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Abstract Background A sustained inflammatory response following spinal cord injury (SCI) contributes to neuronal damage, inhibiting functional recovery. Macrophages, the major participants in the inflammatory response, transform into foamy macrophages after phagocytosing myelin debris, subsequently releasing inflammatory factors and amplifying the secondary injury. Here, we assessed the effect of macrophage scavenger receptor 1 (MSR1) in phagocytosis of myelin debris after SCI and explained its possible mechanism. Methods The SCI model was employed to determine the critical role of MSR1 in phagocytosis of myelin debris in vivo. The potential functions and mechanisms of MSR1 were explored using qPCR, western blotting, and immunofluorescence after treating macrophages and RAW264.7 with myelin debris in vitro. Results In this study, we found improved recovery from traumatic SCI in MSR1-knockout mice over that in MSR1 wild-type mice. Furthermore, MSR1 promoted the phagocytosis of myelin debris and the formation of foamy macrophage, leading to pro-inflammatory polarization in vitro and in vivo. Mechanistically, in the presence of myelin debris, MSR1-mediated NF-κB signaling pathway contributed to the release of inflammatory mediators and subsequently the apoptosis of neurons. Conclusions Our study elucidates a previously unrecognized role of MSR1 in the pathophysiology of SCI and suggests that its inhibition may be a new treatment strategy for this traumatic condition.

Abstract Objective To investigate the clinical efficacy of transumbilical single-incision laparoscopic surgery in the treatment of complicated appendicitis in overweight/obese adolescents. Methods A retrospective analysis was conducted on the clinical data of 226 adolescent patients with complicated appendicitis who were admitted to our hospital from January 2014 to June 2022. Among them, 102 cases underwent transumbilical single-incision laparoscopic appendectomy as the observation group, and another 124 cases underwent conventional three-port laparoscopic appendectomy as the control group. The surgical time, intraoperative blood loss, duration of incisional pain, postoperative flatus time, length of hospital stay, surgical site infection (SSI), satisfaction with cosmetic result, and occurrence of postoperative complications were compared between the two groups. Results Both groups completed the surgery smoothly, and there were no statistically significant differences in gender, age, BMI, duration of illness, white blood cell count, and preoperative CRP value between the two groups (P > 0.05). There were no statistically significant differences in surgical time and intraoperative blood loss between the two groups (P > 0.05). However, the observation group had shorter hospital stays, shorter duration of incisional pain, shorter postoperative time to flatus, and lower overall postoperative complication rates compared to the control group, with statistically significant differences (P

Abstract Kitaev chains in quantum dot-superconductor arrays are a promising platform for the realization of topological superconductivity. As recently demonstrated, even a two-site chain can host Majorana zero modes known as “poor man’s Majorana”. Harnessing the potential of these states for quantum information processing, however, requires increasing their robustness to external perturbations. Here, we form a two-site Kitaev chain using Yu-Shiba-Rusinov states in proximitized quantum dots. By deterministically tuning the hybridization between the quantum dots and the superconductor, we observe poor man’s Majorana states with a gap larger than 70 μeV. The sensitivity to charge fluctuations is also greatly reduced compared to Kitaev chains made with non-proximitized dots. The systematic control and improved energy scales of poor man’s Majorana states realized with Yu-Shiba-Rusinov states will benefit the realization of longer Kitaev chains, parity qubits, and the demonstration of non-Abelian physics.

Growing literature documents the promise of active learning instruction in engaging students in college classrooms. Accordingly, faculty professional development (PD) programs on active learning have become increasingly popular in postsecondary institutions; yet, quantitative evidence on the effectiveness of these programs is limited. Using administrative data and an instructor fixed effects approach, we estimate the effect of an active learning PD program on student performance and persistence at a large public institution. Findings indicate that the training improved subsequent persistence in the same field. Using a subset of instructors whose instruction was observed by independent observers, we identify a positive association between training and implementation of active learning teaching practices. These findings provide suggestive evidence that active learning PD has the potential to improve student outcomes.

Abstract Lymph node metastasis (LNM) is a common invasive feature of hepatocellular carcinoma (HCC) associated with poor clinical outcomes. Through microarray profiling and bioinformatic analyses, we identified the circ-0044539-miR-29a-3p-VEGFA axis as a potential key factor in the progression of HCC LNM. In HCC cells and nude mice, circ-0044539 downregulation or miR-29a-3p upregulation was associated with small tumor size, PI3K-AKT-mTOR pathway inactivation, and downregulation of the key LNM factors (HIF-1α and CXCR4). Furthermore, circ-0044539 was also responsible for exosomal miR-29a-3p secretion. Exosomal miR-29a-3p was then observed to migrate to the LNs and downregulate High-mobility group box transcription factor 1 (Hbp1) in Polymorphonuclear Myeloid-derived suppressor cells (PMN-MDSCs), inducing the formation of a microenvironment suitable for tumor colonization. Overall, circ-0044539 promotes HCC cell LNM abilities and induces an immune-suppressive environment in LNs through exosomes, highlighting its potential as a target for HCC LNM and HCC immunotherapy.

Abstract Background Obesity and the forkhead box O1(FOXO1) affect the survival of breast cancer patients, but the underlying mechanism remains unclear. We aimed to investigate the role of FOXO1 in obesity-associated-breast cancer. Methods We screened 383 breast disease patients from the first affiliated hospital with Nanjing Medical University in 2020. We performed wound healing, transwell, matrigel assays to assess the metastatic ability of cancer cells. We adopted mRNAs sequencing to select the differentially expressed transcripts in breast cancer. We applied immunohistochemistry, western blot, tissue microarrays to assess the level of FOXO1 and epithelial-mesenchymal transition (EMT) pathways. We conducted bioinformatic analysis to investigate interactions between FOXO1 and miR-135b. We used fluorescence in situ hybridization, RT-qPCR to confirm the characteristics of circCNIH4. We conducted luciferase reporter assay, rescue experiments to investigate interactions between circCNIH4 and miR-135b. Results Obesity was positively correlated with the incidence and progression of breast cancer. Adipocytes enhanced the migration of breast cancer and attenuated the effects of FOXO1. MiR-135b was a binding gene of FOXO1 and was regulated by circCNIH4. CircCNIH4 exhibited antitumor activity in vitro and in vivo. Conclusion Adipocytes might accelerate the progression of breast cancer by modulating FOXO1/miR-135b/ circCNIH4 /EMT axis and regulating copper homeostasis.

Abstract Purpose To compare the effects of a single-port-plus-one robotic laparoscopic-modified Lich–Gregoir direct nipple approach and traditional laparoscopic Cohen in treating pediatric primary obstructive megaureter. Materials and methods The clinical data of 24 children with primary obstructive megaureter from January 2021 to November 2021 were analyzed retrospectively. Among them, 12 children (8 boys and 4 girls, the average age were 17.17 ± 6.31 months) treated with the laparoscopic Cohen method were defined as group C. The remaining 12 children (7 boys and 5 girls, the average age was 17.33 ± 6.99 months) underwent single-port-plus-one robotic laparoscopic-modified Lich–Gregoir direct nipple ureteral extravesical reimplantation were defined as group L. The parameters of pre-operation, intraoperative and postoperative were compared. Results There were no differences in the patient characteristics and average follow-up time between the two groups (P > 0.05).The obstruction resolution rate was 100% in both groups. The total operation time in group L is slightly longer than that in group C(P 0.05). The postoperative parameters included blood loss, gross haematuria time, indwelling catheterization time and hospitalization time in group L is shorter than group C(P 0.05). Conclusion Single-port-plus-one robot-assisted laparoscopic-modified Lich–Gregoir direct nipple approach and traditional laparoscopic Cohen are both dependable techniques for ureteral reimplantation in the treatment of pediatric primary obstructive megaureter. Since Lich–Gregoir can preserve the physiological direction of the ureter and direct nipple reimplantation enhances the effect of anti-refluxing, this technique is favorable for being promoted and applied in robot surgery.

Abstract Objective To observe the safety and short-term outcomes of a new way of laparoscopic trocar placement in pediatric robotic-assisted Lich-Gregoir ureteral reimplantation for vesicoureteral reflux. Methods The retrospective study included 32 patients under 14 years diagnosed with primary vesicoureteral reflux (VUR). All these patients underwent robotic-assisted Lich-Gregoir ureteral reimplantation in our department from December 2020 to August 2022. These patients were divided into the following groups according to the different ways of trocar placement: 13 patients in group single-port plus one (SR) and 19 patients in group multiple-port (MR). Patients’ characteristics as well as their perioperative and follow-up data were collected and evaluated. Results There was no significant difference in the data regarding patients’ characteristics and preoperative data. These data included the grade of vesicoureteral reflux according to the voiding cystourethrogram (VCUG), and the differential degree of renal function (DRF) at the following time points: preoperative, postoperative, and comparison of preoperative and postoperative. There was no difference between the two groups. During surgery, the time of artificial pneumoperitoneum establishment, ureteral reimplantation time, and total operative time in the SR group were longer than those in the MR group. Yet only the time of artificial pneumoperitoneum establishment shows a statistical difference (P

Abstract Background Stress hyperglycemia ratio (SHR) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are independently associated with increased mortality risk in diabetic patients with coronary artery disease (CAD). However, the role of these biomarkers in patients with diabetes and multivessel disease (MVD) remains unknown. The present study aimed to assess the relative and combined abilities of these biomarkers to predict all-cause mortality in patients with diabetes and MVD. Methods This study included 1148 diabetic patients with MVD who underwent coronary angiography at Tianjin Chest Hospital between January 2016 and December 2016. The patients were divided into four groups according to their SHR (SHR-L and SHR-H) and NT-proBNP (NT-proBNP-L and NT-proBNP-H) levels. The primary outcome was all-cause mortality. Multivariate Cox regression analyses were performed to evaluate the association of SHR and NT-proBNP levels with all-cause mortality. Results During a mean 4.2 year follow-up, 138 patients died. Multivariate analysis showed that SHR and NT-proBNP were strong independent predictors of all-cause mortality in diabetic patients with MVD (SHR: HR hazard ratio [2.171; 95%CI 1.566–3.008; P

ObjectiveThe purpose of this study is to compare the intraoperative and postoperative outcomes of a trans-umbilical single-site plus one robot-assisted surgery and a trans-umbilical single-site laparoscopic surgery in the treatment of choledochal cysts.MethodsWe retrospectively analyzed clinical data from 49 children diagnosed with choledochal cysts who were admitted to our hospital between June 2020 and December 2023. Among these patients, 24 underwent a trans-umbilical single-site plus one Da Vinci robot-assisted surgery (the robot group) and 25 underwent a trans-umbilical single-site laparoscopic-assisted surgery (the laparoscopic group). We compared differences in intraoperative and postoperative outcomes between the two groups.ResultsThere was no significant difference between the two groups of patients in terms of gender, age, weight, clinical symptoms, maximum cyst diameter, type, postoperative complications, and facial expression, leg movement, activity, crying, and comfortability (FLACC) scoring (p > 0.05). Compared with the patients in the laparoscopic group, those in the robot group had less intraoperative bleeding [10 (8–12) vs. 15 (11.5–18) ml, p

Background: Heart failure with preserved ejection fraction (HFpEF) presents a serious risk to human health. The increased prevalence of sarcopenia in the HFpEF population has a negative impact on patient prognosis. Uric acid (UA) is the byproduct of purine metabolism and is harmful to the cardiovascular system. This study aims to establish the potential relationship between sarcopenia and serum UA in HFpEF patients. Methods: Data were obtained from 180 individuals (aged ≥60 years) with HFpEF admitted to the Geriatric Department of Jiangsu Province Hospital between January 2021 and December 2022. The UA values were grouped into 4 quartiles (Q1-Q4). Logistic generalized linear models and restricted cubic spline (RCS) regression were used to analyze the relationship between sarcopenia and UA. Subgroups based on gender were utilised for further analysis. Results: After adjusting for covariates, odds ratios (ORs) and 95 % confidence intervals (CIs) for sarcopenia prevalence in the 2nd, 3rd, and 4th quartiles were 2.56 (0.57–12.65), 4.94 (1.10–24.49), and 6.95 (1.30–44.25), respectively, unlike the 1st quartile (P for trend = 0.022). The RCS plot demonstrated a positive linear relationship between serum UA levels and sarcopenia (P for non-linearity = 0.190). A sex-based subgroup analysis revealed a statistically significant relationship between UA and sarcopenia in males (P

Recent studies have witnessed that chemical modification can improve the physicochemical and functional properties of plants' polysaccharides. Herein, we modified the natural Lycium barbarum seed dreg polysaccharides (LBSDPs) by sulfation (S-LBSDPs), phosphorylation (P-LBSDPs), and carboxymethylation (C-LBSDPs), and evaluated the chemical composition and antioxidant activity of their derivatives. Natural polysaccharides and their derivatives exhibited typical polysaccharide absorption peaks and characteristic group absorption peaks in FT-IR spectra along with maximum UV absorption. After modification, the total sugar and protein contents of the derivatives were decreased, whereas the uronic acid content was increased. Among the three derivatives, sulfated polysaccharides displayed excellent thermal stability. S-LBSDP and P-LBSDP showed the highest ABTS radical scavenging and reducing power while S-LBSDPs and C-LBSDPs showed better DPPH radical scavenging effect, and P-LBSDPs showed considerable Fe2+ chelating ability. Our data indicate that chemical modifications can impart a positive effect on the antioxidant potential of plant-derived polysaccharides.

Using the Education Longitudinal Study of 2002 (ELS:2002), this paper analyzes students' baccalaureate attainment and early labor market performance, comparing 2-year college and 4-year institution entrants and exploring the potential heterogeneous treatment effects of initiating one's college experience in a 2-year college by individual pre-college academic preparation. Utilizing propensity score matching on a rich set of student demographic characteristics, academic and high school attributes, we find that 2-year college entry sharply reduces baccalaureate aspirants' likelihood of earning a baccalaureate, and such negative effects are particularly pronounced for students in the highest quartile of pre-college math ability. In terms of labor market outcomes, female 2-year college entrants are less likely to gain full-time employment, as compared to their female 4-year institution counterparts. We also examine various mechanisms that may hinder 2-year college entrants' baccalaureate completion, including the impact of 2-year college attendance on early academic progress, challenges of the transfer process, loss of credits at the point of transfer, and post-transfer academic shock. Our results provide suggestive evidence in support of all four mechanisms.

Abstract Three‐dimensional (3D) echocardiography is an emerging technique for assessing right ventricular (RV) volume and function, but 3D‐RV normal values from a large Chinese population are still lacking. The aim of the present study was to establish normal values of 3D‐RV volume and function in healthy Chinese volunteers. A total of 1117 Han Chinese volunteers from 28 laboratories in 20 provinces of China were enrolled, and 3D‐RV images of 747 volunteers with optimal image quality were ultimately analyzed by a core laboratory. Both vendor‐dependent and vendor‐independent software platforms were used to analyze the 3D‐RV images. We found that men had larger RV volumes than women did in the whole population, even after indexing to body surface area, and older individuals had smaller RV volumes. The normal RV volume was significantly smaller than that recommended by the American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines in both sexes. There were significant differences in 3D‐RV measurements between the two vendor ultrasound systems and the different software platforms. The echocardiographic measurements in normal Chinese adults II study revealed normal 3D‐RV volume and function in a large Chinese population, and there were significant differences between the sexes, ages, races, and vendor groups. Thus, normal 3D‐RV values should be stratified by sex, age, race, and vendor.

BackgroundImproving health care in cities with a diverse, international population is crucial for ensuring health equity, particularly for foreigners facing challenges due to cultural and language barriers. This situation is especially relevant in China, a major destination for expatriates and travelers, where optimizing health care services and incorporating international standards in the public sector are vital. Achieving this involves understanding the operational details, cultural and linguistic nuances, and advancing medical digitalization. A strategic approach focusing on cultural competence and awareness of health care systems is essential for effectively navigating health care for foreigners and expatriates in China. ObjectiveThe aim of this study was to perform an in-depth analysis of the subjective and objective experiences of local and international patients in public hospitals in China to provide a basis for enhancing the medical experience of all patients. MethodsA structured questionnaire was provided to patients at an international outpatient service of a top-tier university hospital in China. Qualitative analysis of the survey responses was performed to methodically categorize and analyze medical treatment, focusing on patient demand and satisfaction across four main category elements (“high demand, high satisfaction”; “high demand, low satisfaction”; “low demand, high satisfaction”; and “low demand, low satisfaction”), enabling a detailed cross-sectional analysis to identify areas for improvement. ResultsElements falling under “high demand, high satisfaction” for both Chinese and international patients were primarily in the realms of medical quality and treatment processes. In contrast, elements identified as “high demand, low satisfaction” were significantly different between the two patient groups. ConclusionsThe findings highlight the importance of systematic, objective research in advancing the quality of international health care services within China’s leading academic medical centers. Key to this improvement is rigorous quality control involving both patients and providers. This study highlights the necessity of certifying such centers and emphasizes the role of digital platforms in disseminating information about medical services. This strategy is expected to cater to diverse patient needs, enhancing the overall patient experience. Furthermore, by developing comprehensive diagnosis and treatment services and highlighting the superior quality and costs associated with international health care, these efforts aim to foster a sense of belonging among international patients and increase the attractiveness of China’s medical services for this demographic.

Summary: Epilepsy is a brain disorder affecting up to 1 in 26 individuals. Despite its clinical importance, the molecular mechanisms of epileptogenesis are still far from clarified. Our previous study showed that disruption of Clock in excitatory neurons alters cortical circuits and leads to generation of focal epilepsy. In this study, a GAD-Cre;Clockflox/flox mouse line with conditional Clock gene knockout in inhibitory neurons was established. We observed that seizure latency was prolonged, the severity and mortality of pilocarpine-induced seizure were significantly reduced, and memory was improved in GAD-Cre;Clockflox/flox mice. We hypothesize that mice with CLOCK knockout in inhibitory neurons have increased threshold for seizure, opposite from mice with CLOCK knockout in excitatory neurons. Further investigation showed Clock knockout in inhibitory neurons upregulated the basal protein level of ARC, a synaptic plasticity-associated immediate-early gene product, likely through the BDNF-ERK pathway. Altered basal levels of ARC may play an important role in epileptogenesis after Clock deletion in inhibitory neurons. Although sEPSCs and intrinsic properties of layer 5 pyramidal neurons in the somatosensory cortex exhibit no changes, the spine density increased in apical dendrite of pyramidal neurons in CLOCK knockout group. Our results suggest an underlying mechanism by which the circadian protein CLOCK in inhibitory neurons participates in neuronal activity and regulates the predisposition to epilepsy.

ObjectiveTo compare the efficacy of robot-assisted single-port-plus-one pyeloplasty (RSPY) and laparoscopic single-port pyeloplasty (LSPY) in the treatment of children with ureteropelvic junction obstruction (UPJO).MethodsThe clinical data of 47 children who underwent surgery for UPJO at the Department of the Pediatric Surgery of the Fujian Provincial Hospital from October 2020 to September 2022 were analyzed retrospectively. Of these 47 children, 27 received RSPY while 20 underwent LSPY. The baseline data, operation time, intraoperative anastomosis time, intraoperative blood loss, postoperative hospital stay, complications, total cost, preoperative and postoperative renal parenchymal thickness (PT), anteroposterior renal pelvis diameter (APD), and differential renal function (DRF) of the two groups were compared to evaluate the clinical efficacy of the two surgical methods.ResultsThe results showed that both surgical techniques were successful and no patient transitioned to open surgery. There was no significant difference between the two groups in baseline data, intraoperative blood loss, complications, APD, and PT 6 months after surgery. There was also no significant difference in APD, PT, and DRF 12 months after surgery (all P > 0.05). Compared with the LSPY group, the RSPY group had shorter operation time [(153.04 ± 14.44) vs. (189.90 ± 32.59) min, t = −5.24, P

Triple-negative breast cancer (TNBC) is more prone to recurrence and metastasis relative to other subtypes of breast cancer, leading to an extremely poor prognosis. The increasing potential chemoresistance of TNBC patients is mainly due to that tumor cells escape from apoptosis. In recent years, statins have demonstrated extensive anti-tumor effects. It is worth noting that statins have more effective anti-tumor effects on TNBC cells and drug-resistant breast cancer cells. Therefore, this study examines the superior cytotoxic effects of statins on TNBC cell lines and further explores their potential therapeutic mechanisms. We detected different cell phenotypes and found that statins significantly reduced the cell viability of TNBC cells. Specifically, pitavastatin showed an obvious induction in cell death, cell cycle arrest and oxidative stress in TNBC MDA-MB-231 cells. The reversal effect of iron chelator desferrioxamine (DFO) on the morphological and molecular biological changes induced by pitavastatin has revealed a new mode of cell death induced by pitavastatin: ferroptosis. This ferroptotic effect was strengthened by the decreased expression of glutathione peroxidase 4 (GPx4) as well as newly discovered ferroptosis suppressor protein 1 (FSP1). The data showed that ferroptotic death of MDA-MB-231 cells is autophagy-dependent and mediated by the mevalonate pathway. Finally, we found that therapeutic oral doses of statins can inhibit the growth of transplanted tumors, which establishes statins as a potential treatment for TNBC patients. In conclusion, we found pitavastatin could induce autophagy-dependent ferroptosis in TNBC cells via the mevalonate pathway which may become a potential adjuvant treatment option for TNBC patients.

Background Early reperfusion therapy for acute myocardial infarction (AMI) is an effective approach to reduce mortality in AMI patients. Percutaneous coronary intervention (PCI) is one of the reperfusion therapy modalities, and contrast-induced acute kidney injury (CI-AKI) after PCI has become one of the common causes of AKI. Objective To investigate the risk factors for the development of CI-AKI in AMI patients after PCI, establish a risk prediction model for CI-AKI based on risk factors and evaluate its validity. Methods The clinical data of 1 274 patients who attended the Affiliated Hospital of Xuzhou Medical University diagnosed of AMI and treated with PCI were collected consecutively from 2019 to 2021. According to the chronological order of admission, the included patients were divided into the training group (January 2019 to March 2021, 900 cases) and validation group (April 2021 to December 2021, 374 cases) in a ratio of approximately 7∶3; and divided into the CI-AKI and non-CI-AKI groups according to the diagnostic criteria of CI-AKI. Independent risk factors were screened using univariable Logistic regression analysis, Lasso regression, cross-validation, multivariable Logistic regression analysis, and a nomogram for predicting the risk of CI-AKI was plotted. Their discriminatory power, calibration ability, and clinical application value were evaluated by calculating concordance statistic (C-statistic), plotting calibration curve and decision curve. Results Among the 900 patients in the training group, 109 patients (12.1%) developed CI-AKI after PCI; among the 374 patients in the validation group, 27 patients (7.2%) developed CI-AKI. Multivariable Logistic regression analysis showed that LVEF〔OR=0.903, 95%CI (0.873, 0.934) 〕, platelet distribution width〔OR=1.158, 95%CI (1.053, 1.274) 〕, MPVLR〔OR=1.047, 95%CI (1.016, 1.079) 〕, NHR〔OR=1.072, 95%CI (1.021, 1.124) 〕, Scr〔OR=1.006, 95%CI (1.002, 1.011) 〕, and diuretics〔OR=2.321, 95%CI (1.452, 3.709) 〕 were independent influencing factors for CI-AKI after PCI in AMI patients (P

Abstract Semiconductor nanowires coupled to superconductors can host Andreev bound states with distinct spin and parity, including a spin-zero state with an even number of electrons and a spin-1/2 state with odd-parity. Considering the difference in spin of the even and odd states, spin-filtered measurements can reveal the underlying ground state. To directly measure the spin of single-electron excitations, we probe an Andreev bound state using a spin-polarized quantum dot that acts as a bipolar spin filter, in combination with a non-polarized tunnel junction in a three-terminal circuit. We observe a spin-polarized excitation spectrum of the Andreev bound state, which can be fully spin-polarized, despite strong spin-orbit interaction in the InSb nanowires. Decoupling the hybrid from the normal lead causes a current blockade, by trapping the Andreev bound state in an excited state. Spin-polarized spectroscopy of hybrid nanowire devices, as demonstrated here, is proposed as an experimental tool to support the observation of topological superconductivity.

Currently, the decision boundary of the multi-class anomaly detection algorithm based on deep learning does not sufficiently capture the positive class region, posing a risk of abnormal sample features falling into the domain of normal sample features and potentially leading to misleading outcomes in practical applications. In response to the above problems, this paper proposes a new method called multi-class hypersphere anomaly detection (MMHAD) based on the edge outlier exposure set and margin. The method aims to utilize convolutional neural networks for joint training of all normal object classes, identifying a shared set of outlier exposures, learning compact identification features, and setting appropriate edge parameters to guide the model in mapping outliers outside the hypersphere. This approach enables more comprehensive detection of various types of exceptions. The experiments demonstrate that the algorithm is superior to the most advanced baseline method, with an improvement of 26.0%, 8.2%, and 20.1% on CIFAR-10 and 14.8%, 12.0%, and 20.1% on FMNIST in the cases of (2/8), (5/5), and (9,1), respectively. Furthermore, we investigate the challenging (2/18) case on CIFAR-100, where our method achieves approximately 17.4% AUROC gain. Lastly, for a recycling waste dataset with the (4/1) case, our MMHAD yields a notable 22% enhancement in performance. Experimental results show the effectiveness of the proposed model in multi-classification anomaly detection.

Abstract Background The metastasis of breast cancer (BC) is a complex multi-step pathological process, strictly dependent on the intrinsic characteristics of BC cells and promoted by a predisposing microenvironment. Although immunotherapy has made important progress in metastasis BC, the heterogeneity of PD-L1 in tumor associated macrophages (TAMs) in BC and the underlying mechanisms in the metastasis development of BC are still not completely elucidated. Small extracellular vesicles (sEVs) represent essential interaction mediators between BC cells and TAMs. It is worth noting to explore the underlying mechanisms typical of sEVs and their role in the metastasis development of BC. Methods The structure of sEVs was identified by TEM, while the particle size and amounts of sEVs were detected by BCA and NTA analysis. The specific PD-L1 + CD163 + TAM subpopulation in metastasis BC was identified by scRNA-seq data of GEO datasets and verified by IHC and IF. The function of TAMs and sEVs in metastasis BC was explored by RT-qPCR, WB, IF, flow cytometry and in vivo experiment. The expression profiles of plasma sEVs-miRNA in relation to BC metastasis was analyzed using next-generation sequencing. Further detailed mechanisms of sEVs in the metastasis development of BC were explored by bioinformatics analysis, RT-qPCR, WB and luciferase reporter assay. Results In this study, we identified that the immunosuppressive molecule PD-L1 was more abundant in TAMs than in BC cells, and a specific PD-L1 + CD163 + TAM subpopulation was found to be associated with metastasis BC. Additionally, we found that BC cells-derived sEVs can upregulate the PD-L1 expression and induce the M2 polarization, enhancing the metastasis development both in vitro and in vivo. Also, Clinical data showed that sEV-miR-106b-5p and sEV-miR-18a-5p was in relation to BC metastasis development and poor prognosis of BC patients. Further mechanistic experiments revealed that BC-derived sEV-miR-106b-5p and sEV-miR-18a-5p could synergistically promoted the PD-L1 expression in M2 TAMs by modulating the PTEN/AKT and PIAS3/STAT3 pathways, resulting in the enhancement of the BC cells invasion and metastasis. Conclusions Our study demonstrated that BC-derived sEVs can induce metastasis in BC through miR-106b-5p/PTEN/AKT/PD-L1 and miR-18a-5p/PIAS3/STAT3/PD-L1 pathways in TAMs. Therefore, the inhibition of these specific interactions of signaling pathways would represent a promising target for future therapeutic strategies for treatment of BC.

Abstract Purpose Most Hepatocellular carcinoma (HCC) patients are in advanced or metastatic stage at the time of diagnosis. Prognosis for advanced HCC patients is dismal. This study was based on our previous microarray results, and aimed to explore the promising diagnostic and prognostic markers for advanced HCC by focusing on the important function of KLF2. Methods The Cancer Genome Atlas (TCGA), Cancer Genome Consortium database (ICGC), and the Gene Expression Comprehensive Database (GEO) provided the raw data of this study research. The cBioPortal platform, CeDR Atlas platform, and the Human Protein Atlas (HPA) website were applied to analyze the mutational landscape and single-cell sequencing data of KLF2. Basing on the results of single-cell sequencing analyses, we further explored the molecular mechanism of KLF2 regulation in the fibrosis and immune infiltration of HCC. Results Decreased KLF2 expression was discovered to be mainly regulated by hypermethylation, and indicated a poor prognosis of HCC. Single-cell level expression analyses revealed KLF2 was highly expressed in immune cells and fibroblasts. The function enrichment analysis of KLF2 targets indicated the crucial association between KLF2 and tumor matrix. 33-genes related with cancer associated fibroblasts (CAFs) were collected to identify the significant association of KLF2 with fibrosis. And SPP1 was validated as a promising prognostic and diagnostic marker for advanced HCC patients. CXCR6 CD8+ T cells were noted as a predominant proportion in the immune microenvironment, and T cell receptor CD3D was discovered to be a potential therapeutic biomarker for HCC immunotherapy. Conclusion This study identified that KLF2 is an important factor promoting HCC progression by affecting the fibrosis and immune infiltration, highlighting its great potential as a novel prognostic biomarker for advanced HCC.

The pericarp of Herpetospermum pedunculosum (HPP) has traditionally been used for treating jaundice and hepatitis. However, the specific hepatoprotective components and their safety/efficacy profiles remain unclear. This study aimed to characterize the total cucurbitacins (TCs) extracted from HPP and evaluate their hepatoprotective potential. As a reference, Hu-lu-su-pian (HLSP), a known hepatoprotective drug containing cucurbitacins, was used for comparison of chemical composition, effects, and safety. Molecular networking based on UHPLC-MS/MS identified cucurbitacin B, isocucurbitacin B, and cucurbitacin E as the major components in TCs, comprising 70.3%, 26.1%, and 3.6% as determined by RP-HPLC, respectively. TCs treatment significantly reversed CCl4-induced metabolic changes associated with liver damage in a dose-dependent manner, impacting pathways including energy metabolism, oxidative stress and phenylalanine metabolism, and showed superior efficacy to HLSP. Safety evaluation also showed that TCs were safe, with higher LD50 and no observable adverse effect level (NOAEL) values than HLSP. The median lethal dose (LD50) and NOAEL values of TCs were 36.21 and 15 mg/kg body weight (BW), respectively, while the LD50 of HLSP was 14 mg/kg BW. In summary, TCs extracted from HPP demonstrated promising potential as a natural hepatoprotective agent, warranting further investigation into synergistic effects of individual cucurbitacin components.

Summary: Fibroblast growth factor 9 (FGF9) is a member of the fibroblast growth factor family, which is widely expressed in the central nervous system (CNS). It has been reported that deletion of FGF9 leads to defects in cerebellum development, including Purkinje cell defect. However, it is not clear how FGF9 regulating cerebellar development remains to be determined. Our results showed that in addition to disrupt Bergmann fiber scaffold formation and granule neuron migration, deletion of neuronal FGF9 led to ataxia defects. It affected development and function of Purkinje cells, and also changed the action potential threshold and excitation frequency. Mechanistically, depletion of FGF9 significantly changed neurotransmitter contents in Purkinje cells and led to preferential increase in inflammation, even downregulation in ERK signaling. Together, the data demonstrate that neuronal FGF9 is required for the development and function of Purkinje cells in the cerebellum. Insufficient FGF9 during cerebellum development will cause ataxia defects.

Objective: To investigate the dosimetric effects of using individualized silicone rubber (SR) bolus on the target area and organs at risk (OARs) during postmastectomy radiotherapy (PMRT), as well as evaluate skin acute radiation dermatitis (ARD). Methods: A retrospective study was performed on 30 patients with breast cancer. Each patient was prepared with an individualized SR bolus of 3 mm thickness. Fan-beam computed tomography (FBCT) was performed at the first and second fractions, and then once a week for a total of 5 times. Dosimetric metrics such as homogeneity index (HI), conformity index (CI), skin dose (SD), and OARs including the heart, lungs, and spinal cord were compared between the original plan and the FBCTs. The acute side effects were recorded. Results: In targets' dosimetric metrics, there were no significant differences in D mean and V 105% between planning computed tomography (CT) and actual treatments ( P > .05), while the differences in D 95% , V 95% , HI, and CI were statistically significant ( P .05) except the V 30 of affected lung, which was slightly lower than the planning CT ( P

The blue-crowned laughingthrush Pterorhinus courtoisi (Ménégaux, 1923) is listed as a critically endangered species on the International Union for Conservation of Nature Red List. This species occupies an extremely small known breeding range in China. In this study, we obtain the complete mitochondrial genome of the blue-crowned laughingthrush by using Illumina NovaSeq sequencing. The total length of the genome is 17,875 bp, containing 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes and 2 control regions, with a slight A-T preference (52.84%) in base composition.

ABSTRACTIntroduction Objective structured clinical examination (OSCE) results could be affected by low homogeneity of examiners, non-retrospectiveness of test results, and examiner-cohort effect. In China, many students participate in medical qualification examinations, and this issue is particularly significant. This study aimed to develop a video recording, video-based rating method and compare the reliability of video and on-site ratings to enhance the quality assurance of OSCEs.Methods The subjects of this study were clinical students one year after graduation participating in the clinical skills portion of the National Medical Licensing Examination. The participants were from four cities in Jiangsu province. Participants were randomly allocated to on-site and video rating groups to evaluate the rating methods consistency. We verified the reliability of recording equipment and evaluability of video recording. Moreover, we compared the consistency and equivalence of the two rating methods and analyzed the impact of video recording on scores.Results The reliability of recording equipment and evaluability of video recording were high. Evaluation consistency between experts and examiners was acceptable, and there was no difference in evaluation results (P = 0.61). There was good consistency between video and on-site rating; however, a difference between the two rating methods was detected. The scores of video-based rating group students were lower than those of all students (P

Abstract Purpose To investigate the mechanism underlying the modulation of M1 macrophage polarization by exosomes released from hyperthermia-treated triple-negative breast cancer (TNBC) cells. Materials and methods In this study, the effects of hyperthermia on TNBC cells were examined using cell counting kit-8, apoptosis, and cell cycle assays. Transmission electron microscopy was used to identify the structure of exosomes, while bicinchoninic acid and nanoparticle tracking analysis were used to detect particle size and amounts of exosomes released after hyperthermia. The polarization of macrophages incubated with exosomes derived by hyperthermia-pretreated TNBC cells were assessed by RT-qPCR and flow cytometry analysis. Next, RNA sequencing was performed to determine the targeting molecules changed in hyperthermia-treated TNBC cells in vitro. Finally, the mechanism underlying the modulation of macrophage polarization by exosomes derived from hyperthermia-treated TNBC cells was examined by using RT-qPCR, immunofluorescence and flow cytometry analysis. Results Hyperthermia markedly reduced cell viability in TNBC cells and promoted the secretion of TNBC cell-derived exosomes. The hub genes of hyperthermia-treated TNBC cells were significantly correlated with macrophage infiltration. Additionally, hyperthermia-treated TNBC cell-derived exosomes promoted M1 macrophage polarization. Furthermore, the expression levels of heat shock proteins, including HSPA1A, HSPA1B, HSPA6, and HSPB8, were significantly upregulated upon hyperthermia treatment, with HSPB8 exhibiting the highest upregulation. Moreover, hyperthermia can induce M1 macrophage polarization by promoting exosome-mediated HSPB8 transfer. Conclusion This study demonstrated a novel mechanism that hyperthermia can induce M1 polarization of macrophages via exosome-mediated HSPB8 transfer. These results will help with future development of an optimized hyperthermia treatment regime for clinical application, especially for combination treatment with immunotherapy.

Abstract Background Hepatocellular carcinoma (HCC) has a poor prognosis and new effective treatments are needed. SLC12A5 plays important roles in multiple complex pathological states and is overexpressed in a variety of malignancies. However, the effects of SLC12A5 in HCC have not been determined. Methods SLC12A5 expression was assessed by immunostaining and western blotting. A cell viability assay was used to detect cell proliferation. Flow cytometry was used to evaluate the intracellular calcium concentration and cell cycle. Ferroptosis was detected by transmission electron microscopy, lipid peroxidation, and glutathione assays. Subcutaneous tumor formation experiments were used to validate the tumorigenic effect of SLC12A5 in vivo. RNA‐seq was used to evaluate the molecular mechanisms underlying the effects of SLC12A5. The therapeutic efficacy of targeting SLC12A5 was assessed in a patient‐derived xenograft (PDX) model. Results High SLC12A5 expression was strongly associated with a poor clinical prognosis and promoted HCC growth. Mechanistically, SLC12A5 promoted ER stress to enhance calcium release and upregulated PNCK expression levels. Concomitantly, PNCK was significantly activated by calcium ions released from the ER. PNCK activated and induced the phosphorylation of PI3K/AKT/mTOR pathway components. Furthermore, SLC12A5 inhibited ferroptosis in HCC by upregulating the expression of xCT, a cystine transporter. Conclusion High SLC12A5 levels were correlated with a poor prognosis, promoted tumorigenesis, and inhibited ferroptosis in HCC. These findings suggested that SLC12A5 is a therapeutic target and provide insight into the link between ER stress and ferroptosis in HCC.

Agar, as a seaweed polysaccharide mainly extracted from Gracilariopsis lemaneiformis, has been commercially applied in multiple fields. To investigate factors indicating the agar accumulation in G. lemaneiformis, the agar content, soluble polysaccharides content, and expression level of 11 genes involved in the agar biosynthesis were analysed under 4 treatments, namely salinity, temperature, and nitrogen and phosphorus concentrations. The salinity exerted the greatest impact on the agar content. Both high (40‰) and low (10‰, 20‰) salinity promoted agar accumulation in G. lemaneiformis by 4.06%, 2.59%, and 3.00%, respectively. The content of agar as a colloidal polysaccharide was more stable than the soluble polysaccharide content under the treatments. No significant correlation was noted between the two polysaccharides, and between the change in the agar content and the relative growth rate of the algae. The expression of all 11 genes was affected by the 4 treatments. Furthermore, in the cultivar 981 with high agar content (21.30 ± 0.95%) compared to that (16.23 ± 1.59%) of the wild diploid, the transcriptional level of 9 genes related to agar biosynthesis was upregulated. Comprehensive analysis of the correlation between agar accumulation and transcriptional level of genes related to agar biosynthesis in different cultivation conditions and different species of G. lemaneiformis, the change in the relative expression level of glucose-6-phosphate isomerase II (gpiII), mannose-6-phosphate isomerase (mpi), mannose-1-phosphate guanylyltransferase (mpg), and galactosyltransferase II (gatII) genes was highly correlated with the relative agar accumulation. This study lays a basis for selecting high-yield agar strains, as well as for targeted breeding, by using gene editing tools in the future.

The hydrogenation of carbon dioxide (CO2) to produce light olefins is one of the most promising ways to utilize CO2 in power plant flue gas. However, the low concentration of CO2 (~10%) and the existence of water steam in the flue gas pose great challenges for the catalyst design. To address these problems, we introduced a Mg promoter and hydrophobic component into the Fe-based catalyst to improve the CO2 adsorption capacity and weaken the negative effects of water. The yield of light olefins on an optimized multifunctional Fe-based catalyst increased by 37% in low-concentration CO2 hydrogenation with water steam. A variety of characterizations proved that the Mg promoter played critical roles in regulating the adsorption capacity of CO2, increasing the surface electron density of Fe species, and promoting the formation of iron carbide active sites. The hydrophobic component mainly contributed to constraining the oxidation of iron carbides via water steam. It benefited from the rational design of the catalyst, showing how our multifunctional Fe-based catalyst has great potential for practical application in CO2 utilization.

PurposeTo introduce a new technique of single-port-plus-one robotic laparoscopic-modified Lich-Gregoir direct nipple ureteral extravesical reimplantation and ascertain its validity in the treatment of pediatric primary obstructive megaureter.MethodsBetween January 2021 and November 2021, we retrospectively analyzed the clinical data of 12 children with primary obstructive megaureter who were admitted to the Department of Pediatric Surgery of Fujian Provincial Hospital. All 12 children were treated with single-port-plus-one robotic laparoscopic Lich-Gregoir direct nipple ureteral extravesical reimplantation. Five of them were female and seven were male, including nine cases were simple obstructive type, while the remaining three cases were obstructive with reflux type. The mean age of the children was 17.33 ± 6.99 (10–36) months and the mean follow-up time was 14.16 ± 1.75 (12–17) months. Changes in preoperative and first-year postoperative parameters were compared.ResultsThe mean operative time for all 12 children was 123.58 ± 10.85 (110–145) min, with a mean internal operative time of 101.42 ± 0.85 (90–120) min, a mean operative bleeding time of 2.42 ± 0.67 (2–4) ml, and a mean hematuria duration of 16.08 ± 1.44 (14–19) h. The mean indwelling catheterization time was 2.25 ± 0.45 (2–3) days and the mean hospitalization time was 3.83 ± 0.39 (3–4) days. At the postoperative first year, the ureteral diameter, calyceal diameter, and anterior–posterior renal pelvic diameter were found to be significantly smaller than at the preoperative period (18.83 ± 3.21 mm vs. 6.83 ± 1.27 mm, 13.99 ± 3.58 mm vs. 3.5 ± 2.90 mm, and 34.92 ± 4.25 mm vs. 10.08 ± 1.88 mm, P

Rolling bearing is one of the core components in rotating machinery, and its running status directly affects the operation of the whole equipment. Faults of rolling bearings in the actual working process are often multiple faults. To effectively separate fault sources, the blind source separation method is used for the compound fault diagnosis of rolling bearings. Because of the impact of the number of artificially limited decompositions and quadratic penalty factor on VMD in the decomposition process, and the slow convergence and low accuracy in the objective function of traditional FastICA operation, the VMD algorithm based on the energy loss coefficient and the information entropy is proposed, which adaptively determines the number of modal components and the quadratic penalty factor; The Tukey M estimation is selected as the objective convergence function of the FastICA algorithm to improve its robustness. First, VMD is used to decompose the signal; Secondly, the original signal and the decomposed IMF component are reconstructed, the covariance matrix and the singular value decomposition are constructed, the number of fault sources is estimated by the proximity dominance method, and the decomposed IMF components are filtered through correlation analysis and kurtosis index to build a multi-channel feature set; Finally, the constructed multi-channel feature set is input to the FastICA algorithm based on the Tukey M estimation for the separation of fault source signals to achieve composite fault diagnosis. The compound fault experiment shows that the proposed method in this paper can effectively realize the blind source separation of rolling bearing fault features to realize the compound fault diagnosis in different positions.

Background: Tumor antigenicity and efficiency of antigen presentation jointly influence tumor immunogenicity, which largely determines the effectiveness of immune checkpoint blockade (ICB). However, the role of altered antigen processing and presentation machinery (APM) in breast cancer (BRCA) has not been fully elucidated. Methods: A series of bioinformatic analyses and machine learning strategies were performed to construct APM-related gene signatures to guide personalized treatment for BRCA patients. A single-sample gene set enrichment analysis (ssGSEA) algorithm and weighted gene co-expression network analysis (WGCNA) were combined to screen for BRCA-specific APM-related genes. The non-negative matrix factorization (NMF) algorithm was used to divide the cohort into different clusters and the fgsea algorithm was applied to investigate the altered signaling pathways. Random survival forest (RSF) and the least absolute shrinkage and selection operator (Lasso) Cox regression analysis were combined to construct an APM-related risk score (APMrs) signature to predict overall survival. Furthermore, a nomogram and decision tree were generated to improve predictive accuracy and risk stratification for individual patients. Based on Tumor Immune Dysfunction and Exclusion (TIDE) method, random forest (RF) and Lasso logistic regression model were combined to establish an APM-related immunotherapeutic response score (APMis). Finally, immune infiltration, immunomodulators, mutational patterns, and potentially applicable drugs were comprehensively analyzed in different APM-related risk groups. IHC staining was used to assess the expression of APM-related genes in clinical samples. Results: In this study, APMrs and APMis showed favorable performances in risk stratification and therapeutic prediction for BRCA patients. APMrs exhibited more powerful prognostic capacity and accurate survival prediction compared to conventional clinicopathological features. APMrs was closely associated with distinct mutational patterns, immune cell infiltration and immunomodulators expression. Furthermore, the two APM-related gene signatures were independently validated in external cohorts with prognosis or immunotherapeutic responses. Potential applicable drugs and targets were mined in the APMrs-high group. APM-related genes were further validated in our in-house samples. Conclusion: The APM-related gene signatures established in our study could improve the personalized assessment of survival risk and guide ICB decision-making for BRCA patients.