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Abstract Pancreatic cancer (PC) is one of the most aggressive malignancies worldwide, and few effective therapeutics are available. Osthole (OST), a natural coumarin, has been proven to be a potential anticancer compound. In this study, we found that OST significantly inhibited PC growth both in vitro and in vivo. Notably, the anti-PC effect of OST is mediated by excessive autophagosome accumulation and consequent apoptosis in PC cells. Mechanistically, OST increased the number of autophagosomes via two pathways. First, OST induced autophagy initiation by suppressing the Akt/mTOR signaling pathway. Second, OST induced autophagic arrest by blocking autophagosome-lysosome fusion. Consistently, inhibition of autophagy initiation restored PC cell growth, whereas autophagic flux inhibitors exacerbated the antitumor effect of OST in PC cells, suggesting a cytotoxic role of OST-induced autophagosome accumulation. In addition, we found that OST upregulates the expression of activating transcription factor 3 (ATF3), resulting in inactivation of the Akt/mTOR signaling pathway and autophagy initiation in PC cells. ATF3 overexpression increased the activation of autophagy, and inhibition of ATF3 expression decreased autophagy. Taken together, our study provides new insights into the OST-induced growth inhibitory effect on PC cells, suggesting a promising potential therapeutic role of OST for PC treatment.

Abstract Depression-anxiety comorbidity is commonly attributed to the occurrence of specific symptoms bridging the two disorders. However, the significant heterogeneity of most bridging symptoms presents challenges for psychopathological interpretation and clinical applicability. Here, we conceptually established a common bridging factor (cb factor) to characterize a general structure of these bridging symptoms, analogous to the general psychopathological p factor. We identified a cb factor from 12 bridging symptoms in depression-anxiety comorbidity network. Moreover, this cb factor could be predicted using edge-centric connectomes with robust generalizability, and was characterized by connectome patterns in attention and frontoparietal networks. In an independent twin cohort, we found that these patterns were moderately heritable, and identified their genetic connectome-transcriptional markers that were associated with the neurobiological enrichment of vasculature and cerebellar development, particularly during late-childhood-to-young-adulthood periods. Our findings revealed a general factor of bridging symptoms and its neurobiological architectures, which enriched neurogenetic understanding of depression-anxiety comorbidity.

Abstract Background Diabetic nephropathy (DN) is a serious complication of diabetes mellitus, marked by progressive renal damage. Recent evidence indicates that metabolic reprogramming is crucial to DN pathogenesis, yet its underlying mechanisms are not well understood. This study aimed to examine how metabolic reprogramming-related genes (MRRGs) are differentially expressed and to explore their potential mechanisms in the development of DN. Methods We analyzed the datasets GSE30528 and GSE96804 from the Gene Expression Omnibus (GEO), comprising 50 DN samples and 33 controls. MRRGs were sourced from GeneCards and PubMed. Data preprocessing included batch effect correction using the R package sva, followed by normalization and differential expression analysis with limma (|logFC|> 0.5, adj.p

Abstract D-dimer is a biomarker of coagulation and fibrinolytic system activation in response to the hypercoagulable state of the body. The research aimed to analyze the value of D-dimer in the prognosis of patients with dilated cardiomyopathy (DCM). Patients admitted to our center for the first time with DCM were enrolled consecutively. The clinical characteristics variables were obtained from the electronic medical record system, and the prognostic information was obtained using telephone return visits and a review of repeated hospitalization records. Univariate and multivariate Cox regression was used to explore the association of D-dimer with all-cause mortality. Smooth curve fitting, threshold saturation effect analysis, and subgroup analysis were performed. Ultimately, 534 patients were included. After a follow-up of the enrolled patients, 485 patients obtained prognostic information, of which 159 died from all causes, and the main cause of death was heart failure (89/159), the sudden death accounted for about 17%. The independent positive association between D-dimer and all-cause mortality remained unchanged in both unadjusted and adjusted Cox regression models. In the fully adjusted model, each standard deviation increase in D-dimer was associated with a 14% increase in all-cause mortality (HR = 1.14; 95% CI: 1.02 ~ 1.27; P

Abstract Background Understanding the psychosocial factors influencing self-management behaviors among people living with HIV/AIDS (PLWHA) is crucial for effective medical interventions and improving their quality of life. However, few studies have explored the psychosocial mechanisms influencing self-management behaviors among PLWHA in China. This study, conducted in accordance with STROBE guidelines, uses SEM to explore the roles of social support, self-efficacy, and self-esteem in predicting self-management behaviors among Chinese PLWHA. Methods From March 2023 to July 2023, a convenience sample of 282 PLWHA, recruited from one designated AIDS hospital and one Centers for Disease Control and Prevention in Sichuan Province, China, was surveyed. Data were collected via four validated self-report scales (the Social Support Rating Scale, the General Self-Efficacy Scale, the Self-Esteem Scale, and the HIV/AIDS Patient Self-Management Scale). Structural equation modeling was used to assess the relationships among social support, self-efficacy, self-esteem, and self-management behaviors. Results The new model demonstrated acceptable fit parameters (χ 2 /df = 2.15, GFI = 0.96, AGFI = 0.93, CFI = 0.93, IFI = 0.94, RMSEA = 0.05). The direct effect of social support on self-management behaviors was significant (β = 0.117, P

C-myc is a proto-oncogene that plays an important role in a variety of diseases. There were a lot of research on the correlation between C-myc and human viruses. However, the study about C-myc related to aquatic species virus is very limited. In the present study, the qRT-PCR, cellular immunofluorescence and western blotting determination data reported that C-myc and glutaminase (GLS) genes were significantly upregulated when grouper fin cells (GF-1) were infected with red grouper nervous necrosis virus (RGNNV). After knocking down the C-myc gene, the mRNA and protein levels of GLS, capsid protein (CP) and RNA polymerase (RdRp) of RGNNV were significantly reduced in RGNNV-infected GF-1 cells and the overexpression of the C-myc gene remarkably promoted these genes, which indicated that the replication of the virus and GLS gene were positively regulated by C-myc in RGNNV-infected GF-1 cells. In addition, supplementation of exogenous ATP can partially restore viral replication when RGNNV-infected GF-1 cells were cultured in glutamine-free medium, which confirmed that the glutamine was decomposed into ATP to provide energy for viral replication. Further studies confirmed that overexpression of C-myc can increase the content of ATP in normal cells. To sum up, these data suggested that activation of C-myc gene affected viral replication by regulating GLS expression to drive glutamine dissolution.

Abstract To explore the performance of 99mTc-diethylene triaminepentaacetic acid (DTPA) SPECT/CT texture analysis in evaluating the activity of thyroid-associated ophthalmopathy (TAO) . This retrospective study examined 115 TAO patients from a single institution as an internal cohort and 58 TAO patients from another institution as an external validation set. Patients in the internal cohort were randomly divided into training (n = 81) and internal validation sets (n = 34). Radiomics signatures were constructed with the minimal redundancy maximal relevance and least absolute shrinkage and selection operator algorithms in training set. Multivariate logistic regression analysis was used to develop a clinical model and a combined clinical–radiomics model. Diagnostic performance of models was evaluated using receiver operating characteristic curve analysis, calibration curves and decision curve analysis. Compared with CT and SPECT radiomics models, Rad-scoreSPECT/CT demonstrated the best performance with areas under the receiver operating characteristic curve of 0.94 and 0.91 in the training and test sets, respectively. The combined clinical-radiomics model exhibited significantly better performance in evaluating TAO activity. Our results demonstrate the validity of a multimodal radiomic model of 99mTc-DTPA-SPECT/CT to assess TAO activity. The combined clinical-radiomics model exhibited significantly better diagnostic performance than the clinical model.

Abstract The olfactory sensory system of Drosophila has several advantages, including low power consumption, high rapidity and high accuracy. Here, we present a biomimetic intelligent olfactory sensing system based on the integration of an 18-channel microelectromechanical system (MEMS) sensor array (16 gas sensors, 1 humidity sensor and 1 temperature sensor), a complementary metal‒oxide‒semiconductor (CMOS) circuit and an olfactory lightweight machine-learning algorithm inspired by Drosophila. This system is an artificial version of the biological olfactory perception system with the capabilities of environmental sensing, multi-signal processing, and odor recognition. The olfactory data are processed and reconstructed by the combination of a shallow neural network and a residual neural network, with the aim to determine the noxious gas information in challenging environments such as high humidity scenarios and partially damaged sensor units. As a result, our electronic olfactory sensing system is capable of achieving comprehensive gas recognition by qualitatively identifying 7 types of gases with an accuracy of 98.5%, reducing the number of parameters and the difficulty of calculation, and quantitatively predicting each gas of 3–5 concentration gradients with an accuracy of 93.2%; thus, these results show superiority of our system in supporting alarm systems in emergency rescue scenarios.

Abstract Group 2 innate lymphocytes (ILC2) have an important role in orchestrating sepsis-induced immune response. However, the impact of LC2 on sepsis-induced cardiac injury is still not fully understood. This study investigated the mechanisms governing ILC2 activation within the cardiac tissue after sepsis. In vivo experiments using wild-type and IL-33 deficient mice indicated that the presence of interleukin (IL)-33, which participates in expanding and activating ILC2 cells, was correlated with higher ILC2 levels (246 ± 34 vs. 66 ± 18, p

Abstract Biological organisms can perform flexible and controllable multimodal motion under external stimuli owing to the hierarchical assembly of anisotropic structures across multiple length scales. However, artificial soft actuators exhibit the limited response speed, deformation programmability and movement capability especially in harsh environments because of insufficient anisotropic hierarchy and precision in structural design. Here, we report a programmed assembly directed confinement polymerization method for the fabrication of environmentally tolerant and fast responsive hydrogels with lamellar assembly-confined cellular structure interpenetrated with highly aligned nanopillars by the directional freezing-assisted polymerization in the predesigned anisotropic laminar scaffold. The obtained hydrogel exhibits ultrafast responsiveness and anisotropic deformation exposed to temperature/light/solvent stimulation, maintaining highly consistent responsive deformation capability in all-polarity solvents over 100 days of soaking. Moreover, the hydrogels implement photoactive programmable multi-gait locomotion whose amplitude and directionality are precisely regulated by the intrinsic structure, including controlled crawling and rotation in water and non-polar solvents, and 3D self-propulsion floating and swimming in polar solvents. Thus, this hydrogel with hierarchically ordered structure and dexterous locomotion may be suitable for flexible intelligent actuators serving in harsh solvent environments.

Abstract Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB) are neurodegenerative disorders characterized by the accumulation of α-synuclein aggregates. α-synuclein forms droplets via liquid-liquid phase separation (LLPS), followed by liquid-solid phase separation (LSPS) to form amyloids, how this process is physiologically-regulated remains unclear. β-synuclein colocalizes with α-synuclein in presynaptic terminals. Here, we report that β-synuclein partitions into α-synuclein condensates promotes the LLPS, and slows down LSPS of α-synuclein, while disease-associated β-synuclein mutations lose these capacities. Exogenous β-synuclein improves the movement defects and prolongs the lifespan of an α-synuclein-expressing NL5901 Caenorhabditis elegans strain, while disease-associated β-synuclein mutants aggravate the symptoms. Decapeptides targeted at the α-/β-synuclein interaction sites are rationally designed, which suppress the LSPS of α-synuclein, rescue the movement defects, and prolong the lifespan of C. elegans NL5901. Together, we unveil a Yin-Yang balance between α- and β-synuclein underlying the normal and disease states of PD and DLB with therapeutical potentials.

Introduction: Posterior tibial slope (PTS) plays a vital role in knee stability. PTS of more than 12° may be considered with increased strain on the native anterior cruciate ligament (ACL) fibers. To handle the instability caused by changes in PTS degree, Proximal Tibial Anterior Closing Wedge Osteotomy (PT-ACWO) is adopted by surgeons. Methods: Between October 2015 and October 2019, our department conducted a retrospective analysis of patients who experienced anterior cruciate ligament reconstruction (ACLR) graft failures, with a particular focus on pathological PTS. The time from initial ACLR to revision ranged from 1 to 10 years, with a mean of 2.5 years. Radiological assessments of PTS were conducted, and outcomes were quantified using the International Knee Documentation Committee (IKDC) score, Lysholm score, and Tegner activity scale. The surgical technique and the use of 3D Patient-Specific Instrumentation (PSI) were outlined. Preoperative imaging included the use of Kirschner wires to establish tibial plateau reference points, and 3D-PSI was employed to guide the location and depth of the tibial osteotomy, which was performed obliquely. In a notable instance, a novel tibial tunnel was mapped out, and ortho-bridge system (OBS) fixation was utilized to ensure adequate space for the new tunnel. Results: In a cohort of seven patients with a mean follow-up of 28.1 months, a significant reduction in PTS was noted postoperatively (median [interquartile range, IQR], from 15.27° [13.46°, 16.60°] to 6.25° [5.89°, 6.78°]; P = 0.002). IKDC score improved to 85.10 (80.25, 88.10), P

The glutenites in the Permian Upper Wuerhe Formation in the Fukang Sag of the Junggar Basin possess great potential for oil and gas exploration. However, uncertainties in the reservoir characteristics and formation mechanisms of these glutenites seriously restrict their effective exploration. The study provides a compre- hensive analysis on the characteristics, main controlling factors, and development models of glutenite reservoirs of the Upper Wuerhe Formation in the Fukang Sag of the Junggar Basin using microscopic thin sections, scanning electron microscopy (SEM), and X-ray diffraction (XRD). The results show that: (1) Two types of interstitial materials are observed in the glutenites of the Upper Wuerhe Formation, where the spaces between gravels are primarily interstitially filled with coarser sandy components, and the cementation mainly occurs between these sandy components. (2) The glutenites generally exhibit low porosity, with minimal pore development within gravels, while the pores in sandy interstitial materials are more developed. The reservoir space is mainly composed of intercrystalline and secondary dissolution pores. (3) Diagenetic processes related to reservoir formation mainly occur within the coarse sandy interstitial materials between gravels, mainly involving aluminosilicate dissolution, which results in abundant dissolution pores. (4) In high-energy sedimentary microfacies, such as estuary bars and underwater distributary channels, reservoirs are more favorably developed, where the reservoir space is mainly associated with feldspar dissolution. Fractures and unconformities are the main channels for acidic fluid migration. (5) During the eodiagenesis, acidic fluids, mainly atmospheric water, infiltrated along unconformities, with more significant dissolution near the Beisantai arch. During the middle diagenetic period, dissolution was mainly attributed to organic acid. (6) Three types of reservoirs are developed in the glutenites: atmospheric acid dissolution reservoirs, organic acid dissolution reservoirs, and dual-source acid superimposed dissolution reservoirs. The distribution of these reservoir types determines the exploration strategies for oil and gas reservoirs of glutenites of the Upper Wuerhe Formation in the Fukang Sag of the Junggar Basin. Glutenites in the slope and sag areas and zones of superimposed fault development are the key objectives for oil and gas exploration of glutenite reservoirs of the Upper Wuerhe Formation in Fukang Sag.

Abstract Background The syncytiotrophoblast (SCT) layer in the placenta serves as a crucial physical barrier separating maternal-fetal circulation, facilitating essential signal and substance exchange between the mother and fetus. Any abnormalities in its formation or function can result in various maternal syndromes, such as preeclampsia. The transition of proliferative villous cytotrophoblasts (VCT) from the mitotic cell cycle to the G0 phase is a prerequisite for VCT differentiation and their fusion into SCT. The imprinting gene P57Kip2, specifically expressed in intermediate VCT capable of fusion, plays a pivotal role in driving this key event. Moreover, aberrant expression of P57Kip2 has been linked to pathological placental conditions and adverse fetal outcomes. Methods Validation of STK40 interaction with P57Kip2 using rigid molecular simulation docking and co-immunoprecipitation. STK40 expression was modulated by lentivirus in BeWo cells, and the effect of STK40 on trophoblast fusion was assessed by real-time quantitative PCR, western blot, immunofluorescence, and cell viability and proliferation assays. Co-immunoprecipitation, transcriptome sequencing, and western blot were used to determine the potential mechanisms by which STK40 regulates P57Kip2. Results In this study, STK40 has been identified as a novel interacting protein with P57Kip2, and its expression is down-regulated during the fusion process of trophoblast cells. Overexpressing STK40 inhibited cell fusion in BeWo cells while stimulating mitotic cell cycle activity. Further experiments indicated that this effect is attributed to its specific binding to the CDK-binding and the Cyclin-binding domains of P57Kip2, mediating the E3 ubiquitin ligase COP1-mediated ubiquitination and degradation of P57Kip2. Moreover, abnormally high expression of STK40 might significantly contribute to the occurrence of preeclampsia. Conclusions This study offers new insights into the role of STK40 in regulating the protein-level homeostasis of P57Kip2 during placental development.

Abstract Aberrant activation of tropomyosin receptor kinases (TRKs) is a well-defined oncogenic driver for neurotrophic tropomyosin receptor kinase (NTRK)-fusion cancers, and acquired resistant mutations have emerged with clinical use of the first-generation TRK inhibitors. Here we present BPI-28592, a novel second-generation TRK inhibitor with efficacy against TRK fusion-positive cancers, including those with resistant mutations. Docking simulations indicated no steric hindrance between BPI-28592 and TRK mutants, suggesting its potential to overcome drug resistance. Biochemical assays showed strong inhibition and high selectivity against TRKA, TRKB, and TRKC. The inhibitor significantly reduced cell proliferation and blocked TRK signaling. In vivo studies demonstrated effective tumor suppression in xenograft models harboring TRK fusions with or without resistant mutations. Clinically, BPI-28592 achieved a complete response in a patient with malignant melanoma carrying an AP3S2-NTRK3 fusion (Clinicaltrials. gov identifier: NCT05302843).

Abstract Factor XII (FXII) is the zymogen of the plasma protease FXIIa that activates the intrinsic coagulation pathway and the kallikrein kinin-system. The role of FXII in inflammation has been obscure. Here, we report a single-domain antibody (nanobody, Nb) fused to the Fc region of a human immunoglobulin (Nb-Fc) that recognizes FXII in a conformation-dependent manner and interferes with FXIIa formation. Nb-Fc treatment inhibited arterial thrombosis in male mice without affecting hemostasis. In a mouse model of extracorporeal membrane oxygenation (ECMO), FXII inhibition or knockout reduced thrombus deposition on oxygenator membranes and systemic microvascular thrombi. ECMO increased circulating levels of D-dimer, alkaline phosphatase, creatinine and TNF-α and triggered microvascular neutrophil adherence, platelet aggregation and their interaction, which were substantially attenuated by FXII blockade. Both Nb-Fc treatment and FXII knockout markedly ameliorated immune complex-induced local vasculitis and anti-neutrophil cytoplasmic antibody-induced systemic vasculitis, consistent with selectively suppressed neutrophil migration. In human blood microfluidic analysis, Nb-Fc treatment prevented collagen-induced fibrin deposition and neutrophil adhesion/activation. Thus, FXII is an important mediator of inflammatory responses in vasculitis and ECMO, and Nb-Fc provides a promising approach to alleviate thrombo-inflammatory disorders.

Abstract Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide. Although CRC patients’ survival is improved with surgical resection and immunotherapy, metastasis and recurrence remain major problems leading to poor prognosis. Therefore, exploring pathogenesis and identifying specific biomarkers are crucial for CRC early diagnosis and targeted therapy. CCDC113, a member of CCDC families, has been reported to play roles in ciliary assembly, ciliary activity, PSCI, asthma and early lung cancer diagnosis. However, the functions of CCDC113 in CRC still remain unclear. In this study, we find that CCDC113 is significantly highly expressed in CRC. High expression of CCDC113 is significantly correlated with CRC patients’ poor prognosis. CCDC113 is required for CRC tumorigenesis and metastasis. RNA-seq and TCGA database analysis indicate that CCDC113 is positively correlated with TGF-β signaling pathway. TGF-β signaling pathway inhibitor galunisertib could reverse the increased proliferation and migration ability of CRC cells caused by CCDC113 overexpression in vitro and in vivo. These results indicate that CCDC113 promotes CRC tumorigenesis and metastasis via TGF-β signaling pathway. In conclusion, it is the first time to explore the functions and mechanisms of CCDC113 in CRC tumorigenesis and metastasis. And CCDC113 may be a potential biomarker and therapeutic target for CRC intervention.

Abstract Background Small cell lung carcinoma (SCLC) is characterized by -poor prognosis, -high predilection for -metastasis, -proliferation, and -absence of newer therapeutic options. Elucidation of newer pathways characterizing the disease may allow for development of targeted therapies and consequently favorable outcomes. Methods The current study explored the combinatorial action of arsenic trioxide (ATO) and apatinib (APA) in vitro and in vivo. In vitro models were tested using -H446 and -H196 SCLC cell lines. The ability of drugs to reduce -metastasis, -cell proliferation, and -migration were assessed. Using bioinformatic analysis, differentially expressed genes were determined. Gene regulation was assessed using gene knock down models and confirmed using Western blots. The in vivo models were used to confirm the resolution of pathognomic features in the presence of the drugs. Growth factor receptor bound protein (GRB) 10 expression levels of human small cell lung cancer tissues and adjacent tissues were detected by IHC. Results In combination, ATO and APA were found to significantly reduce -cell proliferation, -migration, and -metastasis in both the cell lines. Cell proliferation was found to be inhibited by activation of Caspase-3, -7 pathway. In the presence of drugs, it was found that expression of GRB10 was stabilized. The silencing of GRB10 was found to negatively regulate the VEGFR2/Akt/mTOR and Akt/GSK-3β/c-Myc signaling pathway. Concurrently, absence of metastasis and reduction of tumor volume were confirmed in vivo. The immunohistochemical results confirmed that the expression level of GRB10 in adjacent tissues was significantly higher than that in human small cell lung cancer tissues. Conclusions Synergistically, ATO and APA have a more significant impact on inhibiting cell proliferation than each drug independently. ATO and APA may be mediating its action through the stabilization of GRB10 thus acting as a tumor suppressor. We thus, preliminarily report the impact of GRB10 stability as a target for SCLC treatment.

Abstract Background Bronchial artery embolization (BAE) is currently an important treatment for hemoptysis. However, there is no consensus in the efficacy and safety of BAE compared to conservative treatment for hemoptysis, which limits the widespread use of BAE in hemoptysis. The objective was to assess the clinical benefit of BAE versus conservative treatment in patients with hemoptysis. Methods A systematic search was conducted on the PubMed, Embase, ScienceDirect, CochraneLibrary, and ClinicalTrials up to March 2023. Both randomized controlled trials (RCTs) and cohort studies reporting rates of recurrent hemoptysis, clinical success, mortality, and complication by BAE and conservative treatment alone for hemoptysis were included. Data were pooled and compared by the use of odds ratio (OR) and 95% confidence interval (CI). Results Twelve studies (three RCTs, nine cohorts) involving 1231 patients met the eligibility criteria. Patients treated with BAE had lower recurrence rates of hemoptysis (26.5% vs. 34.6%; OR 0.37, 95% CI 0.14–0.98), higher clinical success rates (92.2% vs. 80.9%; OR 2.77, 95% CI 1.66–4.61), and lower hemoptysis-related mortality (0.8% vs. 3.2%; OR 0.20, 95% CI 0.05–0.84) compared with conservative treatment alone. There was no significant difference in all-cause mortality between the two groups. In terms of security, the incidence of major complications and minor complications in patients undergoing BAE treatment was 0.2% (1/422) and 15.6%, respectively. Conclusions BAE was more effective than conservative treatment alone in controlling hemoptysis, reducing recurrence, and decreasing hemoptysis-related mortality, with an almost negligible risk of major complications.

Abstract Background For localized prostate cancer, a comprehensive treatment approach centered around radical prostatectomy (RP) is often their optimal choice. Successful RP can typically reduce prostate-specific antigen (PSA) levels to below 0.1 ng/mL within 6 to 8 weeks postoperatively. However, in clinical practice, 5 to 24% of patients may have a PSA ≥ 0.1 ng/mL at 6 to 8 weeks after surgery, a phenomenon known as PSA persistence. Many studies based on data from Europe and United States have shown an association between PSA persistence and poor postoperative outcomes, further analyzing the risk factors for PSA persistence. However, relevant research based on data from China remains scarce. Methods Retrospective study of 1,347 prostate cancer patients who underwent RP at the First Affiliated Hospital of Zhejiang University School of Medicine from July 15, 2016, to August 31, 2022. Based on inclusion criteria, univariate and multivariate logistic regression analyses were conducted to explore the independent risk factors for persistent PSA. Results Among the 826 prostate cancer patients after RP, 124 patients experienced persistent PSA. In univariate logistic regression analysis, robot-assisted laparoscopic radical prostatectomy (RARP), preoperative PSA, high-risk group, preoperative International Society of Urological Pathology (ISUP) grades 2–5, postoperative ISUP grades 3–5, percentage of positive cores, cT3, ≥pT3b, extracapsular extension (EPE), seminal vesicle invasion (SVI), positive surgical margins (PSM) and Prostate Specific Antigen Density (PSAD) were all significantly associated with PSA persistence after RP (P

Abstract We systematically investigate the mass spectrum and two-body open-charm strong decays of charmonium states in a coupled-channel model where the $$^3P_0$$ 3 P 0 quark-antiquark pair creation mechanism is employed. The results of masses, mass shifts, proportions of the $$c\bar{c}$$ c c ¯ component, and open-charm decay widths are provided. The S-D wave mixing angles and di-electric decay widths for vector mesons are also presented. Based on our results, we find that the $$\psi (3770)$$ ψ ( 3770 ) , $$\psi (4040)$$ ψ ( 4040 ) , $$\psi (4160)$$ ψ ( 4160 ) , $$\psi (4360)$$ ψ ( 4360 ) , and $$\psi (4415)$$ ψ ( 4415 ) can be assigned as the $$1^3D_1$$ 1 3 D 1 -, $$3^3S_1$$ 3 3 S 1 -, $$2^3D_1$$ 2 3 D 1 -, $$4^3S_1$$ 4 3 S 1 -, and $$3^3D_1$$ 3 3 D 1 -dominated charmonium states, respectively. The $$\psi _3(3842)$$ ψ 3 ( 3842 ) is a good candidate of the $$\psi _3(1D)$$ ψ 3 ( 1 D ) charmonium state. The calculated mass and strong decay width of $$\chi _{c1}(2P)$$ χ c 1 ( 2 P ) with significant continuum contribution ( $$\sim $$ ∼ 57%) favor the charmonium interpretation for the mysterious $$\chi _{c1}(3872)$$ χ c 1 ( 3872 ) . When considering the large uncertainty in the observed decay width, the possibility to assign the $$\chi _{c0}(3860)$$ χ c 0 ( 3860 ) as the $$\chi _{c0}(2P)$$ χ c 0 ( 2 P ) charmonium state cannot be ruled out. One may describe well the properties of $$\chi _{c2}(3930)$$ χ c 2 ( 3930 ) with the $$\chi _{c2}(2P)$$ χ c 2 ( 2 P ) charmonium. The predictions on properties of other $$c\bar{c}$$ c c ¯ states can be tested by future experiments.

In order to improve the stability of loquat flower flavonoids, loquat flower flavonoids/zein/pectin nanoparticles (LF/Z/P Nps) were prepared by anti-solvent precipitation method. Taking the embedding rate, particle size and Zeta potential as indicators, the effects of polysaccharide species, flavonoids concentration, zein concentration, alcohol-to-water ratio and pectin concentration on the preparation of nanoparticles were explored. The preparation process of nanoparticles was optimized by response surface experiment, and the characteristics of nanoparticles were studied. The results showed that the optimal preparation conditions were determined as follows: Loquat flower flavonoids concentration of 0.135 mg/mL, zein concentration of 2.2 mg/mL, alcohol-to-water ratio of 1:4, and pectin concentration of 0.78 mg/mL. Under these conditions, the embedding rate of nanoparticles was 86.20%±0.91%, the average particle size was 132.13±1.31 nm, the PDI was 0.16±0.01, and the Zeta potential was −33.97±1.46 mV. The nanoparticles were sensitive to pH and Na+, but could effectively maintain the antioxidant and stability of loquat flower flavonoids. In this study, LF/Z/P Nps with good stability were prepared by reverse-solvent precipitation method, which laid a certain theoretical basis for improving the processing adaptability of loquat flower flavonoids.

Abstract The technology of pantograph sinking in the cavity is generally adopted in the new generation of high-speed trains in China for aerodynamic noise reduction in this region. This study takes a high-speed train with a 4-car formation and a pantograph as the research object and compares the aerodynamic acoustic performance of two scale models, 1/8 and 1/1, using large eddy simulation and Ffowcs Williams–Hawkings integral equation. It is found that there is no direct scale similarity between their aeroacoustic performance. The 1/1 model airflow is separated at the leading edge of the panhead and reattached to the panhead, and its vortex shedding Strouhal number (St) is 0.17. However, the 1/8 model airflow is separated directly at the leading edge of the panhead, and its St is 0.13. The cavity’s vortex shedding frequency is in agreement with that calculated by the Rooster empirical formula. The two scale models exhibit some similar characteristics in distribution of sound source energy, but the energy distribution of the 1/8 model is more concentrated in the middle and lower regions. The contribution rates of their middle and lower regions to the radiated noise in the two models are 27.3% and 87.2%, respectively. The peak frequencies of the radiated noise from the 1/1 model are 307 and 571 Hz. The 307 Hz is consistent with the frequency of panhead vortex shedding, and the 571 Hz is more likely to be the result of the superposition of various components. In contrast, the peak frequencies of the radiated noise from the 1/8 scale model are 280 and 1970 Hz. The 280 Hz comes from the shear layer oscillation between the cavity and the bottom frame, and the 1970 Hz is close to the frequency at which the panhead vortex sheds. This shows that the scaled model results need to be corrected before applying to the full-scale model.

A novel topology of modular ferrite magnet flux-switching linear motor (FMFSLM) use for track transport is presented in this paper, which enables more ferrite magnets to be inserted into the primary iron core. The motor has a significant low-cost advantage in long-distance linear drive. The proposed FMFSLM's structure and working principle were introduced. Further, the thrust force expression of the motor was established. The thrust force components triggering thrust force ripple were investigated, and their expressions can be obtained according to the inductances' Fourier series expressions. Resultantly, the relationship between the harmonics of thrust force and that of self- and mutual inductances was revealed clearly. Based on the relationship, a skewed secondary should be practical to reduce the thrust force ripple. Thus, the effect of employing a skewed secondary to the proposed FMFSLM was investigated, and an optimized skewing span distance was determined. Finite element analysis (FEA) was conducted to validate the exactness of the theoretical analysis. The simulation results indicate that the strategy of suppressing thrust force ripple has a significant effect. Meanwhile, the motor maintains a good efficiency characteristic. The results of the prototype experiment are in good agreement with FEAs, which further verifies the proposed modular interior FMFSLM's practicability.

Abstract This study explores disparities and opportunities in healthcare information provided by AI chatbots. We focused on recommendations for adjuvant therapy in endometrial cancer, analyzing responses across four regions (Indonesia, Nigeria, Taiwan, USA) and three platforms (Bard, Bing, ChatGPT-3.5). Utilizing previously published cases, we asked identical questions to chatbots from each location within a 24-h window. Responses were evaluated in a double-blinded manner on relevance, clarity, depth, focus, and coherence by ten experts in endometrial cancer. Our analysis revealed significant variations across different countries/regions (p

Abstract Friction is not an inherent attribute in natural science. Indeed, there are various friction phenomena present in social systems. In this study, the researchers developed the general concept of social friction and distinguished the two-dimensional structure of explicit-implicit social friction phenomena. Specifically, explicit friction includes institutional friction, economic friction, behavioral friction, and migration friction. Implicit friction includes cultural friction, cognitive friction, interpersonal friction, technological friction, and information friction. Physical theories such as friction force, classical mechanics, and functional principles have been introduced to construct a social friction force model. This paper describes the emergence and evolution of social friction phenomena from the mechanics perspective and clarifies the various characteristics of social friction force in different areas. This study also provides a new theoretical perspective for examining social friction phenomena and adds innovative content to intersection studies in physics and the social sciences.

Abstract Background Postoperative delirium (POD) often occurs in oncology patients, further increasing the medical and financial burden. Robotic technology in lower abdominal tumors resection reduces surgical trauma but increases risks such as carbon dioxide (CO2) absorption. This study aimed to investigate the differences in their occurrence of POD at different end-tidal CO2 levels. Method This study was approved by the Ethics Committee of Affiliated Hospital of He Bei University (HDFY-LL-2022-169). The study was registered with the Chinese Clinical Trials Registry on URL: http://www.chictr.org.cn , Registry Number: ChiCTR2200056019 (Registry Date: 27/08/2022). In patients scheduled robotic lower abdominal tumor resection from September 1, 2022 to December 31, 2022, a comprehensive delirium assessment was performed three days postoperatively using the CAM scale with clinical review records. Intraoperative administration of different etCO2 was performed depending on the randomized grouping after intubation. Group L received lower level etCO2 management (31-40mmHg), and Group H maintained the higher level(41-50mmHg) during pneumoperitoneum. Data were analyzed using Pearson Chi-Square or Wilcoxon Rank Sum tests and multiple logistic regression. Preoperative mental status score, alcohol impairment score, nicotine dependence score, history of hypertension and diabetes, duration of surgery and worst pain score were included in the regression model along with basic patient information for covariate correction analysis. Results Among the 103 enrolled patients, 19 (18.4%) developed postoperative delirium. The incidence of delirium in different etCO2 groups was 21.6% in Group L and 15.4% in Group H, respectively, with no statistical differences. In adjusted multivariate analysis, age and during of surgery were statistically significant predictors of postoperative delirium. The breath-hold test was significantly lower postoperatively, but no statistical differences were found between two groups. Conclusion With robotic assistant, the incidence of postoperative delirium in patients undergoing lower abdominal tumor resection was not modified by different end-tidal carbon dioxide management, however, age and duration of surgery were positively associated risk factors.

Abstract Quantifying the complexity of traffic scenarios not only provides an essential foundation for constructing the scenarios used in autonomous vehicle training and testing, but also enhances the robustness of the resulting driving decisions and planning operations. However, currently available quantification methods suffer from inaccuracies and coarse‐granularity in complexity measurements due to issues such as insufficient specificity or indirect quantification. The present work addresses these challenges by proposing a comprehensive entropy‐based model for quantifying traffic scenario complexity across multiple dimensions based on a consideration of the essential components of the traffic environment, including traffic participants, static elements, and dynamic elements. In addition, the limitations of the classical information entropy models applied for assessing traffic scenarios are addressed by calculating magnitude entropy. The proposed entropy‐based model is analyzed in detail according to its application to simulated traffic scenarios. Moreover, the model is applied to real world data within a naturalistic driving dataset. Finally, the effectiveness of the proposed quantification model is illustrated by comparing the complexity results obtained for three typical traffic scenarios with those obtained using an existing multi‐factor complexity quantification method.

AIM: To report a one-year clinical outcomes of low-dose laser cycloplasty (LCP) among malignant glaucoma patients. METHODS: In this prospective, multicenter, non-comparative clinical study, participants with malignant glaucoma were recruited and underwent LCP at eight ophthalmic centers in China. Patients were followed up at 1wk, 1, 3, 6, and 12mo. Intraocular pressure (IOP), number of glaucoma medications, anterior chamber depth (ACD), and complications were recorded. Anatomical success was defined as the reformation of the anterior chamber based on slit-lamp biomicroscopy. Recurrence was defined by the presence of a shallow or ?at anterior chamber after initial recovery from treatment. RESULTS: A total of 34 eyes received LCP. Mean IOP and medications decreased from 36.1±11.5 mm Hg with 3.3±1.5 glaucoma medications pre-treatment to 20.9±9.8 mm Hg (P

This study introduces an innovative approach of utilizing ZnO nanorod growing technology to the sateen fabric in order to improve its ballistic performance. Through SEM, FTIR, XRD and XPS analyses, ZnO nanorods with majority length of 1000–1500 nm and fineness of 200–600 nm have been deposited on the surface of sateen fabric surface Compared the fabric with ZnO nanorods (S-11-Nrs) with its neat counterpart, the mechanical properties of S-11-Nrs are increased, especially the inter-filament friction and fabric tensile breaking strength. However, in the impact process, the number of filaments involved in the impact is reduced and the filaments are mainly failure by the shear action of the bullets. Due to these positive and negative effects, the energy absorption of S-11-Nrs displays inferior ballistic energy absorption. Nevertheless, at lower areal density, in the non-perforation test, S-11-Nrs presents less BFS and shows better resistance to the consecutive shotting process compared with the neat fabric. The reason is that the increase of inter-filament friction limits the movement of filaments and thus results in less BFS. In addition, the flexibility, air permeability and moisture permeability are still kept. This research offers valuable insights for the design and development of comfortable soft body armor.

BackgroundCerebral white matter hyperintensity (WMH) is a pivotal imaging feature of cerebral small vessel disease (CSVD), closely correlated with an elevated risk of ischemic stroke (IS). Trimethylamine N-oxide (TMAO), a metabolite of gut microbiota, is increasingly associated with IS and atherosclerosis. However, the intricate relationship between TMAO and WMH remains ambiguous. This study aimed to study the connection between plasma TMAO and WMH. Furthermore, it assessed the potential of TMAO as a risk evaluation instrument for WMH.MethodsIn this cross-sectional study, we categorized WMH into periventricular WMH (P-WMH) and deep WMH (D-WMH), based on its locations. The severity of WMH was assessed and grouped according to the Fazekas scale. Plasma TMAO levels were quantitatively determined. We established the correlation between plasma TMAO levels and WMH severity using a Logistic regression model. Additionally, we employed ROC curves to evaluate the diagnostic efficacy of plasma TMAO concentration in distinguishing the severity of WMH.ResultsA higher plasma TMAO tertile was significantly linked to a higher Fazekas score, encompassing the overall score, P-WMH score, and D-WMH score (p 0.5, while the AUC for moderate WMH was0.5.ConclusionPlasma TMAO levels exhibited a significant correlation with both overall and region-specific WMH severity. Furthermore, the plasma TMAO levels displayed robust predictive capability for D-WMH.

The Chinese medicinal plant Thesium chinense Turcz. is the only plant used in the manufacture of Bairui Granules. However, to date, there has been very little research into the cytotoxic activity of active substances derived from Bairui Granules. Using chemical separation and spectroscopic methods, phenolic compounds 1–5 were identified as methyl-p-hydroxycinnamate, vanillin, kaempferol, isorhamnetin-3-O-glucoside, and astragalin, respectively. UPLC-MS/MS analyses revealed that compounds 1–5 were present at concentrations of 0.006 ± 0.002, 1.63 ± 0.87, 3.65 ± 0.83, 26.97 ± 11.41, and 27.67 ± 2.91 μg/g, respectively in Bairui Granules. Compounds 1, 2, and 4 were detected here for the first time in Bairui Granules. Using co-culture experiments, isorhamnetin-3-O-glucoside (4) was found to be beneficial to the proliferation Chinese hamster ovary (CHO) cells (6.46% ± 0.86% to 38.45% ± 9.04%), natural killer cells from human umbilical cord blood (UCB NK cells) (25.68% ± 0.02% to 70.81% ± 0.26%), and mesenchymal stem cells from human umbilical cord blood (UCB MSC cells) (1.66% ± 0.05% to 27.64% ± 0.51%) when the concentration was similar to that found in Bairui granules. Moreover, vanillin (2) was conducive to UCB NK cells proliferation (28.21% ± 0.44%) at a concentration of 64 μg/mL, while maintaining cell viability. UCB NK cell proliferation was promoted at rates of 41.03% ± 0.48% to 67.22% ± 0.68% when astragalin (5) was present at low concentrations (8 and 16 μg/mL). Methyl-p-hydroxycinnamate (1) and vanillin (2) at different concentrations both had an inhibitory effect on the proliferation of natural killer cells from human peripheral blood (PB NK cells), but the inhibitory concentration ranges of these compounds were not equivalent to the concentration ranges of the compounds in Bairui Granules. These results provide a foundation for the safe use of T. chinense preparations.

The detection of antimitochondrial antibodies (AMA) is the specific diagnostic marker for primary biliary cholangitis. Indeed, it is the most specific autoantibody in clinical autoimmunity, with a high titer directed response to the inner lipoyl domain of PDC-E2. The current international reference for AMA detection is based upon sera samples of PBC patients. In rheumatic diseases, i.e. rheumatoid arthritis, great efforts are placed at development of international standards. In this study, we report the development of a monoclonal chimeric IgG1 antibody as a reference for AMA testing. A monoclonal 4G6 antibody was constructed from a murine monoclonal antibody specific for the inner lipoyl domain (ILD) of PDC-E2, by combining the variable region with the constant region of human IgG1. The 4G6 antibody recognizes all AMA epitopes containing the ILD of PDC-E2, including the classical BPO recombinant antigen in all currently available diagnostic methods. The binding affinity of the 4G6 antibody to PDC-E2 and BPO antigen reaches KD value of 7.22 × 10−11 M and 4.55 × 10−11 M, which is sufficient to use as a quantitative reference for all AMA tests. The unlimited availability of the 4G6 antibody makes it a promising candidate for use as an AMA reference or assay calibrator for the international community.

To elucidate the feasibility of applying the Maillard reaction (MR) to the development of Lentinula edodes umami seasoning, this study quantitatively analyzed the main umami substances in the products and evaluated their sensory quality. Simultaneously, the rheology, thermal stability, zeta potential, and particle size of the products were also studied. The results indicated that after the MR, the content of umami amino acids in Lentinula edodes hydrolysates (LEHs) decreased from 17.72 mg/g to 12.70 mg/g, while the content of umami nucleotides increased from 0.61 mg/g to 1.36 mg/g. The equivalent umami concentration of MR products was high, at 293.84 ± 11.05 g MSG/100 g. Taste activity value indicated that 5’-GMP, Asp, and Glu were the key umami substances. MR increased the umami sensory score, particle size, absolute zeta potential, and viscosity of LEHs, and altered their thermal stability. These results support the application of MR in the mushroom umami seasoning.

ABSTRACT: Aflatoxin B1 (AFB1) a mycotoxin found in chicken feed that possess a global hazard to poultry health. However different potent compounds like bovine lactoferrin (bLF) may prove to be protective effects against AFB1. This study aims to explore the protective effect of bLF against AFB1-induced injury in the liver and kidney in broiler. For this purpose, 600 broilers chicks were randomly alienated into 5 groups (n = 120 each): negative control; positive control (3 mg/kg AFB1), and bLF high, medium, and low dosage groups (600 mg/kg, 300 mg/kg, and 150 mg/kg, respectively). The results highlight that AFB1 toxicity in birds exhibited low feed intake, reduction in weight gain, and a decrease in FCR while, bLF regulated these adverse effects. Meanwhile, AFB1 group showed higher levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) and lower levels of superoxide dismutase (SOD) and glutathione (GSHpx) in liver, while urea and creatinine were decline in kidney. Supplementation with bLF effectively controlled these biomarkers and control the negative effects of toxicity. Furthermore, hematoxylin and eosin (H&E) staining exhibited normal morphological structures within liver and kidney in the bLF treated groups, while degenerative changes were observed in AFB1 group. Similarly, bLF, decreased oxidative stress and thus prevented apoptosis in the liver and kidney cells of the birds. Whereas, mRNA level of mitochondrial apoptosis related gene including Bcl-2 (Bak and Bax), caspase-3 and caspase-9 was upregulated, while bcl2 gene were downregulated in AFB1 group. Dietary supplementation of bLF effectively normalizes the expression of these genes. AFB1 exposed birds shown to decrease gene expression level of the crucial component of Nrf2 pathway, responsible to regulate antioxidant defense. Interestingly, bLF reverse these detrimental effects of and restore the normal expression levels of Nrf2 pathway. Conclusively, our findings demonstrate that bLF mitigates the detrimental effects of AFB1, besides regulation of the apoptosis-related genes via mitochondrial pathways. These findings validate that the bLF (600 mg/kg) could be used as protective agent against AFB1-induced liver and kidney damage.

Purpose: To present a case of delayed recurrent hyphema following toric ICL implantation. Observations: This case reports a 24-year-old Asian female who presented with sudden decrease in vision in the right eye, accompanied by recurrent massive anterior chamber hemorrhage, six months after bilateral implantation of toric ICL with central holes for myopia correction. Despite initial conservative treatment with immobilization and intraocular pressure (IOP)-lowering medication at another hospital, the hyphema persisted. At our hospital, her corrected visual acuity (CDVA) in the right eye was counting fingers (CF) at 50 cm, with visible blood clots and hyphema in the anterior chamber, and an IOP of 40 mmHg. Ultrabiomicroscopy (UBM) indicated a large amount of hyphema in the anterior chamber. Initially, the patient was treated with a combination of three IOP-lowering medications: brimonidine eye drops, brinzolamide eye drops, and timolol eye drops, but the condition recurred. Two weeks later, we performed an anterior chamber hyphema evacuation and ICL removal surgery in the right eye. Postoperatively, the patient's IOP stabilized and her vision gradually recovered. One month after the surgery, a follow-up examination showed a CDVA of LogMAR 0.6 in the affected eye. Conclusion and importance: This case report is essential for characterizing a rare and serious complication following toric ICL implantation, highlighting the importance of close monitoring and timely intervention.

Snow depth (SD) plays a critical role in evaluating snow disasters, simulating hydrological processes and maintaining surface radiation balance etc. This study presents the first comprehensive evaluation of three SD products—SD-AMSR2, SD-Globsnow, and SD-SPM—derived from passive microwave remote sensing across the Mongolian Plateau. These products are developed through methods such as empirical microwave polarization difference, satellite and ground data integration, and machine learning with physical snow process models. The key findings included: 1) SD-SPM and SD-Globsnow had significantly lower values than SD-AMSR2, with SD-Globsnow showing less coverage in high-latitude areas. All products struggled with accuracy during deep snow and transitional seasons. 2) Validation against 66 stations showed that SD-SPM and SD-Globsnow were more accurate than SD-AMSR2, with SD-Globsnow performing best overall. SD-SPM was particularly stable and robust across all stations, excelling in May and September. 3) In snow identification, SD-SPM demonstrated the highest consistency of with fractional snow cover data, achieving over 80% agreement across most regions. 4) SD-SPM exhibited the strongest correlation with fractional snow cover data, especially in certain land cover types and timeframes. These results can provide insights for integrating multiple SD algorithms, aiding in snow disaster prediction and regional water resource management.

Bamboo fiber (BF) has emerged as a promising natural, environmentally friendly material for use in composite materials. The steam explosion process plays a crucial role in preparing BFs suitable for composites. In this study, the effects of solid–liquid ratio, explosion pressure, and explosion holding time on BF preparation were investigated by orthogonal experiments, and the structural and chemical changes occurring during the separation of BF were also investigated. The results showed that the combined method of alkali treatment and steam explosion successfully produced BFs with good morphology. The highest yield of fine fibers (39.07%) was obtained at a solid–liquid ratio of 2:1, explosion pressure of 2.2 MPa, and explosion holding time of 4 min. BFs obtained using the optimal values exhibited dispersed fiber bundles, partial removal of hemicellulose and lignin, and improved crystallinity. Furthermore, the hygroscopicity of BFs decreased, reaching a minimum of 15% under the optimal process conditions. The optimization of steam explosion parameters can help to improve the extraction efficiency of fine fibers for composites and promote the industrialization of BFs prepared by steam explosion.

Introduction Involved site radiation therapy (ISRT) is a widely used treatment for primary ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma with control rates over 85%; however, its complications could reach 30%–50%. Intralesional rituximab injection has shown promising results with remission rates between 65% and 100% and minimal complications. This study aimed to conduct a multicentre randomised controlled clinical trial to compare the safety and efficacy of intralesional rituximab injection versus ISRT on primary ocular adnexal MALT lymphoma.Methods and analysis This is a multicentre randomised controlled trial and will be conducted at eight ophthalmic departments and institutes in China. 108 patients with primary ocular adnexal MALT lymphoma will be enrolled and randomised to undergo intralesional rituximab injection or ISRT. Comprehensive examinations will be performed before and after the treatment. The primary outcome is the cumulative occurrence rate of complications of grade ≥2 within 5 years after treatment commencement. The main secondary outcome is overall response rate, and progression-free survival, time to next treatment and overall survival will also be compared between the groups.Ethics and dissemination Ethical approval has been obtained from the Ethics Committee of the Zhongshan Ophthalmic Center (ID: 2023KYPJ125-3; V.20240818) and the ‘5010 Plan’ evaluation committee at Sun Yat-sen University, Guangzhou, China, and all subcentres. All the participants will be required to provide written informed consent. The results will be disseminated through scientific meetings and published in peer-reviewed journals.Trial registration number NCT06190301.

IntroductionMucosal-associated invariant T (MAIT) cells are a predominant subset of innate-like T cells in humans, characterized by diverse gene expression profiles and functional capabilities. However, the factors influencing the transcriptomes and effector functions of MAIT cells, particularly at mucosal barriers, remain largely unclear.MethodsIn this study, we employed single-cell RNA sequencing (scRNA-seq) and functional assays to investigate the transcriptomic and functional characteristics of intestinal MAIT cells in mouse models during aging. We also extended scRNA-seq analysis to human intestinal MAIT cells to compare their gene expression patterns with those observed in aged mice.ResultsOur findings demonstrated that the transcriptomes and functional capabilities of intestinal MAIT cells shifted from MAIT17 to MAIT1 profiles with aging in mouse models, with notable changes in the production of cytotoxic molecules. Further scRNA-seq analysis of human intestinal MAIT cells revealed a segregation into MAIT1 and MAIT17 subsets, displaying gene expression patterns that mirrored those seen in aged mouse models. The transcription factor RORγt was expressed in both MAIT1 and MAIT17 cells, acting to repress IFNγ production while promoting IL17 expression. Moreover, reduced expression of RORC and Il17A was correlated with poorer survival outcomes in colorectal cancer patients.DiscussionThese results suggest that aging induces a functional shift between MAIT1 and MAIT17 cells, which may be influenced by transcriptional regulators like RORγt. The observed alterations in MAIT cell activity could potentially impact disease prognosis, particularly in colorectal cancer. This study provides new insights into the dynamics of MAIT cell responses at mucosal barriers, highlighting possible therapeutic targets for modulating MAIT cell functions in aging and disease.

Abstract Molecular features are incorporated into the integrated diagnostic system for adult diffuse gliomas. Of these, copy number variation (CNV) markers, including both arm‐level (1p/19q codeletion, +7/−10 signature) and gene‐level (EGFR gene amplification, CDKN2A/B homozygous deletion) changes, have revolutionized the diagnostic paradigm by updating the subtyping and grading schemes. Shallow whole genome sequencing (sWGS) has been widely used for CNV detection due to its cost‐effectiveness and versatility. However, the parallel detection of glioma‐associated CNV markers using sWGS has not been optimized in a clinical setting. Herein, we established a model‐based approach to classify the CNV status of glioma‐associated diagnostic markers with a single test. To enhance its clinical utility, we carried out hypothesis testing model‐based analysis through the estimation of copy ratio fluctuation level, which was implemented individually and independently and, thus, avoided the necessity for normal controls. Besides, the customization of required minimal tumor fraction (TF) was evaluated and recommended for each glioma‐associated marker to ensure robust classification. As a result, with 1× sequencing depth and 0.05 TF, arm‐level CNVs could be reliably detected with at least 99.5% sensitivity and specificity. For EGFR gene amplification and CDKN2A/B homozygous deletion, the corresponding TF limits were 0.15 and 0.45 to ensure the evaluation metrics were both higher than 97%. Furthermore, we applied the algorithm to an independent glioma cohort and observed the expected sample distribution and prognostic stratification patterns. In conclusion, we provide a clinically applicable algorithm to classify the CNV status of glioma‐associated markers in parallel.

Event-based cameras are suitable for human action recognition (HAR) by providing movement perception with highly dynamic range, high temporal resolution, high power efficiency and low latency. Spike Neural Networks (SNNs) are naturally suited to deal with the asynchronous and sparse data from the event cameras due to their spike-based event-driven paradigm, with less power consumption compared to artificial neural networks. In this paper, we propose two end-to-end SNNs, namely Spike-HAR and Spike-HAR++, to introduce spiking transformer into event-based HAR. Spike-HAR includes two novel blocks: a spike attention branch, which enables model to focus on regions with high spike rates, reducing the impact of noise to improve the accuracy, and a parallel spike transformer block with simplified spiking self-attention mechanism, increasing computational efficiency. To better extract crucial information from high-level features, we modify the architecture of the spike attention branch and extend it in Spike-HAR to a higher dimension, proposing Spike-HAR++ to further enhance classification performance. Comprehensive experiments were conducted on four HAR datasets: SL-Animals-DVS, N-LSA64, DVS128 Gesture and DailyAction-DVS, to demonstrate the superior performance of our proposed model. Additionally, the proposed Spike-HAR and Spike-HAR++ require only 0.03 and 0.06 mJ, respectively, to process a sequence of event frames, with model sizes of only 0.7 and 1.8 M. This efficiency positions it as a promising new SNN baseline for the HAR community. Code is available at Spike-HAR++.

African swine fever (ASF) is a devastating disease that can kill almost all infected pigs, causing great damage to the pig industry and destabilizing the global economy. Here, we developed a specific assay that combined multiple cross-displacement amplification (MCDA) with a nanoparticle-based lateral flow biosensor (LFB) for early and rapid identification of the African swine fever virus (ASFV-MCDA-LFB). We first designed a set of MCDA primers to recognize 10 different regions of the target ASFV B646L gene. Subsequently, the MCDA reaction was monitored with various methods: MG chromogenic reagents, agarose gel electrophoresis, real-time turbidity, and LFB. The ASFV-MCDA-LFB assay was optimized and evaluated with target nucleic acid templates extracted from various pathogens and simulated whole blood samples. As a result, the detection of limit (LOD) of the ASFV assay was 200 copies/reaction within 30 min, and no cross-reaction were observed with other non-ASFV viruses and common pathogens in this study. The evaluation assays demonstrated that the ASFV-MCDA-LFB method here is rapid, objective, easy-to-use, and low-cost detection method which can be used as a diagnostic or screening tool with competitive potential for point-of-care testing (POCT) of ASFV.

ObjectivesPatients with minor ischemic stroke (MIS) have substantial disability rates at 90 days. Our study aimed to explore the association between the systemic inflammation response index (SIRI) and 3-month functional outcomes in patients with MIS.MethodsWe conducted a prospective observational study in patients with MIS [defined as a National Institutes of Health Stroke Scale (NIHSS) score of 0–3] admitted within 24 h from symptoms onset. Blood samples for the SIRI measurement were collected on admission. The primary outcome measure was poor outcomes at 90 days (defined as a modified Rankin Scale score of 2–6). Univariate and multivariate logistic analyses were performed to assess the association between the SIRI and the risk of 3-month poor outcomes.ResultsA total of 152 patients with MIS were enrolled, of which 24 cases (15.8%) had poor outcomes at 90 days. The median SIRI level was 1.27 [interquartile range (IQR), 0.77–1.92, ×10^9 /L] on admission. MIS patients with poor outcomes had higher levels of the SIRI than patients with good outcomes (poor outcomes: median, 1.93, IQR: 1.17–3.28, ×10^9 /L; good outcomes: median, 1.21, IQR: 0.71–1.80, ×10^9 /L; p = 0.003). The high SIRI level group (SIRI >1.27 × 10^9 /L) had significantly higher rates of poor outcomes at 90 days (22.4% vs. 9.2%, p = 0.026). After adjusting for age, baseline NIHSS score, prehospital delay, Trial of Org 10,172 in Acute Stroke Treatment (TOAST) classification, and other confounders in multivariate analyses, an elevated SIRI level remained independently associated with an increased risk of poor outcomes in patients with MIS [odds ratio (OR): 1.57, 95% confidence interval (CI): 1.12–2.20; p = 0.010]. Meanwhile, a high level of the SIRI (>1.27 × 10^9/L) was still an independent risk factor for 3-month poor outcomes (OR: 4.80, 95%CI: 1.51–15.29; p = 0.008) in MIS patients.ConclusionDisability at 90 days was common in patients with MIS. An elevated SIRI was associated with poor outcomes in MIS patients. The SIRI might be a promising biomarker candidate that can help identify high-risk MIS patients with poor outcomes for reaching individual therapeutic decisions in clinical trials.

Background Pathological cardiac hypertrophy stands as a pivotal mechanism contributing to diverse cardiovascular diseases, ultimately leading to heart failure. Despite its clinical significance, the intricate molecular mechanisms instigating pathological cardiac hypertrophy remain inadequately understood. In this study, we aim to further reveal its complex pathogenesis by exploring the role of Fas apoptotic inhibitory molecule 2 (FAIM2) in modulating pathological cardiac hypertrophy. Methods and Results We used phenylephrine‐induced hypertrophic cardiomyocytes and also generated cardiac‐specific knockout mice and adeno‐associated virus serotype 9‐Faim2 mice to evaluate the function of FAIM2 in pathological myocardial hypertrophy. Furthermore, unbiased RNA‐sequencing analysis was used to identify the direct target and corresponding molecular events contributing to FAIM2 function. Ultimately, our study revealed a downregulation of FAIM2 expression in phenylephrine‐induced hypertrophic cardiomyocytes and pressure overload–induced hypertrophic hearts. FAIM2 exhibited a significant attenuation of phenylephrine‐induced enlargement of primary neonatal rat cardiomyocytes, whereas FAIM2 knockdown aggravated the hypertrophic response. Furthermore, Faim2 gene knockout significantly exacerbated cardiac hypertrophy and heart fibrosis in vivo. Mechanistic investigations unveiled that FAIM2 exerts its inhibitory effect by suppressing TAK1‐JNK1/2‐p38 MAPK signaling cascades, thereby mitigating cardiac hypertrophy. Conclusions Our findings position FAIM2 as a novel negative regulator of pathological cardiac hypertrophy through its inhibitory action on mitogen‐activated protein kinase signaling activation. This identification of FAIM2's role provides crucial insights that may pave the way for the development of effective therapeutic strategies aimed at mitigating pathological cardiac hypertrophy, addressing a critical need in cardiovascular disease management.

Improving the reproductive ability and fertility of male ruminants is a central concern in animal husbandry. Phytogenic feed additives, known for their anti-inflammatory, antioxidant, and immunomodulatory properties, are commonly used in animal feed. Icariin (ICA), the primary flavonoid glucoside derived from Epimedium, is a traditional tonic in Chinese herbal medicine. However, its potential to enhance the reproductive performance of male ruminants remains unclear. In this study, twelve healthy adult male dairy goats were divided into two groups. The goats received oral administration of ICA at doses of 0 (control) and 50 mg/kg body weight daily for a consecutive period of 80 days during the breeding season. The effects of ICA on the reproductive performance was analyzed by histological examinations, semen quality analysis, and ELISA experiments. ELISA results showed a progressive increase in serum levels of GnIH, LH, and testosterone with the prolonged ICA treatment (p

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious viral disease that causes significant economic losses to the swine industry worldwide. PRRS virus (PRRSV) infection is a receptor-mediated endocytosis and replication process. The purpose of this study was to determine the localization and expression of four important PRRSV receptors in immunological organs of piglets. After piglets were infected with PRRSV, Hematoxylin and Eosin staining, immunofluorescence, and Western blot were used to perform histopathological examination and receptors distribution analysis. The results showed that PRRSV caused severe damage to the piglets’ immune organs, including atrophy of the thymus and swelling of lymph node. Histopathological lesions were mainly observed in the lung and lymph node and were characterized by interstitial pneumonia, collapsed follicles, exhaustion of germinal centers, and extensive hemorrhage. Immunofluorescence staining and Western blot results showed that the receptors of CD163 and NMHCII-A were mainly distributed in the thymus, hilar lymph nodes, and mesenteric lymph nodes. However, Sn and vimentin receptors were expressed at low levels in the immune organs of piglets. The distribution of the four receptors in the immune organs was more concentrated in the cortex but was more scattered in the medulla. Compared to the control group, the relative expression of the four receptors increased significantly in most immune organs after viral infection. In conclusion, our study examined the distribution and expression of four PRRSV receptors in immunological organs. We observed a significant increase in the expression of Sn, CD163, and vimentin following viral infection. These findings may provide potential targets for future antiviral reagent design or vaccine development.

BackgroundMild cognitive impairment (MCI) is generally considered to have a high risk of progression to Alzheimer’s disease. Our study aimed to investigate the abnormal functional connectivity (FC) in prefrontal cortex (PFC) in patients with MCI and explore the relationship between the observed changes and cognitive function.MethodsSixty-seven patients with MCI and 71 healthy individuals were recruited for this study. All participants underwent the Montreal Cognitive Assessment (MoCA) and functional near-infrared spectroscopy (fNIRS) examinations.ResultsCompared with healthy controls (HC), the patients with MCI exhibited significantly lower MoCA scores (p

This article delves into the intricate interplay between tumors, particularly gynecologic malignancies, and neutrophil extracellular traps (NETs). The relationship between tumors, specifically gynecologic malignancies, and NETs is a multifaceted and pivotal area of study. Neutrophils, pivotal components of the immune system, are tasked with combating foreign invaders. NETs, intricate structures released by neutrophils, play a vital role in combating systemic infections but also play a role in non-infectious conditions such as inflammation, autoimmune diseases, and cancer. Cancer cells have the ability to attract neutrophils, creating tumor-associated neutrophils, which then stimulate the release of NETs into the tumor microenvironment. The impact of NETs within the tumor microenvironment is profound and intricate. They play a significant role in influencing cancer development and metastasis, as well as modulating tumor immune responses. Through the release of proteases and pro-inflammatory cytokines, NETs directly alter the behavior of tumor cells, increasing invasiveness and metastatic potential. Additionally, NETs can trigger epithelial-mesenchymal transition in tumor cells, a process associated with increased invasion and metastasis. The interaction between tumors and NETs is particularly critical in gynecologic malignancies such as ovarian, cervical, and endometrial cancer. Understanding the mechanisms through which NETs operate in these tumors can offer valuable insights for the development of targeted therapeutic interventions. Researchers are actively working towards harnessing this interaction to impede tumor progression and metastasis, opening up new avenues for future treatment modalities. As our understanding of the interplay between tumors and NETs deepens, it is anticipated that novel treatment strategies will emerge, potentially leading to improved outcomes for patients with gynecologic malignancies. This article provides a comprehensive overview of the latest research findings on the interaction between NETs and cancer, particularly in gynecologic tumors, serving as a valuable resource for future exploration in this field.