice with mouse-adapted strains of influenza virus has been widely used to establish mouse pneumonia models. Intranasal inoculation is the traditional route for constructing an influenza virus-induced pneumonia mouse model, while intratracheal inoculation has been gradually applied in recent years. In this article, the pathogenicity of influenza virus-induced pneumonia mouse models following intranasal and aerosolized intratracheal inoculation were compared. Methods By comparing the two ways of influenza inoculation, intranasal and intratracheal, a variety of indices such as survival rate, body weight change, viral titer and load, pathological change, lung wet/dry ratio, and inflammatory factors were investigated. Meanwhile, the transcriptome was applied for the initial exploration of the mechanism underlying the variations in the results between the two inoculation methods. Results The findings suggest that aerosolized intratracheal infection leads to more severe lung injury and higher viral loads in the lungs compared to intranasal infection, which may be influenced by the initial site of infection, sialic acid receptor distribution, and host innate immunity. Conclusion Intratracheal inoculation is a better method for modelling severe pneumonia in mice than intranasal infection.

Abstract Background Given today’s competitive climate, graduates in stomatology face the dilemma of deciding whether to pursue higher education, obtain a master’s degree, or focus on clinical careers. However, their career planning tendencies and decision-making factors have not been clarified. This study aimed to analyze these aspects among stomatology undergraduate students at the Southwest Medical University (SWMU) in China. Methods This cross-sectional study between July and August 2022 included undergraduate students majoring in stomatology at SWMU. A cross-sectional online questionnaire was used to gather data on the respondents’ plans after graduation. The questionnaire included inquiries into their intentions regarding postgraduate education and standardized training. Additionally, the survey explored whether the respondents preferred academic or professional master’s degrees, which stomatology subspecialty they preferred, and the factors that influenced their choices. Results One hundred dental undergraduate students participated in this survey. Results indicated that 91.0% of respondents chose to pursue a master’s degree after graduation. Moreover, 80.2% of the respondents chose the professional master rather than the academic master as their first choice. Orthodontics, oral and maxillofacial surgery, and oral implantology were the top three subspecialties that students preferred. Personal interest, expected revenue, and family suggestions were the main factors influencing subspecialty selection. Conclusions The study reveals that stomatology undergraduate students face challenges and a dilemma at graduation. Due to the fierce competition in the job market, graduates aspire to pursue postgraduate studies instead of entering the workforce immediately after graduation. Students need to understand the employment landscape in oral medicine and familiarize themselves with the work patterns of various subspecialties while remaining flexible in charting their career paths.

Abstract Objective This study was to analyze the clinical outcomes and prognostic factors of dedifferentiated central chondrosarcomas (DCCS) in extremities. Methods A retrospective study was conducted on 49 patients (27 males, 22 females) who underwent surgical treatment between January 2001 and March 2023 in our institution. All patients were diagnosed with dedifferentiated central chondrosarcomas by needle biopsy or postoperative histopathological examination. The general characters, treatment and clinical outcomes were recorded in the follow-up and all surgical-related complications that occurred were recorded in this study. Overall, these data were used to analyse the prognostic factors of DCCS. Results 49 patients were included in this retrospective study and there were no patients lost in the follow-up period. The median diagnosis age of all patients was 57 years old (ranging from 17 to 87) and the median follow-up time was 34 months (range, 1-289). The average tumor size was 9.6 ± 2.4 cm (3.0-15.5). Median overall survival (OS) and progression-free survival (PFS) were 34 and 23 months, respectively. The 1-year, 2-year, 5-year, and 10-year OS were 87.8% (95% CI 77.6%-98.0%), 71.4% (35/49), 28.6% (14/49) and 18.4% (9/49). And the 1-year, 2-year, 5-year, and 10-year PFS were 75.5% (95% CI 63.6%-87.4%), 49.0% (35/49), 26.5% (14/49) and 16.3% (9/49). Multiple variate analyses indicated metastasis, pathological fracture, Enneking staging and surgical margin were independent prognostic factors in extremity dedifferentiated central chondrosarcomas. Conclusions Dedifferentiated central chondrosarcomas in extremities still had a grave prognosis. Metastasis, pathological fracture, Enneking staging, and surgical margin were independent risk factors for prognosis. Evidence level IV Therapic.

Objective Traditional exploration and geochemical studies have primarily focused on the extraction, interpretation and evaluation of metallogenic element anomalies. This approach, however, overlooks valuable ore prospecting information, which may be provided by other major and trace elements. Consequently, altered minerals cannot be effectively extracted, and geochemical data is under utilized for ore prospecting. Therefore, the author extracts alteration minerals from a mineralogical perspective and make metallogenic prediction. Methods This paper introduces a new method for extracting alteration minerals based on geochemical data and the stoichiometric ratios of different elements in the mineral chemical formula, referred to as the general element ratio analysis. Results Based on geochemical data obtained from 1∶ 25 000 debris geochemical survey in the Gaoshishan area of the Beishan orogenic belt, results show that sericite, K-feldspar and other alteration minerals are closely related to porphyry deposits, which can be effectively identified from SiO2, Al2O3, Na2O, K2O and other data. The mapping results reveal that sericite is mostly distributed along the intrusion's margins, while K-feldspar is mainly concentrated in the center of theintrusion. Then, based on the ore-controlling factors and ore-prospecting information, such as alteration minerals, magmatic rocks, structures, and traditional geochemical anomalies. This study further conducts metallogenic prediction for the Gaoshishan area using the weight-of-evidence method, delineating five target areas. Conclusion The alteration information extracted in this study has been validated through field investigations confirming that the proposed method is feasible and can provide critical prospecting insights beyond those offered by traditional metallogenic prediction methods.

Abstract Hypertension has become a major contributor to the morbidity and mortality of cardiovascular diseases worldwide. Despite the evidence of the anti‐hypertensive effect of gastrodia‐uncaria granules (GUG) in hypertensive patients, little is known about its potential therapeutic targets as well as the underlying mechanism. GUG components were sourced from TCMSP and HERB, with bioactive ingredients screened. Hypertension‐related targets were gathered from DisGeNET, OMIM, GeneCards, CTD, and GEO. The STRING database constructed a protein–protein interaction network, visualized by Cytoscape 3.7.1. Core targets were analyzed via GO and KEGG using R package ClusterProfiler. Molecular docking with AutodockVina 1.2.2 revealed favorable binding affinities. In vivo studies on hypertensive mice and rats validated network pharmacology findings. GUG yielded 228 active ingredients and 1190 targets, intersecting with 373 hypertension‐related genes. PPI network analysis identified five core genes: AKT1, TNF‐α, GAPDH, IL‐6, and ALB. Top enriched GO terms and KEGG pathways associated with the anti‐hypertensive properties of GUG were documented. Molecular docking indicated stable binding of core components to targets. In vivo study showed that GUG could improve vascular relaxation, alleviate vascular remodeling, and lower blood pressure in hypertensive animal models possibly through inhibiting inflammatory factors such as AKT1, mTOR, and CCND1. Integrated network pharmacology and in vivo experiment showed that GUG may exert anti‐hypertensive effects by inhibiting inflammation response, which provides some clues for understanding the effect and mechanisms of GUG in the treatment of hypertension.

In order to solve the problem of mine water surge prediction, we introduce deep learning theory, combine long short-term memory network (LSTM) and gated circulation unit (GRU), select mine water surge as the research object, and establish a mine water surge prediction model based on LSTM-GRU. Taking the mine water inflow of a mine in Shaanxi Province as sample data, the data set was divided into a training set and a test set using a 7∶3 ratio, and the gradient descent algorithm with good model training effect was selected to determine the network model parameters and regularization parameters. In order to prove the prediction accuracy of the LSTM-GRU model, the prediction results were compared with those obtained by the traditional ARIMA model and the LSTM model to predict mine water gusher, respectively. The results show that: the mean absolute percentage error (RMSE), root mean square error (MAE), mean absolute error (MAPE) and coefficient of determination (R2) of the LSTM-GRU composite model are 70.51, 53.4, 2.80% and 0.86, indicating that the model has high prediction accuracy and reliability. The prediction effect is better than the traditional ARIMA model and LSTM model.

Abstract Background Gastroparesis is a major complication following complete mesocolic excision (CME) and significantly impacts patient outcomes. This study aimed to create a machine learning model to pinpoint key risk factors before, during, and after surgery, effectively predicting the risk of gastroparesis after CME. Methods The study involved 1146 patients with colon cancer, out of which 95 developed gastroparesis. Data were collected on 34 variables, including demographics, chronic conditions, pre-surgery test results, types of surgery, and intraoperative details. Four machine learning techniques were employed: extreme gradient boosting (XGBoost), random forest (RF), support vector machine (SVM), and k-nearest neighbor (KNN). The evaluation involved k-fold cross-validation, receiver operating characteristic (ROC) analysis, calibration curves, decision curve analysis (DCA), and external validation. Results XGBoost excelled in its performance for predictive models. ROC analysis showed high accuracy for XGBoost, with area under the curve (AUC) scores of 0.976 for the training set and 0.906 for the validation set. K-fold cross-validation confirmed the model's stability, and calibration curves indicated high predictive accuracy. Additionally, DCA highlighted XGBoost’s superior patient benefits for intervention treatments. An AUC of 0.77 in external validation demonstrated XGBoost's strong generalization ability. Conclusion The XGBoost-fueled predictive model for post-surgery colon cancer patients proved highly effective. It underlined gastroparesis as a significant post-operative issue, associated with advanced age, prolonged surgeries, extensive intraoperative blood loss, surgical techniques, low serum protein levels, anemia, diabetes, and hypothyroidism.

Abstract Purpose This study aimed to analyse the clinical outcomes of preoperative adjuvant denosumab therapy (PADT) combined with resection and arthrodesis for recurrent grade 3 giant cell tumor of bone (GCTB) in the distal radius. Methods A retrospective study was conducted on twenty-three patients (8 males, 15 females) who were treated with the adjuvant denosumab combined with en bloc resection (EBR) and arthrodesis for biopsy confirmed recurrent Campanacci III giant cell tumor of bone in the distal radius between January 2015 and December 2022. All 23 patients were treated with wrist arthrodesis reconstruction using autogenous free iliac crest bone graft (ICBG), bridging plate and screws. The local control, metastasis and overall survival were evaluated during the follow-up period. Functional outcomes were evaluated using the Disabilities of the Arm, Shoulder and Hand (DASH) score, Musculoskeletal Tumor Society Score (MSTS-87 and MSTS-93), and grip strength in the follow-up period. Additionally, all surgical or denosumab-related complications that occurred were recorded in this study. Results Twenty-three patients were included in this retrospective study and no patients were lost in the follow-up period. The average patient age was 32.5 ± 10.2 years (range, 19–53 years) and the mean follow-up time was 35.5 ± 18.4 months (range, 13–72 months). The average tumor length was 71.7 ± 8.7 mm (range, 50 to 85 mm) and bone reconstruction length was 78.5 ± 8.5 mm (range, 60 to 90 mm). Four patients (17.4%) had secondary local recurrence after reoperation and two patients had (8.7%) multiple recurrences. One patient (4.3%) was deceased in the last follow-up due to multiple metastases. The estimated 5-year recurrence-free survival rate was 81.3% and 5-year metastasis-free survival rate was 95.7%. The mean union time was 8.5 ± 1.9 (6–12) months and the overall survivorship of the allograft was 82.7% (21/23) at an average 35 month follow-up. The average MSTS-87 and MSTS-93 scores were 27.8 ± 1.6 (range, from 23 to 30) and 91.5 ± 5.0 (range, from 76 to 100), and the average DASH score was 8.9 ± 3.2 (range, from 3 to 15), respectively. The average grip strength was 64.6 ± 15.7% (range, from 30 to 95%) of the uninvolved side. Eight patients (34.7%) had at least one complication in the follow-up time. Two autografts (8.7%) were removed due to local recurrence and bone nonunion, and the average autograft survival time was 32.8 ± 18.5 months (range, 12 to 72 months). Conclusions Preoperative adjuvant denosumab therapy (PADT) combined with en bloc resection and arthrodesis is a promising method for the treatment of recurrent Campanacci III GCTB in distal radius with acceptable short-term local control and functional satisfaction. Level of evidence: level IV Therapeutic.

Background The incidence density of metabolic dysfunction-associated fatty liver disease (MAFLD) and the effect of a healthy lifestyle on the risk of MAFLD remain unknown. We evaluated the prevalence and incidence density of MAFLD and investigated the association between healthy lifestyle and the risk of MAFLD. Methods A cross-sectional analysis was conducted on 37,422 participants to explore the prevalence of MAFLD. A cohort analysis of 18,964 individuals was conducted to identify the incidence of MAFLD, as well as the association between healthy lifestyle and MAFLD. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) with adjustments for confounding factors. Results The prevalence of MAFLD, non-alcoholic fatty liver disease, and their comorbidities were 30.38%, 28.09%, and 26.13%, respectively. After approximately 70 thousand person-years of follow-up, the incidence densities of the three conditions were 61.03, 55.49, and 51.64 per 1,000 person-years, respectively. Adherence to an overall healthy lifestyle was associated with a 19% decreased risk of MAFLD (HR, 0.81; 95% CI, 0.72 to 0.92), and the effects were modified by baseline age, sex, and body mass index (BMI). Subgroup analyses revealed that younger participants, men, and those with a lower BMI experienced more significant beneficial effects from healthy lifestyle. Conclusion Our results highlight the beneficial effect of adherence to a healthy lifestyle on the prevention of MAFLD. Health management for improving dietary intake, physical activity, and smoking and drinking habits are critical to improving MAFLD.

Abstract Lower-grade gliomas (LGGs), despite their generally indolent clinical course, are characterized by invasive growth patterns and genetic heterogeneity, which can lead to malignant transformation, underscoring the need for improved prognostic markers and therapeutic strategies. This study utilized single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq to identify a novel cell type, referred to as "Prol," characterized by increased proliferation and linked to a poor prognosis in patients with LGG, particularly under the context of immunotherapy interventions. A signature, termed the Prol signature, was constructed based on marker genes specific to the Prol cell type, utilizing an artificial intelligence (AI) network that integrates traditional regression, machine learning, and deep learning algorithms. This signature demonstrated enhanced predictive accuracy for LGG prognosis compared to existing models and showed pan-cancer prognostic potential. The mRNA expression of the key gene PTTG1 from the Prol signature was further validated through quantitative reverse transcription polymerase chain reaction (qRT-PCR). Our findings not only provide novel insights into the molecular and cellular mechanisms of LGG but also offer a promising avenue for the development of targeted biomarkers and therapeutic interventions.

Abstract Background Coronary artery thrombosis and myocardial ischemia caused by giant coronary aneurysms are the main causes of death in children with Kawasaki disease. The use of thrombolytic therapy in children with Kawasaki disease who have coronary thrombosis is a controversial topic, especially with respect to the timing of treatment. Case presentation In this article, we report a case of a child aged two years and nine months with Kawasaki disease whose coronary arteries had no involvement in the acute phase. However, by only one week after discharge, the patient returned because we found giant coronary aneurysms complicated by thrombosis via echocardiography. Despite aggressive thrombolytic therapy, the child developed myocardial ischemia during thrombolytic therapy. Fortunately, because of timely treatment, the child’s thrombus has dissolved, and the myocardial ischemia has resolved. Conclusions This case suggests that for patients at high risk of coronary artery aneurysms, echocardiography may need to be reviewed earlier. Low-molecular-weight heparin should be added to antagonize the early procoagulant effects of warfarin when warfarin therapy is initiated. In the case of first-detected coronary thrombosis, aggressive thrombolytic therapy may be justified, particularly during the acute and subacute phases of the disease course.

Abstract P2X receptors, a subfamily of ligand-gated ion channels activated by extracellular ATP, are implicated in various physiopathological processes, including inflammation, pain perception, and immune and respiratory regulations. Structural determinations using crystallography and cryo-EM have revealed that the extracellular three-dimensional architectures of different P2X subtypes across various species are remarkably identical, greatly advancing our understanding of P2X activation mechanisms. However, structural studies yield paradoxical architectures of the intracellular domain (ICD) of different subtypes (e.g., P2X3 and P2X7) at the apo state, and the role of the ICD in P2X functional regulation remains unclear. Here, we propose that the P2X3 receptor’s ICD has an apo state conformation similar to the open state but with a less tense architecture, containing allosteric sites that influence P2X3’s physiological and pathological roles. Using covalent occupancy, engineered disulfide bonds and voltage-clamp fluorometry, we suggested that the ICD can undergo coordinated motions with the transmembrane domain of P2X3, thereby facilitating channel activation. Additionally, we identified a novel P2X3 enhancer, PSFL77, and uncovered its potential allosteric site located in the 1α3β domain of the ICD. PSFL77 modulated pain perception in P2rx3 +/+, but not in P2rx3 −/−, mice, indicating that the 1α3β, a “tunable” region implicated in the regulation of P2X3 functions. Thus, when P2X3 is in its apo state, its ICD architecture is fairly ordered rather than an unstructured outward folding, enabling allosteric modulation of the signaling of P2X3 receptors.

Abstract The Qinghai-Tibet Plateau (QTP), renowned for its exceptional biological diversity, is home to numerous endemic species. However, research on the virology of vulnerable vertebrates like yaks remains limited. In this study, our objective was to use metagenomics to provide a comprehensive understanding of the diversity and evolution of the gut virome in yak populations across different regions of the QTP. Our findings revealed a remarkably diverse array of viruses in the gut of yaks, including those associated with vertebrates and bacteriophages. Notably, some vertebrate-associated viruses, such as astrovirus and picornavirus, showed significant sequence identity across diverse yak populations. Additionally, we observed differences in the functional profiles of genes carried by the yak gut virome across different regions. Moreover, the virus-bacterium symbiotic network that we discovered holds potential significance in maintaining the health of yaks. Overall, this research expands our understanding of the viral communities in the gut of yaks and highlights the importance of further investigating the interactions between viruses and their hosts. These data will be beneficial for revealing the crucial role that viruses play in the yak gut ecology in future studies.

Abstract Apoptotic bodies (ABs) are extracellular vesicles released during apoptosis and possess diverse biological activities. Initially, ABs were regarded as garbage bags with the main function of apoptotic cell clearance. Recent research has found that ABs carry and deliver various biological agents and are taken by surrounding and distant cells, affecting cell functions and behavior. ABs-mediated intercellular communications are involved in various physiological processes including anti-inflammation and tissue regeneration as well as the pathogenesis of a variety of diseases including cancer, cardiovascular diseases, neurodegeneration, and inflammatory diseases. ABs in biological fluids can be used as a window of altered cellular and tissue states which can be applied in the diagnosis and prognosis of various diseases. The structural and constituent versatility of ABs provides flexibility for tailoring ABs according to disease diagnostic and therapeutic needs. An in-depth understanding of ABs’ constituents and biological functions is mandatory for the effective tailoring of ABs including modification of bio membrane and cargo constituents. ABs’ tailoring approaches including physical, chemical, biological, and genetic have been proposed for bench-to-bed translation in disease diagnosis, prognosis, and therapy. This review summarizes the updates on ABs tailoring approaches, discusses the existing challenges, and speculates the prospects for effective diagnostic and therapeutic applications.

Dracocephalum is a large genus comprises approximately 80 species of perennial herbs, mainly distributed in high elevation regions of temperate and Central Asia, with about half native to China. Within the genus, D. argunense and D. integrifolium are important herbs with great medicinal value. We sequenced plastomes of these two species for the first time. These plastomes showed a typical quadripartite structure and the length varied from 149,978 bp (D. integrifolium) to 150,802 bp (D. argunense). Plastomes of D. argunense and D. integrifolium included 127 and 133 genes, respectively. Phylogenetic analyses supported the monophyly of the redefined Dracocephalum and systematic relationships within the sampled species were well resolved. Our study added new genetic information about D. argunense and D. integrifolium and has great potential for further diversity studies, phylogenetic studies, and understanding of evolutionary history in Dracocephalum.

Wind power has been developing rapidly as a key measure to mitigate human-driven global warming. The understanding of the development and impacts of wind farms on local climate and vegetation is of great importance for their rational use but is still limited. In this study, we combined remote sensing and on-site investigations to identify wind farm locations in Inner Mongolia and performed landscape pattern analyses using Fragstats. We explored the impacts of wind farms on land surface temperature (LST) and vegetation net primary productivity (NPP) between 1990 and 2020 by contrasting these metrics in wind farms with those in non-wind farm areas. The results showed that the area of wind farms increased rapidly from 1.2 km2 in 1990 to 10,755 km2 in 2020. Spatially, wind farms are mainly clustered in three aggregation areas in the center. Further, wind farms increased nighttime LST, with a mean value of 0.23 °C, but had minor impacts on the daytime LST. Moreover, wind farms caused a decline in NPP, especially over forest areas, with an average reduction of 12.37 GC/m². Given the impact of wind farms on LST and NPP, we suggest that the development of wind farms should fully consider their direct and potential impacts. This study provides scientific guidance on the spatial pattern of future wind farms.

To examine the reliability and validity of revised Parental Phubbing Scale (PPS) and measure the level of parental phubbing, 701 Chinese children aged 3-6 years and their parents were investigated. The results indicated that: (1) the construct validity of the PPS was supported by the best-fit one-factor model; (2) concurrent validity was established by demonstrating that the PPS was positively related to parental smartphone addiction; (3) the PPS was positively correlated with authoritarian parenting style, established the predictive validity; (4) internal reliability was satisfactory. The results also showed that fathers' and mothers' phubbing were at the intermediate level; moreover, phubbing levels were highest among parents aged 31-40. The findings conclude that PPS can be used as a reliable and valid measure to evaluate parents' phubbing and also highlight the need for further research on mothers' and fathers' phubbing.

Abstract Background There were limited data investigating platelet indices in predicting peritoneal dialysis (PD) outcomes on comorbidities. The aim of this study was to evaluate the association between platelet indices and new-onset comorbidity and all-cause mortality in PD patients. Methods A single-center, retrospective observational cohort study was conducted in incident PD patients from 28 December 2011 to 24 January 2018, and followed up until 31 December 2022. Time to the first new-onset cardiovascular disease (CVD) and time to the first new-onset infection event after PD were identified as the primary outcomes. All-cause mortality was identified as the secondary endpoint. The correlation between platelet indices and comorbidities and all-cause mortality were assessed by Cox model. Data of liver disease status was not collected and analyzed. Survival curves were performed by Kaplan-Meier method with log-rank tests. Results A total of 250 incident PD patients with a median follow-up of 6.79 (inter-quarter range 4.05, 8.89) years was included. A total of 81 and 139 patients experienced the first new-onset CVD and infection event respectively during the follow-up period. High mean platelet volume (MPV) was independently associated with high risk of time to the first new-onset CVD (HR 1.895, 95% CI 1.174–3.058, p = 0.009) and all-cause mortality (HR 1.710, 95% CI 1.155–2.531, p = 0.007). Patients with low mean platelet volume to platelet count ratio (MPV/PC) were prone to occur the new-onset infection events (log rank 5.693, p = 0.017). Low MPV/PC (HR 0.652, 95% CI 0.459–0.924, p = 0.016) was significantly associated with the time to the first new-onset infection event on PD. Conclusions Platelet indices were associated with the new-onset CVD, infectious comorbidities and all-cause mortality on PD. Low MPV/PC was associated with time to the first new-onset infection event in PD patients. Moreover, high MPV was associated with new-onset CVD and all-cause mortality in the incident PD patients.

Abstract Purpose To assess the interactive relationship between blood pressure status and diabetic mellitus (DM) with ganglion cell complex (GCC) thickness in elderly individuals in rural China. Methods Participants aged 50 years and older in a rural area of Daxing District, Beijing, were recruited in this study from October 2018 to November 2018. All subjects underwent a comprehensive systemic and ocular examination. Blood pressure status was graded as normotension, controlled hypertension and uncontrolled hypertension according to blood pressure measurements and the use of any medication for hypertension treatment. GCC parameters were measured by spectral-domain optical coherence tomography (SD-OCT). Generalized linear models (GLM) adjusted for related potential confounders were used to assess the interaction between DM and blood pressure status. Results Among 1415 screened subjects (2830 eyes), a total of 1117 eyes were enrolled in the final analysis. GLM analysis showed a significant interactive relationship between DM with uncontrolled hypertension status (β = 3.868, p = 0.011). GCC thickness would decrease 0.255 μm per year as the age increased (β=-0.255, p

Abstract Background Ventricular-arterial coupling (VAC) has garnered increasing interest in critical care. The prognostic significance of left ventricular-arterial coupling (LVAC) in this context remains a topic of debate. Objective This study aimed to explore the association between LVAC and patient outcomes in sepsis. Methods Patients with sepsis or septic shock admitted to the intensive care unit (ICU) were included. LVAC was evaluated using the arterial elastance (Ea)/left ventricular end-systolic elastance (Ees) ratio. Prognostic indicators, including 30-day mortality, length of ICU stay, mechanical ventilation (MV), changes in delta lactate levels, and oxygen index were also collected. Results A total of 388 patients were enrolled in this study. A U-shaped relationship was observed between LVAC and 30-day mortality, with an optimal LVAC value of 1.19 identified. For LVAC values above 1.19, the odds ratio (OR) for 30-day mortality was 1.07 (95% confidence interval [CI] 1.01–1.14). Below this threshold, OR was 0.85 (95% CI 0.73, 0.99). Similarly, in the curve for ICU-free days, a β value of − 8.64 (95% CI − 16.53, − 0.76) was noted for LVAC values over 1.26. For ventilator-free time, the kink point was 1.24, with significant β values on both sides of this threshold [− 226.49 (95% CI − 411.59, − 41.38) and 147.67 (95% CI 12.40, 282.93), respectively]. Conclusions This study established U-shaped associations between LVAC and various clinical outcomes in septic patients. Optimizing LVAC could potentially enhance patient prognosis. Given the slight variations in optimal LVAC values across different patient populations, individualized LVAC titration may be beneficial in improving clinical outcomes.

Abstract In this paper, we investigate the quasi-two-body decays $$B_c \rightarrow K_0^{*}(1430,1950) D_{(s)} \rightarrow K \pi D_{(s)}$$ B c → K 0 ∗ ( 1430 , 1950 ) D ( s ) → K π D ( s ) within the perturbative QCD (PQCD) framework. The S-wave two-meson distribution amplitudes (DAs) are introduced to describe the final state interactions of the $$K\pi $$ K π pair, which involve the time-like form factors and the Gegenbauer polynomials. In the calculations, we adopt two kinds of parameterization schemes to describe the time-like form factors: one is the relativistic Breit–Wigner (RBW) formula, which is usually more suitable for the narrow resonances, and the other is the LASS line shape proposed by the LASS Collaboration, which includes both the resonant and nonresonant components. We find that the branching ratios and the direct CP violations for the decays $$B_c \rightarrow K_0^{*}(1430) D_{(s)}$$ B c → K 0 ∗ ( 1430 ) D ( s ) obtained from those of the quasi-two-body decays $$B_c \rightarrow K_0^{*}(1430) D_{(s)} \rightarrow K \pi D_{(s)}$$ B c → K 0 ∗ ( 1430 ) D ( s ) → K π D ( s ) under the narrow width approximation (NWA) can be consistent well with the previous PQCD results calculated in the two-body framework by assuming that $$K^*_0(1430)$$ K 0 ∗ ( 1430 ) is the lowest lying $$\bar{q} s$$ q ¯ s state, which is the so-called scenario II (SII). We conclude that the LASS parameterization is more suitable to describe the $$K_0^{*}(1430)$$ K 0 ∗ ( 1430 ) than the RBW formula, and the nonresonant components play an important role in the branching ratios of the decays $$B_c \rightarrow K_0^{*}(1430) D_{(s)} \rightarrow K \pi D_{(s)}$$ B c → K 0 ∗ ( 1430 ) D ( s ) → K π D ( s ) . In view of the large difference between the decay width measurements for the $$K_0^{*}(1950)$$ K 0 ∗ ( 1950 ) given by BaBar and LASS collaborations, we calculate the branching ratios and the CP violations for the quasi-two-body decays $$B_c \rightarrow K_0^{*}(1950) D_{(s)} \rightarrow K \pi D_{(s)}$$ B c → K 0 ∗ ( 1950 ) D ( s ) → K π D ( s ) by using two values, $$\Gamma _{K^*_0(1950)}=0.100\pm 0.04$$ Γ K 0 ∗ ( 1950 ) = 0.100 ± 0.04 GeV and $$\Gamma _{K^*_0(1950)}=0.201\pm 0.034$$ Γ K 0 ∗ ( 1950 ) = 0.201 ± 0.034 GeV, besides the two kinds of parameterizations for the resonance $$K^*_0(1950)$$ K 0 ∗ ( 1950 ) . We find that the branching ratios and the direct CP violations for the decays $$B_c \rightarrow K_0^{*}(1950) D_{(s)} \rightarrow K \pi D_{(s)}$$ B c → K 0 ∗ ( 1950 ) D ( s ) → K π D ( s ) have not as large difference between the two parameterizations as the case of decays involving the $$K^*_0(1430)$$ K 0 ∗ ( 1430 ) , especially for the results with $$\Gamma _{K^*_0(1950)}=0.201\pm 0.034$$ Γ K 0 ∗ ( 1950 ) = 0.201 ± 0.034 GeV. The effect of the nonresonant component in the $$K^*_0(1950)$$ K 0 ∗ ( 1950 ) may be not so serious as that in the $$K^*_0(1430)$$ K 0 ∗ ( 1430 ) . The quasi-two-body decays $$B^+_c \rightarrow K^{*+}_0(1430) D^{0} \rightarrow K^0 \pi ^+ D^{0}$$ B c + → K 0 ∗ + ( 1430 ) D 0 → K 0 π + D 0 and $$B^+_c \rightarrow K^{*0}_0(1430) D^{+} \rightarrow K^+ \pi ^- D^{+}$$ B c + → K 0 ∗ 0 ( 1430 ) D + → K + π - D + have large branching ratios, which can reach to the order of $$10^{-4}$$ 10 - 4 and are most likely to be observed in the future LHCb experiments. Furthermore, the branching ratios of the quasi-two-body decays $$B_c \rightarrow K_0^{*}(1950) D_{(s)} \rightarrow K \pi D_{(s)}$$ B c → K 0 ∗ ( 1950 ) D ( s ) → K π D ( s ) are about one order smaller than those of the corresponding decays $$B_c \rightarrow K_0^{*}(1430) D_{(s)} \rightarrow K \pi D_{(s)}$$ B c → K 0 ∗ ( 1430 ) D ( s ) → K π D ( s ) .

Convolutional neural network (CNN) models are widely used in landslide susceptibility assessment due to their powerful feature extraction capabilities, and traditional CNN is no longer able to meet the requirements. Therefore, this paper proposes a multi-scale convolutional neural networks (MSCNN) model that can take into account deep and shallow features. By increasing the depth of the model and expanding the receptive field of samples, the MSCNN can tap deeper and more stable features to improve the reliability of landslide susceptibility assessment in complex scenarios. In this study, Shenzhen City is selected as the research area, and 12 landslide conditioning factors of landslides in Shenzhen City were selected based on systematic and representative principles. A multi-scale convolutional neural network landslide susceptibility assessment model is constructed and compared with methods such as multilayer perceptron (MLP), support vector machine (SVM), and random forest (RF). The results show that the AUC value (0.99) of the MSCNN model constructed in this paper is higher than that of MLP (0.97), SVM (0.91), and RF (0.85), which proves that the proposed MSCNN model has excellent prediction ability. The area of extremely high susceptibility in Shenzhen City is approximately 105.3 km², accounting for 4.98% of the total area of the study area, mainly distributed in Longgang District with steep slopes, sparse vegetation cover, and frequent human engineering activities. Slope, surface roughness, and surface relief are identified as the main conditioning factors affecting landslides in Shenzhen City. The landslide susceptibility mapping implemented in this paper reflects the current distribution of landslide disasters in Shenzhen City, providing data support and key technical support for future landslide disaster prevention and control in Shenzhen City.

Abstract This study aimed to construct a novel pelvis-prostate model BPPP which consists of body mass index (BMI), prostate volume (PV), pelvic cavity index (PCI) and prostate-muscle index (PMI) to predict the immediate urinary continence after Retzius-sparing robot assisted laparoscopic radical prostatectomy (RS-RARP). The perioperative data of patients with prostate cancer who underwent RS-RARP in the department of urology of Nanjing Drum Tower Hospital from June 2018 to June 2022 were retrospectively analyzed. 280 patients were eligible for this study in total. Multivariate analysis showed that BMI, PV, PCI, PMI and NVB preservation were significantly associated with immediate urinary continence after RS-RARP. Subgroup analysis showed that patients with low BMI, low PV, high PCI and high PMI had a higher recovery rate of immediate urinary continence. The area under the curve of BPPP (BMI + PV + PCI + PMI) for predicting the immediate recovery of urinary continence after RS-RARP was 0.726. Delong test showed that the area under the curve of the combined test for predicting the immediate urinary continence after RS-RARP was better compared with single parameter (p

Abstract Macrophages may acquire a reparative phenotype that supports tissue repair and remodeling in response to tissue injury. However, the metabolic requirements underpinning this process are incompletely understood. Here, we show that posttranslational modification (PTM) of PPARγ regulates lipid synthesis in response to wound microenvironmental cues and that metabolic rewiring orchestrates function of reparative macrophages. In injured tissues, repair signaling leads to decreased macrophage PPARγ threonine 166 (T166) phosphorylation, which results in a partially active PPARγ transcriptional program comprised of increased binding activity to the regulator regions of lipid synthesis-associated genes, thereby increased lipogenesis. The accumulated lipids serve as signaling molecules, triggering STAT3-mediated growth factor expression, and supporting the synthesis of phospholipids for the expansion of the endoplasmic reticulum (ER), which is required for protein secretion. Genetic or pharmacological inhibition of PPARγ T166 phosphorylation promotes the reparative function of macrophages and facilitates tissue regeneration. In summary, our work identifies PPARγ T166-regulated lipid biosynthesis as an essential pathway for meeting the anabolic demands of the activation and function of macrophages and provides a rationale for potential therapeutic targeting of tissue repair.

Abstract Background The prognostic value of the pretreatment prognostic nutritional index (PNI) for gynaecological malignancies remain unclear. This meta-analysis aimed to explore the predictive significance of the PNI for gynaecological tumours. Methods The PubMed, Embase, Web of Science, and Cochrane Library databases were searched up to January 30, 2024, to identify relevant studies. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess the associations of the PNI with overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) in patients with gynaecological tumours. We examined the correlation of the PNI with clinicopathological parameters of patients with gynaecological carcinoma by utilizing pooled odds ratios (ORs) and 95% CIs. Results A total of 28 articles involving 9,428 patients were included in the meta-analysis. The results revealed that a low PNI significantly predicted worse OS (HR = 1.60, 95% CI: 1.39–1.84, P

In recent years, surface molecular imprinting technology has drawn a lot of attention for its application in sample pretreatment for food analysis. Due to the complexity of the food matrix, there are high requirements for the sensitivity and selectivity of food detection. Surface molecularly imprinted polymers are polymerized on the surface of a solid support, and when the template is removed, a cavity is formed to adsorb the target or its structural analogues. Various targets ranging from contaminants, toxicants and adulterants to natural active ingredients can be efficiently imprinted, thus making it easier to extract them from food matrices like dairy products, fruits and vegetables, meat products, and drinks. Owing to their potential to improve the selectivity and adsorption capacity and hence the accuracy of analysis, multi-template imprinting strategies and virtual template imprinting have become research hotspots. This article summarizes the design strategies, carrier types, preparation methods of surface molecularly imprinted polymers and reviews the progress made over the past five years in their application in sample pretreatment for food analysis in order to provide a reference for the application of surface molecularly imprinted technology in food analysis.

Abstract Background This study aimed to evaluate the effectiveness and safety of recombinant human endostatin (Rh-endostatin) plus programmed cell death 1 (PD-1) inhibitors and chemotherapy as first-line treatment for advanced or metastatic non-small cell lung cancer (NSCLC) in a real-world setting. Methods This was a retrospective study on patients with EGFR/ALK-negative, advanced or metastatic NSCLC. Patients received Rh-endostatin plus PD-1 inhibitors and chemotherapy every three weeks for 4 to 6 cycles. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results A total of 68 patients were included in this retrospective analysis. As of data cutoff (December 13, 2022), the median follow-up of 21.4 months (interquartile range [IQR], 8.3-44.4 months). The median PFS and OS was 22.0 (95% confidence interval [CI]: 16.6-27.4) and 31.0 months (95% CI: 23.4-not evaluable [NE]), respectively. The ORR was 72.06% (95% CI: 59.85-82.27%), and DCR was 95.59% (95% CI: 87.64-99.08%). Patients with stage IIIB/IIIC NSCLC had significantly longer median PFS (23.4 vs. 13.2 months), longer median OS (not reached vs. 18.0 months), and higher ORR (89.2% vs. 51.6%) than those with stage IV NSCLC (all p ≤ 0.001). The ORR was higher in patients with high PD-L1 expression (tumor proportion score [TPS] ≥ 50%) than in those with low PD-L1 expression or positive PD-L1 expression (75% vs. 50%, p = 0.025). All patients experienced treatment-related adverse events (TRAEs), and ≥ grade 3 TRAEs occurred in 16 (23.53%) patients. Conclusions Rh-endostatin combined with PD-1 inhibitors plus chemotherapy as first-line treatment yielded favorable effectiveness with a manageable profile in patients with advanced or metastatic NSCLC, representing a promising treatment modality.

Abstract Lipid nanoparticle-assisted mRNA inhalation therapy necessitates addressing challenges such as resistance to shear force damage, mucus penetration, cellular internalization, rapid lysosomal escape, and target protein expression. Here, we introduce the innovative “LOOP” platform with a four-step workflow to develop inhaled lipid nanoparticles specifically for pulmonary mRNA delivery. iLNP-HP08LOOP featuring a high helper lipid ratio, acidic dialysis buffer, and excipient-assisted nebulization buffer, demonstrates exceptional stability and enhanced mRNA expression in the lungs. By incorporating mRNA encoding IL-11 single chain fragment variable (scFv), scFv@iLNP-HP08LOOP effectively delivers and secretes IL-11 scFv to the lungs of male mice, significantly inhibiting fibrosis. This formulation surpasses both inhaled and intravenously injected IL-11 scFv in inhibiting fibroblast activation and extracellular matrix deposition. The HP08LOOP system is also compatible with commercially available ALC0315 LNPs. Thus, the “LOOP” method presents a powerful platform for developing inhaled mRNA nanotherapeutics with potential for treating various respiratory diseases, including idiopathic pulmonary fibrosis.

Abstract Background High levels of lactate are positively associated with prognosis and mortality in pulmonary hypertension (PH). Lactate dehydrogenase A (LDHA) is a key enzyme for the production of lactate. This study is undertaken to investigate the role and molecular mechanisms of lactate and LDHA in PH. Methods Lactate levels were measured by a lactate assay kit. LDHA expression and localization were detected by western blot and Immunofluorescence. Proliferation and migration were determined by CCK8, western blot, EdU assay and scratch-wound assay. The right heart catheterization and right heart ultrasound were measured to evaluate cardiopulmonary function. Results In vitro, we found that lactate promoted proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) in an LDHA-dependent manner. In vivo, we found that LDHA knockdown reduced lactate overaccumulation in the lungs of mice exposed to hypoxia. Furthermore, LDHA knockdown ameliorated hypoxia-induced vascular remodeling and right ventricular dysfunction. In addition, the activation of Akt signaling by hypoxia was suppressed by LDHA knockdown both in vivo and in vitro. The overexpression of Akt reversed the inhibitory effect of LDHA knockdown on proliferation in PASMCs under hypoxia. Finally, LDHA inhibitor attenuated vascular remodeling and right ventricular dysfunction in Sugen/hypoxia mouse PH model, Monocrotaline (MCT)-induced rat PH model and chronic hypoxia-induced mouse PH model. Conclusions Thus, LDHA-mediated lactate production promotes pulmonary vascular remodeling in PH by activating Akt signaling pathway, suggesting the potential role of LDHA in regulating the metabolic reprogramming and vascular remodeling in PH.

Abstract Background Sleeping late has been a common phenomenon and brought harmful effects to our health. The purpose of this study was to investigate the association between sleep timing and major adverse cardiovascular events (MACEs) in patients with percutaneous coronary intervention (PCI). Methods Sleep onset time which was acquired by the way of sleep factors questionnaire in 426 inpatients was divided into before 22:00, 22:00 to 22:59, 23:00 to 23:59 and 24:00 and after. The median follow-up time was 35 months. The endpoints included angina pectoris (AP), new myocardial infarction (MI) or unplanned repeat revascularization, hospitalization for heart failure, cardiac death, nonfatal stroke, all-cause death and the composite endpoint of all events mentioned above. Cox proportional hazards regression was applied to analyze the relationship between sleep timing and endpoint events. Results A total of 64 composite endpoint events (CEEs) were reported, including 36 AP, 15 new MI or unplanned repeat revascularization, 6 hospitalization for heart failure, 2 nonfatal stroke and 5 all-cause death. Compared with sleeping time at 22:00–22:59, there was a higher incidence of AP in the bedtime ≥ 24:00 group (adjusted HR: 5.089; 95% CI: 1.278–20.260; P = 0.021). In addition, bedtime ≥ 24:00 was also associated with an increased risk of CEEs in univariate Cox regression (unadjusted HR: 2.893; 95% CI: 1.452–5.767; P = 0.003). After multivariable adjustments, bedtime ≥ 24:00 increased the risk of CEEs (adjusted HR: 3.156; 95% CI: 1.164–8.557; P = 0.024). Conclusion Late sleeping increased the risk of MACEs and indicated a poor prognosis. It is imperative to instruct patients with PCI to form early bedtime habits.

Aiming at the issue of low accuracy in crop mapping and growth monitoring caused by imprecise calibration of radar time-series data, this paper proposed a Synthetic Aperture Radar (SAR) spatio-temporal error compensation method. By constructing a compensation reference image using the buildings with stable backscattering coefficients in the study area, the error correction of time-series SAR data was realized based on the compensation model. The compensated SAR data were used to establish the Sugarcane Growth Index (SGI) according to the growth curve of sugarcane. The sugarcane area was extracted after combining the compensated SGI and optical image, and the accuracy of F1 on sugarcane distribution extraction was 92.12%. There was an improvement of 4.11% compared with no compensation method. On this basis, the newly planted and ratoon sugarcane were further classified by the expectation maximization algorithm based on the compensated SAR image at the seedling stage. The newly planted sugarcane and the ratoon sugarcane could be accurately distinguished with area extraction accuracy of 82.06% and 80.59%, respectively. Moreover, the compensated SAR data of time series during the tillering to maturity stages were used to estimate the sugarcane height, yielding an R2 value of 0.717 using a quadratic polynomial model. The Spatio-temporal error compensation method for distributed targets proposed in this study can reduce the loss of SAR data across various times and regions, and achieve accurate results of sugarcane distribution extraction and plant height estimation.