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Abstract Retinal ischemia–reperfusion (IR) injury is a basic pathological procedure in clinic and associated with various ischemic retinal diseases, including glaucoma, diabetic retinopathy, retinal vascular occlusion, etc. The purpose of this work is to investigate the effect of ciclopirox olamine (CPX) on retinal IR injury and further explore the underlying mechanism. In vitro assay exhibited that CPX exhibited significant neuroprotection against oxygen glucose deprivation (OGD) and oxidative stress-induced injuries in 661W photoreceptor cells. OGD injury showed a proinflammatory phenotype characterized by significantly increased production of cytokines (IL-6, IL-23 and TNF-α), while CPX significantly inhibited their secretion. In addition, the in vivo experiment demonstrated that CPX significantly preserved the normal thickness of the retina. Therefore, we suggest that CPX is identified in our research as a prospective therapeutic agent for retinal IR injury.

Abstract Formaldehyde (FA) is a chemical that facilitates crosslinking between DNA and proteins. It is widely used in various biochemical assays, such as chromosome conformation capture (3C) and Chromatin Immunoprecipitation (ChIP). While the concentration and temperature of FA treatment are recognized as crucial factors in crosslinking, their quantitative effects have largely remained unexplored. In this study, we employed 3C as a model system to systematically assess the impacts of these two factors on crosslinking. Our findings indicate that the strength of crosslinking significantly influences chromatin conformation detection at nearly all known structural levels. Specifically, a delicate balance between sensitivity and reliability is required when detecting higher-level structures, such as chromosome compartments. Conversely, intense crosslinking is preferred when targeting lower-level structures, such as topologically associated domains (TADs) or chromatin loops. Based on our data, we propose a conceptual molecular thermal motion model to elucidate the roles of these two factors in restricting FA crosslinking. Our results not only shed light on the previously overlooked confounding factor in FA crosslinking but also highlight the need for caution in new technology developments that rely on FA crosslinking.

Abstract Osteoarthritis is a degenerative joint disease with joint pain as the main symptom, caused by fibrosis and loss of articular cartilage. Due to the complexity and heterogeneity of osteoarthritis, there is a lack of effective individualized disease-modifying osteoarthritis drugs in clinical practice. Chondrocyte senescence is reported to participate in occurrence and progression of osteoarthritis. Here we show that small molecule 10-hydroxy-2-decenoic acid suppresses cartilage degeneration and relieves pain in the chondrocytes, cartilage explants from osteoarthritis patients, surgery-induced medial meniscus destabilization or naturally aged male mice. We further confirm that 10-hydroxy-2-decenoic acid exerts a protective effect by targeting the glycosylation site in the Asp_Arg_Hydrox domain of aspartyl β-hydroxylase. Mechanistically, 10-hydroxy-2-decenoic acid alleviate cellular senescence through the ERK/p53/p21 and GSK3β/p16 pathways in the chondrocytes. Our study uncovers that 10-hydroxy-2-decenoic acid modulate cartilage metabolism by targeting aspartyl β-hydroxylase to inhibit chondrocyte senescence in osteoarthritis. 10-hydroxy-2-decenoic acid may be a promising therapeutic drug against osteoarthritis.

To investigate the protective effect of selenated Acanthopanax polysaccharide (Se-ASPS) against D-galactose-induced (D-gal) oxidative damage in mice. The oxidative damage model of mice was established by intrabitoneal injection of D-gal. The mice in the high, medium and low dose groups were supplemented with 200, 100 and 50 mg/kg·bw of selenated Acanthopanax polysaccharide, respectively. The mice were gavaged continuous intragastric administration for 28 days. Changes in body weight and feed intake and organ indices of mice in each group were compared, and HE staining was used to observe liver lesions in mice. Serum, heart, liver, spleen and kidney tissues were analyzed for SOD, CAT, GSH-Px, MDA, AST, ALT using the kit. Compared with the D-gal model group, both selenated Acanthopanax polysaccharide groups significantly increased the body weights of mice (P

Abstract Background Loiasis is one of the significant filarial diseases for people living in West and Central Africa with wide endemic area but is not seen in China. As economy booms and international traveling increase, China faces more and more imported parasitic diseases that are not endemic locally. Loiasis is one of the parasitic diseases that enter China by travelers infected in Africa. The better understanding of the clinical and laboratory features of loa loa infection will facilitate the diagnosis and treatment of loiasis in China. Methods The study targeted travelers who were infected with L. loa in endemic Africa regions and returned to Beijing between 2014 and 2023. Epidemiological, clinical, and biological data as well as treatment of these patients were collected. Results Total 21 cases were identified as L. loa infection based on their typical clinical manifestations and parasite finding. All cases had a history of travel to Africa for more than 6 months, most of them are the construction workers dispatched to West Africa with outdoor activities. Calabar swelling (n = 19; 90.5%) and pruritus (n = 11; 52.4%) were among the most common clinical symptoms followed by muscle pain (n = 7; 33.3%) and skin rash (n = 2; 9.5%). The adult worms were observed in the eyelid or subconjunctiva (n = 2; 9.5%) and subcutaneous tissues (n = 2; 9.5%). Although all patients presented with a high eosinophil count (> 0.52 × 109/L), only two cases displayed microfilariae in fresh venous blood and positive for filarial antigen. A cut section of adult worm was observed through biopsy on a skin nodule surrounded by lymphocytes, plasma cells and eosinophils. All subjects were positive in PCR targeting L. loa ITS-1. The constructed phylogenetic tree based on the amplified ITS-1 sequences identified their genetical relation to the L. Loa from Africa. All patients treated with albendazole and diethylcarbamazine were recovered without relapse. Conclusion This study provides useful information and guideline for physicians and researchers in non-endemic countries to diagnose and treat loiasis and L. loa infections acquired from endemic regions.

Conveyor belt is one of the most important transportation equipment in underground coal mines. Anchor rod, channel steel, large gangue, and other foreign objects that are mixed with the conveyor belt during conveying operations cause the belt to tear, clog the coal drop opening, and cause other serious safety incidents. They seriously affect the efficiency of transportation and even threaten the lives of workers. Aiming at the existing conveyor belt foreign object detection algorithm’s problems such as weak characterization of slender objects and poor weak semantic feature extraction, a foreign object detection algorithm based on low-level feature enhancement with Transformer is designed, notated as FET–YOLO. Firstly, to address the problem that existing detection networks have difficulty in extracting features of elongated objects, deformable convolution is introduced to enhance the network’s adaptability to the shape characteristics of elongated foreign objects, and the MobileViT module is used to increase the differentiation between the foreign objects and the background in the image, in order to extract features that are more consistent with the diversity of the elongated foreign objects and to weaken the interference of background noise.Secondly, constructing a low-level feature enhancement module LFEM, to improve the representation of weak semantic features of foreign objects in the detection network in order to reduce the probability of wrong detection.Finally, the introduction of gsconv reduces the information loss due to changes in the size of the feature map and ensures that the network extracts features efficiently while reducing the number of model parameters. The training set and validation set are produced by using the video of conveyor belt work in an underground coal mine. The proposed algorithm is compared to three other conveyor belt detection algorithms, and the experimental results show that the proposed algorithm can better solve the problems of poor detection of elongated objects and difficulty in weak semantic feature extraction in conveyor belt foreign object target detection, with higher detection accuracy. For images with a resolution size of 640×640, the performance metrics mAP@0.5 can be up to 0.875, mAP@0.5:0.95 can be up to 0.543, and the detection speed is 75 fps.

Abstract The study aimed to systematically compare the effects of psychological interventions on relieving fear of cancer recurrence (FCR) by a systematic review and network meta‐analysis (NMA). The relevant randomized controlled trials were searched from China National Knowledge Infrastructure, Wanfang Database, VIP Database for Chinese Technical Periodicals, Chinese Biomedical Literature Database, Cochrane Library, Pubmed, Web of Science, CINAHL, PsycINFO, and Embase. The retrieval time was from the establishment of each database to January 23, 2024. Review Manager 5.4 software was used to evaluate the quality of each literature that met the inclusion and exclusion criteria. Stata16.0 was used for NMA. Standardized mean differences (SMDs) of patients' FCR outcomes and 95% confidence intervals (CIs) were used to determine the effects. Inconsistency test, network map, surface under the cumulative rankings curve (SUCRA), comparison‐adjusted funnel plot were performed. A total of 41 articles were included, with 4056 patients and 15 psychological interventions. Six psychological interventions (NT, Narrative Therapy; ACT, Accept and Commitment Therapy; GT, Therapy based on Gratitude‐Expanded Behavior Theory; Blend Cognitive Behavior Therapy; PERMA, PERMA Therapy; CBT, Cognitive Behavior Therapy) were effective in alleviating FCR in the short term compared with usual care, whereas the effects of ACT, GT, and CBT were sustained up to more than 3 months postintervention. NT ranked as most likely to alleviate FCR, (SUCRA: 89.8%, SMD: −2.89, 95% CI: −4.08 to −1.69), followed by ACT (SUCRA: 88.1%, SMD: −2.83, 95% CI: −4.38 to −1.27) in short‐term effects. GT ranked as most likely to alleviate FCR in long‐term effects (SUCRA: 100%, SMD: −3.35, 95% CI: −4.21 to −2.50), followed by ACT (SUCRA: 88.9%, SMD: −1.64, 95% CI: −2.36 to −0.91). However, most of the quality of evidence for pairwise comparison was rated as “very low” to “low.” The evidence can help inform evidence‐based practice and guide healthcare providers in deciding on the most effective psychological interventions for FCR, which should also be viewed with caution due to the low level of the quality.

Abstract Background Development of hematopoietic stem and progenitor cells (HSPC) is a multi-staged complex process that conserved between zebrafish and mammals. Understanding the mechanism underlying HSPC development is a holy grail of hematopoietic biology, which is helpful for HSPC clinical application. Chromatin conformation plays important roles in transcriptional regulation and cell fate decision; however, its dynamic and role in HSPC development is poorly investigated. Methods We performed chromatin structure and multi-omics dissection across different stages of HSPC developmental trajectory in zebrafish for the first time, including Hi-C, RNA-seq, ATAC-seq, H3K4me3 and H3K27ac ChIP-seq. Results The chromatin organization of zebrafish HSPC resemble mammalian cells with similar hierarchical structure. We revealed the multi-scale reorganization of chromatin structure and its influence on transcriptional regulation and transition of cell fate during HSPC development. Nascent HSPC is featured by loose conformation with obscure structure at all layers. Notably, PU.1 was identified as a potential factor mediating formation of promoter-involved loops and regulating gene expression of HSPC. Conclusions Our results provided a global view of chromatin structure dynamics associated with development of zebrafish HSPC and discovered key transcription factors involved in HSPC chromatin interactions, which will provide new insights into the epigenetic regulatory mechanisms underlying vertebrate HSPC fate decision.

Abstract Background Diabetic sarcopenia is a disease‐related skeletal muscle disorder that causes progressive symptoms. The complete understanding of its pathogenesis is yet to be unravelled, which makes it difficult to develop effective therapeutic strategies. This study investigates how MFG‐E8 affects mitophagy and the protective role of D‐pinitol (DP) in diabetic sarcopenia. Methods In vivo, streptozotocin‐induced diabetic SAM‐R1 (STZ‐R1) and SAM‐P8 (STZ‐P8) mice (16‐week‐old) were used, and STZ‐P8 mice were administrated of DP (150 mg/kg per day) for 6 weeks. Gastrocnemius muscles were harvested for histological analysis including transmission electron microscopy. Proteins were evaluated via immunohistochemistry (IHC), immunofluorescence (IF), and western blotting (WB) assay. In vitro, advanced glycation end products (AGEs) induced diabetic and D‐galactose (DG) induced senescent C2C12 models were established and received DP, MFG‐E8 plasmid (Mover)/siRNA (MsiRNA), or 3‐MA/Torin‐1 intervention. Proteins were evaluated by IF and WB assay. Immunoprecipitation (IP) and co‐immunoprecipitation (CO‐IP) were used for hunting the interacted proteins of MFG‐E8. Results In vivo, sarcopenia, mitophagy deficiency, and up‐regulated MFG‐E8 were confirmed in the STZ‐P8 group. DP exerted protective effects on sarcopenia and mitophagy (DP + STZ‐P8 vs. STZ‐P8; all P

Abstracts Coinfusion of unrelated cord blood (UCB) units in haploidentical hematopoietic cell transplantation (haplo-HCT) (haplo-cord HCT) for hematopoietic malignancies showed promising results in previous reports, but the efficiency of haplo-cord HCT in acute myeloid leukemia (AML) still lacks sufficient evidence. This multicenter, randomized, phase 3 trial (ClinicalTrials.gov NCT03719534) aimed to assess the efficacy and safety of haplo-cord HCT in AML patients. A total of 268 eligible patients aged 18–60 years, diagnosed with measurable residual disease in AML (excluding acute promyelocytic leukemia), with available haploidentical donors and suitable for allotransplantation, were randomly allocated (1:1) to receive haplo-cord HCT (n = 134) or haplo-HCT (n = 134). The 3-year overall survival (OS) was the primary endpoint in this study. Overall median follow-up was 36.50 months (IQR 24.75–46.50). The 3-year OS of Haplo-cord HCT group was better than haplo-HCT group (80.5%, 95% confidence interval [CI]: 73.7–87.9 vs. 67.8% 95% CI 60.0–76.5, p = 0.013). Favorable progression-free survival (70.3%, 95% CI 62.6–78.8 vs. 57.6%, 95% CI 49.6–67.0, p = 0.012) and cumulative incidence of relapse (12.1%, 95% CI 12.0–12.2 vs. 30.3%, 95% CI 30.1–30.4, p = 0.024) were observed in haplo-cord HCT group. Grade 3–4 adverse events (AEs) within two years posttransplantation in the two groups were similar. Haplo-cord HCT patients exhibited a faster cumulative incidence of neutrophil recovery (p = 0.026) and increased T-cell reconstitution in the early period posttransplantation. Haplo-cord HCT can improve OS in AML patients without excessive AEs, which may exert additional benefits for recipients of haplo-HCT.

Introduction: A deadly gynecological cancer, ovarian cancer (OV), has a poor prognosis because of late-stage diagnosis and few targeted therapies. Addressing the tumor microenvironment (TME) in solid tumors has shown promise since it is crucial in promoting cancer progression. Methods: We obtained bulk RNA-seq data from TCGA-OV, GSE26712, GSE102073, and ICGC cohorts, as well as scRNA-seq data from EMTAB8107, GSE118828, GSE130000, and GSE154600 cohorts using the TISCH2 database. The ConsensusClusterPlus package was used to cluster the OV tumor tissues hierarchically to determine two molecularly different groups (C1 and C2). A total of ten different types of machine learning techniques with 101 combinations were used for prognostic model construction. Using eight TME algorithms integrated into the IOBR R package, the bulk RNA-seq dataset was analyzed. For in vitro experiments, OVCAR3 and SKOV3, two OV cell lines, were used. The migratory potential of the ovarian cancer cells was assessed using Transwell assay, while proliferation was assessed using CCK8 assay. Results: Based on TME-related gene set expression, two distinct molecular subgroups (C1 and C2) were identified through consensus clustering, with C1 showing higher TME activity. Further analysis indicated that C1 had increased cancer-associated fibroblasts (CAFs), M1 macrophages, and CD8+ T cells, suggesting a more activated and pro-inflammatory TME. Drug sensitivity analysis revealed that 5-Fluorouracil might be beneficial to C1 patients. Functional differences between C1 and C2 were identified, including cell adhesion, mononuclear cell differentiation, and leukocyte migration. A machine learning model was developed to create a TME-related prognostic signature, demonstrating strong prognostic capabilities across multiple datasets. High-risk patients showed a more immune-suppressive TME and higher tumor stemness. ScRNA-seq disclosed a highly activated TME-related signature in OV. Cancer cell lines had significantly higher SH2D1A mRNA expression than normal ovarian epithelial cells. We observed that SH2D1A knockdown in 2 ovarian cancer cell lines (OVCAR3 and SKOV3) reduced migration and proliferation through a series of in-vitro experiments. Conclusion: TME-associated genes were efficient in ovarian cancer molecular subtyping. A TME-based prognosis model was constructed for vigorous prognostic stratification efficacy across multiple datasets. Moreover, we identified a pivotal role of SH2D1A in promoting proliferation and migration in ovarian cancer.

Forest fire risk prediction is a crucial link in maintaining forest ecological security. Machine learning, due to its powerful non-linear modeling capabilities, has been widely applied in forest fire risk prediction research. However, existing studies often focus on the direct information provided by multiple environmental factor features when constructing the feature space, while overlooking the deeper information conveyed by feature cross-correlations. Additionally, fire risk prediction predominantly relies on single-model forecasting, exhibiting slightly insufficient generalization and stability in models. Model fusion algorithms (MFA) can combine the advantages of multiple models to compensate for this limitation. In this study, a machine learning framework, FC-StackGNB, combining feature crosses (FC) and model fusion, is proposed. This framework employs the FC method to analyze the temporal trends of various environmental factors influencing fire occurrence, constructing multiple seasonal cross features (SCFs) capable of effectively capturing the non-linear relationship between environmental factors and time. Moreover, the framework develops a Gaussian Naive Bayes (GNB) optimized stacking MFA to fully leverage the strengths of different ML algorithms. Results demonstrate that the introduction of SCFs effectively enhances the prediction performance of six machine learning models, with the mean values of five evaluation metrics (Accuracy, Precision, Recall, F1-score, and ROC_AUC) increasing by 1.58% to 6.30%. The fusion model constructed based on the StackGNB algorithm can effectively handle the multicollinearity issue of features, exhibiting significantly better prediction performance than single models, particularly in improving the Recall metric (increasing by around 3% and 5% compared to the top two ranked single models respectively), which signifies the model’s ability to predict positive samples (i.e., high-risk fire areas). The proposed modeling framework effectively enhances the robustness and prediction performance of the models, offering new modeling insights for subsequent research. This study holds significant importance for enhancing the level of forest fire risk warning.

ABSTRACT Microbial immigration is an ecological process in natural environments; however, the ecological trade-off mechanisms that govern the balance between species extinction and migration are still lacking. In this study, we investigated the mechanisms underlying the migration of diazotrophic communities from soil to leaves across six natural mangrove habitats in southern China. The results showed that the diazotrophic alpha and beta diversity exhibited significant regional and locational variations. The diazotrophic species pool gradually increased from the leaves to nonrhizosphere soil at each site, exhibiting a vertical distribution pattern. Mantel test analyses suggested that climate factors, particularly mean annual temperature, significantly influenced the structure of the diazotrophic community. The diazotrophic community assembly was mainly governed by dispersal limitation in soil and root samples, whereas dispersal limitation and ecological drift were dominant in leaves. Partial least squares path modeling revealed that the species pool and soil properties, particularly the oxidation-reduction potential and pH, were closely linked to the species-immigration ratio of diazotrophic communities. Our study provides novel insights for understanding the ecological trait diversity patterns and spread pathways of functional microbial communities between below- and aboveground habitats in natural ecosystems.IMPORTANCEEnvironmental selection plays key roles in microbial transmission. In this study, we have provided a comprehensive framework to elucidate the driving patterns of the ecological trade-offs in diazotrophic communities across large-scale mangrove habitats. Our research revealed that Bradyrhizobium japonicum, Marinobacterium lutimaris, and Agrobacterium tumefaciens were more abundant in root-associated soil than in leaves by internal and external pathways. The nonrhizospheric and rhizospheric soil samples harbored the most core amplicon sequence variants, indicating that these dominant diazotrophs could adapt to broader ecological niches. Correlation analysis indicated that the diversities of the diazotrophic community were regulated by biotic and abiotic factors. Furthermore, this study found a lower species immigration ratio in the soil than in the leaves. Both species pool and soil properties regulate the species-immigration mechanisms of the diazotrophic community. These results suggest that substantial species immigration is a widespread ecological process, leading to alterations in local community diversity across diverse host environments.

After more than 30 years of extensive investigation, impressive progress has been made in identifying the neural correlates of consciousness (NCC). However, the functional role of spatiotemporally distinct consciousness-related neural activity in conscious perception is debated. An influential framework proposed that consciousness-related neural activities could be dissociated into two distinct processes: phenomenal and access consciousness. However, though hotly debated, its authenticity has not been examined in a single paradigm with more informative intracranial recordings. In the present study, we employed a visual awareness task and recorded the local field potential (LFP) of patients with electrodes implanted in cortical and subcortical regions. Overall, we found that the latency of visual awareness-related activity exhibited a bimodal distribution, and the recording sites with short and long latencies were largely separated in location, except in the lateral prefrontal cortex (lPFC). The mixture of short and long latencies in the lPFC indicates that it plays a critical role in linking phenomenal and access consciousness. However, the division between the two is not as simple as the central sulcus, as proposed previously. Moreover, in 4 patients with electrodes implanted in the bilateral prefrontal cortex, early awareness-related activity was confined to the contralateral side, while late awareness-related activity appeared on both sides. Finally, Granger causality analysis showed that awareness-related information flowed from the early sites to the late sites. These results provide the first LFP evidence of neural correlates of phenomenal and access consciousness, which sheds light on the spatiotemporal dynamics of NCC in the human brain.

BackgroundTo assess the bioequivalence between Gan & Lee (GL) glargine U300 and Toujeo® regarding pharmacokinetics (PK), pharmacodynamics (PD), and safety in Chinese healthy male participants.MethodsA single-center, randomized, double-blind, single-dose, two-preparation, two-sequence, four-cycle repeated crossover design study was performed to compare GL glargine U300 and Toujeo® in 40 healthy participants. The primary PK endpoints were the area under the curve of glargine metabolites, M1 concentration from 0 to 24 hours (AUC0-24h), and the maximum glargine concentration within 24 hours post-dose (Cmax). The primary PD endpoints were the area under the glucose infusion rate (GIR) curve from 0 to 24 hours (AUCGIR.0-24h) and the maximum GIR within 24 hours post-dose (GIRmax).ResultsGL Glargine U300 demonstrated comparable PK parameters (AUC0–24h, Cmax, AUC0–12h, and AUC12–24h of M1) and PD responses [AUCGIR.0–24h, GIRmax, AUCGIR.0–12h, and AUCGIR.12–24h] to those of Toujeo®, as indicated by 90% confidence intervals ranging from 80% to 125%. No significant disparities in safety profiles were observed between the two treatment groups, and there were no reported instances of serious adverse events.ConclusionThe PK, PD, and safety of GL glargine U300 were bioequivalent to that of Toujeo®.Clinical trial registrationhttps://www.chinadrugtrials.org.cn/, identifier CTR20212419.

Treatments of inflammatory bowel disease (IBD) are diverse, but their efficacy is limited, and it is therefore urgent to find better therapies. Controlling mucosal inflammation is a must in IBD drug treatment. The occurrence of anti-tumor necrosis factor α (TNF-α) monoclonal antibodies has provided a safer and more efficacious therapy. However, this kind of treatment still faces failure in the form of loss of response. β-Carboline alkaloids own an anti-inflammatory pharmacological activity. While Kumujan B contains β-carboline, its biological activity remains unknown. In this study, we attempted to determine the anti-inflammatory effects of Kumujan B using both the TNF-α- induced in vitro inflammation and DSS-induced in vivo murine IBD models. Our data show that Kumujan B attenuated the expression of interleukin 1β (IL-1β) and interleukin 6 (IL-6) induced by TNF-α in mouse peritoneal macrophages. Kumujan B suppressed c-Jun N-terminal protein kinases (JNK) signaling, especially c-Jun, for anti-inflammatory response. Furthermore, Kumujan B promoted K11-linked ubiquitination and degradation of c-Jun through the proteasome pathway. In an in vivo study, Kumujan B inhibited the expression of IL-1β, IL-6, and TNF-α and improved the colon barrier function in dextran sulfate sodium salt (DSS)-induced experimental mice colitis. Kumujan B exhibited in vivo and in vitro anti-inflammatory effects, making it a potential therapeutic candidate for treating IBD.

Abstract Background The occurrence of massive retroperitoneal hematoma caused by intercostal artery bleeding is exceedingly uncommon. Case presentation A middle-aged male presented to the hospital after a fall. Computed tomography scan revealed a massive retroperitoneal hematoma without any evidence of organ or major vessel rupture. The angiogram revealed extravasation from a branch of the twelfth intercostal artery, and successful transcatheter arterial embolization was performed on this specific artery. Conclusions The possibility of intercostal artery rupture should be considered in cases of retroperitoneal hematomas, and accurate diagnosis can be achieved through imaging studies. Transcatheter arterial embolization represents an effective treatment modality.

Abstract Objective The preoperative identification of tumor grade in chondrosarcoma (CS) is crucial for devising effective treatment strategies and predicting outcomes. The study aims to build and validate a CT-based radiomics nomogram (RN) for the preoperative identification of tumor grade in CS, and to evaluate the correlation between the RN-predicted tumor grade and postoperative outcome. Methods A total of 196 patients (139 in the training cohort and 57 in the external validation cohort) were derived from three different centers. A clinical model, radiomics signature (RS) and RN (which combines significant clinical factors and RS) were developed and validated to assess their ability to distinguish low-grade from high-grade CS with area under the curve (AUC). Additionally, Kaplan-Meier survival analysis was applied to examine the association between RN-predicted tumor grade and recurrence-free survival (RFS) of CS. The predictive accuracy of the RN was evaluated using Harrell’s concordance index (C-index), hazard ratio (HR) and AUC. Results Size, endosteal scalloping and active periostitis were selected to build the clinical model. Three radiomics features, based on CT images, were selected to construct the RS. Both the RN (AUC, 0.842) and RS (AUC, 0.835) were superior to the clinical model (AUC, 0.776) in the validation set (P = 0.003, 0.040, respectively). A correlation between Nomogram score (Nomo-score, derived from RN) and RFS was observed through Kaplan-Meier survival analysis in the training and test cohorts (log-rank P

Background: Theta burst TUS (tbTUS) can induce increased cortical excitability in human, but how different sonication parameters influence the effects are still unknown. Objective: To examine how a range of sonication parameters, including acoustic intensity, pulse repetition frequency, duty cycle and sonication duration, influence the effects of tbTUS on human motor cortical excitability. Methods: 14 right-handed healthy subjects underwent 8 sessions with different tbTUS parameters in a randomized, cross-over design on separate days. The original tbTUS protocol was studied in one session and one parameter was changed in each of the seven sessions. To examine changes in cortical excitability induced by tbTUS, we measured the motor-evoked potential (MEP) amplitude, resting motor threshold, short-interval intracortical inhibition and intracortical facilitation, as well as short-interval intracortical facilitation before and up to 90 min after tbTUS. Results: All conditions increased MEP amplitudes except the condition with low acoustic intensity of 10 W/cm2. Pulse repetition frequency of 5 Hz produced higher MEP amplitudes compared to pulse repetition frequencies of 2 and 10 Hz. In addition, higher duty cycles (5%, 10%, and 15%) and longer sonication durations (40, 80, and 120 s) were associated with longer duration of increased MEP amplitudes. Resting motor threshold remained stable in all conditions. For paired-pulse TMS measures, tbTUS reduced short-interval intracortical inhibition and enhanced short-interval intracortical facilitation, but had no effect on intracortical facilitation. Conclusions: Ultrasound bursts repeated at theta (∼5 Hz) frequency is optimal to produce increased cortical excitability with the range of 2–10 Hz. Furthermore, there was a dose-response effect regarding duty cycle and sonication duration in tbTUS for plasticity induction. The aftereffects of tbTUS were associated with a shift of the inhibition/excitation balance toward less inhibition and more excitation in the motor cortex. These findings can be used to determine the optimal tbTUS parameters in neuroscience research and treatment of neurological and psychiatric disorders.

The importance of producing clean energy without any pollutants, including carbon dioxide and nitrogen oxides, has increased due to climate changes caused by global warming. Wind turbine can produce clean energy. To use a wind turbine, the feasibility of using a wind turbine in that area should be checked. In this research, energy, exergy, economic as well as exergy destruction analyses were conducted for the feasibility of using the Nordex wind turbine in Manjiil city. According to the meteorological organization report, the number of winds in Manjiil city was obtained, and the average speed, average power, energy efficiency, exergy efficiency, exergy destruction and economic cost were calculated using existing equations. According to the outcomes of this research, the average power produced, energy efficiency and exergy destruction are high in the months with high average wind speed, and these months have lower exergy efficiency and economic cost. The cost of electricity generated in October is 0.0194 S/kWh, which is the lowest. The cost of electricity generated in December is 0.0292$/kWh, which is the highest. Also, the effects of cut speed, rated speed and failure speed on wind turbine performance were investigated. As the nominal speed increases, exergy destruction, production entropy and economic cost increase and energy efficiency and exergy efficiency decrease.

The complementary intervention to modulate diabetes mellitus (DM) metabolism has recently brought the global attention, since DM has become among the global burden diseases. Where, several related pathways elevate the production of superoxide in consequences. For example, the flux of glycation-derived end products (AGEs) could lead to the deactivation of insulin signaling pathways. In that context, many vitamins and phytochemicals in natural sources have high antioxidant impacts that reduce oxidative stress and cell damages. These chemicals could be applied as bioactive antidiabetic agents. Their mode of actions could be from regulating the intracellular reactive oxygen species (ROS) which cause several pro-inflammatory pathways related to the oxidative stress (OS) and DM. Besides, they have a great potential to control the epigenetic mutations and hyperglycemia and help in back the blood glucose to the normal level. Therefore, the current review addresses the important role of natural functional antioxidants in DM management and its association with its OS complications.

Abstract Background Cardiovascular disease (CVD) is recognized as a primary and severe comorbidity in patients with type 2 diabetes mellitus (T2DM) and is also identified as a leading cause of mortality within this population. Consequently, the identification of novel biomarkers for the risk stratification and progression of CVD in individuals with T2DM is of critical importance. Methods This retrospective cohort study encompassed 979 patients diagnosed with T2DM, of whom 116 experienced CVD events during the follow‐up period. Clinical assessments and comprehensive blood laboratory analyses were conducted. Age‐ and sex‐adjusted Cox proportional hazard regression analysis was utilized to evaluate the association between lipoprotein‐associated phospholipase A2 (Lp‐PLA2), C1q/tumor necrosis factor‐related protein 3 (CTRP‐3), and the incidence of CVD in T2DM. The diagnostic performance of these biomarkers was assessed through receiver operating characteristic (ROC) curve analysis and the computation of the area under the curve (AUC). Results Over a median follow‐up of 84 months (interquartile range: 42 [32–54] months), both novel inflammatory markers, Lp‐PLA2 and CTRP‐3, and traditional lipid indices, such as low‐density lipoprotein cholesterol and apolipoprotein B, exhibited aberrant expression in the CVD‐afflicted subset of the T2DM cohort. Age‐ and sex‐adjusted Cox regression analysis delineated that Lp‐PLA2 (hazard ratio [HR] = 1.007 [95% confidence interval {CI}: 1.005–1.009], p

ABSTRACT: This study aimed to evaluate the effect of low molecular weight Acanthopanax polysaccharides on simulated digestion, probiotics, and intestinal flora of broilers in vitro. The experiments were carried out by H2O2-Vc degradation of Acanthopanax polysaccharides, in vitro simulated digestion to evaluate the digestive performance of polysaccharides with different molecular weights, in vitro probiotic evaluation of the probiotic effect of polysaccharides on lactobacilli and bifidobacteria, in vitro anaerobic fermentation and high-throughput sequencing of 16S rRNA genes to study the impact of Acanthopanax polysaccharides on the intestinal flora of broilers, and the effect of Acanthopanax polysaccharides on the short-chain fatty acids of intestines were determined by GC-MS method. The results showed that the molecular weight of Acanthopanax polysaccharide (ASPS) was 9,543 Da, and the molecular weights of polysaccharides ASPS-1 and ASPS-2 were reduced to 4,288 Da and 3,822 Da after degradation, and the particle sizes, PDIs, and viscosities were also significantly decreased. ASPS-1 has anti-digestive properties and better in vitro probiotic properties. The addition of ASPS-1 regulates the structure of intestinal microorganisms by regulating fecalibacterium to produce short-chain fatty acids, promoting the colonization of beneficial bacteria such as fecalibacterium, paraprevotella and diminishing the prevalence of detrimental bacteria such as Fusobacteria. Interestingly the ASPS-1 group found higher levels of Paraprevotella, which degraded trypsin in the gut, reducing inflammation, acted as a gut protector, and was influential in increasing the levels of acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, and total SCFAs in the fermented feces. Therefore, the degraded ASPS-1 can better regulate the structure of intestinal flora and promote the production of SCFAs, creating possibilities for its use as a potential prebiotic, which is conducive to the intestinal health of poultry.

ObjectivePropofol and etomidate are the most commonly used sedative agents in procedural sedation, each with its own advantages and disadvantages. However, there remains considerable controversy regarding the optimal ratio for the mixture of these two drugs, warranting further investigation. Therefore, this study aims to investigate the optimal ratio for combining propofol and etomidate during gastroscopy.MethodsThis study is a prospective, double-blinded, randomized controlled clinical trial. One hundred and sixty-two patients from July 2019 to December 2022 were evenly classified into three groups using a random number table as follows: (1) P group (propofol); (2) EP1 group (5 mL etomidate +10 mL propofol); (3) EP2 group (10 mL etomidate +10 mL), 54 patients per group. The medications, including a pre-sedation dose of 50 μg/kg dezocine followed by sedatives, ceasing when the patient’s eyelash reflex vanished, indicating adequate sedation. Mean arterial pressure (MAP), heart rate (HR), and peripheral oxygen saturation (SpO2) measurements taken before anesthesia (T1), immediately after the administration of sedatives (T2), immediately gastroscopic insertion (T3) and immediately recovery (T4) were determined. Additional, perioperative related outcomes and adverse events were also recorded.ResultsThe EP2 group exhibited a higher MAP at T2 compared to the P and EP1 groups (p

ABSTRACT Malignant central airway stenosis is treated with airway stent placement, but post-placement microbial characteristics remain unclear. We studied microbial features in 60 patients post-stent placement, focusing on changes during granulation tissue proliferation. Samples were collected before stent (N = 29), after stent on day 3 (N = 20), and after granulation tissue formation (AS-GTF, N = 43). Metagenomic sequencing showed significant respiratory tract microbiota changes with granulation tissue. The microbiota composition, dominated by Actinobacteria, Firmicutes, and Proteobacteria, was similar among the groups. At the species level, the AS-GTF group exhibited significant differences, with Peptostreptococcus stomatis and Achromobacter xylosoxidans enriched. Analysis based on tracheoesophageal fistula presence identified Tannerella forsythia and Stenotrophomonas maltophilia as the main differential species, enriched in the fistula subgroup. Viral and fungal detection showed Human gammaherpesvirus 4 and Candida albicans as the main species, respectively. These findings highlight microbiota changes after stent placement, potentially associated with granulation tissue proliferation, informing stent placement therapy and anti-infective treatment optimization.IMPORTANCEMalignant central airway stenosis is a life-threatening condition that can be effectively treated with airway stent placement. However, despite its clinical importance, the microbial characteristics of the respiratory tract following stent insertion remain poorly understood. This study addresses this gap by investigating the microbial features in patients with malignant central airway stenosis after stent placement, with a specific focus on microbial changes during granulation tissue proliferation. The findings reveal significant alterations in the diversity and structure of the respiratory tract microbiota following the placement of malignant central airway stents. Notably, certain bacterial species, including Peptostreptococcus stomatis and Achromobacter xylosoxidans, exhibit distinct patterns in the after-stent granulation tissue formation group. Additionally, the presence of tracheoesophageal fistula further influences the microbial composition. These insights provide valuable references for optimizing stent placement therapy and enhancing clinical anti-infective strategies.

BackgroundWest syndrome (WS) is a devastating epileptic encephalopathy with onset in infancy and early childhood. It is characterized by clustered epileptic spasms, developmental arrest, and interictal hypsarrhythmia on electroencephalogram (EEG). Hypsarrhythmia is considered the hallmark of WS, but its visual assessment is challenging due to its wide variability and lack of a quantifiable definition. This study aims to analyze the EEG patterns in WS and identify computational diagnostic biomarkers of the disease.MethodLinear and non-linear features derived from EEG recordings of 31 WS patients and 20 age-matched controls were compared. Subsequently, the correlation of the identified features with structural and genetic abnormalities was investigated.ResultsWS patients showed significantly elevated alpha-band activity (0.2516 vs. 0.1914, p

Summary: CD8+ T cells are rendered exhausted in tumor and chronic infection. Among heterogeneous exhausted T cells, a subpopulation of progenitor-like (Tpex) cells have been found important for long-term tumor or pathogen control and are also the main responders in immunotherapy. Using an RFP reporter mouse for the orphan nuclear receptor NR4A1, originally characterized as critical in T cell dysfunction, we discover that the reporter is highly expressed in Tpex cells in tumor and chronic infection. Enforced expression of Nr4a1 promotes Tpex cell accumulation, whereas tumor control is improved after Nr4a1 deletion, associated with increased effector function but decreased long-term maintenance of CD8+ T cells. Integrating chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) analysis, NR4A1 is found to bind and promote the expression of Tpex-related genes, as well as suppress terminal differentiation-associated genes. This study therefore has identified a key role of NR4A1 in Tpex regulation and provides a promising target for immunotherapy.

IntroductionTranscranial direct current stimulation (tDCS) has emerged as a therapeutic option to mitigate symptoms in individuals with autism spectrum disorder (ASD). Our study investigated the effects of a two-week regimen of tDCS targeting the left dorsolateral prefrontal cortex (DLPFC) in children with ASD, examining changes in rhythmic brain activity and alterations in functional connectivity within key neural networks: the default mode network (DMN), sensorimotor network (SMN), and dorsal attention network (DAN).MethodsWe enrolled twenty-six children with ASD and assigned them randomly to either an active stimulation group (n=13) or a sham stimulation group (n=13). The active group received tDCS at an intensity of 1mA to the left DLPFC for a combined duration of 10 days. Differences in electrical brain activity were pinpointed using standardized low-resolution brain electromagnetic tomography (sLORETA), while functional connectivity was assessed via lagged phase synchronization.ResultsCompared to the typically developing children, children with ASD exhibited lower current source density across all frequency bands. Post-treatment, the active stimulation group demonstrated a significant increase in both current source density and resting state network connectivity. Such changes were not observed in the sham stimulation group.ConclusiontDCS targeting the DLPFC may bolster brain functional connectivity in patients with ASD, offering a substantive groundwork for potential clinical applications.

Superpixel segmentation is an essential step of object-oriented remote sensing image classification; the accuracy of the superpixel segmentation boundary will directly affect the classification result. Most of the traditional superpixel segmentation algorithms rely on spectral similarity and spatial connectivity to construct superpixels. They cannot find the accurate boundary in the complex scenes, such as the spatial distribution of ground features being relatively broken, and large differences in the size and shape, especially long-thin shape and circular shape. Aiming at this problem, a superpixel segmentation algorithm based on an anisotropic diffusion model named ADS is proposed and applied to image classification. The anisotropic diffusion model originated in thermodynamics has excellent properties in which the diffusion is continuous and smooth and its diffusion speed depends on the medium, which provides convenience for smoothing homogeneous regions and establishing boundary constraints for different ground objects. With this advantage, the diffusion flux model is established to consider the influence of boundary factors and used to simulate the dissimilarity measure with boundary constraints between pixels and seed points by combining the traditional spectral and spatial distance. Then, the seed points of superpixel are optimized under the K-means framework. The effectiveness of the proposed algorithm is tested and verified with different spatial resolutions, such as Landsat 8 with 30 m, Sentinel-2 with 10 m, and SkySat with 0.5 m. A large number of experiments show that the proposed algorithm can better correct the superpixel boundary-fitting deviation problem in complex scenes and effectively promote the improvement of image classification accuracy.

Abstract Background Krascheninnikovia ceratoides, a perennial halophytic semi-shrub belonging to the genus Krascheninnikovia (Amarathaceae), possesses noteworthy ecological, nutritional, and economic relevance. This species is primarily distributed across arid, semi-arid, and saline-alkaline regions of the Eurasian continent, encompassing Inner Mongolia, Xinjiang, Qinghai, Gansu, Ningxia, and Tibet. Results We reported the comprehensive chloroplast (cp) genome of K. ceratoides, characterized by a circular conformation spanning 151,968 bp with a GC content of 36.60%. The cp genome encompassed a large single copy (LSC, 84,029 bp), a small single copy (SSC, 19,043 bp), and a pair of inverted repeats (IRs) regions (24,448 bp each). This genome harbored 128 genes and encompassed 150 simple sequence repeats (SSRs). Through comparative analyses involving cp genomes from other Cyclolobeae (Amarathaceae) taxa, we observed that the K. ceratoides cp genome exhibited high conservation, with minor divergence events in protein-coding genes (PCGs) accD, matK, ndhF, ndhK, ycf1, and ycf2. Phylogenetic reconstructions delineated K. ceratoides as the sister taxon to Atriplex, Chenopodium, Dysphania, and Suaeda, thus constituting a robust clade. Intriguingly, nucleotide substitution ratios (Ka/Ks) between K. ceratoides and Dysphania species for ycf1 and ycf2 genes surpassed 1.0, indicating the presence of positive selection pressure on these loci. Conclusions The findings of this study augment the genomic repository for the Amarathaceae family and furnish crucial molecular instruments for subsequent investigations into the ecological adaptation mechanisms of K. ceratoides within desert ecosystems.

Abstract Objective To evaluate the efficacy of the CT-based intratumoral, peritumoral, and combined radiomics signatures in predicting progression-free survival (PFS) of patients with chondrosarcoma (CS). Methods In this study, patients diagnosed with CS between January 2009 and January 2022 were retrospectively screened, and 214 patients with CS from two centers were respectively enrolled into the training cohorts (institution 1, n = 113) and test cohorts (institution 2, n = 101). The intratumoral and peritumoral radiomics features were extracted from CT images. The intratumoral, peritumoral, and combined radiomics signatures were constructed respectively, and their radiomics scores (Rad-score) were calculated. The performance of intratumoral, peritumoral, and combined radiomics signatures in PFS prediction in patients with CS was evaluated by C-index, time-dependent area under the receiver operating characteristics curve (time-AUC), and time-dependent C-index (time C-index). Results Eleven, 7, and 16 features were used to construct the intratumoral, peritumoral, and combined radiomics signatures, respectively. The combined radiomics signature showed the best prediction ability in the training cohort (C-index, 0.835; 95%; confidence interval [CI], 0.764–0.905) and the test cohort (C-index, 0.800; 95% CI, 0.681–0.920). Time-AUC and time C-index showed that the combined signature outperformed the intratumoral and peritumoral radiomics signatures in the prediction of PFS. Conclusion The CT-based combined signature incorporating intratumoral and peritumoral radiomics features can predict PFS in patients with CS, which might assist clinicians in selecting individualized surveillance and treatment plans for CS patients. Critical relevance statement Develop and validate CT-based intratumoral, peritumoral, and combined radiomics signatures to evaluate the efficacy in predicting prognosis of patients with CS. Key points • Reliable prognostic models for preoperative chondrosarcoma are lacking. • Combined radiomics signature incorporating intratumoral and peritumoral features can predict progression-free survival in patients with chondrosarcoma. • Combined radiomics signature may facilitate individualized stratification and management of patients with chondrosarcoma. Graphical Abstract

Currently, resting-state electroencephalography (rs-EEG) has become an effective and low-cost evaluation way to identify autism spectrum disorders (ASD) in children. However, it is of great challenge to extract useful features from raw rs-EEG data to improve diagnosis performance. Traditional methods mainly rely on the design of manual feature extractors and classifiers, which are separately performed and cannot be optimized simultaneously. To this end, this paper proposes a new end-to-end diagnostic method based on a recently emerged graph convolutional neural network for the diagnosis of ASD in children. Inspired by related neuroscience findings on the abnormal brain functional connectivity and hemispheric asymmetry characteristics observed in autism patients, we design a new Regional-asymmetric Adaptive Graph Convolutional Neural Network (RAGNN). It utilizes a hierarchical feature extraction and fusion process to learn separable spatiotemporal EEG features from different brain regions, two hemispheres, and a global brain. In the temporal feature extraction section, we utilize a convolutional layer that spans from the brain area to the hemisphere. This allows for effectively capturing temporal features both within and between brain areas. To better capture spatial characteristics of multi-channel EEG signals, we employ adaptive graph convolutional learning to capture non-Euclidean features within the brain’s hemispheres. Additionally, an attention layer is introduced to highlight different contributions of the left and right hemispheres, and the fused features are used for classification. We conducted a subject-independent cross-validation experiment on rs-EEG data from 45 children with ASD and 45 typically developing (TD) children. Experimental results have shown that our proposed RAGNN model outperformed several existing deep learning-based methods (ShaollowNet, EEGNet, TSception, ST-GCN, and CGRU-MDGN).

Osteoarthritis (OA) etiology is multifactorial, and its prevalence is growing globally. The Gut microbiota shapes our immune system and impacts all aspects of health and disease. The idea of utilizing probiotics to treat different conditions prevails. Concerning musculoskeletal illness and health, current data lack the link to understand the interactions between the host and microbiome. We report that S. thermophilus, L. pentosus (as probiotics), and γ-aminobutyric acid (GABA) harbour against osteoarthritis in vivo and alleviate IL-1β induced changes in chondrocytes in vitro. We examined the increased GABA concentration in mice's serum and small intestine content followed by bacterial treatment. The treatment inhibited the catabolism of cartilage and rescued mice joints from degradation. Furthermore, the anabolic markers upregulated and decreased inflammatory markers in mice knee joints and chondrocytes. This study is the first to represent GABA's chondrogenic and chondroprotective effects on joints and human chondrocytes. This data provides a foundation for future studies to elucidate the role of GABA in regulating chondrocyte cell proliferation. These findings opened future horizons to understanding the gut-joint axis and OA treatment. Thus, probiotic/GABA therapy shields OA joints in mice and could at least serve as adjuvant therapy to treat osteoarthritis.

Cartilage development is controlled by the highly synergistic proliferation and differentiation of growth plate chondrocytes, in which the Indian hedgehog (IHH) and parathyroid hormone-related protein-parathyroid hormone-1 receptor (PTHrP-PTH1R) feedback loop is crucial. The inositol-requiring enzyme 1α/X-box-binding protein-1 spliced (IRE1α/XBP1s) branch of the unfolded protein response (UPR) is essential for normal cartilage development. However, the precise role of ER stress effector IRE1α, encoded by endoplasmic reticulum to nucleus signaling 1 (ERN1), in skeletal development remains unknown. Herein, we reported that loss of IRE1α accelerates chondrocyte hypertrophy and promotes endochondral bone growth. ERN1 acts as a negative regulator of chondrocyte proliferation and differentiation in postnatal growth plates. Its deficiency interrupted PTHrP/PTH1R and IHH homeostasis leading to impaired chondrocyte hypertrophy and differentiation. XBP1s, produced by p-IRE1α-mediated splicing, binds and up-regulates PTH1R and IHH, which coordinate cartilage development. Meanwhile, ER stress cannot be activated normally in ERN1-deficient chondrocytes. In conclusion, ERN1 deficiency accelerates chondrocyte hypertrophy and cartilage mineralization by impairing the homeostasis of the IHH and PTHrP/PTH1R feedback loop and ER stress. ERN1 may have a potential role as a new target for cartilage growth and maturation.

Abstract In the study of brain functional connectivity networks, it is assumed that a network is built from a data window in which activity is stationary. However, brain activity is non-stationary over sufficiently large time periods. Addressing the analysis electroencephalograph (EEG) data, we propose a data segmentation method based on functional connectivity network structure. The goal of segmentation is to ensure that within a window of analysis, there is similar network structure. We designed an intuitive and flexible graph distance measure to quantify the difference in network structure between two analysis windows. This measure is modular: a variety of node importance indices can be plugged into it. We use a reference window versus sliding window comparison approach to detect changes, as indicated by outliers in the distribution of graph distance values. Performance of our segmentation method was tested in simulated EEG data and real EEG data from a drone piloting experiment (using correlation or phase-locking value as the functional connectivity strength metric). We compared our method under various node importance measures and against matrix-based dissimilarity metrics that use singular value decomposition on the connectivity matrix. The results show the graph distance approach worked better than matrix-based approaches; graph distance based on partial node centrality was most sensitive to network structural changes, especially when connectivity matrix values change little. The proposed method provides EEG data segmentation tailored for detecting changes in terms of functional connectivity networks. Our study provides a new perspective on EEG segmentation, one that is based on functional connectivity network structure differences.

The application of 3D reconstruction technology in building images has been a novel research direction. In such scenes, the reconstruction with proper building details remains challenging. To deal with this issue, I propose a KD-tree and random sample consensus-based 3D reconstruction model for 2D building images. Specifically, the improved KD-tree algorithm with the random sampling consistency algorithm has a better matching rate for the two-dimensional image data extraction of the stadium scene. The number of discrete areas in the stadium scene increases with the increase in the number of images. The sparse 3D models can be transformed into dense 3D models to some extent using the screening method. In addition, we carry out some simulation experiments to assess the performance of the proposed algorithm in this paper in terms of stadium scenes. The results reflect that the error of the proposal is significantly lower than that of the comparison algorithms. Therefore, it is proven that the proposal can be well-suitable for 3D reconstruction in building images.

Abstract Mazdutide is a once-weekly glucagon-like peptide-1 (GLP-1) and glucagon receptor dual agonist. We evaluated the efficacy and safety of 24-week treatment of mazdutide up to 6 mg in Chinese overweight adults or adults with obesity, as an interim analysis of a randomised, two-part (low doses up to 6 mg and high dose of 9 mg), double-blind, placebo-controlled phase 2 trial (ClinicalTrials.gov, NCT04904913). Overweight adults (body-mass index [BMI] ≥24 kg/m2) accompanied by hyperphagia and/or at least one obesity-related comorbidity or adults with obesity (BMI ≥ 28 kg/m2) were randomly assigned (3:1:3:1:3:1) to once-weekly mazdutide 3 mg, 4.5 mg, 6 mg or matching placebo at 20 hospitals in China. The primary endpoint was the percentage change from baseline to week 24 in body weight. A total of 248 participants were randomised to mazdutide 3 mg (n = 62), 4.5 mg (n = 63), 6 mg (n = 61) or placebo (n = 62). The mean percentage changes from baseline to week 24 in body weight were −6.7% (SE 0.7) with mazdutide 3 mg, −10.4% (0.7) with 4.5 mg, −11.3% (0.7) with 6 mg and 1.0% (0.7) with placebo, with treatment difference versus placebo ranging from −7.7% to −12.3% (all p

Abstract Background Patients with chronic obstructive pulmonary disease (COPD) commonly have coexisting comorbidities that contribute to higher exacerbation frequency, poorer health status, and increased all-cause mortality; however, there are only a few studies available on the sex discrepancy in the comorbidity distribution and outcomes among COPD patients, and there is limited information about the discrepancy in all-cause mortality between men and women. Methods Based on data from the U.S. National Health and Nutrition Examination Survey conducted between 2007 and 2012, we compared participants aged 40–79 years with spirometry-defined COPD to compare the prevalence of comorbidities between men and women. The survival of the subjects was documented, and the sex discrepancy was determined using Kaplan–Meier analysis. Comorbidities and all-cause mortality were analyzed by using a Cox proportional hazards model to determine their strength of association in different sex groups. Results Compared to men, women had a significantly higher prevalence of asthma (OR 1.93, 95% CI 1.46 to 2.57, p

Abstract Osteoarthritis (OA) is a full-joint, multifactorial, degenerative and inflammatory disease that seriously affects the quality of life of patients due to its disabling and pain-causing properties. ER stress has been reported to be closely related to the progression of OA. The inositol-requiring enzyme 1α/X-box-binding protein-1 spliced (IRE1α/XBP1s) pathway, which is highly expressed in the chondrocytes of OA patients, promotes the degradation and refolding of abnormal proteins during ER stress and maintains the stability of the ER environment of chondrocytes, but its function and the underlying mechanisms of how it contributes to the progression of OA remain unclear. This study investigates the role of IRE1α/ERN1 in OA. Specific deficiency of ERN1 in chondrocytes spontaneously resulted in OA-like cartilage destruction and accelerated OA progression in a surgically induced arthritis model. Local delivery of AdERN1 relieved degradation of the cartilage matrix and prevented OA development in an ACLT-mediated model. Mechanistically, progranulin (PGRN), an intracellular chaperone, binds to IRE1α, promoting its phosphorylation and splicing of XBP1u to generate XBP1s. XBP1s protects articular cartilage through TNF-α/ERK1/2 signaling and further maintains collagen homeostasis by regulating type II collagen expression. The chondroprotective effect of IRE1α/ERN1 is dependent on PGRN and XBP1s splicing. ERN1 deficiency accelerated cartilage degeneration in OA by reducing PGRN expression and XBP1s splicing, subsequently decreasing collagen II expression and triggering collagen structural abnormalities and an imbalance in collagen homeostasis. This study provides new insights into OA pathogenesis and the UPR and suggests that IRE1α/ERN1 may serve as a potential target for the treatment of joint degenerative diseases, including OA.

Abstract Recent studies linking adult height to diabetes risk remain controversial and few were from Asia. This study, therefore, aimed to explore the association of adult height with diabetes risk in a Chinese population. This retrospective cohort study was a secondary analysis of data from the DATADRYAD website, involving 211,172 non-diabetic individuals aged ≥ 20 years from the health screening program in China. Cox regression models were employed to evaluate hazard ratios (HRs) with 95% confidence interval (CI) of diabetes related to height. During an average 3.12-year follow-up, 4156 (1.97%) subjects reported developing diabetes. After adjusting for potential confounding factors, an inverse association of height with diabetes risk was observed among men and women [HR per 10 cm (95% CI), 0.78 (0.73–0.83) and 0.76 (0.68–0.86), respectively]. Moreover, subgroup analyses indicated the inverse association was only detected in individuals with aged

To enhance the nutritional value of Acanthopanax senticosus leaves (AL), a fermentation process was conducted using a probiotic Bacillus mixture, and the changes in chemical constituents and biological activities before and after fermentation were compared. A response surface methodology was employed to optimize the liquid fermentation conditions of AL based on their influence on polyphenol content. Non-targeted metabolomics analysis was performed using LC-MS/MS to reveal the differing profiles of compounds before and after fermentation. The results indicated that Bacillus subtilis LK and Bacillus amyloliquefaciens M2 significantly influenced polyphenol content during fermentation. The optimal fermentation conditions were determined to be a fermentation time of 54 h, a temperature of 39.6 °C, and an inoculum size of 2.5% (v/v). In comparison to unfermented AL, the total polyphenol and flavonoid contents, as well as the free radical scavenging capacities measured by DPPH and ABTS assays, and the activities of β-glucosidase and endo-glucanase, were significantly increased. The non-targeted metabolomics analysis identified 1348 metabolites, of which 829 were classified as differential metabolites. A correlation analysis between the differential metabolites of polyphenols, flavonoids, and antioxidant activity revealed that 13 differential metabolites were positively correlated with antioxidant activity. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of the differential metabolites identified 82 pathways, with two of the top 25 metabolic pathways related to flavonoids. This study explores the potential for enhancing the active ingredients and biological effects of AL through probiotic fermentation using Bacillus strains.

The existence of propane (C3H8) in a CO2-oil mixture has great potential for increasing CO2 solubility and decreasing minimum miscibility pressure (MMP). In this study, the enhanced solubility, reduced viscosity, and lowered MMP of CO2-saturated crude oil in the presence of various amounts of C3H8 have been systematically examined at the reservoir conditions. Experimentally, a piston-equipped pressure/volume/temperature (PVT) cell is first validated by accurately reproducing the bubble-point pressures of the pure component of C3H8 at temperatures of 30, 40, and 50 °C with both continuous and stepwise depressurization methods. The validated cell is well utilized to measure the saturation pressures of the CO2-C3H8-oil systems by identifying the turning point on a P-V diagram at a given temperature. Accordingly, the gas solubilities of a CO2, C3H8, and CO2-C3H8 mixture in crude oil at pressures up to 1600 psi and a temperature range of 25–50 °C are measured. In addition, the viscosity of gas-saturated crude oil in a single liquid phase is measured using an in-line viscometer, where the pressure is maintained to be higher than its saturation pressure. Theoretically, a modified Peng–Robinson equation of state (PR EOS) is utilized as the primary thermodynamic model in this work. The crude oil is characterized as both a single and multiple pseudo-component(s). An exponential distribution function, together with a logarithm-type lumping method, is applied to characterize the crude oil. Two linear binary interaction parameters (BIP) correlations have been developed for CO2-oil binaries and C3H8-oil binaries to accurately reproduce the measured saturation pressures. Moreover, the MMPs of the CO2-oil mixture in the presence and absence of C3H8 have been determined with the assistance of the tie-line method. It has been found that the developed mathematical model can accurately calculate the saturation pressures of C3H8 and/or CO2-oil systems with an absolute average relative deviation (AARD) of 2.39% for 12 feed experiments. Compared to CO2, it is demonstrated that C3H8 is more soluble in the crude oil at the given pressure and temperature. The viscosity of gas-saturated crude oil can decrease from 9.50 cP to 1.89 cP and the averaged MMP from 1490 psi to 1160 psi at 50 °C with the addition of an average 16.02 mol% C3H8 in the CO2-oil mixture.

One of the crucial factors influencing the growth and viability of larvae and juveniles is their opening diets. The objective of this study was to identify suitable initial feed options for M. macropterus larvae and juveniles. A total of 1200 newly hatched M. macropterus with an average weight of 18.3 mg and an average length of 11.58 mm were selected and randomly divided into four groups. The fish were fed with different opening diets, including rotifer, Artemia nauplii, Tubifex, and micro-diet from six days after hatching (dahs), respectively. Growth indices and activities of digestive enzymes were assessed at 10, 15, 20, 25, 30, 35, and 40 dahs. Histological examination of the structure of the digestive tract was performed at 40 dahs, while survival rates were also documented. The results demonstrated that different diets had no effect on the survival rate of larvae and juveniles of M. macropterus. The growth performance indices were ranked as follows: Tubifex group > Artemia nauplii group > micro-diet group > rotifer group. Remarkably, the Tubifex group exhibited superior growth performance, which was also reflected in the structure of the digestive tract and digestive enzyme activity. Therefore, it is recommended to include Tubifex in the diet of M. macropterus larvae and juvenile during the standardized farming process.

As data science advances, automated machine learning (AutoML) gains attention for lowering barriers, saving time, and enhancing efficiency. However, with increasing data dimensionality, AutoML struggles with large-scale feature sets. Effective feature selection is crucial for efficient AutoML in multi-task applications. This study proposes an efficient modeling framework combining a multi-stage feature selection (MSFS) algorithm and AutoSklearn, a robust and efficient AutoML framework, to address high-dimensional data challenges. The MSFS algorithm includes three stages: mutual information gain (MIG), recursive feature elimination with cross-validation (RFECV), and a voting aggregation mechanism, ensuring comprehensive consideration of feature correlation, importance, and stability. Based on multi-source and time series remote sensing data, this study pioneers the application of AutoSklearn for forest fire risk prediction. Using this case study, we compare MSFS with five other feature selection (FS) algorithms, including three single FS algorithms and two hybrid FS algorithms. Results show that MSFS selects half of the original features (12/24), effectively handling collinearity (eliminating 11 out of 13 collinear feature groups) and increasing AutoSklearn’s success rate by 15%, outperforming two FS algorithms with the same number of features by 7% and 5%. Among the six FS algorithms and non-FS, MSFS demonstrates the highest prediction performance and stability with minimal variance (0.09%) across five evaluation metrics. MSFS efficiently filters redundant features, enhancing AutoSklearn’s operational efficiency and generalization ability in high-dimensional tasks. The MSFS–AutoSklearn framework significantly improves AutoML’s production efficiency and prediction accuracy, facilitating the efficient implementation of various real-world tasks and the wider application of AutoML.

Abstract Vibrio is a salt‐tolerant heterotrophic bacterium that occupies an important ecological niche in marine environments. However, little is known about the contribution of resource diversity to the marine Vibrio diversity and community stability. In this study, we investigated the association among resource diversity, taxonomic diversity, phylogenetic diversity, and community stability of marine Vibrio in the Beibu Gulf. V. campbellii and V. hangzhouensis were the dominant groups in seawater and sediments, respectively, in the Beibu Gulf. Higher alpha diversity was observed in the sediments than in the seawater. Marine Vibrio community assembly was dominated by deterministic processes. Pearson's correlation analysis showed that nitrite (NO2−‐N), dissolved inorganic nitrogen (DIN), ammonium (NH4+‐N), and pH were the main factors affecting marine Vibrio community stability in the surface, middle, and bottom layers of seawater and sediment, respectively. Partial least‐squares path models (PLS‐PM) demonstrated that resource diversity, water properties, nutrients, and geographical distance had important impacts on phylogenetic and taxonomic diversity. Regression analysis revealed that the impact of resource diversity on marine Vibrio diversity and community stability varied across different habitats, but loss of Vibrio diversity increases community stability. Overall, this study provided insights into the mechanisms underlying the maintenance of Vibrio diversity and community stability in marine environments.

BackgroundThe correlation of clinical characteristics of cerebral palsy (CP) and the magnetic resonance imaging classification system (MRICS) for (CP) is inconsistent. Specifically, the variance in rehabilitation potential across MRICS remains underexplored.AimsTo investigate the clinical characteristics and potential for rehabilitation in children with CP based on MRICS.Materials and methodsChildren with CP admitted to the Department of Rehabilitation, Children's Hospital of Chongqing Medical University between 2017 and 2021 were included in the study. Qualified cases underwent a follow-up period of at least one year. The clinical characteristics of CP among different MRICS were analyzed, then the rehabilitation potential was explored by a retrospective cohort study.ResultsAmong the 384 initially enrolled children, the male-to-female ratio was 2.3:1, and the median age of diagnosis was 6.5 months (interquartile range: 4–12). The most prevalent MRICS categorization was predominant white matter injury (40.6%), followed by miscellaneous (29.2%) and predominant gray matter injury (15.6%). For the predominant white matter injury and miscellaneous categories, spastic diplegia emerged as the leading subtype of CP, with incidences of 59.6% and 36.6%, respectively, while mixed CP (36.7%) was the most common type in children with predominant gray matter. Notably, 76.4% of children with predominant white matter injury were classified as levels I–III on the gross motor function classification system (GMFCS), indicating significantly less severity than other groups (χ2 = 12.438, p = 0.013). No significant difference across MRICS categories was observed for the manual ability classification system (MACS) (H = 8.176, p = 0.085). Rehabilitation potential regarding fine motor function and adaptability based on Gesell assessment was dependent on MRICS over the follow-up period. Children with normal MRI scans exhibited superior rehabilitation outcomes. Commencing rehabilitation at an earlier stage produced consistent and beneficial results in terms of fine motor function and adaptability across all MRICS categories. Moreover, participants below 2 years of age demonstrated enhanced rehabilitation potential regarding fine motor outcomes and adaptability within the MRICS framework.ConclusionMRICS displayed a significant association with clinical characteristics and rehabilitation efficacy in children with CP.

Microorganisms, especially rare microbial species, are crucial in estuarine ecosystems for driving biogeochemical processes and preserving biodiversity. However, the understanding of the links between ecosystem multifunctionality (EMF) and the diversity of rare bacterial taxa in estuary ecosystems remains limited. Employing high-throughput sequencing and a variety of statistical methods, we assessed the diversities and assembly process of abundant and rare bacterioplankton and their contributions to EMF in a subtropical estuary. Taxonomic analysis revealed Proteobacteria as the predominant phylum among both abundant and rare bacterial taxa. Notably, rare taxa demonstrated significantly higher taxonomic diversity and a larger species pool than abundant taxa. Additionally, our findings highlighted that deterministic assembly processes predominantly shape microbial communities, with heterogeneous selection exerting a stronger influence on rare taxa. Further analysis reveals that rare bacterial beta-diversity significantly impacts to EMF, whereas alpha diversity did not. The partial least squares path modeling (PLS-PM) analysis demonstrated that the beta diversity of abundant and rare taxa, as the main biotic factor, directly affected EMF, while temperature and total organic carbon (TOC) were additional key factors to determine the relationship between beta diversity and EMF. These findings advance our understanding of the distribution features and ecological knowledge of the abundant and rare taxa in EMF in subtropical estuaries, and provide a reference for exploring the multifunctionality of different biospheres in aquatic environments.

Summary: Focusing attention in visual working memory (vWM) depends on the ability to filter distractors and expand the scope of targets. Although many properties of attention processes in vWM have been well documented, it remains unclear how the mechanisms of neurovascular coupling (NVC) function during attention processes in vWM. Here, we show simultaneous multimodal data that reveal the similar temporal and spatial features of attention processes during vWM. These similarities lead to common NVC outcomes across individuals. When filtering out distractors, the electroencephalography (EEG)-informed NVC displayed broader engagement across the frontoparietal network. A negative correlation may exist between behavioral metrics and EEG-informed NVC strength related to attention control. On a dynamic basis, NVC features exhibited higher discriminatory power in predicting behavior than other features alone. These results underscore how multimodal approaches can advance our understanding of the role of attention in vWM, and how NVC fluctuations are associated with actual behavior.