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Abstract This study investigated the impact of LNP023 on the AMPK/mTOR signaling pathway in lupus nephritis (LN) and its effects on autophagy and oxidative stress. A mouse model of LN was established, and renal injury was confirmed by assessing various LN markers, including antinuclear antibody, ds‐DNA, anti‐Sm antibody, and others. Mice were treated with LNP023, the AMPK activator AICAR, or the AMPK inhibitor dorsomorphin. Renal injury and fibrosis were evaluated using HE and Masson staining. Expression levels of AMPK, mTOR, LC3, Beclin1, and p62 were assessed by immunohistochemistry and Western blot. Oxidative stress and inflammatory markers were measured by polymerase chain reaction and enzyme‐linked immunosorbent assay. LN mice exhibited low AMPK/p‐AMPK and high mTOR/p‐mTOR levels, alongside significant renal injury, fibrosis, reduced autophagy, and elevated oxidative stress. LNP023 treatment improved these parameters, with enhanced effects when combined with AICAR. Conversely, dorsomorphin reversed LNP023's therapeutic benefits. The complement factor B inhibitor LNP023 promotes kidney health in LN mice by mediating the AMPK/mTOR pathway, promoting autophagy, and attenuating oxidative stress.

ObjectiveTo analyze the characteristics of forensic clinical sex identification cases after sex reassignment surgery for transsexualism, discuss the main point of forensic clinical sex identification in China based on domestic and foreign sex change policies and related cases, so as to standardize relevant identification.MethodsA total of 39 cases of forensic clinical sex identification were collected from Center for Forensic Science, Shanghai Medical College of Fudan University in recent years, and the ratio of sex, identification time, the location of surgery, secondary sex characteristic and other information were statistically analyzed.ResultsTransgender woman accounted for 97.4% of the cases, and 94.9% of the cases were operated in Thailand. All cases were identified after the sex reassignment surgery, and at least one of the secondary sex characteristics was consistent with the postoperative primary sexual characters. There were only 2 cases in which auxiliary examination was applied.ConclusionForensic clinical sex identification should be based on the principle that the primary and secondary sex characteristics are consistent with the changed sex.

Objective To explore the biomarkers and potential mechanisms of chronic restraint stress-induced myocardial injury in hyperlipidemia ApoE-/- mice. Methods The hyperlipidemia combined with the chronic stress model was established by restraining the ApoE-/- mice. Proteomics and bioinformatics techniques were used to describe the characteristic molecular changes and related regulatory mechanisms of chronic stress-induced myocardial injury in hyperlipidemia mice and to explore potential diagnostic biomarkers. Results Proteomic analysis showed that there were 43 significantly up-regulated and 58 significantly down-regulated differentially expressed proteins in hyperlipidemia combined with the restraint stress group compared with the hyperlipidemia group. Among them, GBP2, TAOK3, TFR1 and UCP1 were biomarkers with great diagnostic potential. KEGG pathway enrichment analysis indicated that ferroptosis was a significant pathway that accelerated the myocardial injury in hyperlipidemia combined with restraint stress-induced model. The mmu_circ_0001567/miR-7a/Tfr-1 and mmu_circ_0001042/miR-7a/Tfr-1 might be important circRNA-miRNA-mRNA regulatory networks related to ferroptosis in this model. Conclusion Chronic restraint stress may aggravate myocardial injury in hyperlipidemia mice via ferroptosis. Four potential biomarkers are selected for myocardial injury diagnosis, providing a new direction for sudden cardiac death （SCD） caused by hyperlipidemia combined with the restraint stress.

The widespread application of magnetic fluid seals in mechanical devices highlights the significant impact of temperature on the stability of these sealing systems. This paper investigates the magnetic field characteristics and thermal properties of magnetic fluid in sealing devices through both numerical simulations and experimental methods. The effects of rotational speed, magnetic fluid solid content, and heating power on the magnetic fluid temperature of the magnetic sealing device were analyzed. The numerical simulation findings indicate that the viscosity the of magnetic fluid significantly contributes to enhanced energy dissipation, while the temperature of the magnetic fluid rises with increasing rotational speed. The initial-phase transition point of the magnetic fluid and its correlation with phase transition volume relative to shaft rotational speed was determined. The experimental results show that the magnetic fluid temperature rises continuously and the time to reach stability increases with the increase in power, and the same is true for the magnetic fluid with a different solid content. Under the same power, the temperature variation is not large, and the magneto-liquid variation is consistent with that in the numerical simulation. This research provides theoretical insights for designing magnetic fluid sealing devices.

Objectives To investigate the role of circRNA regulators MBNL1 and QKI in the progression of esophageal squamous cell carcinoma. Background MBNL1 and QKI are pivotal regulators of pre-mRNA alternative splicing, crucial for controlling circRNA production – an emerging biomarker and functional regulator of tumor progression. Despite their recognized roles, their involvement in ESCC progression remains unexplored. Methods The expression levels of MBNL1 and QKI were examined in 28 tissue pairs from ESCC and adjacent normal tissues using data from the GEO database. Additionally, a total of 151 ESCC tissue samples, from stage T1 to T4, consisting of 13, 43, 87, and 8 cases per stage, respectively, were utilized for immunohistochemical (IHC) analysis. RNA sequencing was utilized to examine the expression profiles of circRNAs, lncRNAs, and mRNAs across 3 normal tissues, 3 ESCC tissues, and 3 pairs of KYSE150 cells in both wildtype (WT) and those with MBNL1 or QKI knockouts. Transwell, colony formation, and subcutaneous tumorigenesis assays assessed the impact of MBNL1 or QKI knockout on ESCC cell migration, invasion, and proliferation. Results ESCC onset significantly altered MBNL1 and QKI expression levels, influencing diverse RNA species. Elevated MBNL1 or QKI expression correlated with patient age or tumor invasion depth, respectively. MBNL1 or QKI knockout markedly enhanced cancer cell migration, invasion, proliferation, and tumor growth. Moreover, the absence of either MBNL1 or QKI modulated the expression profiles of multiple circRNAs, causing extensive downstream alterations in the expression of numerous lncRNAs and mRNAs. While the functions of circRNA and lncRNA among the top 20 differentially expressed genes remain unclear, mRNAs like SLCO4C1, TMPRSS15, and MAGEB2 have reported associations with tumor progression. Conclusions This study underscores the tumor-suppressive roles of MBNL1 and QKI in ESCC, proposing them as potential biomarkers and therapeutic targets for ESCC diagnosis and treatment.

The potential of geometrically induced terahertz surface wave technology for communications can only be realized if communication links based on them are studied and benchmarked. The frequency‐dependent transmission characteristics of interconnects based on three different archetypal textured surfaces (namely, gratings, dominos, nails) are analyzed numerically and the impact of the geometry and realistic surface roughness on the maximum capacity and energy efficiency is quantified. Unlike conventional hollow waveguides, the analysis shows that the capacity of uncoated corrugated surfaces is limited by loss and not dispersion. This work provides the guidelines for the design of terahertz surface wave interconnects.

Abstract Background Porcine epidemic diarrhea (PED) is a contagious intestinal disease caused by porcine epidemic diarrhea virus (PEDV) characterized by vomiting, diarrhea, anorexia, and dehydration, which has caused huge economic losses around the world. However, it is very hard to find completely valid approaches to control the transmission of PEDV. At present, vaccine immunity remains the most effective method. To better control the spread of PED and evaluate the validity of different immunization strategies, 240 PED outbreak cases from 577 swine breeding farms were collected and analyzed. The objective of the present study was to analyze the epidemic regularity of PEDV and evaluate two kinds of different immunization strategies for controlling PED. Results The results showed that the main reasons which led to the outbreak of PED were the movement of pig herds between different pig farms (41.7%) and delaying piglets from the normal production flow (15.8%). The prevalence of PEDV in the hot season (May to October) was obviously higher than that in the cold season (January to April, November to December). Results of different vaccine immunity cases showed that immunization with the highly virulent live vaccine (NH-TA2020 strain) and the commercial inactivated vaccine could significantly decrease the frequency of swine breeding farms (5.9%), the duration of PED epidemic (1.70 weeks), and the week batches of dead piglets (0.48 weeks weaned piglets), compared with immunization with commercial attenuated vaccines and inactivated vaccine of PED. Meanwhile, immunization with the highly virulent live vaccine and the commercial inactivated vaccine could bring us more cash flows of Y̶275,274 per year than immunization with commercial live attenuated vaccine and inactivated vaccine in one 3000 sow pig farm within one year. Conclusion Therefore, immunization with highly virulent live vaccine and inactivated vaccine of PED is more effective and economical in the prevention and control of PED in the large-scale swine farming system.

This paper introduces the prototype design, magnetic field analysis and experimental test of a double-rotating ferrofluid vane micropump with an embedded fixed magnet. The micropump is based on the working principle of a positive-displacement pump, as well as the magnetic characteristics and flow properties of magnetic fluid. Through the numerical analysis of the pump cavity magnetic field and the experimental test, the structural parameters of the micropump are optimized reasonably. The pumping flow and pumping height of the micropump were characterized at different driving speeds. The maximum pumping flow rate is approximately 410 μL/min, and the maximum pumping height is approximately 111.4 mm water column. The micropump retains the advantages of simple structure, easy manufacture, flexible control, self-sealing, self-lubrication, low heat production, etc., and can block the pumped liquid backflow. The resulting double-rotating ferrofluid blades can improve pumping efficiency and pumping capacity, and can improve pumping reliability and stability to a certain extent.

The oxidation of benzylic alcohols is an important transformation in modern organic synthesis. A plethora of photoredox protocols have been developed to achieve the aerobic oxidation of alcohols into carbonyls. Recently, several groups described that ultraviolet (UV) or purple light can initiate the aerobic oxidation of benzylic alcohols in the absence of an external catalyst, and depicted different mechanisms involving the photoinduction of •O2− as a critical reactive oxygen species (ROS). However, based on comprehensive mechanistic investigations, including control experiments, radical quenching experiments, EPR studies, UV–vis spectroscopy, kinetics studies, and density functional theory calculations (DFT), we elucidate here that HOO•, which is released via the H2O2 elimination of α-hydroxyl peroxyl radicals [ArCR(OH)OO•], serves as the real chain carrier for the autocatalytic photooxidation of benzylic alcohols. The mechanistic ambiguities depicted in the precedent literature are clarified, in terms of the crucial ROS and its evolution, the rate-limiting step, and the primary radical cascade. This work highlights the necessity of stricter mechanistic analyses on UV-driven oxidative reactions that involve aldehydes’ (or ketones) generation.

IntroductionThe detection of African swine fever virus (ASFV) is commonly performed using quantitative real-time PCR (qPCR), a widely used virological method known for its high sensitivity and specificity. However, qPCR has a limitation in distinguishing between infectious and inactivated virus, which can lead to an overestimation of viral targets.MethodsTo provide insights into ASFV infectivity, we evaluated the suitability of PMAxx, an improved version of propidium monoazide (PMA), as a means to differentiate between infectious and non-infectious ASFV. Pre-treatment with 50 μM PMAxx for 15 min significantly reduced the qPCR signal of ASFV in the live vaccine. Additionally, thermal treatment at 85°C for 5 min effectively inactivated the live ASFV in the vaccine. Based on a standard curve, the sensitivity of the PMAxx-qPCR assay was estimated to be approximately 10 copies/μL. Furthermore, we observed a strong agreement between the results obtained from PMAxx-qPCR and pig challenge experiments. Moreover, we utilized the PMAxx-qPCR assay to investigate the persistence of ASFV, revealing a close relationship between viral persistence and factors such as temperature and type of piggery materials.ConclusionThe findings of this study suggest that pre-treating viruses with PMAxx prior to qPCR is a reliable method for distinguishing between infectious and non-infectious ASFV. Thus, integrating of PMAxx-qPCR into routine diagnostic protocols holds potential for improving the interpretation of positive ASFV results obtained through qPCR.

Background: Evidence for the preferred neoadjuvant therapy regimen in triple-negative breast cancer (TNBC) is not yet established. Methods: Literature search was conducted from inception to February 12, 2022. Phase 2 and 3 randomized controlled trials (RCTs) investigating neoadjuvant therapy for TNBC were eligible. The primary outcome was pathologic complete response (pCR); the secondary outcomes were all-cause treatment discontinuation, disease-free survival or event-free survival (DFS/EFS), and overall survival. Odd ratios (OR) with 95% credible intervals (CrI) were used to estimate binary outcomes; hazard ratios (HR) with 95% CrI were used to estimate time-to-event outcomes. Bayesian network meta-analysis was implemented for each endpoint. Sensitivity analysis and network meta-regression were done. Results: 41 RCTs (N = 7109 TNBC patients) were eligible. Compared with anthracycline- and taxane-based chemotherapy (ChT), PD-1 inhibitor plus platinum plus anthracycline- and taxane-based ChT was associated with a significant increased pCR rate (OR 3.95; 95% CrI 1.81–9.44) and a higher risk of premature treatment discontinuation (3.25; 1.26–8.29). Compared with dose-dense anthracycline- and taxane-based ChT, the combined treatment was not associated with significantly improved pCR (OR 2.57; 95% CrI 0.69–9.92). In terms of time-to-event outcomes, PD-1 inhibitor plus platinum plus anthracycline- and taxane-based ChT was associated with significantly improved DFS/EFS (HR 0.42; 95% CrI 0.19–0.81). Conclusions: PD-1 inhibitor plus platinum and anthracycline- and taxane-based ChT was currently the most efficacious regimen for pCR and DFS/EFS improvement in TNBC. The choice of chemotherapy backbone, optimization of patient selection with close follow-up and proactive symptomatic managements are essential to the antitumor activity of PD-1 inhibitor.

Porcine rotavirus A (PoRVA) is an enteric pathogen capable of causing severe diarrhea in suckling piglets. Investigating the prevalence and molecular characteristics of PoRVA in the world, including China, is of significance for disease prevention. In 2022, a total of 25,768 samples were collected from 230 farms across China, undergoing porcine RVA positivity testing. The results showed that 86.52% of the pig farms tested positive for porcine RVA, with an overall positive rate of 51.15%. Through the genetic evolution analysis of VP7, VP4 and VP6 genes, it was revealed that G9 is the predominant genotype within the VP7 segment, constituting 56.55%. VP4 genotypes were identified as P[13] (42.22%), P[23] (25.56%) and P[7] (22.22%). VP6 exhibited only two genotypes, namely I5 (88.81%) and I1 (11.19%). The prevailing genotype combination for RVA was determined as G9P[23]I5. Additionally, some RVA strains demonstrated significant homology between VP7, VP4 and VP6 genes and human RV strains, indicating the potential for human RV infection in pigs. Based on complete genome sequencing analysis, a special PoRVA strain, CHN/SD/LYXH2/2022/G4P[6]I1, had high homology with human RV strains, revealing genetic reassortment between human and porcine RV strains in vivo. Our data indicate the high prevalence, major genotypes, and cross-species transmission of porcine RVA in China. Therefore, the continuous monitoring of porcine RVA prevalence is essential, providing valuable insights for virus prevention and control, and supporting the development of candidate vaccines against porcine RVA.

The secondary metabolites of marine fungi with rich chemical diversity and biological activity are an important and exciting target for natural product research. This study aimed to investigate the fungal community in Quanzhou Bay, Fujian, and identified 28 strains of marine fungi. A total of 28 strains of marine fungi were screened for small-scale fermentation by the OSMAC (One Strain-Many Compounds) strategy, and 77 EtOAc crude extracts were obtained and assayed for cancer cell inhibition rate. A total of six strains of marine fungi (P-WZ-2, P-WZ-3-2, P-WZ-4, P-WZ-5, P56, and P341) with significant changes in cancer cell inhibition induced by the OSMAC strategy were analysed by UPLC-QTOF-MS. The ACD/MS Structure ID Suite software was used to predict the possible structures with inhibitory effects on cancer cells. A total of 23 compounds were identified, of which 10 compounds have been reported to have potential anticancer activity or cytotoxicity. In this study, the OSMAC strategy was combined with an untargeted metabolomics approach based on UPLC-QTOF-MS to efficiently analyse the effect of changes in culture conditions on anticancer potentials and to rapidly find active substances that inhibit cancer cell growth.

To fully understand the water quality status of the Yuyao section in the Yaojiang River Basin, we utilized the single factor and comprehensive water quality identification index methods, as well as factor analysis in this study. The single factor water quality assessment results showed that the common parameters exceeding the standard in both the wet and dry seasons included dissolved oxygen and total nitrogen, which were inferior to the target water quality grade III by 1–6 grades. The comprehensive water quality order reaching the target grade III was Hutang River (87.5%), Changling River (50.0%), Yaojiang River (43.8%), and Linzhou River (37.5%). The comprehensive water quality in the dry season (90.0% standard-achieving rate) was better than that in the wet season (25.0% standard-achieving rate). These results suggested that the surface runoff might considerably impact water quality. The factor analysis results showed that the basin surveyed in 2018 was mainly polluted by urban sewage and agricultural sources, while the primary pollution source in 2019 was agricultural pollution. Integrated with comprehensive water quality assessment results, in this study, we demonstrated that the series of water treatment projects carried out in Yuyao City positively impacted municipal sewage treatment. HIGHLIGHTS A method was applied to intuitively identify whether the water quality grade conforms to the functional area standard and the number of water quality parameters that fail to meet the standard.; Surface runoff might significantly impact the water quality.; Series of water treatment projects carried out in Yuyao City played a positive role in reducing the deterioration effect of urban sewage on the water quality.;

Boletes are favored by consumers because of their unique flavor, rich nutrition and delicious taste. However, the different nutritional values of each species lead to obvious price differences, so shoddy products appear on the market, which affects food safety. The aim of this study was to find a rapid and effective method for boletes species identification. In this paper, 1,707 samples of eight boletes species were selected as the research objects. The original Mid-Infrared (MIR) spectroscopy data were adopted for support vector machine (SVM) modeling. The 11,949 spectral images belong to seven data sets such as two-dimensional correlation spectroscopy (2DCOS) and three-dimensional correlation spectroscopy (3DCOS) were used to carry out Alexnet and Residual network (Resnet) modeling, thus we established 15 models for the identification of boletes species. The results show that the SVM method needs to process complex feature data, the time cost is more than 11 times of other models, and the accuracy is not high enough, so it is not recommended to be used in data processing with large sample size. From the perspective of datasets, synchronous 2DCOS and synchronous 3DCOS have the best modeling results, while one-dimensional (1D) MIR Spectrum dataset has the worst modeling results. After comprehensive analysis, the modeling effect of Resnet on the synchronous 2DCOS dataset is the best. Moreover, we use large-screen visualization technology to visually display the sample information of this research and obtain their distribution rules in terms of species and geographical location. This research shows that deep learning combined with 2DCOS and 3DCOS spectral images can effectively and accurately identify boletes species, which provides a reference for the identification of other fields, such as food and Chinese herbal medicine.

Abstract Background Z score utility is emphasized in classifying coronary artery lesions in Kawasaki disease patients. The present study is the largest such multicenter Chinese pediatric study about coronary artery diameter reference values and Z score regression equation to date. It is useful in Chinese pediatric echocardiography. Methods A multicenter cohort was assembled, which consisted of 852 healthy children between 1 month and 17 years of age, ten children were excluded because their ultrasound images were not clear, or lost in following up. Diameters of the right coronary artery, left coronary artery, and left anterior descending coronary artery were assessed using echocardiography. Data were body surface area (BSA)-corrected using BSA calculated via either the Stevenson BSA formula or the Haycock BSA formula. Coronary artery diameter reference values and Z score regression equations were established for use in the Chinese pediatric population. Results No difference was observed between coronary artery diameter data corrected using BSAste or BSAhay. Of the five assessed regression models, the exponential model exhibited the best fit and was therefore selected as the basis for derivation of the SZ method. When comparing Z scores, those produced by the SZ method conformed to the standard normal distribution, while those produced by the D method did not. In addition, there was a statistically significant difference between Z scores produced by the SZ and D methods (P

Abstract Background Pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs) are commonly used drug-delivering devices for patients with chronic airway diseases. Appropriate peak inhalation flow rate (PIFR) and inhaler technique is essential for effective therapy. We aimed at optimizing inhalation therapy through the analysis of PIFRs in patients with chronic obstructive pulmonary disease (COPD) or asthma as well as the effect of technique training using In-Check DIAL® to help patients to achieve their optimal inspiratory flow rates. Methods The study continuously enrolled patients who were diagnosed as COPD or asthma from respiratory clinics. PIFRs were described and analyzed between the newly-diagnosed and follow-up patients, and the stable and acute exacerbation patients, respectively. Every participant was trained inhaler technique using In-Check DIAL®. PIFRs before and after training was compared by self-control analysis. Results Among a total of 209 patients, the average age was 56.9 years. For DPIs users, 10.8% patients had a PIFR

Graft-versus-host disease (GVHD) is a life-threatening systemic complication of allogeneic hematopoietic stem cell transplantation (HSCT) characterized by dysregulation of T and B cell activation and function, scleroderma-like features, and multi-organ pathology. The treatment of cGVHD is limited to the management of symptoms and long-term use of immunosuppressive therapy, which underscores the need for developing novel treatment approaches. Notably, there is a striking similarity between cytokines/chemokines responsible for multi-organ damage in cGVHD and pro-inflammatory factors, immune modulators, and growth factors secreted by senescent cells upon the acquisition of senescence-associated secretory phenotype (SASP). In this pilot study, we questioned the involvement of senescent cell-derived factors in the pathogenesis of cGVHD triggered upon allogeneic transplantation in an irradiated host. Using a murine model that recapitulates sclerodermatous cGVHD, we investigated the therapeutic efficacy of a senolytic combination of dasatinib and quercetin (DQ) administered after 10 days of allogeneic transplantation and given every 7 days for 35 days. Treatment with DQ resulted in a significant improvement in several physical and tissue-specific features, such as alopecia and earlobe thickness, associated with cGVHD pathogenesis in allograft recipients. DQ also mitigated cGVHD-associated changes in the peripheral T cell pool and serum levels of SASP-like cytokines, such as IL-4, IL-6 and IL-8Rα. Our results support the involvement of senescent cells in the pathogenesis of cGVHD and provide a rationale for the use of DQ, a clinically approved senolytic approach, as a potential therapeutic strategy.

Ovarian carcinosarcoma (OCS) is a rare, highly aggressive and rapidly progressing malignant tumor with an extremely poor prognosis. So far, due to the low incidence of OCS, there are no large-scale prospective studies exploring the standard care of OCS patients. There is no uniform and effective treatment for OCS. Within the development of precision medicine, targeted therapies (such as PARP inhibitors) have been widely used in epithelial ovarian cancer and various other solid tumors. Here, we report a BRCAwt patient with advanced OCS who experienced a second and a third cytoreductive surgery in June 2017 and October 2019 and has been on niraparib maintenance therapy for more than 20 months after receiving second-line and third-line chemotherapy.

Peritoneal metastases from invasive lobular carcinoma (ILC) of breast are uncommon and usually related to poor prognosis due to difficulty of detection in clinical practice and drug resistance. Therefore, recognizing the entities of peritoneal metastases of ILC and the potential mechanism of drug resistance is of great significance for early detection and providing accurate management. We herein report a case of a 60-year-old female who presented with nausea and vomiting as the first manifestation after treated with abemaciclib (a CDK4/6 inhibitor) plus fulvestrant for 23 months due to bone metastasis of ILC. Exploratory laparotomy found multiple nodules in the peritoneum and omentum, and immunohistochemistry confirmed that the peritoneal metastatic lesions were consistent with ILC. Palliative therapy was initiated, but the patient died two months later due to disease progression with malignant ascites. Whole exome sequencing (WES) was used to detect the tumor samples and showed the peritoneal metastatic lesions had acquired ESR1 and PI3KCA mutations, potentially explaining the mechanism of endocrine therapy resistance. We argue that early diagnosis of peritoneal metastasis from breast cancer is crucial for prompt and adequate treatment and WES might be an effective supplementary technique for detection of potential gene mutations and providing accurate treatment for metastatic breast cancer patients.

Immune response which involves distinct immune cells is associated with prognosis of breast cancer. Nonetheless, less study have determined the associations of different types of immune cells with patient survival and treatment response. In this study, A total of 1,502 estrogen receptor(ER)-negative breast cancers from public databases were used to infer the proportions of 22 subsets of immune cells. Another 320 ER-negative breast cancer patients from Guangdong Provincial People’s Hospital were also included and divided into the testing and validation cohorts. CD8+ T cells, CD4+ T cells, B cells, and M1 macrophages were associated with favourable outcome (all p