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Abstract Background Esophageal cancer is a significant global health concern, ranking seventh in incidence and sixth in mortality. It encompasses two pathological types: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma, with ESCC being more prevalent globally and associated with higher mortality rates. The POU (Pit-Oct-Unc) domain family transcription factors, comprising 15 members, play important roles in embryonic development and organ formation. Aberrant expression of POUs has been observed in several human cancers, influencing cell proliferation, tumor invasion, and drug resistance. However, their specific role in ESCC remains unknown. Methods We analyzed TCGA and GEO databases to assess POUs expression in ESCC tissues. Kaplan-Meier and ROC analyses were used to evaluate the prognostic value of POUs. Gene Set Enrichment Analysis and Protein-Protein interaction network were used to explore the potential pathway. Functional assays (Cell Counting Kit-8, EdU Staining assay, and cloning formation assay) and mechanism analyses (RNA-seq, flow cytometry, and Western blot) were conducted to determine the effects of POU4F1 knockdown on ESCC cell phenotypes and signaling pathways. Results POU4F1 and POU6F2 were upregulated in various cancer tissues, including ESCC, compared to normal tissues. POU4F1 expression was significantly correlated with patient survival and superior to previous models (AUC = 0.776). Knockdown of POU4F1 inhibited ESCC cell proliferation and affected cell cycle, autophagy, and DNA damage pathways in ESCC cells. Conclusion POU4F1 is a novel and promising prognostic and therapeutic target for ESCC patients, providing insights into potential treatment strategies.

Abstract Background The prevalence of obesity is escalating. Previous research has concentrated on the link between frailty and obesity; however, the association between prefrailty and obesity has been less studied. Prefrailty screening and intervention may prevent or postpone frailty in older persons. Objective The study was to investigate into the relationship between prefrailty and several obesity indicators in Chinese community-dwelling older individuals. Methods This research employed the Frailty Screening Index to investigate the frailty phenotype of people living in Shanghai. Bioelectrical impedance analysis was used for evaluating body composition. Results There were 510 participants (39.0%) with high visceral adipose areas. Participants with a high visceral adipose area showed a higher risk of prefrailty (adjusted OR, 1.53; 95% CI, 1.19–1.96), according to multivariate models. When body mass index (BMI) and visceral fat area (VFA) were combined, it was discovered that having an overweight BMI with normal VFA was a protective factor for prefrailty (corrected OR, 0.62; 95% CI, 0.43–0.90), but having a normal weight but excess VFA increased the risk of prefrailty (corrected OR, 1.87; 95% CI, 1.15–3.03). Conclusion Visceral fat obesity is an independent risk factor for prefrailty in Chinese older adults. Implementing targeted interventions, such as dietary modifications, increased physical activity, and other lifestyle changes, could play a crucial role in reducing the risk of prefrailty and improving overall health outcomes in this population.

Background Surgical treatment for hinge failure in mega‐prosthesis continues to be a challenge. This study introduces a new method for treating hinge failure by using a unilateral prosthesis and hinge revision. Case Presentation We here present two patients who underwent mega‐prosthesis reconstruction after resection of osteosarcoma in the distal femur. To address the issue of knee hyperextension after mega‐prosthesis reconstruction, one patient underwent three revision surgeries, two surgeries were performed using the original hinge, and one surgery involved a newly designed hinge. To resolve the problem of dislocation, one patient underwent three revisions, with the first two revisions not involving hinge replacement and the third revision involving a newly designed hinge. Two replacements of unilateral prosthesis and hinge renovations were successful. Conclusions Unilateral prosthesis and newly designed hinge device revision are effective in treating the failure of old‐fashioned mega‐prosthesis hinges.

Abstract Background Patients with coronavirus disease 2019 have a high incidence of thrombosis that decreases after recovery. When coronavirus disease 2019 is accompanied by diseases prone to thrombosis, risk of post-infection thrombotic events may increase. Case presentation We report a case of digital ischemic gangrene in a 24-year-old Chinese female with systemic lupus erythematosus after recovery from coronavirus disease 2019. The pathogenesis was related to clinical characteristics of systemic lupus erythematosus, hypercoagulability caused by coronavirus disease 2019, and second-hit due to viral infection. Conclusion Patients with autoimmune diseases should remain alert to autoimmune system disorders induced by severe acute respiratory syndrome coronavirus 2 and other viruses. Treatment for these patients should be strictly standardized, and appropriate anticoagulation methods should be selected to prevent thrombosis.

Abstract Background Studies on single-target PET imaging of gastrin-releasing peptide receptor (GRPR), prostate-specific membrane antigen (PSMA), or neurotensin receptor 1(NTR1) have been reported. However, the performance of these three targets in the progression of PCa remains unclear. Our study aims to compare the expression of GRPR, PSMA, and NTR1 in patients with prostatic intraepithelial neoplasia (PIN), prostate cancer (PCa), and lymph node metastasis. We synthesized molecular probes targeting the markers to achieve a non-invasive precise detection of PCa patients with PET/CT imaging. Methods In this study, the expression of GRPR, PSMA, and NTR1 was evaluated by immunohistochemistry in 34 PIN, 171 PCa, and 22 lymph node metastasis tissues of patients. The correlation between their expression and the clinicopathological parameters of PCa patients was assessed. Sixteen PCa patients with different Gleason scores (GS) underwent dual-tracer (68Ga-NOTA-RM26 and 68Ga-NOTA-PSMA617) PET/CT. Results In the PIN stage, the expression of GRPR was significantly higher than that of PSMA and NTR1 (P

Background Revision of tumor‐type prosthetic fractures is very challenging in clinical work. Traditional repair methods may not be able to meet the needs of complex cases or cause greater bone damage. Therefore, more effective and reliable solutions need to be found. Case Presentation This study presents a novel revision technique for managing fractures of tumor‐type total elbow prostheses. A 57‐year‐old female patient was diagnosed with a left distal humeral bone tumor accompanied by pathological fracture and underwent customized tumor‐type total elbow prosthesis arthroplasty. After 5 years, she experienced pain and encountered difficulty in flexing the left elbow while lifting heavy objects. The X‐ray examination revealed a fracture of the distal humeral prosthesis. As a response, the elbow joint was initially explored, and the damaged component of the prosthesis was extracted. Subsequently, we utilized 3D printing technology to design a split‐piece sleeve prosthesis and effectively restored the fractured left distal humerus implant. During the 2‐year follow‐up, The X‐ray demonstrated satisfactory positioning of the prosthesis, which remained securely affixed without any indications of loosening. The Mayo Elbow Performance Score (MEPS) reached 80 points, the Musculoskeletal Tumor Society (MSTS) attained a score of 28 points, and the range of motion of the elbow was measured between 25° and 110°, revealing favorable functional outcomes. Conclusion The utilization of a 3D printed split‐piece sleeve prosthesis presents a viable clinical treatment strategy for addressing fractures in tumor‐type elbow prostheses.

The S(IV)–Fe(II)/PM pretreatment has demonstrated preliminary potential as an effective ultrafiltration (UF) pretreatment technology. However, a comprehensive understanding of its impact on UF membrane fouling control and the dynamic evolution of membrane fouling during prolonged operation is still lacking. In this study, a relatively prolonged fouling experiment was conducted. Results revealed that the S(IV)–Fe(II)/PM pretreatment exhibited superior performance over Al(III) coagulation pretreatment in mitigating the transmembrane pressure difference and addressing both reversible and irreversible membrane fouling. The application of a cluster analysis method to classify membrane fouling evolution stages further confirmed that S(IV)–Fe(II)/PM pretreatment effectively decelerated the rate of membrane fouling evolution. The surface cake layer of UF membranes pretreated with S(IV)–Fe(II)/PM exhibited greater looseness and smoothness. It also showed better results than Al(III) coagulation pretreatment in reducing the accumulation of organic foulants, controlling the Si content and reducing the total microorganisms and live microorganisms in the UF feed water. Variance Partitioning Analysis indicated that the combined contribution of organic, inorganic, and biological foulants was the most significant for UF membranes after S(IV)–Fe(II)/PM pretreatment (50.4%) and UF membranes after Al(III) coagulation pretreatment (70.2%). These findings underscore the efficacy of S(IV)–Fe(II)/PM pretreatment in controlling UF membrane fouling under prolonged operation. HIGHLIGHTS S(IV)/Fe(II)/PM pretreatment efficiently mitigated UF membrane fouling during long-term operation.; S(IV)/Fe(II)/PM pretreatment yielded a long uncontaminated stage and accelerated contaminated stage.; S(IV)/Fe(II)/PM pretreatment suppressed the contribution of organic–inorganic–biological composite fouling.;

Abstract Depression is a serious psychiatric illness that causes great inconvenience to the lives of elderly individuals. However, the diagnosis of depression is somewhat subjective. Nontargeted gas chromatography (GC)/liquid chromatography (LC)–mass spectrometry (MS) was used to study the plasma metabolic profile and identify objective markers for depression and metabolic pathway variation. We recruited 379 Chinese community-dwelling individuals aged ≥ 65. Plasma samples were collected and detected by GC/LC‒MS. Orthogonal partial least squares discriminant analysis and a heatmap were utilized to distinguish the metabolites. Receiver operating characteristic curves were constructed to evaluate the diagnostic value of these differential metabolites. Additionally, metabolic pathway enrichment was performed to reveal metabolic pathway variation. According to our standard, 49 people were included in the depression cohort (DC), and 49 people age- and sex-matched individuals were included in the non-depression cohort (NDC). 64 metabolites identified via GC‒MS and 73 metabolites identified via LC‒MS had significant contributions to the differentiation between the DC and NDC, with VIP values > 1 and p values

Background/Purpose: Autonomic nervous system (ANS) disorders may occur in skeletal muscle disease, but the link between them has not been fully established. Studying the relationship between them may yield insights into the mechanisms and treatment of disease. This study aimed to explore the association between heart rate variability (HRV), sarcopenia, and subscales of sarcopenia (muscle mass, muscle strength, and physical mobility). Methods: 2514 community-dwelling older Chinese participants were included in this study. The Asian Working Group for Sarcopenia guidelines were used to define sarcopenia. HRV was measured by 90-s electrocardiogram RR interval data. All HRV parameters were transformed using natural logarithms. Multiple regression analysis and multivariate linear regression was performed using potential correlates. Results: The overall prevalence of sarcopenia was 15.1 % (18.5 % in males and 12.6 % in females). In the logistic regression analysis model, there was a significant association between log-transformed standard deviation of RR interval (lnSDNN) (OR = 0.736, p = 0.019), log-transformed coefficient of variation of RR intervals (lnCVRR) (OR = 0.751, p = 0.020), log-transformed low-frequency power (lnLF) (OR = 0.861, p = 0.008), log-transformed high-frequency power (lnHF) (OR = 0.864, p = 0.003) and sarcopenia in the general population after adjusting for age, sex, body mass index (BMI), daily activity levels, hypertension, heart disease and cardiac drugs. In addition, in multivariate linear regression, lnSDNN (β = 0.146, p = 0.001), lnCVRR (β = 0.120, p = 0.010), lnLF (β = 0.066, p = 0.002) and lnHF (β = 0.065, p

Abstract In this study, we deposited Ti3C2Tx-modified, rare-earth-doped PbO2 on the surface of a carbon fabric via electrodeposition. The surface morphology and electronic structure of the electrode were characterized with SEM, XRD and XPS. The layered Ti3C2Tx did not change the structure of β-PbO2, and at the same time, it improved the crystallinity of the material and reduced the grains of PbO2. Electrochemical experiments showed that the addition of Ti3C2Tx increased the electrochemical activity of the electrode and produced more H2O2, which contributed to the degradation of pollutants. The efficiency of sulfamethoxazole (SMX) degradation reached 95% after 120 min at pH 3 with a current density of 50 mA/cm2. Moreover, the electrode has good cycling performance, and the degradation efficiency was still 80% after 120 min after 10 cycles of recycling. Based on the intermediates identified by HPLC‒MS, a mechanism for SMX degradation was proposed. Our results will provide a new idea for the development of efficient electrocatalytic degradation of antibiotics.

Objective: To explore the associations between dietary zinc intake and cardiovascular diseases (CVDs), including congestive heart failure (CHF), coronary heart disease (CHD), angina, heart attack, and cerebrovascular accident (CVA), this study was performed. Setting: Data from the National Health and Nutrition Examination Survey (2005–2018) were used in this study. Dietary zinc intake was stratified into quartiles. Restricted cubic splines were constructed to assess nonlinear associations and identify cut-off values based on the type of nonlinearity. Binary logistic regressions were performed using the cut-offs. Results: Positive associations were detected between the second, third, and fourth quantiles of dietary zinc intake and decreased risks of overall CVDs (Q2: OR = 0.83, 95 % CI = 0.72–0.96; Q3: OR = 0.83, 95 % CI = 0.71–0.96; Q4: OR = 0.79, 95 % CI = 0.67–0.93). The second, third, and fourth quantiles were significantly associated with decreased risks of various CVDs (all P 0.05). Restricted cubic spline regression revealed significant nonlinear trends for associations of dietary zinc intake with the risk of developing CVDs and CHF (both P for nonlinear

Primary intraosseous malignant peripheral nerve sheath tumors (MPNSTs) are rare yet highly aggressive neoplasms originating from peripheral nerves. Typically manifesting as soft tissue masses accompanied by pain or functional impairment, these tumors pose significant challenges in management. Surgical intervention remains the cornerstone of treatment for patients with MPNST lacking distant metastasis, with generally modest success rates. In cases of recurrence and metastasis, the pursuit of effective systemic therapies has been a focus of clinical investigation. Herein, we present a case study involving an elderly female patient with refractory MPNST. In light of surgical limitations, a multimodal therapeutic approach combining chemotherapy, denosumab, and subsequent administration of anlotinib was pursued following collaborative consultation. This regimen yielded noteworthy clinical benefits, exemplifying a promising avenue in the management of challenging MPNST cases.

IntroductionNatural plants are valuable resources for exploring new bioactive compounds. Artemisia vulgaris L. is a traditional Chinese medicinal herb that has been historically used for treating multiple diseases. Active compounds isolated and extracted from A. vulgaris L. typically possess immunomodulatory and anti-inflammatory properties. Artemvulactone E (AE) is a new sesquiterpene lactone isolated and extracted from A. vulgaris L. with unclear biological activities.MethodsThe immunoregulatory effects of AE on macrophages were assessed by ELISA, RT-qPCR, immunofluorescence, and western blot assay. The effect of AE on lipopolysaccharide (LPS) -relates signaling pathways was examined by western blot assay. In zebrafish models, the larvae were yolk-microinjected with LPS to establish inflammation model and the effect of AE was evaluated by determining the survival rate, heart rate, yolk sac edema size, neutrophils and macrophages infiltration of zebrafish. The interaction between AE and Toll-like receptor 4 (TLR4) was examined by molecular docking and dynamic stimulation.ResultsAE reduced the expression and secretion of pro-inflammatory cytokines (TNF-α and IL-6), inflammatory mediators iNOS and COX-2, as well as decreases the production of intracellular NO and ROS in LPS-stimulated macrophages. In addition, AE exerted its anti-inflammatory effect synergistically by inhibiting MAPK/JAK/STAT3-NF-κB signaling pathways. Furthermore, AE enhanced the survival rate and attenuated inflammatory response in zebrafish embryos treated with LPS. Finally, the molecular dynamics results indicate that AE forms stable complexes with LPS receptor TLR4 through the Ser127 residue, thus completely impairing the subsequent activation of MAPK-NF-κB signaling.ConclusionAE exhibits notable anti-inflammatory activity and represents as a potential agent for treating inflammation-associated diseases.

Abstract Background The objective of this study was to detect the urinary levels of chlorpyrifos, paraquat, and cyproconazole in residents living in Fuyang City and to analyze the correlation between these urinary pesticides levels and the severity of fatty liver disease (FLD). Methods All participants’ fat fraction (FF) values were recorded by MRI (Magnetic resonance imaging). First-morning urine samples were collected from 53 participants from Fuyang Peoples’Hospital. The levels of three urinary pesticides were measured using β-glucuronidase hydrolysis followed by a. The results were analyzed by using Pearson correlation analysis and binary logistic regression analysis to reveal the correlation between three urinary pesticides and the severity of fatty liver. Results 53 individuals were divided into 3 groups based on the results from MRI, with 20 cases in the normal control group, 16 cases in the mild fatty liver group, and 17 cases in the moderate and severe fatty liver group. Urinary chlorpyrifos level was increased along with the increase of the severity of fatty liver. Urinary paraquat level was significantly higher both in the low-grade fatty liver group and moderate & serve grade fatty liver group compared with the control group. No significant differences in urinary cyproconazole levels were observed among the three groups. Furthermore, urinary chlorpyrifos and paraquat levels were positively correlated with FF value. And chlorpyrifos was the risk factor that may be involved in the development of FLD and Receiver Operating Characteristic curve (ROC curve) analysis showed that chlorpyrifos and paraquat may serve as potential predictors of FLD. Conclusion The present findings indicate urinary chlorpyrifos and paraquat were positively correlated with the severity of fatty liver. Moreover, urinary chlorpyrifos and paraquat have the potential to be considered as the predictors for development of FLD. Thus, this study may provide a new perspective from the environmental factors for the diagnosis, prevention, and treatment of FLD.

ObjectivesWhen a large-bow naval ship encounters adverse sea conditions, bow flare slamming causes a hull girder whipping response which threatens the security of global longitudinal strength. The whipping bending moment resulting from slamming is related to the level of hull stiffness and bow flare shape. However, there are great differences in the structural arrangement and profile of different ship types, so it is necessary to carry out whipping response analysis.MethodsFirst, the COMPASS-WALCS-NE nonlinear time-domain hydro-elastic method is used to predict the hull girder response, and the results are compared and verified through a self-running subsection model test. Next, based on the obtained time histories of the resultant bow impact force, ship motion posture at typical moments and global load response of hull girders, the phase difference of high-and low-frequency components in the waveloads is analyzed, and the correlation between the midship's slamming moment and resultant bow flare slamming force is studied. Finally, the sensitivity analysis of the main design parameters affecting vertical bending moment is carried out.ResultsIn the designed sea conditions, the resultant slamming force has two peaks during bow water entry which correspond to the processes of bottom impact and bow flare impact respectively. The whipping bending moment is mainly caused by bow flare impact, but as the impact area is large and the resultant force far away from the midship, the slamming moment is at the same level as the wave bending moment. The slamming moment is very sensitive to changes in wave height.Conclusions The results of this study indicate that the effect of whipping impact resulting from slamming should be considered in the global longitudinal strength evaluation of large-bow naval ships; among them, the sagging vertical bending moment needs to be directly superimposed on the still water bending moment component and low-frequency wave load component, while the hogging vertical bending moment should be reduced to a certain extent and then superimposed considering dam-ping dissipation.

ABSTRACTBackground Previous research has established that nicotine withdrawal can ameliorate cardiovascular and pulmonary function in smokers. Nevertheless, the impact on physical fitness and athletic performance remains under-investigated.Objective To evaluating the impacts of nicotine withdrawal on both exercise performance and exercise-associated physical capabilities in nicotine-dependent individuals.Study design A comprehensive systematic review and meta-analysis.Data sources The data was compiled from databases such as PubMed, Scopus, Web of Science, Cochrane Central, and EBSCO.Study selection The selection criteria required studies to elucidate the effects of nicotine withdrawal on exercise performance or exercise-related physical abilities. Moreover, the selected studies needed to provide discernible experimental results.Data synthesis and analysis The random effects model was employed in data analysis, utilizing the standardized mean difference (SMD) and the 95% confidence intervals (95% CIs) to estimate participants’ exercise performance and physical abilities, referencing the Mean ±SD during baseline and withdrawal states.Results Out of the selected studies, 10 trials were included, encompassing 13,538 participants aged 18 to 65 years. The findings suggest that nicotine withdrawal could potentially enhance sports performance (SMD = 0.45, 95% CI: 0.03 to 0.88; I^2 = 83%), particularly in terms of aerobic capacity. Short-term nicotine withdrawal (spanning 12 to 24 hours) might lead to a decline in participants’ physical abilities in certain aspects like reaction time and sustained attention (SMD = −0.83, 95% CI: −1.91 to 0.25; I^2 = 79%), whereas long-term withdrawal (lasting 48 hours or more) demonstrated an opposing trend (SMD = 0.25, 95% CI: 0.12 to 0.39; I^2 = 81%). Overall, the results show that long-term nicotine withdrawal exhibited some positive impacts on sports performance and exercise-related physical ability, with the withdrawal duration being an indicator of subsequent physical performance.Conclusions Mid- to long-term (≥3 months) nicotine withdrawal significantly improved the exercisers’ exercise-related physical ability and sports performance. Conversely, short-term (≤24 hours) nicotine withdrawal considerably hampered exercisers’ performance and physical cognition. It is suggested that exercises avoid abrupt nicotine cessation prior to competitions, as long-term nicotine withdrawal has been shown to significantly enhance exercise-related physiological capacities and athletic performance. By referring to existing literatures we also found that athletes with existing nicotine addiction may could consume nicotine 15–30 minutes before competition to enhance athletic performance and physical function.PROSPERO registration number CRD42023411381.

ObjectiveDepression is a common comorbidity in hypertensive older adults, yet depression is more difficult to diagnose correctly. Our goal is to find predictive models of depression in hypertensive patients using a combination of various machine learning (ML) methods and metabolomics.MethodsMethods We recruited 379 elderly people aged ≥65 years from the Chinese community. Plasma samples were collected and assayed by gas chromatography/liquid chromatography-mass spectrometry (GC/LC-MS). Orthogonal partial least squares discriminant analysis (OPLS-DA), volcano diagrams and thermograms were used to distinguish metabolites. The attribute discriminators CfsSubsetEval combined with search method BestFirst in WEKA software was used to find the best predicted metabolite combinations, and then 24 classification methods with 10-fold cross-validation were used for prediction.Results34 individuals were considered hypertensive combined with depression according to our criteria, and 34 subjects with hypertension only were matched according to age and sex. 19 metabolites by GC-MS and 65 metabolites by LC-MS contributed significantly to the differentiation between the depressed and non-depressed cohorts, with a VIP value of more than 1 and a P value of less than 0.05. There were multiple metabolic pathway alterations. The metabolite combinations screened with WEKA for optimal diagnostic value included 12 metabolites. The machine learning methods with AUC values greater than 0.9 were bayesNet and random forests, and their other evaluation measures are also better.ConclusionAltered metabolites and metabolic pathways are present in older adults with hypertension combined with depression. Methods using metabolomics and machine learning performed quite well in predicting depression in hypertensive older adults, contributing to further clinical research.

BackgroundSuperior mesenteric arteriovenous fistula is a rare and difficult complication after abdominal trauma. Utilizing comprehensive endovascular treatment represents an effective approach to managing this condition.Case presentationWe report a case involving a 53-year-old female with a history of trauma who presented with complaints of abdominal pain, malaise, and melena. A computed tomographic scan revealed the presence of a superior mesenteric arteriovenous fistula. The fistula was occluded using four Interlock detachable coils, and a covered stent was positioned over the arteriovenous fistula in the superior mesenteric artery. Following endovascular treatment, the patient's abdominal pain and melena symptoms disappeared.ConclusionUtilizing covered stents and Interlock detachable coils for endovascular treatment of a superior mesenteric arteriovenous fistula proves to be both feasible and highly effective.

Objective: To explore the treatment effect and potential mechanism on gut microbiota, nutrition, and metabolism of Fufang Duzheng Tablet (DZGP) on rheumatoid arthritis (RA). Methods: Collagen-induced arthritis rats’ models were established and divided into three groups: model control group (FK), DZGP group (FZ, 0.45 g/kg/d), and methotrexate group (FM, 1.35 mg/kg), which were treated by gavage for 28 days. The physiopathologic changes of joints and body weight in each group were recorded; the morphology of synovial and ankle tissues was observed by hematoxylin-eosin staining, and the level of serum TNF-α and IL-1β was tested by ELISA. UPLC/MS-MS and network pharmacological analysis were used to identify the serum components, and 16S rDNA sequencing analysis was applied to the intestinal contents of rats. Results: DZGP treatment significantly alleviated arthritis symptoms, pathological manifestations, toe thickness, and TNF-α and IL-1β levels in RA rats. We identified 105 metabolites and 18 components in the serum of DZGP-group rats. The main therapeutic targets of DZGP for anti-RA were TP53, epidermal growth factor receptor, and AKT1. Molecular docking showed that there was good binding efficiency between core components and main targets. 16S rDNA sequencing showed that DZGP treatment regulated the structure of the gut microbiota. Conclusion: DZGP showed a good anti-inflammatory effect on RA and played an important role in improving the structure of the gut microbiota in RA rats.

ObjectiveTo explore the value of 18F-fluordeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) semi-quantitative parameters of primary tumor combined with squamous cell carcinoma antigen (SCC-Ag) in predicting lymph node metastasis (LNM) of cervical cancer (FIGO 2018 stage I-II).Materials and MethodsA total of 65 patients with stage I-II cervical cancer underwent 18F-FDG PET/CT were included in our study. Comparing the primary tumor 18F-FDG PET/CT semi-quantitative parameters and SCC-Ag between the LNM group and the non-LNM group. Logistic regression and receiver operating characteristic (ROC) were used to analyze the value of 18F-FDG PET/CT metabolic parameters and SCC-Ag in predicting LNM.ResultsThere were 14 and 51 patients were classified as having LNM and NLNM. The semi-quantitative parameters, including the maximum standardized uptake value (SUVmax), the mean standardized uptake value (SUVmean), the peak standardized uptake value (SUVpeak), the total lesion glycolysis (TLG), the metabolic tumor volume (MTV) of the tumor and SCC-Ag were all significantly higher in LNM than in NLNM (SUVmax, 16.07 ± 7.81 vs 11.19 ± 4.73, SUVmean, 9.16 ± 3.48 vs 6.29 ± 2.52, SUVpeak, 12.70 ± 5.26 vs 7.65 ± 3.26, MTV, 22.77 ± 12.36 vs 7.09 ± 5.21, TLG, 211.01 ± 154.25 vs 43.38 ± 36.17, SCC-Ag, 5.39 ± 4.56 vs 2.13 ± 2.50, all p

Cottonseed is a by-product of cotton industry, but its broad application in human diets has not been fully elucidated. This study aims to analyse the nutritional composition of cotton sprouts and investigate metabolic and transcriptomic differences under light and darkness. The findings revealed that the glanded ZM41 yellow cotton sprouts were rich in protein (2.8 %), vitamin E (0.443 mg/100 g), and minerals, with < 0.01 % free gossypol. Moreover, protein, aspartic acid (1,026 mg/100 g), and serine (136 mg/100 g) reached their highest levels in nine-day-old sprouts, while no significant differences were observed in the other nutrients on the 7th, 9th, or 11th day. The average quantitative values of 64 cottonseed varieties found gossypol (27.9 mg/kg), protein (3.6 %), potassium (1,487.3 mg/kg), calcium (506.2 mg/kg) and magnesium (330.2 mg/kg). Integrated metabolome and transcriptome analyses revealed that 317 out of 1,880 metabolites were differentially accumulated between light and dark conditions, wherein the downregulation of structural genes encoding CHI, F3H, FLS, DFR, F3′H, ANS, LAR and ANR resulted in decreased flavonoid levels in dark-cultivated sprouts, while the upregulation of HMGR and 2-ODD-1 enhanced the biosynthesis of gossypol. This study provides insights into the nutritional and metabolic aspects of cotton sprouts, offering a reference for potential commercial applications.

IntroductionRapid identification of infected individuals through viral RNA or antigen detection followed by effective personal isolation is usually the most effective way to prevent the spread of a newly emerging virus. Large-scale detection involves mass specimen collection and transportation. For biosafety reasons, denaturing viral transport medium has been extensively used during the SARS-CoV-2 pandemic. However, the high concentrations of guanidinium isothiocyanate (GITC) in such media have raised issues around sufficient GITC supply and laboratory safety. Moreover, there is a lack of denaturing transport media compatible with SARS-CoV-2 RNA and antigen detection.MethodsHere, we tested whether supplementing media containing low concentrations of GITC with ammonium sulfate (AS) would affect the throat-swab detection of SARS-CoV-2 or a viral inactivation assay targeting coronavirus and other enveloped and non-enveloped viruses. The effect of adding AS to the media on RNA stability and its compatibility with SARS-CoV-2 antigen detection were also tested.Results and discussionWe found that adding AS to the denaturing transport media reduced the need for high levels of GITC, improved SARS-COV-2 RNA detection without compromising virus inactivation, and enabled the denaturing transport media compatible with SARS-CoV-2 antigen detection.

ObjectiveTo compare the clinical outcomes of microwave-assisted intralesional curettage(MAIC) with those of en bloc resection and autogenous fibular reconstruction (EBR-AFR) for treating grade III giant cell tumor of the bone (GCTB) of the distal radius and to elucidate the indications for wrist preservation surgery.Materials and methodsIn this retrospective study, 19 patients with grade III GCTB of the distal radius who underwent surgery at three medical institutions were included and categorized based on their surgical pattern. Seven patients underwent MAIC and internal fixation with bone cement (MAIC group) and 12 underwent EBR-AFR (EBR-AFR group). To evaluate the function of the affected limb postoperatively, wrist range of motion, grip strength, Musculoskeletal Tumor Society (MSTS) scores were recorded.ResultsThe follow-up time of the MAIC group was 73.57 ± 28.61 (36–116) months, with no recurrence or lung metastasis. In contrast, the follow-up time of the EBR-AFR group was 55.67 ± 28.74 (36–132) months, with 1 case of local recurrence (8.3%, 1/12) and 1 case of lung metastasis (8.3%, 1/12). The wrist flexion, extension, supination, pronation, grip strength were better in the MAIC group than in the EBR-AFR group. Although there was no statistically significant difference in the MSTS score between the two groups, it is noteworthy that the MAIC group exhibited significantly superior emotional acceptance and hand positioning compared to the EBR-AFR group(p < 0.05).ConclusionThe functional outcomes of the MAIC group are better. The treatment strategy for grade III GCTB of the distal radius should be determined based on the specific preoperative imaging findings. Nevertheless, MAIC can be the preferred surgical approach for most patients with grade III GCTB of the distal radius, particularly for young patients.

BackgroundPulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small-cell lung cancer (NSCLC), which is resistant to chemotherapy and radiotherapy with a poor prognosis. PSC is highly malignant and is prone to recurrence even after surgery. The programmed death-ligand 1 (PD-L1) tumor cell proportion score (TPS) 5%, TERT and TP53 gene mutations were detected in this patient accompanied by multiple metastatic sites. The anlotinib is a novel multitarget tyrosine kinase inhibitor (TKI) that could be effective for advanced NSCLC and some sarcoma patients. Limited clinical trials and case reports have shown that PSC patients with gene mutations and PD-L1 expression have good responses to multitarget antiangiogenic drug and immune checkpoint inhibitors (ICIs). In this article, we reported a case with metastatic PSC diagnosed by Computed Tomography (CT)-guided needle biopsy treated with immunotherapy combined with antiangiogenic drugs as a neoadjuvant chemotherapy (NACT). PSC is controlled and the patient achieves successfully limb salvage treatment by surgical resection. Therefore, targeted therapy and immunotherapy can provide sufficient surgical opportunities for limb salvage in the treatment of metastatic PSC patients.Case summaryA 69-year-old male diagnosed with malignant bone tumor in the proximal femur was admitted to our hospital in June 2022 with recurrent fever as well as swelling and pain in the left thigh for twenty days. The initial computed tomography (CT) scan of the chest showed a pulmonary cavity (20 mm × 30 mm) and scattered lung masses. Subsequently, he underwent a CT-guided needle biopsy to distinguish the essence of osteolytic bone destruction and soft tissue mass in the left proximal femur which showed metastatic sarcomatoid carcinoma histology. Genetic testing revealed TERT c.-124C mutation (abundance 8.81%), TP53 p.R342 mutation (abundance 11.35%), tumor mutational burden (TMB) 7.09 muts/Mb, microsatellite stability (MSS), and PD-L1 (SP263) TPS 5% were also detected. The patient was tentatively treated with a combination of antiangiogenic drug and PD-1 inhibitor. After one course, the tumor volume significantly reduced in magnetic resonance imaging (MRI) and pathological fracture occurred in the femur after combined treatment. The patient received proximal femoral tumor resection and prosthesis replacement after defervescence. Sequentially sintilimab with anlotinib were administered for over 1 year. Finally, the local tumor was well controlled, and no obvious drug-related adverse reactions were observed. The lesions in the lung remained in partial response (PR) for more than 16 months and complete response (CR) of metastatic tumor in the proximal femur was observed through imaging examinations.ConclusionThis is the first reported case of a metastatic PSC in femur showing a favorable response to the treatment consisting of anlotinib combined with sintilimab. This case suggests that antiangiogenic therapy combined with immunotherapy may benefit patients with metastatic PSC in the preoperative adjuvant therapy for limb salvage.

Background: The purpose of this study was to compare the efficacy and safety of utidelone plus capecitabine for advanced first-line versus second-line or above therapy in metastatic breast cancer patients who had previously received anthracycline and taxane. At the same time, we compared the efficacy of utidelone plus capecitabine and vinorelbine plus cisplatin in advanced first-line treatment of metastatic breast cancer. Patients and methods: A retrospective cohort of 11 patients with metastatic breast cancer previously treated with anthracycline and taxane (including neoadjuvant and adjuvant therapies) for advanced first-line with utidelone plus capecitabine, 32 patients treated with second-line or above, and 60 patients with vinorelbine plus cisplatin between October 2011 and August 2022 was collected. The first and second groups were treated with utidelone plus capecitabine, and the third group was treated with vinorelbine plus cisplatin. The primary endpoint was progression-free survival (PFS), and secondary endpoints were overall survival (OS), objective response rate (ORR), and treatment safety. Results: By 03/31/2023, median PFS reached 11.70 months (95 % CI 0.093–0.141) in utidelone plus capecitabine group in the advanced first-line therapy, compared to 5.60 months (95 % CI 0.025–0.079) in the second-line or above therapy [HR 0.42, (95 % CI 0.226–0.787), P = 0.0077]. In utidelone plus capecitabine, the median OS was not reached in the advanced first-line therapy, with a mean overall survival of 23.16 months (95 % CI 0.198–0.265); whereas the median OS in the second-line or above therapy was 19.50 months (95 % CI 0.083–0.307), with a mean overall survival of 16.89 months (95 % CI 0.136–0.202) [HR 0.26, (95 % CI 0.098–0.678), P = 0.0495]. The ORR for advanced first-line therapy was 27.27 % (95%CI 0.060, 0.610) compared with 15.63 % (95%CI 0.053, 0.328) for second-line or above. In advanced first-line therapy, utidelone plus capecitabine was superior to vinorelbine plus cisplatin with a median PFS of 6.12 months (95 % CI 0.051–0.072) [HR 0.49, (95 % CI 0.286–0.839), P = 0.0291]. Compared with utidelone plus capecitabine, the median OS in vinorelbine plus cisplatin advanced first-line therapy group was 35.37 months (95 % CI 0.258–0.449), and the mean overall survival was 40.79 months (95 % CI 0.315–0.501) [HR 0.54, (95 % CI 0.188–1.568), P = 0.2587]. The ORR for vinorelbine plus cisplatin was 18.33 % (95 % CI 0.095, 0.304). The most common adverse events in our study were neurological toxicity, hand-foot syndrome, hematological toxicity, gastrointestinal toxicity, and hepatic and renal function abnormalities. There were no deaths due to adverse effects during the utidelone plus capecitabine treatment period. Conclusions: In MBC, advanced first-line therapy with utidelone plus capecitabine resulted in more favorable PFS, OS, and ORR than second-line or above therapy. In advanced first-line therapy, utidelone plus capecitabine had superior PFS, and ORR compared with vinorelbine plus cisplatin. This study concludes that utidelone plus capecitabine is a more valuable chemotherapy option in advanced first-line MBC.

Due to the low permeability, small pore throat, and poor pore connectivity of ultra-low permeability reservoirs, fracturing was required to improve the flow environment of oil in the reservoir during its development. The combination of fracturing and oil displacement could reduce the complexity of the development of ultra-low permeability reservoirs. It was feasible to synthesize new surfactants to prepare fracturing oil displacement agents, but the research and development of new surfactants were difficult and costly. This paper aimed to experimentally investigate the imbibition displacement mechanism of fracturing flooding by combining the surfactant of chemical flooding with the fracturing fluid. With the conditions of the ultra-low permeability reservoir in block Y of Changqing Oilfield, the mechanism of remaining oil start-up and fractured oil displacement agent enhanced oil recovery in the ultra-low permeability reservoir was studied by microfluidic model experiment and NMR experiment. A mixture of fracture oil displacement agents was obtained by mixing heavy alkyl benzene sulfonate surfactant, a nonionic surfactant, and a betaine-type amphoteric surfactant. HAS-6C, HAS-5E, and HAS-5G were selected for their interfacial tension reaching 10−3 mN/m. Oil–water​ interfacial tension of HAS-5E was the lowest, which can be reduced to 10−4 mN/m. The ability to alter the wettability of HAS-6C was the most significant, which could make the contact angle go down to 64.5°. The multi-round dynamic and static imbibition experiments showed that the combination of selected surfactant and slickwater can greatly improve the imbibition recovery, of which HAS-6C could enhance oil recovery by 17%. The HAS-5E system with the lowest interfacial tension had the best effect of starting clustered residual oil, and the clustered residual oil saturation was reduced by 48.8%. The HAS-6C system with stronger wettability had the best effect of starting throat-like residual oil, and the throat-like residual saturation was reduced by 10.8%.

Background Limb salvage surgery is the preferred treatment for most malignant bone tumors, but postoperative infection treatment is very challenging. Simultaneously controlling infection and solving bone defects are clinical treatment challenges. Case Presentation Here we describe a new technique for treating bone defect infection after bone tumor surgery. An 8‐year‐old patient suffered an incision infection after osteosarcoma resection and bone defect reconstruction. In response, we designed her a personalized, anatomically matched, antibiotic‐loaded, bone cement spacer mold using 3D printing technology. The patient's infection was cured, and limb salvage was successful. In follow‐up, the patient had returned to normal postoperative chemotherapy and was able to walk with the help of a cane. There was no obvious pain in the knee joint. At 3 months after operation, the range of motion of the knee joint was 0°–60°. Conclusion The 3D printing spacer mold is an effective solution for treating the infection with large bone defect.

Bioactive glass nanoparticles (BGNs) are applied widely in tissue regeneration. Varied micro/nanostructures and components of BGNs have been designed for different applications. In the present study, nanorod-shaped mesoporous zinc-containing bioactive glass nanoparticles (ZnRBGNs) were designed and developed to form the bioactive content of composite materials for hard/soft tissue repair and regeneration. The nanostructure and components of the ZnRBGNs were characterized, as were their cytocompatibility and radical-scavenging activity in the presence/absence of cells and their ability to modulate macrophage polarization. The ZnRBGNs possessed a uniform rod shape (length ≈ 500 nm; width ≈ 150 nm) with a mesoporous structure (diameter ≈ 2.4 nm). The leaching liquid of the nanorods at a concentration below 0.5 mg/mL resulted in no cytotoxicity. More significant improvements in the antioxidant and M1-polarization-inhibiting effects and the promotion of M2 polarization were found when culturing the cells with the ZnRBGNs compared to when culturing them with the RBGNs. The doping of the Zn element in RBGNs may lead to improved antioxidant and anti-inflammatory effects, which may be beneficial in tissue regeneration/repair.

Understanding future ecosystem services (ESs) is crucial for optimizing ecosystems and devising sustainable development strategies. This study used China’s Loess Plateau as a case study to investigate key ESs from 2020 to 2100. It accomplished this by coupling the Patch-Generating Land Use Simulation and the Integrated Valuation of Ecosystem Services and Trade-offs models under 3 shared socioeconomic pathways (SSP119, SSP245, and SSP585 scenarios). The results showed the following: (a) The generated land use exhibits strong performance, with an overall accuracy of 0.92. Among projected future land-use and land-cover changes, forests are expected to increase by 31.3% and 29.1% on the Loess Plateau under the SSP119 and SSP245 scenarios, respectively. (b) Between 2020 and 2100, soil conservation (SC) is projected to increase by 127.1% and 8.34%, carbon storage (CS) is projected to increase by 39.8% and 8.1%, while water yield (WY) is expected to decrease by 0.5% and 39.4% under the SSP119 and SSP245 scenarios, respectively. (c) The SSP245 scenario demonstrates the most substantial growth synergy area across the entire Loess Plateau. In this scenario, synergy areas related to SC&CS, CS&WY, and SC&WY are projected to increase by 39.1% and 20.6% while decreasing by 21.1%. These findings identified the most suitable scenario for enhancing ESs and optimizing trade-off relationships throughout the Loess Plateau. The research framework presented here can be applied to other vulnerable ecological regions worldwide.

PurposeFor early diagnosis of osteoporosis (OP), plasma metabolomics of OP was studied by untargeted LC/GC−MS in a Chinese elderly population to find possible diagnostic biomarkers.MethodsA total of 379 Chinese community-dwelling older adults aged ≥65 years were recruited for this study. The BMD of the calcaneus was measured using quantitative ultrasound (QUS), and a T value ≤-2.5 was defined as OP. Twenty-nine men and 47 women with OP were screened, and 29 men and 36 women were matched according to age and BMI as normal controls using propensity matching. Plasma from these participants was first analyzed by untargeted LC/GC−MS, followed by FC and P values to screen for differential metabolites and heatmaps and box plots to differentiate metabolites between groups. Finally, metabolic pathway enrichment analysis of differential metabolites was performed based on KEGG, and pathways with P ≤ 0.05 were selected as enrichment pathways.ResultsWe screened metabolites with FC>1.2 or FC

Giant cell tumors of the spine have a high recurrence rate owing to their special anatomical site; hence, further treatment after recurrence is very challenging. Achieving effective tumor control and improving the long-term quality of life of the patients are the main treatment purposes to consider for recurrent giant cell tumors of the spine. A patient showing giant cell tumor recurrence of the thoracic spine after curettage received denosumab combined with precision radiotherapy, through which the tumor gained good control and the patient could regain normal functioning. A review of the relevant literature suggested that denosumab combined with radiotherapy is an effective new approach for the treatment of recurrent giant cell tumors of the spine.

Abstract Multi-key membership testing plays a crucial role in computing systems and networking applications, encompassing web search, mail systems, distributed databases, firewalls, and network routing. Traditional approaches, such as the Bloom filter, encounter limitations within this specific context. Addressing these challenges, we propose the Multi-key Learned Bloom Filter (MLBF), a hybrid method that combines machine learning techniques with the Bloom filter. The MLBF introduces a value-interaction-based multi-key classifier and a multi-key Bloom filter. Furthermore, we introduce an Interval-based MLBF approach, which categorizes keys into specific intervals based on data distribution to minimize the False Positive Rate (FPR). Additionally, MLBF incorporates an out-of-distribution (OOD) detection component to identify data shifts. Through extensive experimental evaluations on three authentic datasets, we demonstrate the superiority of the proposed MLBF in terms of FPR and query efficiency.

Abstract Atherosclerosis is a chronic lipid-driven inflammatory response of the innate and adaptive immune systems, and it is responsible for several cardiovascular ischemic events. The present study aimed to determine immune infiltration-related biomarkers in carotid atherosclerotic plaques (CAPs). Gene expression profiles of CAPs were extracted from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between the CAPs and control groups were screened by the “limma” package in R software. Immune cell infiltration between the CAPs and control groups was evaluated by the single sample gene set enrichment analysis. Key infiltrating immune cells in the CAPs group were screened by the Wilcoxon test and least absolute shrinkage and selection operator regression. The weighted gene co-expression network analysis was used to identify immune cell-related genes. Hub genes were identified by the protein–protein interaction (PPI) network. Receiver operating characteristic curve analysis was performed to assess the gene’s ability to differentiate between the CAPs and control groups. Finally, we constructed a miRNA-gene-transcription factor network of hub genes by using the ENCODE database. Eleven different types of immune infiltration-related cells were identified between the CAPs and control groups. A total of 1,586 differentially expressed immunity-related genes were obtained through intersection between DEGs and immune-related genes. Twenty hub genes were screened through the PPI network. Eventually, 7 genes (BTK, LYN, PTPN11, CD163, CD4, ITGAL, and ITGB7) were identified as the hub genes of CAPs, and these genes may serve as the estimable drug targets for patients with CAPs.

Using visible light as energy to form free radicals has important synthetic value. A novel and efficient visible-light-mediated strategy has been developed for the generation of thiobenzene radicals through cerium-catalyzed activation of the disulfides. Through this photochemical reaction, various 3-sulfenylated quinoxalin-2(1H)-ones can be conveniently obtained in good yields with good functional group tolerance. Our transformation provides an alternative that allows rapid access to various C3 sulfenylated quinoxalin-2(1H)-ones in a sustainable and practical manner.

In this paper, we study initial boundary value problems for the following fully nonlocal Boussinesq equation $ _0^{C}D_{t}^{\beta}u+(-\Delta)^{\sigma}u+(-\Delta)^{\sigma}{_0^{C}D_{t}^{\beta}}u = -(-\Delta)^{\sigma}f(u) $ with spectral fractional Laplacian operators and Caputo fractional derivatives. To our knowledge, there are few results on fully nonlocal Boussinesq equations. The main difficulty is that each term of this equation has nonlocal effect. First, we obtain explicit expressions and some rigorous estimates of the Green operators for the corresponding linear equation. Further, we get global existence and some decay estimates of weak solutions. Second, we establish new chain and Leibnitz rules concerning $ (-\Delta)^{\sigma} $. Based on these results and small initial conditions, we obtain global existence and long-time behavior of weak solutions under different dimensions $ N $ by Banach fixed point theorem.

Type II diabetes mellitus (TIIDM) remains a challenging clinical issue for both dentists and orthopedists. By virtue of persistent hyperglycemia and altered host metabolism, the pathologic diabetic micromilieu with chronic inflammation, advanced glycation end products accumulation, and attenuated biomineralization severely impairs bone regeneration efficiency. Aiming to “remodel” the pathologic diabetic micromilieu, we 3D-printed bioscaffolds composed of Sr-containing mesoporous bioactive glass nanoparticles (Sr-MBGNs) and gelatin methacrylate (GelMA). Sr-MBGNs act as a biomineralization precursor embedded in the GelMA-simulated extracellular matrix and release Sr, Ca, and Si ions enhancing osteogenic, angiogenic, and immunomodulatory properties. In addition to angiogenic and anti-inflammatory outcomes, this innovative design reveals that the nanocomposites can modulate extracellular matrix reconstruction and simulate biomineralization by activating lysyl oxidase to form healthy enzymatic crosslinked collagen, promoting cell focal adhesion, modulating osteoblast differentiation, and boosting the release of OCN, the noncollagenous proteins (intrafibrillar mineralization dependent), and thus orchestrating osteogenesis through the Kindlin-2/PTH1R/OCN axis. This 3D-printed bioscaffold provides a multifunctional biomineralization-inspired system that remodels the “barren” diabetic microenvironment and sheds light on the new bone regeneration approaches for TIIDM.

Ultrasonic elliptical vibration-assisted cutting (UEVC) has been successfully applied in the precision and ultra-precision machining of hard and brittle materials due to its advantages of a low cutting force and minimal tool wear. This study developed a novel double-excitation ultrasonic elliptic vibration-assisted cutting (D-UEVC) device by coupling ultrasonic vibrations in orthogonal dual paths. A two-degree-of-freedom vibration system of the D-UEVC was modeled, form which the elliptical trajectory of the end under different phase angle φ values was derived. The initial dimensions of the D-UEVC device were obtained through theoretical calculations. Subsequently, with the aid of finite element analysis methods, structural dynamic analysis of the device was conducted to obtain the elliptical vibration trajectory under different phase differences of the excitation source. In order to verify the cutting trajectory and cutting performance of the D-UEVC device, a prototype of the device was developed, and a series of vibration performance tests as well as the Inconel 718 cutting experiment were conducted. The experimental results illustrated that the D-UEVC device can achieve the elliptical vibration trajectory at the tool tip with a resonant frequency of 36.5 KHz. The adjustable elliptical vibration trajectories covered a range of ±4 μm in the axial and radial directions. Compared with the surface roughness Ra = 0.36 μm under the conventional cutting, the surface roughness of Inconel 718 under D-UEVC was Ra = 0.215 μm. Thus, the surface quality can be significant improved by utilizing the D-UEVC device.

Recent advancements in applications of deep neural network for bearing fault diagnosis under variable operating conditions have shown promising outcomes. However, these approaches are limited in practical applications due to the complexity of neural networks, which require substantial computational resources, thereby hindering the advancement of automated diagnostic tools. To overcome these limitations, this study introduces a new fault diagnosis framework that incorporates a tri-channel preprocessing module for multidimensional feature extraction, coupled with an innovative diagnostic architecture known as the Lightweight Ghost Enhanced Feature Attention Network (GEFA-Net). This system is adept at identifying rolling bearing faults across diverse operational conditions. The FFE module utilizes advanced techniques such as Fast Fourier Transform (FFT), Frequency Weighted Energy Operator (FWEO), and Signal Envelope Analysis to refine signal processing in complex environments. Concurrently, GEFA-Net employs the Ghost Module and the Efficient Pyramid Squared Attention (EPSA) mechanism, which enhances feature representation and generates additional feature maps through linear operations, thereby reducing computational demands. This methodology not only significantly lowers the parameter count of the model, promoting a more streamlined architectural framework, but also improves diagnostic speed. Additionally, the model exhibits enhanced diagnostic accuracy in challenging conditions through the effective synthesis of local and global data contexts. Experimental validation using datasets from the University of Ottawa and our dataset confirms that the framework not only achieves superior diagnostic accuracy but also reduces computational complexity and accelerates detection processes. These findings highlight the robustness of the framework for bearing fault diagnosis under varying operational conditions, showcasing its broad applicational potential in industrial settings. The parameter count was decreased by 63.74% compared to MobileVit, and the recorded diagnostic accuracies were 98.53% and 99.98% for the respective datasets.

Abstract Periodontitis imparting the increased risk of atherosclerotic cardiovascular diseases is partially due to the immune subversion of the oral pathogen, particularly the Porphyromonas gingivalis (P. gingivalis), by inducing apoptosis. However, it remains obscure whether accumulated apoptotic cells in P. gingivalis-accelerated plaque formation are associated with impaired macrophage clearance. Here, we show that smooth muscle cells (SMCs) have a greater susceptibility to P. gingivalis-induced apoptosis than endothelial cells through TLR2 pathway activation. Meanwhile, large amounts of miR-143/145 in P.gingivalis-infected SMCs are extracellularly released and captured by macrophages. Then, these miR-143/145 are translocated into the nucleus to promote Siglec-G transcription, which represses macrophage efferocytosis. By constructing three genetic mouse models, we further confirm the in vivo roles of TLR2 and miR-143/145 in P. gingivalis-accelerated atherosclerosis. Therapeutically, we develop P.gingivalis-pretreated macrophage membranes to coat metronidazole and anti-Siglec-G antibodies for treating atherosclerosis and periodontitis simultaneously. Our findings extend the knowledge of the mechanism and therapeutic strategy in oral pathogen-associated systemic diseases.

Abstract Introduction Adverse drug events (ADEs) are associated with poor outcomes and increased costs but may be prevented with prediction tools. With the National Institute of Health All of Us (AoU) database, we employed machine learning (ML) to predict selective serotonin reuptake inhibitor (SSRI)-associated bleeding. Methods The AoU program, beginning in 05/2018, continues to recruit ≥ 18 years old individuals across the United States. Participants completed surveys and consented to contribute electronic health record (EHR) for research. Using the EHR, we determined participants who were exposed to SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, vortioxetine). Features (n = 88) were selected with clinicians’ input and comprised sociodemographic, lifestyle, comorbidities, and medication use information. We identified bleeding events with validated EHR algorithms and applied logistic regression, decision tree, random forest, and extreme gradient boost to predict bleeding during SSRI exposure. We assessed model performance with area under the receiver operating characteristic curve statistic (AUC) and defined clinically significant features as resulting in > 0.01 decline in AUC after removal from the model, in three of four ML models. Results There were 10,362 participants exposed to SSRIs, with 9.6% experiencing a bleeding event during SSRI exposure. For each SSRI, performance across all four ML models was relatively consistent. AUCs from the best models ranged 0.632–0.698. Clinically significant features included health literacy for escitalopram, and bleeding history and socioeconomic status for all SSRIs. Conclusions We demonstrated feasibility of predicting ADEs using ML. Incorporating genomic features and drug interactions with deep learning models may improve ADE prediction.

Bone-related diseases refer to a group of skeletal disorders that are characterized by bone and cartilage destruction. Conventional approaches can regulate bone homeostasis to a certain extent. However, these therapies are still associated with some undesirable problems. Fortunately, recent advances in nanomaterials have provided unprecedented opportunities for diagnosis and therapy of bone-related diseases. This review provides a comprehensive and up-to-date overview of current advanced theranostic nanomaterials in bone-related diseases. First, the potential utility of nanomaterials for biological imaging and biomarker detection is illustrated. Second, nanomaterials serve as therapeutic delivery platforms with special functions for bone homeostasis regulation and cellular modulation are highlighted. Finally, perspectives in this field are offered, including current key bottlenecks and future directions, which may be helpful for exploiting nanomaterials with novel properties and unique functions. This review will provide scientific guidance to enhance the development of advanced nanomaterials for the diagnosis and therapy of bone-related diseases.

Abstract Background Tumor prostheses of the distal femur after revision surgery is associated with high rates of aseptic loosening, which has introduced great challenges to the survival of patients, but only a few studies have evaluated their X-ray imaging. The purpose of this study was to analyze the risk factors for recurrence of aseptic loosening and make recommendations to reduce the incidence of aseptic loosening after revision surgery of tumor prostheses in the distal femur. Method A retrospective analysis was performed on 23 patients who had revision surgery for distal femur prostheses due to aseptic loosening between June 2002 and June 2021. They were divided into two groups based on the condition of the prostheses after revision surgery: loosening group (9 patients) and control group (14 patients). Following the initial replacement, the length and diameter of the prosthetic intramedullary stem were measured through the standard full-length anteroposterior X-ray imaging of both lower limbs. The osteotomy length, femoral length and diameter, femoral intramedullary stem diameter, hip-knee-ankle angle (HKAA), mechanical lateral distal femoral angle (mLDFA), mechanical medial proximal tibial angle (mMPTA), and so on were measured as well. Following that, statistical analysis was performed. Results Patients in the loosening group had statistically significant differences in the ratio of prostheses length to femur length (71.89 ± 6.62) and the ratio of intramedullary stem diameter to femoral diameter (25.50 ± 6.90) (P

Abstract Purpose Esophageal squamous cell carcinoma (ESCC) remains one of the most common causes of cancer death due to the lack of effective therapeutic options. New targets and the targeted drugs are required to be identified and developed. Methods Highly expressed genes in ESCA were identified using the edgeR package from public datasets. Immunostaining assay verified the high expression level of EFNA1 in ESCC. CCK-8, colony formation and wound healing assays were performed to examine the role of EFNA1 and EPHA2 in ESCC progression. Cell cycle was analyzed by flow cytometry and autophagy activation was determined by autophagolysosome formation using transmission electron microscopy. The small molecule targeting to EFNA1 was identified by molecular docking and the anti-tumor effects were verified by in vitro and in vivo models with radiation treatment. Results EFNA1 was highly expressed in esophageal cancer and significantly associated with poor prognosis. Downregulation of EFNA1 remarkably inhibited cell proliferation and migration. Furthermore, decreased EFNA1 significantly suppressed the expression of cMYC along with its representative downstream genes involved in cell cycle, and activated autophagy. Similar effects on ESCC progression were obtained from knockdown of the corresponding receptor, EPHA2. The potential small molecule targeting to EFNA1, salvianolic acid A (SAA), could significantly suppress ESCC progression and increase the sensitivity to radiotherapy. Conclusion We revealed that EFNA1 facilitated the ESCC progression via the possible mechanism of activating cMYC-modulated cell proliferation and suppressing autophagy, and identified SAA as a potential drug targeting EFNA1, providing new options for the future treatments for ESCC patients.

Highlights An atomically dispersed catalyst with unprecedented N8V4 Co-Ni dual-metal sites is synthesized, which shows interesting asymmetric in situ structural evolution and serves as a quasi-bifunctional catalyst for water splitting. The flexible C–OH groups generated by in situ oxidation can reversibly turn on/off the hydrogen-bonding interaction with the oxygen evolution reaction intermediates to break the conventional scaling relationship.

Abstract To assess the safety and efficacy of endovascular embolization techniques, we compared the short- to medium-term prognosis of coil embolization for symptomatic visceral aneurysms (SVAA) and asymptomatic visceral aneurysms (ASVAA) to identify risk factors associated with 30-day mortality. Explore the symptom profile and intrinsic associations of SVAA. A retrospective study of 66 consecutive patients at two tertiary care hospitals from 2010 to 2020 compared the short- to mid-term outcomes of 22 symptomatic VAAs and 44 asymptomatic VAAs treated with coil embolization. Univariate and log-rank tests were used to analyze the prognostic impact of SVAA and ASVAA. SVAA group had significantly higher 30-day mortality than ASVAA group (2(9.1%) vs 0, P = 0.042), both patients who died had symptomatic pseudoaneurysms. Perioperative complications such as end-organ ischemia (P = 0.293) and reintervention (P = 1) were similar in both groups. No difference in event-free survival was identified between the two groups (P = 0.900), but we found that the majority of pseudoaneurysms were SVAA (4/5) and that they had a much higher event rate than true aneurysms. In addition, dyslipidemia may be an influential factor in the development of VAA (P = 0.010). Coil embolization is a safe and effective method of treatment for VAA. Most pseudoaneurysms have symptoms such as abdominal pain and bleeding, and in view of their risk, more attention should be paid to symptomatic patients and the nature of the aneurysm should be determined as soon as possible to determine the next stage of treatment.

Abstract Macrophage efferocytosis of apoptotic osteoblasts (apoOBs) is a key osteoimmune process for bone homeostasis. However, apoOBs frequently accumulate in aged bone marrow, where they may mount proinflammatory responses and progressive bone loss. The reason why apoOBs are not cleared during aging remains unclear. In this study, it is demonstrated that aged apoOBs upregulate the immune checkpoint molecule CD47, which is controlled by SIRT6‐regulated transcriptional pausing, to evade clearance by macrophages. Using osteoblast‐ and myeloid‐specific gene knockout mice, SIRT6 is further revealed to be a critical modulator for apoOBs clearance via targeting CD47‐SIRPα checkpoint. Moreover, apoOBs activate SIRT6‐mediated chemotaxis to recruit macrophages by releasing apoptotic vesicles. Two targeting delivery strategies are developed to enhance SIRT6 activity, resulting in rejuvenated apoOBs clearance and delayed age‐related bone loss. Collectively, the findings reveal a previously unknown linkage between immune surveillance and bone homeostasis and targeting the SIRT6‐regulated mechanism can be a promising therapeutic strategy for age‐related bone diseases.

At present, the treatment of recurrent pelvic osteosarcoma is too simple, and most of the patients are treated with chemotherapy, radiotherapy, and/or combined surgery. Here, we report a 29-year-old man diagnosed with local recurrent pelvic osteosarcoma. Imaging showed that the tumor had obvious enhancement and abundant blood vessels. There was no indication of surgery. After the patient’s consent was obtained, we used anlotinib as a sequential treatment to chemotherapy. During the first course of adjuvant chemotherapy, we treated the patient with intensity-modulated radiotherapy (IMRT) with a total dose of 60 Gy equivalents. No disease recurrence was reported at 25 months after multimodal combination therapy.

Background Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is the central enzyme of glycolysis and plays important regulatory roles in plant growth and development and responses to adverse stress conditions. However, studies on the characteristics and functions of cotton GAPDH family genes are still lacking. Methods In this study, genome-wide identification of the cotton GAPDH gene family was performed, and the phylogeny, gene structures, promoter progenitors and expression profiles of upland cotton GAPDH gene family members were explored by bioinformatics analysis to highlight potential functions. The functions of GhGAPDH9 in response to drought stress were initially validated based on RNA-seq, qRT‒PCR, VIGS techniques and overexpression laying a foundation for further studies on the functions of GAPDH genes. Results This study is the first systematic analysis of the cotton GAPDH gene family, which contains a total of 84 GAPDH genes, among which upland cotton contains 27 members. Quantitative, phylogenetic and covariance analyses of the genes revealed that the GAPDH gene family has been conserved during the evolution of cotton. Promoter analysis revealed that most cis-acting elements were related to MeJA and ABA. Based on the identified promoter cis-acting elements and RNA-seq data, it was hypothesized that Gh_GAPDH9, Gh_GAPDH11, Gh_GAPDH19 and Gh_GAPDH21 are involved in the response of cotton to abiotic stress. The expression levels of the Gh_GAPDH9 gene in two drought-resistant and two drought-sensitive materials were analyzed by qRT‒PCR and found to be high early in the treatment period in the drought-resistant material. The silencing of Gh_GAPDH9 based on virus-induced gene silencing (VIGS) technology resulted in significant leaf wilting or whole-plant dieback in silenced plants after drought stress compared to the control. The content of—malondialdehyde (MDA) in cotton leaves was significantly increased, and the content of proline (Pro) and chlorophyll (Chl) was reduced. In addition, the leaf wilting and dryness of transgenic lines under drought stress were lower than those of wild-type Arabidopsis, indicating that Gh_GAPDH9 is a positive regulator of drought resistance. In conclusion, our results demonstrate that GAPDH genes play an important role in the response of cotton to abiotic stresses and provide preliminary validation of the function of the Gh_GAPDH9 gene under drought stress. These findings provide an important theoretical basis for further studies on the function of the Gh_GAPDH9 gene and the molecular mechanism of the drought response in cotton.

Climate anomalies and human disturbances exert complex effects on regional carbon sequestration (CS), causing ecosystem CS to either increase or decrease due to factors such as vegetation greening, climate extremes, land use/land cover (LULC) changes, and farming systems. This study employs the patch-level land use simulation model to forecast changes in various land-use types in the Xinjiang Uyghur Autonomous Region, China, between 2020 and 2060 under different climatic conditions. The Intergovernmental Panel on Climate Change has proposed shared socioeconomic pathways (SSPs) as potential socioeconomic and environmental trajectories that might influence the region’s future land-use patterns. Three salient findings emerged: (1) LULC displayed considerable variation across future climate scenarios, with a notable rise in forest and grassland cover and a marked decrease in cropland areas under the SSP126 scenario. Conversely, the SSP585 scenario witnessed a substantial cropland expansion, paralleled by a decrease in forest and grassland areas; (2) CS exhibited significant disparities across different future climate scenarios. Xinjiang achieved a peak CS of 9.81 Pg between 2020 and 2060 under the SSP126 scenario, marking an increase of 335.22 Tg in 2060 compared to that in 2020. The SSP585 scenario registered the lowest CS at 9.41 Pg, indicating a decline of 50.07 Tg in 2060 relative to 2020; (3) The impacts of longitude and latitude on CS in Xinjiang predominantly arose from shifts in forest area and vegetation cover based on latitude, which positively influenced CS. In contrast, a decrease in vegetation cover and a subsequent decline in CS were evident with increasing longitude, particularly in the Altai, Tianshan, and Kunlun Mountains. These findings hold significant implications for formulating CS management strategies for terrestrial ecosystems and enhancing ecological preservation in Xinjiang.