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Anthropogenic land greening is a vital strategy to combat the global warming crisis. However, the changing external environment and endowment factors may constrain the effectiveness of land greening. It remains unclear how to quantify and optimize land greening strategies scientifically. This article reviewed the theoretical foundations of land greening, pointing out that climate governance and human settlement quality improvement have gradually become the two core objectives of land greening since the 20th century. Multi-source and multi-scale experimental and observational surveys are important techniques for detecting and evaluating long-term land greening in the context of climate change, especially by forming experimental and observational networks. The theoretical mechanisms of interactions among climate, humans, and vegetation were also explored. For modeling approaches, hybrid modeling based on Earth system coupling theory may be the most promising but challenging approach. Four main challenges of scientific land greening were also discussed, including knowledge gaps related to land greening mechanisms, unclear multifaceted effects of land greening, lack of forward-looking quantitative assessment, and difficulties in evaluating synergies and trade-offs among assessment targets. Based on these, a strategic framework was proposed, including systematic observation, mechanism research, expectation assessment, and scientific planning for scientific greening programs in the Guangdong–Hong Kong–Macao Greater Bay Area. This review underscored the importance of proactively implementing land greening programs and provided guidelines for scientific greening based on cutting-edge theory and methods.

Previous studies of water use for coal-fired power generation may have overlooked inter-sectoral impacts in the supply chain. Indeed, to devise effective water conservation strategies during the ongoing energy transition, it is of utmost importance to analyze the sectoral water use structures and flows in the supply chain and identify the sources of water scarcity. Therefore, based on the power sector-split environmentally extended input‒output (EEIO) model and the life cycle assessment (LCA) idea, we comprehensively analyze the nexus between coal-fired power generation and water use from a sectoral perspective. Our findings reveal a complex and diverse water use structure in coal-fired power generation. The technology of production inherently determines the high intensity of water withdrawal, and the close intersectoral linkages, particularly with agriculture, construction, and some industrial sectors, in the production process result in an intricate web of indirect water withdrawal and blue water footprint (WF). Moreover, the grey WF, primarily sourced from coal mining and indirectly tied to tertiary industries, underscores critical areas for attention in water pollution management. Finally, water use in the coal-fired power sector is projected to remain at elevated levels in the short to medium term under various transition strategies. Following an in-depth exploration of the coal-fired power‒water use nexus, the findings can offer new perspectives and specific entry points for sustainable energy development and water resource management.

Introduction The adverse effects of secondhand smoke (SHS) exposure on health have been well established. Using the NHMS 2002: Adolescent Health Survey (AHS), this study attempts to evaluate the extent and factors associated with SHS exposure among Malaysian school-going adolescents. Methods We conducted the NHMS 2022: AHS to gather a representative sample of school-age teenagers. We employed a cross-sectional study design and a multi-stage sampling procedure. We utilized a pre-validated self-administered questionnaire to collect data from the selected respondents. The data analysis included adjusted odds ratios (AORs) with 95% confidence intervals (95% CIs). Additionally, we investigated the possible two-way interactions between the independent variables. Results The SHS prevalence was 42.0%. Exposure to secondhand smoke (SHS) was associated with male gender (AOR=1.28; 95 CI: 1.20–1.38), older age (AOR=1.46; 95% CI: 1.33–1.60), Malay (AOR=1.88; 95% CI: 1.49–2.37), Bumiputra Sabah (AOR=2.23; 95% CI: 1.67–2.99), Bumiputra Sarawak (AOR=2.43; 95% CI: 1.80–3.28), and Chinese ethnicity (AOR=2.89; 95 CI: % 2.30–3.64), as well as current smoking (AOR=2.78; 95% CI: 2.50–3.09), having separated or divorced parents (AOR=1.12; 95% CI: 1.02–1.23), and parental tobacco product use (AOR=4.75; 95% CI: 4.44–5.08). We found significant interactions between: 1) Age group with gender and ethnicity; 2) Gender and ethnicity; and 3) Parental smoking status with gender, response to tobacco use, parents' marital status, and ethnicity. Conclusions Parental characteristics, sociodemographic characteristics, and SHS exposure are strongly correlated. In addition, there is evidence of smoking displacement to the house from other areas by parents/guardians. This study offers a fresh perspective on how these variables influence the likelihood of SHS exposure for Malaysian school-age teenagers. More efforts should focus on parental variables and sociodemographic traits, especially parental smoking cessation support.

In the wake of the COVID-19 pandemic, global efforts to mitigate the spread of the virus have led to widespread lockdowns and movement restrictions. Earlier studies have reported a notable positive correlation between nitrogen dioxide (NO2) levels and mobility during the initial 2020 lockdowns. However, our explorative investigation in Southeast Asia observed that, despite their similar spatial distribution, NO2 does not consistently align with mobility patterns. This observation indicates the existence of additional influential factors apart from mobility contributing to NO2 variation, necessitating a more comprehensive examination. Subsequently, we developed a trained Multi-Layer Perceptron (MLP) model and leveraged SHapley Additive exPlanations (SHAP) values. Our analysis extends beyond mobility to encompass diverse potential factors such as travel modes and meteorological factors. The model results suggest that, while as expected mobility has a strong impact on NO2 column density, a more accurate prediction requires considering different travel modes (i.e. driving and walking). Furthermore, the study reveals that spatio-temporal heterogeneity and meteorological factors also play roles in shaping NO2 level. These findings emphasize the importance of integrating such multifaceted considerations in future NO2 study for a more accurate and holistic understanding.

Hepatic ischemia‒reperfusion injury (HIRI) is a common and inevitable complication of hepatic trauma, liver resection, or liver transplantation. It contributes to postoperative organ failure or tissue rejection, eventually affecting patient prognosis and overall survival. The pathological mechanism of HIRI is highly complex and has not yet been fully elucidated. The proposed underlying mechanisms include mitochondrial damage, oxidative stress imbalance, abnormal cell death, immune cell hyperactivation, intracellular inflammatory disorders and other complex events. In addition to serious clinical limitations, available antagonistic drugs and specific treatment regimens are still lacking. Therefore, there is an urgent need to not only clarify the exact etiology of HIRI but also reveal the possible reactions and bottlenecks of existing drugs, helping to reduce morbidity and shorten hospitalizations. We analyzed the possible underlying mechanism of HIRI, discussed various outcomes among different animal models and explored neglected potential therapeutic strategies for HIRI treatment. By thoroughly reviewing and analyzing the literature on HIRI, we gained a comprehensive understanding of the current research status in related fields and identified valuable references for future clinical and scientific investigations.

Obtaining high-performance cathodes is critical for protonic ceramic fuel cells (PCFCs), as cathode performance significantly impacts fuel cell performance. A full understanding of the interactions among the diverse properties of cathode materials would benefit cathode design. In this study, PrBaFe2O6−δ (PBF) was doped with various dopants, including cobalt (Co), Ni, Cu, Zn, and Mn. Experiments and first-principles calculations are used to study the key properties of dopant-modified PrBaFe2O6−δ, including oxygen vacancy (VO) creation, hydration ability, proton mobility, and oxygen reduction reaction (ORR) activity. There is no perfect dopant that can improve every property to its full potential. Instead, different dopants can impact different properties of the material. Co-dopant has the best cathode performance since it balances the material’s instinctive properties, even though it does not provide a significant advantage in the formation of VO. PCFC utilizing Co-doped PrBaFe2O6−δ cathode has a high performance of 1680 mW·cm−2 at 700 °C, which is greater than that of the other dopant-tailored PrBaFe2O6−δ cathodes reported in this study and is one of the largest ever recorded for PrBaFe2O6−δ-based cathodes for PCFCs. Co-doped PrBaFe2O6−δ cathode is further demonstrated to be robust, with excellent operational stability. This study not only provides a potential cathode candidate for PCFCs but also suggests an intriguing approach to cathode design by carefully examining and balancing different vital properties of the material.

ObjectiveTo address the problem of ultra-short baseline (USBL) relative navigation and positioning during the dynamic docking of an autonomous underwater vehicle (AUV) in shallow water, a compensated unscented particle filter (CUPF) algorithm based on a disturbance observer is proposed. MethodsThe CUPF algorithm compensates for missing values in the USBL data based on the dead reckoning model, estimates the unknown disturbances in the dynamic docking of the AUV using observer technology and filters outliers in the USBL data combined with the unscented particle filter to realize the estimation of the AUV's state. Results The lake trial data shows that the proposed CUPF algorithm can effectively remove outliers and fill in missing values for USBL positioning with a speed estimation error of less than 15% and computation time reduced by 57% compared with traditional methods. ConclusionsThe CUPF algorithm can improve the positioning accuracy of USBL while smoothing the AUV motion trajectory and state estimation by fully utilizing relative measurement information for AUV docking.

Celastrol is an active compound from the root of Tripterygium wilfordii Hook F that shows great potential in the treatment of inflammation, cancer, neurodegeneration, diabetes, and obesity. However, the clinical application of celastrol has been hindered by its low bioavailability and severe systemic toxicity. The aim of this review was to discuss the druggability, molecular targets, and nanocarrier delivery of the natural triterpenoid, celastrol, against chronic diseases. We sequentially investigated the physicochemical properties of celastrol using online tools (pkCSM and SwissADME), reviewed the recent studies on the molecular mechanisms underlying the therapeutic effects of celastrol, and examined the potential of nanoparticle-mediated delivery systems for safe and effective delivery of celastrol. The cancer-related targets and pathways involved were further predicted through network pharmacologic analysis. This review provides molecular insights into the pharmacologic activities and molecular mechanisms underlying celastrol, as well as useful information for the selection of nanocarrier drug delivery system for the clinical delivery of celastrol against various chronic diseases.

Abstract Background context Physical activities such as walking and climbing stairs are pervasive in human daily life. Individuals with scoliosis frequently encounter dysfunction in their muscle recruitment. Multiple studies have corroborated the presence of muscle dysfunction in individuals diagnosed with scoliosis. However, there is currently a noteworthy research gap regarding the exploration of changes in muscle characteristics and disparities from those observed in individuals without scoliosis during everyday activities, specifically stair climbing. Purpose This study aims to examine the unique patterns of muscle activity during daily life in individuals with scoliosis and distinguish the specific differences between scoliosis patients and the healthy controls. The findings of this study are significantly important for the future accurate assessment of scoliosis and the development of rehabilitation treatment plans. Study design Case–control study. Sample size Twenty eight idiopathic scoliosis patients and twenty eight controls. Outcome measures Root Mean Square(RMS), Maximum Voluntary Isometric Contraction(MVIC)%, RMS ratio(RMS convex / RMS concave). Methods The surface electromyography (sEMG) device used in this study was the Delsys Trigno, with a sampling frequency of 1500 Hz. It recorded the activation level, peak contraction, and average activation level of the erector spinae (at T6, T10, and L3 levels), gluteus maximus, gluteus medius, external oblique, and rectus abdominis muscles during three different types of locomotion for both the 28 individuals with idiopathic scoliosis and the 28 control participants. Results The movement patterns of the idiopathic scoliosis patients significantly differ from those of the normal population during level walking and ascending or descending stairs. In level walking, there is an asymmetry in the activation levels of the T6 and L3 erector spinae muscles, with lower activation on the convex side compared to the concave side. Similarly, during stair ascent, the activation of the T6 and T10 erector spinae muscles is asymmetric, with higher activation on the convex side than the concave side. Moreover, during stair descent, the activation of the T6 erector spinae muscle is asymmetric, with higher activation on the convex side than the concave side. Conclusions During level walking and stair activities, idiopathic scoliosis patients exhibit pronounced abnormal movement patterns that significantly differ from those of the control group. Under different activity conditions such as level walking, ascending and descending stairs, idiopathic scoliosis patients demonstrate abnormal muscle activation in different segments of the spine. It is crucial for clinicians to prioritize the symmetry of muscle activation in the spinal region of idiopathic scoliosis patients and consider incorporating symmetry training for these muscles.

Abstract Background Gram-negative bacteria are the main bacterial pathogens infecting Chinese giant salamanders (Andrias davidianus; CGS) in captivity and the wild, causing substantial economic losses in the CGS industry. However, the molecular mechanisms underlying pathogenesis following infection remain unclear. Results Spleen-derived macrophages from healthy CGS were isolated, cultured, and identified using density gradient centrifugation and immunofluorescence. A macrophage transcriptome database was established 0, 6, and 12 h post lipopolysaccharide stimulation using RNA-sequencing. In the final database 76,743 unigenes and 4,698 differentially expressed genes (DEGs) were functionally annotated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results showed that DEGs were concentrated in toll-like receptor–nuclear factor kappa B-related immune pathways. Ten DEGs were validated 12 h after lipopolysaccharide (LPS) stimulation. Although the common LPS recognition receptor toll-like receptor 4 was not activated and the key adaptor protein MyD88 showed no significant response, we observed significant up-regulation of the following adaptors: toll/interleukin-1 receptor domain-containing adaptor inducing interferon-β, tumour necrosis factor receptor-associated factor 6, and transforming growth factor-β activated kinase 1, which are located downstream of the non-classical MyD88 pathway. Conclusions In contrast to that in other species, macrophage activation in CGS could depend on the non-classical MyD88 pathway in response to bacterial infection. Our study provides insights into the molecular mechanisms regulating CGS antibacterial responses, with implications for disease prevention and understanding immune evolution in amphibians.

Abstract In recent times, automated detection of diseases from pathological images leveraging Machine Learning (ML) models has become fairly common, where the ML models learn detecting the disease by identifying biomarkers from the images. However, such an approach requires the models to be trained on a vast amount of data, and healthcare organizations often tend to limit access due to privacy concerns. Consequently, collecting data for traditional centralized training becomes challenging. These privacy concerns can be handled by Federation Learning (FL), which builds an unbiased global model from local models trained with client data while maintaining the confidentiality of local data. Using FL, this study solves the problem of centralized data collection by detecting deformations in images of Red Blood Cells (RBC) in a decentralized way. To achieve this, RBC data is used to train multiple Deep Learning (DL) models, and among the various DL models, the most efficient one is considered to be used as the global model inside the FL framework. The FL framework works by copying the global model’s weight to the client’s local models and then training the local models in client-specific devices to average the weights of the local model back to the global model. In the averaging process, direct averaging is performed and alongside, weighted averaging is also done to weigh the individual local model’s contribution according to their performance, keeping the FL framework immune to the effects of bad clients and attacks. In the process, the data of the client remains confidential during training, while the global model learns necessary information. The results of the experiments indicate that there is no significant difference in the performance of the FL method and the best-performing DL model, as the best-performing DL model reaches an accuracy of 96% and the FL environment reaches 94%-95%. This study shows that the FL technique, in comparison to the classic DL methodology, can accomplish confidentiality secured RBC deformation classification from RBC images without substantially diminishing the accuracy of the categorization. Finally, the overall validity of the classification results has been verified by employing GradCam driven Explainable AI techniques.

Abstract Cucumis melo L., commonly known as melon, is a crucial horticultural crop. The selection and breeding of superior melon germplasm resources play a pivotal role in enhancing its marketability. However, current methods for melon appearance phenotypic analysis rely primarily on expert judgment and intricate manual measurements, which are not only inefficient but also costly. Therefore, to expedite the breeding process of melon, we analyzed the images of 117 melon varieties from two annual years utilizing artificial intelligence (AI) technology. By integrating the semantic segmentation model Dual Attention Network (DANet), the object detection model RTMDet, the keypoint detection model RTMPose, and the Mobile-Friendly Segment Anything Model (MobileSAM), a deep learning algorithm framework was constructed, capable of efficiently and accurately segmenting melon fruit and pedicel. On this basis, a series of feature extraction algorithms were designed, successfully obtaining 11 phenotypic traits of melon. Linear fitting verification results of selected traits demonstrated a high correlation between the algorithm-predicted values and manually measured true values, thereby validating the feasibility and accuracy of the algorithm. Moreover, cluster analysis using all traits revealed a high consistency between the classification results and genotypes. Finally, a user-friendly software was developed to achieve rapid and automatic acquisition of melon phenotypes, providing an efficient and robust tool for melon breeding, as well as facilitating in-depth research into the correlation between melon genotypes and phenotypes.

Abstract To elucidate the expression profiles, methylation states, and clinicopathological significance of the PRDM gene family, focusing on the MECOM gene's role in uterine endometrial cancer (UCEC) and its molecular interactions with the TGF-beta signaling pathway. Our methodology combined detailed bioinformatics analyses using UALCAN and GEPIA with in vitro assessments in HEC-1-A cells. Techniques included CRISPR-Cas9 for gene editing and various cellular assays (CCK-8, flow cytometry, Transwell) to evaluate the effects of MECOM on cell proliferation, migration, and apoptosis, alongside Western blot analysis for protein regulation in the TGF-beta pathway. MECOM was upregulated in UCEC tissues, influencing tumor cell behavior significantly. Knockout studies demonstrated reduced proliferation and migration and increased apoptosis, while overexpression showed reverse effects. Mechanistically, MECOM modulated critical proteins within the TGF-beta pathway, impacting cell cycle dynamics and apoptotic processes. The PRDM gene family, particularly MECOM, plays a crucial role in the pathogenesis and progression of UCEC, suggesting its utility as a target for novel therapeutic interventions. Our findings offer valuable insights for future research and potential clinical application in managing uterine endometrial cancer.

Abstract Background Substantial evidence indicates that measuring leukocyte telomere length (LTL) is a useful tool that may be considered as a valuable biomarker of individual biological age, correlating with numerous chronic disorders. However, to date, there has been a lack of in-depth understanding regarding the current landscape and forthcoming developments in the LTL field. Therefore, this study aimed to utilize bibliometric methods to summarize the knowledge structure, current focus, and emerging directions in this field. Method Scientific publications on LTL spanning the period from 2000 to 2022 were acquired from the Web of Science Core Collection database. Several bibliometric tools including CiteSpace, VOSviewer, and an online website were utilized for bibliometric analysis. The primary evaluations encompassed investigating the major contributors and their collaborative relationships among countries/regions, institutions, and authors, conducting co-citation analyses of authors, journals, as well as reference, examining reference bursts, as well as performing co-occurrence analyses of keywords. Results There are 1818 papers with 66,668 citations identified. Both the annual publication and citation counts on LTL exhibited significant upward trends. The United States emerged as the most prominent contributor, as evidenced by the greatest volume of papers and the highest H-index value. University of California San Francisco and Aviv A were identified as the most productive institution and author in this domain, respectively. Reference analysis revealed that longitudinal study and mendelian randomization study are the most concerned research method in this field recently. Keywords analysis showed that the most concerned diseases in LTL fields were aging, inflammation, cardiovascular diseases, endocrine diseases, neurological and psychiatric diseases, and cancers. In addition, the following research directions such as “COPD”, “mendelian randomization”, “adiposity”, “colorectal cancer”, “National Health and Nutrition Examination Survey (NHNES)”, “telomerase reverse transcriptase”, “pregnancy” have garnered increasing attention in recent times and hold the potential to evolve into research foci in the foreseeable future. Conclusion This is the first bibliometric study that provides comprehensive overview of LTL research. The findings of this study could become valuable references for investigators to explore and address the current and emerging challenges in LTL research.

Abstract Background The failure of disease-modifying osteoarthritis drugs (DMOADs) trials lies mainly in the heterogeneity of the disease, which calls for a more precise population with specific progression and outcomes. This study aimed to determine whether and which MRI-based structural phenotype of knee osteoarthritis (KOA) is associated with short-term structural progression and subsequent total knee replacement (TKR). Methods A longitudinal study was conducted among participants with baseline Kellgren-Lawrence grade (KLG) ≥ 2 from the Osteoarthritis Initiative (OAI). The structural phenotypes at baseline were defined as subchondral bone, meniscus/cartilage and inflammatory phenotypes according to the MRI Osteoarthritis Knee Score (MOAKS). The primary outcome was the progression of structural abnormalities within 24 months and multivariable logistic regressions were applied to evaluate the associations. The secondary outcome was the incidence of TKR during 108 months. Cox regressions and Kaplan–Meier survival curves were used for the analysis. Results A total of 733 participants with KOA were finally included in our study, with 493 (67.3%) having the three main structural phenotypes. For the primary outcome, the subchondral bone phenotype (OR [95% CI]:1.71 [1.02, 2.83], 1.52 [1.06, 2.18], 1.65 [1.11, 2.42], respectively) and the inflammatory phenotype (OR [95% CI]: 1.69 [1.05, 2.74], 1.82 [1.31, 2.52], 2.15 [1.48, 3.14], respectively) were both associated with the short-term progression of joint space narrowing, osteophytes and sclerosis in 24 months, whereas the meniscus/cartilage phenotype was only associated with the progression of osteophytes and sclerosis. For the secondary outcome, the subchondral bone phenotype (HR [95% CI]: 1.71 [1.06–2.78]) and inflammatory phenotype (HR [95%CI]: 2.00 [1.02–2.67]) were associated with shorter time to subsequent TKR, but not the meniscus/cartilage phenotype. Besides, the cumulative effect when the structural phenotype overlapped was confirmed in both outcomes. Conclusions The subchondral bone phenotype and inflammatory phenotype were associated with the progression of joint space narrowing, osteophytes and sclerosis in 24 months, along with subsequent TKR in 108 months. Besides, additive effects of overlapped phenotypes were further determined. These phenotypes could serve as valuable screening tools for future clinical trials and provide guidance for risk evaluation.

Abstract The selective incorporation of a deuterium atom into small molecules with high selectivity is highly valuable for medical and chemical research. Unfortunately, this remains challenging due to the complete deuteration caused by commonly used hydrogen isotope exchange strategies. We report the development of a photocatalytic selective monodeuteration protocol utilizing C–C bond as the unconventional functional handle. The synergistic combination of radical-mediated C–C bond scission and deuterium atom transfer processes enables the effective constructions of benzylic CDH moieties with high selectivity for monodeuteration. The combinational use of a bisphosphonium photocatalyst, thiol catalyst, and CH3OD deuteration agent provides operationally simple conditions for photocatalytic monodeuteration. Moreover, the photoinduced electron transfer process of the bisphosphonium photocatalyst is elucidated through a series of spectroscopy experiments, identifying a peculiar back electron transfer process that can be regulated by subsequent nucleophilic additions.

Abstract Background Circular RNAs (circRNAs) have emerged as a prominent class of covalently closed single-stranded RNA molecules that exhibit tissue-specific expression and potential as biomarkers in extracellular vesicles (EVs) derived from liquid biopsies. Still, their characteristics and applications in EVs remain to be unveiled. Methods We performed a comprehensive analysis of EV-derived circRNAs (EV-circRNAs) using transcriptomics data obtained from 1082 human body fluids, including plasma, urine, cerebrospinal fluid (CSF), and bile. Our validation strategy utilized RT-qPCR and RNA immunoprecipitation assays, complemented by computational techniques for analyzing EV-circRNA features and RNA-binding protein interactions. Results We identified 136,327 EV-circRNAs from various human body fluids. Significantly, a considerable amount of circRNAs with a high back-splicing ratio are highly enriched in EVs compared to linear RNAs. Additionally, we discovered brain-specific circRNAs enriched in plasma EVs and cancer-associated EV-circRNAs linked to clinical outcomes. Moreover, we demonstrated that EV-circRNAs have the potential to serve as biomarkers for evaluating immunotherapy efficacy in non-small cell lung cancer (NSCLC). Importantly, we identified the involvement of RBPs, particularly YBX1, in the sorting mechanism of circRNAs into EVs. Conclusions This study unveils the extensive repertoire of EV-circRNAs across human biofluids, offering insights into their potential as disease biomarkers and their mechanistic roles within EVs. The identification of specific circRNAs and the elucidation of RBP-mediated sorting mechanisms open new avenues for the clinical application of EV-circRNAs in disease diagnostics and therapeutics.

Abstract Introduction Cognitive dysfunction is believed to be among the core features of Bipolar Depression(BD-D). However, its evaluation and available treatments are limited. Here, we conducted a longitudinal follow-up clinical trial using the THINC-it tool to evaluate temporal sensitivity to change over time in cognitive function among patients with bipolar depression from a Chinese cohort. It is helpful to verify whether the scale can continuously and reliably measure cognitive function in different time points and reduce the measurement error caused by time factors. Hope our findings could provide insights into the significance of the THINC-it tool as an iterative clinical cognitive evaluation tool. Methods A total of 120 patients with bipolar depression(40 males and 80 females, respectively) alongside 100 healthy controls(23 males and 77 females, respectively) were recruited in the study. All participants were interviewed for 8 weeks, using the 17-item Hamilton Depression Rating Scale (HAMD-17) and the Young Mania Rating Scale(YMRS). The primary dependent measure was the previously validated THINC-it tool, followed by psychometric analysis. Results Repeated measures of the THINC-it tool at baseline, one-week, and eight-week periods were conducted after controlling for age, gender, and education effects. Results from the general linear model revealed no significant time differences in variances(P > 0.05). Similarly, adjusting for confounding factors (age, gender, education, and HAMD-17 scores), results from the longitudinal analysis showed that there were no significant differences in cognitive impairment over time(P > 0.05). However, we found significant differences between BD-D and Healthy Control(HC) groups with regards to Spotter, Codebreaker, Trails, Perceived Deficits Questionnaire for Depression-5-items(PDQ-5-D), and THINC-it Total composite(P

Abstract Early T-cell precursor lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) is a distinct subtype of T-ALL/LBL, characterized by a poor response to initial chemotherapy, a high relapse rate, and an inferior outcome. The treatment options for ETP-ALL/LBL are currently limited, and there are no reported clinical trials available for ETP-ALL/LBL. From June 2018 to June 2022, we conducted a single-arm, single-center, phase 2 trial (NCT03553238) in newly diagnosed ETP-ALL/LBL (age 14–55). Patients (N = 54) received pediatric-inspired chemotherapy plus tucidinostat, which was orally administered once daily at a dosage of 10 mg from induction to consolidation therapy. The primary endpoint was 3 year event-free survival (EFS). Secondary endpoints were overall survival (OS), relapse-free survival (RFS), complete remission rate and adverse events. The composite complete remission (CRc, complete response [CR] plus complete response with incomplete blood count recovery [CRi]) rate and MRD negativity after induction therapy was 91% (49 of 54 patients) and 65% (35 of 54 patients), respectively. The MRD negativity after consolidation was achieved in 87% patients (47 of 54 patients). With a median follow-up of 39.3 months (IQR, 20.6 to 60.0), the 3 year EFS rate was 67.7% (95% CI 56.2–81.7), the 3 year OS rate was 71.5% (95% CI 60.2–84.9) and the 3 year RFS rate was 67.5% (95% CI 55.9–81.6). The most common grade 3–4 adverse events were neutropenia (94%), anemia (85%), thrombocytopenia (76%), and infection (53%). Tucidinostat plus pediatric regimen is an effective and well-tolerated regimen for new diagnosed ETP-ALL/LBL, with high CRc and MRD negativity rates, as well as encouraging survival outcomes.

Abstract Background Genetic factors, including the Hedgehog Interacting Protein (HHIP) gene, play a crucial role in Chronic Obstructive Pulmonary Disease (COPD) susceptibility. This study examines the association between HHIP gene polymorphisms and COPD susceptibility, phenotypes, and serum IL-17 and IL-18 levels in a Han Chinese population. Methods A case-control study was conducted with 300 COPD patients and 300 healthy controls in Chinese Han population. Participants underwent genotyping for HHIP gene polymorphisms, pulmonary function tests, and quantitative CT scans. DNA samples were sequenced using a custom chip targeting the HHIP gene. Serum IL-17 and IL-18 levels were measured by enzyme-linked immunosorbent assay. Associations between SNPs, COPD susceptibility, and phenotypes were analyzed using logistic and multiple linear regression models, adjusting for confounders. Results Our study identified the rs11100865 polymorphism in the HHIP gene as significantly associated with COPD susceptibility (OR 2.479, 95% CI 1.527–4.024, P = 2.39E-04) after screening 114 SNPs through rigorous quality control. Stratified analyses further indicated this association was particularly in individuals aged 60 or older. Serum levels of IL-17 and IL-18 were significantly elevated in COPD patients compared to controls, with rs11100865 showing a notable association with IL-18 levels (B = 49.654, SE = 19.627, P = 0.012). However, no significant associations were observed between rs11100865 and serum IL-17 levels, COPD-related imaging parameters, or clinical phenotypes. Conclusion This study identified a significant association between HHIP gene polymorphisms and COPD susceptibility in a Han Chinese population, with connections to inflammation, but found no significant associations between this SNP and COPD-related imaging or clinical phenotypes. Trial registration www.chictr.org.cn ID: ChiCTR2300071579 2023-05-18.

Abstract Background Persistent innate and adaptive immune responses in the brain contribute to the progression of Alzheimer’s disease (AD). APOE4, the most important genetic risk factor for sporadic AD, encodes apolipoprotein E4, which by itself is a potent modulator of immune response. However, little is known about the immune hub that governs the crosstalk between the nervous and the adaptive immune systems. Transient receptor potential vanilloid type 1 (TRPV1) channel is a ligand-gated, nonselective cation channel with Ca2+ permeability, which has been proposed as a neuroprotective target in AD. Methods Using Ca2+-sensitive dyes, dynamic changes of Ca2+ in microglia were measured, including exogenous Ca2+ uptake and endoplasmic reticulum Ca2+ release. The mRFP-GFP-tagged LC3 plasmid was expressed in microglia to characterize the role of TRPV1 in the autophagic flux. Transcriptomic analyses and flow cytometry were performed to investigate the effects of APOE4 on brain microglia and T cells from APOE-targeted replacement mice with microglia-specific TRPV1 gene deficiency. Results Both APOE4 microglia derived from induced pluripotent stem cells of AD patients and APOE4-related tauopathy mouse model showed significantly increased cholesterol biosynthesis and accumulation compared to their APOE3 counterparts. Further, cholesterol dysregulation was associated with persistent activation of microglia and elevation of major histocompatibility complex II-dependent antigen presentation in microglia, subsequently accompanied by T cell infiltration. In addition, TRPV1-mediated transient Ca2+ influx mitigated cholesterol biosynthesis in microglia by suppressing the transcriptional activation of sterol regulatory element-binding protein 2, promoted autophagic activity and reduced lysosomal cholesterol accumulation, which were sufficient to resolve excessive immune response and neurodegeneration in APOE4-related tauopathy mouse model. Moreover, microglia-specific deficiency of TRPV1 gene accelerated glial inflammation, T cell response and associated neurodegeneration in an APOE4-related tauopathy mouse model. Conclusions The findings provide new perspectives for the treatment of APOE4-dependent neurodegeneration including AD.

Abstract Atherosclerosis (AS) poses a significant threat to human life and health. However, conventional antiatherogenic medications exhibit insufficient targeting precision and restricted therapeutic effectiveness. Moreover, during the progression of AS, macrophages undergo polarization toward the proinflammatory M1 phenotype and generate reactive oxygen species (ROS) to accelerate the occurrence of inflammatory storms, and ingest excess lipids to form foam cells by inhibiting cholesterol efflux. In our study, we developed a macrophage membrane-functionalized hollow mesoporous manganese dioxide nanomedicine (Col@HMnO2-MM). This nanomedicine has the ability to evade immune cell phagocytosis, enables prolonged circulation within the body, targets the inflammatory site of AS for effective drug release, and alleviates the inflammatory storm at the AS site by eliminating ROS. Furthermore, Col@HMnO2-MM has the ability to generate oxygen autonomously by breaking down surplus hydrogen peroxide generated at the inflammatory AS site, thereby reducing the hypoxic microenvironment of the plaque by downregulating hypoxia-inducible factor (HIF-1α), which in turn enhances cholesterol efflux to inhibit foam cell formation. In an APOE−/− mouse model, Col@HMnO2-MM significantly reduced inflammatory factor levels, lipid storage, and plaque formation without significant long-term toxicity. In summary, this synergistic treatment significantly improved the effectiveness of nanomedicine and may offer a novel strategy for precise AS therapy.

Abstract Purpose This study aims to investigate the risk factors for lymph node metastasis (LNM) in synchronous multiple primary lung cancer (sMPLC) using clinical and CT features, and to offer guidance for preoperative LNM prediction and lymph node (LN) resection strategy. Materials and methods A retrospective analysis was conducted on the clinical data and CT features of patients diagnosed with sMPLC at the Third Affiliated Hospital of Kunming Medical University from January 1, 2018 to December 31, 2022. Patients were classified into two groups: the LNM group and the non-LNM (n-LNM) group. The study utilized univariate analysis to examine the disparities in clinical data and CT features between the two groups. Additionally, multivariate analysis was employed to discover the independent risk variables for LNM. The diagnostic efficacy of various parameters was evaluated using the receiver operating characteristic (ROC) curve. Results Among the 688 patients included in this study, 59 exhibited LNM. Univariate analysis revealed significant differences between the LNM and n-LNM groups in terms of gender, smoking history, CYFRA21-1 level, CEA level, NSE level, lesion type, total lesion diameter, main lesion diameter, spiculation sign, lobulation sign, cavity sign, and pleural traction sign. Logistic regression identified CEA level (OR = 1.042, 95%CI: 1.009-1.075), lesion type (OR = 9.683, 95%CI: 3.485-26.902), and main lesion diameter (OR = 1.677, 95%CI: 1.347-2.089) as independent predictors of LNM. The regression equation for the joint prediction was as follows: logit(p)= -7.569+0.041*CEA level +2.270* lesion type +0.517* main lesion diameter.ROC curve analysis showed that the AUC for CEA level was 0.765 (95% CI, 0.694–0.836), for lesion type was 0.794 (95% CI, 0.751–0.838), for main lesion diameter was 0.830 (95% CI, 0.784–0.875), and for the combine predict model was 0.895 (95% CI, 0.863–0.928). Conclusion The combination of clinical and imaging features can better predict the status of LNM of sMPLC, and the prediction efficiency is significantly higher than that of each factor alone, and can provide a basis for lymph node management decision.

Abstract Background Triple‐negative breast cancer (TNBC), which is so called because of the lack of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2) receptors on the cancer cells, accounts for 10%–15% of all breast cancers. The heterogeneity of the tumor microenvironment is high. However, the role of plasma cells controlling the tumor migration progression in TNBC is still not fully understood. Methods We analyzed single‐cell RNA sequencing data from five HER2 positive, 12 ER positive/PR positive, and nine TNBC samples. The potential targets were validated by immunohistochemistry. Results Plasma cells were enriched in TNBC samples, which was consistent with validation using data from The Cancer Genome Atlas. Cell communication analysis revealed that plasma cells interact with T cells through the intercellular adhesion molecule 2–integrin–aLb2 complex, and then release interleukin 1 beta (IL1B), as verified by immunohistochemistry, ultimately promoting tumor growth. Conclusion Our results revealed the role of plasma cells in TNBC and identified IL1B as a new prognostic marker for TNBC.

Abstract Background Blocking the RhoA/ROCK II/MLC 2 (Ras homolog gene family member A/Rho kinase II/myosin light chain 2) signaling pathway can initiate neuroprotective mechanisms against neurological diseases such as stroke, cerebral ischemia, and subarachnoid hemorrhage. Nevertheless, it is not clear whether and how disrupting the RhoA/ROCK II/MLC 2 signaling pathway changes the pathogenic processes of the blood–brain barrier (BBB) after intracerebral hemorrhage (ICH). The present investigation included the injection of rat caudal vein blood into the basal ganglia area to replicate the pathophysiological conditions caused by ICH. Methods Scalp acupuncture (SA) therapy was performed on rats with ICH at the acupuncture point “Baihui”‐penetrating “Qubin,” and the ROCK selective inhibitor fasudil was used as a positive control to evaluate the inhibitory effect of acupuncture on the RhoA/ROCK II/MLC 2 signaling pathway. Post‐assessments included neurological deficits, brain edema, Evans blue extravasation, Western blot, quantitative polymerase chain reaction, and transmission electron microscope imaging. Results We found that ROCK II acts as a promoter of the RhoA/ROCK II/MLC 2 signaling pathway, and its expression increased at 6 h after ICH, peaked at 3 days, and then decreased at 7 days after ICH, but was still higher than the pre‐intervention level. According to some experimental results, although 3 days is the peak, 7 days is the best time point for acupuncture treatment. Starting from 6 h after ICH, the neurovascular structure and endothelial cell morphology around the hematoma began to change. Based on the changes in the promoter ROCK II, a 7‐day time point was selected as the breakthrough point for treating ICH model rats in the main experiment. The results of this experiment showed that both SA at “Baihui”‐penetrating “Qubin” and treatment with fasudil could improve the expression of endothelial‐related proteins by inhibiting the RhoA/ROCK II/MLC 2 signaling pathway and reduce neurological dysfunction, brain edema, and BBB permeability in rats. Conclusion This study found that these experimental data indicated that SA at “Baihui”‐penetrating “Qubin” could preserve BBB integrity and neurological function recovery after ICH by inhibiting RhoA/ROCK II/MLC 2 signaling pathway activation and by regulating endothelial cell–related proteins.

Abstract Classifying emission reduction zones on different scales has important implications for the ecological protection and high‐quality development of the Yellow River Basin. Based on remote sensing data and a light‐carbon conversion model, carbon footprints at provincial, municipal, and county scales in the Yellow River Basin are measured. The spatiotemporal evolution critical paths of carbon footprints at the three spatial scales are compared and classified into different zones using spatiotemporal evolution analysis methods. The conclusions are as follows: (1) The carbon footprint increased over the years. The spatial distributions of carbon footprints at the three scales are not only consistent but also different. The study of carbon footprints at the county scale is more conducive to the summary of the spatiotemporal evolution and the formulation of detailed emission reduction schemes. (2) Four provinces, 48 cities, and 373 counties are designated as a “core protected zone”; three provinces, 29 cities, and 177 counties are designated as a “strictly governed zone”; one province, 12 cities, and 47 counties are designated as a “key restricted zone”; four cities and 39 counties are designated as an “alert diffusion zone.” (3) The agglomeration expansion trend and the spillover effect of high‐carbon footprint units at the county scale are more obvious. Further enhancement of the path‐locking characteristics of the carbon footprints of counties will make governance more difficult. Effective governance of carbon footprint at the county scale is of urgent concern. These results provide scientific evidence for multiscale carbon emission control and zoning policy formulation in the Yellow River Basin.

Abstract In this study, nonaxisymmetric endwall contouring technology is employed as a passive control strategy to enhance the stable operating range of a centrifugal compressor with an asymmetric volute. The endwall contouring method is applied to the hub‐side wall of the vaned diffuser within a centrifugal compressor stage. Instead of utilizing a flat hub as the baseline diffuser, various diffuser configurations featuring hub‐side contoured endwalls are explored, with adjustments in the peak radial position and peak height of the convex and concave profiles. Numerical simulations are conducted to evaluate the performance of the centrifugal compressor stage with both the baseline and contoured vaned diffusers. The investigation explores the underlying flow control mechanisms and establishes the effective endwall contouring guidelines. The findings highlight the effectiveness of endwall contouring in enhancing the stable operating range of centrifugal compressors. Notably, a substantial enhancement of 15.1% in the stable operating range is achieved by employing the contoured diffuser with the peak radial position near the vane leading edge (LE) and the peak height at 20% of the vane height. The endwall contoured diffusers reduce the positive LE incidence angles to direct the fluid toward the suction side (SS), and increase the radial velocity near the SS to suppress the hub‐suction corner separations in the diffuser passages near the volute tongue. These improvements collectively contribute to the enhancement of diffuser flow characteristics. Finally, a set of effective endwall contouring guidelines is proposed to guide the endwall contouring design for enhancing the stable operating range of centrifugal compressors.

This is an article in the field of mineral processing engineering. The volcanic bertrandite ore used in this study was obtained from Xinjiang, China. Mineral and multi-elemental compositions were characterized to identify the disseminated grain size and occurrence of valuable minerals, and systematic flotation tests were carried out. In the presence of activator sodium fluoride in the grinding process, grinding fineness and reagents dosages were optimized. It was shown that with grinding fineness of -0.074 mm 85%, dosages of pH regulator sodium carbonate, inhibitor sodium silicate, and collector sodium oleate of 1 500 g/t, 1 000 g/t, and 2 000 g/t respectively, a coarse concentrate was generated with BeO grade of 6.03% and recovery of 97.02%.This coarse concentrate was reground to -0.045 mm 90% and enriched by two cleaning stages yielding a clean concentrate assaying 8.40% BeO with a BeO recovery of 78.09%, while BeO content of the coarse tailing was degraded to 0.003% after one scavenger flotation. The closed-circuit flotation test of "one-coarse, one-scavenger, three-cleaning separation, and integrated middling recirculated to coarse separation" has generated a concentrate with BeO grade of 8.12% and recovery of 80.99%, meeting the requirements of beryllium process for BeO content in raw materials .

Yu Yang,1,2 Shuqi Wang,1,3 Boying Jia,1,3 Shuchun Chen1,3 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 3Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, 348 heping West Road, Shijiazhuang, Hebei, 050051, People’s Republic of China, Tel/Fax +86 311 85988406, Email chenshuc2014@163.comPurpose: To investigate the relationship between the triglyceride-glucose (TyG) index and pulmonary function metrics among the general population undergoing health examinations.Materials and Methods: The enrollment totaled 696 participants. Fasting triglycerides and glucose levels were used to calculate the TyG index. Participants were divided into two categories according to their median TyG: one with high TyG and the other with low TyG. A portable spirometer was used to assess lung function. Fundamental clinical features and lung function indicators were compared between the two groups, and the relationship between the TyG index and lung function parameters was explored.Results: Compared with the low TyG group, the high TyG group exhibited significantly reduced levels of FEV1/FVC, FVC% pred, FEV1% pred, FEV3% pred, FEV3/FVC, FEF75, FEF75% pred, FEF25-75% pred, and MVV% pred, suggesting poor pulmonary function. The TyG index was significantly inversely correlated with multiple pulmonary function metrics, including FVC% pred, FEV1% pred, FEV3% pred, FEV1/FVC, FEV3/FVC, FEF75, FEF75% pred and FEF25-75% pred, which persisted even after accounting for confounding variables.Conclusion: In summary, the present study establishes a correlation between the TyG index and some lung function indicators, offering a new indicator of metabolic abnormalities related to lung functionality.Keywords: triglyceride-glucose index, lung function, insulin resistance, FEV1, FVC

Xiaosu Guo,1– 4,* Huimin Shi,1,2,* Yuteng Sun,1 Yuan Xing,1– 3 Xin Guo,1– 3 Zhiyuan Shen,1– 3 Mengyi Zheng,1 Yaxin Zhang,1 Yicun Jia,1 Ye Li,1 Junqiang Bao,1,2 Shujuan Tian1– 3 1Department of Neurology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Neurology, Hebei Hospital, Xuanwu Hospital, Capital Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3Neuromedical Technology Innovation Center of Hebei Province, Shijiazhuang, Hebei, People’s Republic of China; 4Brain Aging and Cognitive Neuroscience Laboratory of Hebei Province, Shijiazhuang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shujuan Tian; Junqiang Bao, Department of Neurology, The First hospital of Hebei Medical University, Shijiazhuang, Hebei, 050030, People’s Republic of China, Tel +86-0311-87156309, Email 57203005@hebmu.edu.cn; 57903004@hebmu.edu.cnPurpose: To summarize the clinical manifestations, laboratory findings, and magnetic resonance imaging (MRI) characteristics of anti-leucine-rich glioma-inactivated 1 (LGI1) antibody encephalitis (anti-LGI1 antibody encephalitis) and explore the electroencephalogram (EEG) features.Patients and Methods: We retrospectively analyzed the medical history of 16 patients diagnosed with anti-LGI1 antibody encephalitis at the First Hospital of Hebei Medical University from 2021 to 2023. EEGs of patients with anti-LGI1 antibody encephalitis and healthy individuals were analyzed. Based on Video-EEG signal analysis of EEG δ, θ, α, β frequency bands, weighted phase lag index values were calculated to form brain network matrices, studying differences in coherence between brain regions of patients with anti-LGI1 antibody encephalitis and healthy individuals.Results: Patients with anti-LGI1 antibody encephalitis often presented with subacute onset seizures and cognitive decline. Routine test of cerebrospinal fluid was mostly normal. Serum testing revealed hyponatremia in 62.50% of patients, along with positive serum antinuclear antibodies, decreased vitamin B12, and abnormal cytokines such as interleukin-6. Head MRI revealed abnormal lesions related to the disease in seven cases (43.75%), mainly located in the unilateral or bilateral frontal and temporal lobes of the hippocampus. The EEG mainly showed generalized and focal slow waves, sometimes with focal discharges. Brain network functional connectivity analysis found a significant weakening of functional connections in the frontal-temporal lobe in the δ and β frequency bands. Intravenous pulse corticosteroids and intravenous immunoglobulin are first-line immunotherapies for anti-LGI1 antibody-related encephalitis. The disease recovery and cognitive decline improved in most patients.Conclusion: Anti-LGI1 antibody encephalitis is characterized by seizures and cognitive dysfunction. Serum may show abnormalities in immune indicators such as cytokines. Head MRI mainly reveals abnormal signals in the frontal-temporal lobes and the hippocampus. EEG brain network connectivity analysis reveals characteristic weakening of functional connections in the frontal-temporal lobe in the δ and β frequency bands.Keywords: anti-LGI1 antibody encephalitis, epilepsy, electroencephalogram, brain network functional connectivity, immunotherapy

With rapid development and maturity of single-cell measurements, single-cell biology and pathology has become an emerging discipline to understand the disease. However, it is important to address concerns raised by clinicians as to how to apply single-cell measurements for clinical practice, translate the signals of single-cell systems biology into determination of clinical phenotype, and predict patient response to therapies. This paper proposes a new system coined as the clinical artificial intelligent single-cell (caiSC) with the dynamic generator of clinical single-cell informatics, artificial intelligent analyzers, molecular multimodal reference boxes, clinical inputs and outputs, and AI-based computerization. This system provides reliable and rapid information for impacting clinical diagnoses, monitoring, and prediction of the disease at the single-cell level. The caiSC represents an important step and milestone to translate the single-cell measurement into clinical application, assist clinicians’ decision-making, and improve the quality of medical services. There is increasing evidence to support the possibility of the caiSC proposal, since the corresponding biotechnologies associated with caiSCs are rapidly developed. Therefore, we call the special attention and efforts from various scientists and clinicians on the caiSCs and believe that the appearance of the caiSCs can shed light on the future of clinical molecular medicine.

Abstract Background Micrococcus antarcticus (M. antarcticus) is an aerobic Gram-positive spherical actinobacterium that was initially isolated from Chinese Great-Wall station in Antarctica in 2000. M. antarcticus was considered to be of low pathogenicity, no previous cases of human infection by this organism have been reported. Here we describe the first report with community-acquired pneumonia (CAP) caused by M. antarcticus. Case presentation An 87-year-old female was presented to the Central Hospital of Wuhan in November 2023 with a chief complaint of cough, sputum production, and chest tightness for 2 weeks. Microbial culture of the patient’s bronchoalveolar lavage fluid (BALF) and identification of the isolates using Matrix-assisted laser desorption ionization/time of flight mass spectrometry (MALDI-TOF MS) and 16S rRNA gene sequencing revealed M. antarcticus infection. Combined with clinical symptoms, laboratory and imaging examination, the patient was diagnosed with CAP. Then cefoperazone/sulbactam and levofloxacin was administrated, the patient’s condition was improved and she was discharged after a week after admission, no abnormalities were detected during a 5-month follow-up. Conclusions This case highlights that M. antarcticus, first identified from a patient with CAP, is an extremely rare pathogenic microorganism. Clinicians should be aware of its potential as a pathogen in the diagnosis and treatment of CAP.

Abstract The human endometrium is a highly regenerative tissue capable of undergoing scarless repair during the menstruation and postpartum phases. This process is mediated by endometrial adult stem/progenitor cells. During the healing of endometrial injuries, swift reepithelization results in the rapid covering of the wound surface and facilitates subsequent endometrial restoration. The involvement of endogenous endometrial epithelial stem cells, stromal cells, and bone marrow-derived cells in the regeneration of the endometrial epithelium has been a subject of prolonged debate. Increasing evidence suggests that the regeneration of the endometrial epithelium mainly relies on epithelial stem cells rather than stromal cells and bone marrow-derived cells. Currently, no consensus has been established on the identity of epithelial stem cells in the epithelial compartment. Several markers, including stage-specific embryonic antigen-1 (SSEA-1), sex-determining region Y-box 9 (SOX9), neural-cadherin (N-cadherin), leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5), CD44, axis inhibition protein 2 (Axin2), and aldehyde dehydrogenase 1A1 (ALDH1A1), have been suggested as potential candidate markers for endometrial epithelial stem cells. The identification of endometrial epithelial stem cells contributes to our understanding of endometrial regeneration and offers new therapeutic insights into diseases characterized by regenerative defects in the endometrium, such as intrauterine adhesion. This review explores different perspectives on the origins of human and mouse endometrial epithelial cells. It summarizes the potential markers, locations, and hierarchies of epithelial stem cells in both human and mouse endometrium. It also discusses epithelial cell-based treatments for intrauterine adhesion, hoping to inspire further research and clinical application of endometrial epithelial stem cells. Graphical abstract

Abstract The quest to understand the molecular mechanisms of tumour metastasis and identify pivotal biomarkers for cancer therapy is increasing in importance. Single-omics analyses, constrained by their focus on a single biological layer, cannot fully elucidate the complexities of tumour molecular profiles and can thus overlook crucial molecular targets. In response to this limitation, we developed a multiobjective recommendation system (RJH-Metastasis 1.0) anchored in a multiomics knowledge graph to integrate genome, transcriptome, and proteome data and corroborative literature evidence and then conducted comprehensive analyses of colorectal cancer with liver metastasis (CRCLM). A total of 25 key genes significantly associated with CRCLM were recommended by our system, and GNB1, GATAD2A, GBP2, MACROD1, and EIF5B were further highlighted. Specifically, GNB1 presented fewer mutations but elevated RNA transcription and protein expression in CRCLM patients. The role of GNB1 in promoting the malignant behaviours of colon cancer cells was demonstrated via in vitro and in vivo studies. Aberrant expression of GNB1 could be regulated by METTL1-driven m7G modification. METTL1 knockdown decreased m7G modification in the 3’ UTR of GNB1, increasing its mRNA transcription and translation during liver metastasis. Furthermore, GNB1 induced the formation of an immunosuppressive microenvironment by promoting the CLEC2C-KLRB1 interaction between memory B cells and KLRB1+PD-1+CD8+ cells. GNB1 expression and the efficacy of PD-1 antibody-based treatment in CRCLM patients were significantly correlated. In summary, our recommendation system can be used for effective exploration of key molecules in colorectal cancer, among which GNB1 was identified as a critical CRCLM promoter and immunotherapy biomarker in colorectal cancer patients.

Abstract Background Obesity is one of the public health issues that seriously threatens human health. This study aimed to investigate the effects of wheat bran oil (WBO) on body weight and fat/lipid accumulation in high-fat diet (HFD)-induced obese rats and further explore the possible mechanisms by microbiome and metabolome analyses. Methods Fifty Sprague-Dawley (SD) rats were fed either a normal chow diet (B group, n = 10) or HFD (n = 40) for 14 weeks to establish an obesity model. The HFD-induced obese rats were further divided into four groups and given WBO at 0 mL/kg (M group), 1.25 mL/kg (WBO-L group), 2.5 mL/kg (WBO-M group), and 5 mL/kg (WBO-H group) by oral gavage for 9 weeks. The body weight of rats was weighed weekly. The gut microbiota structure was analyzed using 16 S rDNA high-throughput sequencing. The liver metabolite profile was determined using UHPLC-QE-MS non-target metabolomics technology. Results In this study, WBO treatment reduced body weight gain, fat and lipid accumulation, and ameliorated hepatic steatosis and inflammation. WBO treatment increased the relative abundance of Romboutsia and Allobaculum and decreased that of Candidatus_Saccharimonas, Alloprevotella, Rikenellaceae_RC9_gut_group, Alistipes, Parabacteroides, UCG-005, Helicobacter, Colidextribacter, and Parasutterella compared with the M group. A total of 22 liver metabolites were significantly altered by WBO treatment, which were mainly involved in taurine and hypotaurine metabolism, nicotinate and nicotunamide metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and ether lipid metabolism. Conclusions WBO alleviated body weight gain and fat/lipid accumulation in HFD-induced obese rats, which may be related to altered gut microbiota and liver metabolites.

Abstract Background Immunosuppressive therapy plays a crucial role in treating membranous nephropathy, with previous studies highlighting its benefits for patients with primary membranous nephropathy (PMN). Guidelines suggest that the management of membranous nephropathy should be tailored to individual risk levels. However, there is a lack of real-world studies examining the effects of immunosuppressive therapy on renal outcomes in PMN patients. This study aimed to investigate the relationship between immunosuppressive therapy and renal prognosis in PMN patients. Methods This was a real-world retrospective study including patients diagnosed with PMN in Shenzhen Second People’s Hospital and Hechi People’s Hospital. Univariate and multivariate Cox regression analysis and Kaplan-Meier survival analysis were used. Results After propensity score-matching, 464 PMN patients were included and they were assigned to conservative and immunosuppressive group in a 1:1 ratio. Immunosuppressive therapy was the protective factor of renal composite outcome (HR = 0.65, p

Abstract Long non-coding RNAs (lncRNAs), such as SNHG6, have been identified as crucial regulators in the progression of various cancers, including esophageal squamous cell carcinoma (ESCC). Although the role of SNHG6 in ESCC is not completely understood, our findings demonstrated that SNHG6 expression is upregulated in ESCC tissues compared to adjacent normal tissues. Furthermore, elevated levels of SNHG6 are significantly correlated with higher TNM stage and poorer clinical prognosis in ESCC patients. Functionally, both in vivo and in vitro experiments have shown that knocking down SNHG6 inhibits proliferation, invasion, and metastasis. Luciferase reporter assays and Ago2-RIP assay confirm that SNHG6 functions as a competing endogenous RNA (ceRNA) by sponging miR-26b-5p to modulate ITGB1 expression in ESCC. Given that ITGB1 is instrumental in EMT and metastasis, we assessed the expression of EMT-related proteins. The findings suggest that miR-26b-5p and reduced ITGB1 expression can reverse the EMT induced by lncRNA SHNG6, as demonstrated through rescue analysis. Overall, this study aims to elucidate the molecular mechanisms through which SNHG6 promotes EMT and metastasis in ESCC, providing a novel theoretical foundation for understanding ESCC progression and identifying new targets for improving outcomes in metastatic ESCC.

Abstract Cardia gastric cancer (CGC) is prevalent in East Asia, and noninvasive, cost-effective screening methods are needed. This study investigated the diagnostic value of serum pepsinogen (PG), gastrin-17 (G-17), Helicobacter pylori (H. pylori) antibodies, and proteomic profiling for CGC and precancerous lesions. We conducted a case-control study involving biopsy-confirmed patients with CGC (n = 60), low-grade intraepithelial neoplasia (CLGD, n = 60), high-grade intraepithelial neoplasia (CHGD, n = 64), and healthy controls (n = 120) matched for age and sex from high-incidence areas in China. Serological markers including PGI, PGII, G-17, and H. pylori were measured using ELISA and Western blot, while plasma protein markers were assessed using Olink® technology. The VSOLassoBag algorithm and nine machine learning (ML) algorithms were employed to identify crucial features and construct predictive models. Various evaluation metrics, including the area under the receiver-operating-characteristic curve (AUC), were utilized to compare predictive performance. Elevated PGII levels, decreased PGR, and H. pylori infection were significantly associated with an increased risk of CGC and precancerous lesions (P for trend

Abstract Obesity is a serious global health issue. Emerging evidence indicates that the gut microbiota may contribute to the development of obesity, possibly by instigating inflammatory processes. The objective of this research is to conduct a comparative analysis of the gut microbiota composition in obese and normal-weight Uygur adults, while examining the associations with adipocyte-related factors and dietary variables. According to the inclusion and exclusion criteria, twenty-seven Uygur adults with obesity and twenty Uygur adults with normal-weight were recruited from a local community. Anthropometric measurements and blood samples were collected. Gut microbiota composition was analyzed using 16 S rRNA gene sequencing. Adipocyte-related factors were measured using enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed to compare the gut microbiota composition between the two groups and to identify correlations between gut microbiota and adipocyte-related factors. Compared with the normal-weight group, the obese group exhibited a marked reduction in both diversity and richness of the gut microbiota, alongside a decrease in Ruminococcaceae_UCG_014, Coprococcus_2, and Parabacteroides, and an increase in Megamonas and Lachnoclostridium, implying a potential link to the development of obesity. Individuals with obesity were found to have higher Leptin (LEP), Interleukin-6 (IL-6), and C-reactive protein (CRP) than normal-weight individuals. Obese Uygur adults exhibited a gut microbiota characterized by diminished diversity and richness relative to normal-weight individuals. Parabacteroides, Megamonas, and Lachnoclostridium may play an important role in the development of obesity in Uygur population. Underlying mechanisms need further investigation.

Abstract Diagnosing diseases heavily relies on cell pathology images, but the extensive data in each manual identification of relevant cells labor-intensive, especially in regions with a scarcity of qualified healthcare professionals. This study aims to develop an intelligent system to enhance the diagnostic accuracy of cytopathology images by addressing image noise and segmentation issues, thereby improving the efficiency of medical professionals in disease diagnosis. We introduced an innovative system combining a self-supervised algorithm, SDN, for image denoising with data enhancement and image segmentation using the UPerMVit model. The UPerMVit model’s novel attention mechanisms and modular architecture provide higher accuracy and lower computational complexity than traditional methods. The proposed system effectively reduces image noise and accurately segments annotated images, highlighting cellular structures relevant to medical staff. This enhances diagnostic accuracy and aids in the accurate identification of pathological cells. Our intelligent system offers a reliable tool for medical professionals, improving diagnostic efficiency and accuracy in cytopathologic image analysis. It provides significant technical support in regions lacking adequate medical expertise.

Abstract Bartonella are vector-borne gram-negative facultative intracellular bacteria that can infect a wide spectrum of mammals, and are recognized as emerging human pathogens. This study aimed to investigate the prevalence and molecular characteristics of Bartonella infections in small mammals within the Qinghai Menyuan section of Qilian Mountain National Park, China. Small mammals were captured, and the liver, spleen and kidney were collected for Bartonella detection and identification using a combination of real-time PCR targeting the transfer-mRNA (ssrA) gene and followed by sequencing of the citrate synthase (gltA) gene. A total of 52 rodents were captured, and 36 rodents were positive for Bartonella, with a positivity rate of 69.23% (36/52). Bartonella was detected in Cricetulus longicaudatus, Microtus oeconomus, Mus musculus, and Ochotona cansus. The positivity rate was significantly different in the different habitats. Two Bartonella species were observed, including Bartonella grahamii and Bartonella heixiaziensis, and B. grahamii was the dominant epidemic strain in this area. Phylogenetic analysis showed that B. grahamii mainly clustered into two clusters, which were closely related to the Apodemus isolates from China and Japan and the local plateau pika isolates, respectively. In addition, genetic polymorphism analysis showed that B. grahamii had high genetic diversity, and its haplotype had certain regional differences and host specificity. Overall, high prevalence of Bartonella in small mammals in the Qinghai Menyuan section of Qilian Mountain National Park. B. grahamii is the dominant strain with high genetic diversity and potential pathogenicity to humans, and corresponding control measures should be considered.

Abstract This research simulates the behavior of a tornado on a double-slope roof using the Ward tornado generator and the $$SS{T_{k - \omega }}$$ turbulence model. The effects of different ground roughness, slope angle, and wind field position on the tornado load characteristics of gable roofs were studied. The tornado-generating device established the tornado field under various working conditions, and the simulation results were compared with the experimental data to verify the reliability of the simulation results. The wind pressure distribution of gable roofs with four different slope angles was analyzed to find the most unfavorable roof condition of the tornado field. The gable roof’s aerodynamic and wind pressure characteristics at various places in the tornado field were explored by comparing the wind pressure coefficients at five distinct positions on smooth and rough ground. The lift-drag and wind pressure coefficients of five kinds of ground roughness were calculated to determine the influence of different ground roughness on the aerodynamic force and partial pressure distribution of the gable roof. The ground roughness reduces the vortex ratio because the ground roughness reduces the maximum tangential wind speed and the radius of the vortex core. Therefore, the gable roof’s suction increases as the updraft increases.

Abstract Background It was reported that more than 96% of autism spectrum disorder (ASD) children are accompanied with different degrees of sensory processing abnormalities, and up to 50% of ASD children exhibit abnormal auditory response. Studies have confirmed that some ASD children’s abnormal auditory response may be related to their abnormal auditory processing. Prior research demonstrated that ASD children’s auditory processing has high heterogeneity, thus, ASD children’s auditory processing may have different developmental trajectories. However, no study has concentrated on the developmental trajectories of ASD children’s auditory processing. In addition, auditory processing plays a crucial role in ASD children’s language development, thus, ASD children’s different language development outcomes may be related to different auditory processing development tracks. Therefore, this study aims to explore the developmental trajectory of auditory processing in ASD children and analyze the relationship between different developmental trajectories of auditory processing and language impairment. Methods/Design In this study, 220 ASD children aging 3 years and 0 months to 4 years and 11 months are recruited as the research objects, and their demographic characteristics are collected. The subjects are tested for peripheral hearing, intelligence, and autism symptoms. Furthermore, ASD children’s auditory processing and language development are evaluated at baseline, 1 year, and 2 years later. In addition, ASD children’s auditory processing is evaluated by electrophysiological test and the Preschool Auditory Processing Assessment Scale. Moreover, ASD children’s language skills are assessed using the Language Development Assessment Scale for Children Aged 1–6. The various categories of the developmental trajectory of ASD children’s auditory processing are examined through the latent category growth model. Additionally, a hierarchical regression model is developed to analyze the predictive impact of different auditory processing development trajectories on language impairment in ASD children. Discussion This longitudinal study will explore the categories of auditory processing developmental trajectories in ASD children, and analyze the relationship between different categories of auditory processing developmental trajectories and language development, providing new ideas and targeted targets for the rehabilitation training of language impairment in ASD children, as well as promoting early and accurate interventions for ASD children.

Abstract Elderly individuals display metabolite alterations that may contribute to development of cognitive impairment following surgery and anesthesia. However, these relationships remain largely unexplored. The study aims to assess the S-methyl-5-thioadenosine (MTA) is associated with postoperative delayed neurocognitive recovery (dNCR). We assess altered metabolites following anesthesia/surgery in both mice and patients to identify blood biomarkers of dNCR. Preoperative and postoperative plasma metabolites are determined by widely targeted metabolomics. The brains of mice with anesthesia/surgery show decreased MTA and activated MTA phosphorylase. Mice also show that preoperative administration of MTA can prevent inflammation and cognitive decline. In clinical patients, we detect lower preoperative serum MTA levels in those who developed dNCR. Both low preoperative and postoperative blood MTA levels are associated with increased risk of postoperative dNCR. These results suggest that anesthesia/surgery induces cognitive decline through methionine synthesis pathways and that MTA could be a perioperative predictor of dNCR.

Abstract Background The association between plasma free fatty acid (FFA) and the outcomes in the heart failure (HF) patients remains unclear. Methods A cohort study among HF patients was performed. Plasma FFA was analyzed as both a continuous and a categorical variable (grouped by tertiles) to assess its association with composite cardiovascular (CV) death and HF hospitalization (CV death & HHP), CV death alone, and all-cause mortality (ACM) using Cox regression models. Subgroup analyses of HF patients with preserved ejection fraction (HFpEF) and mildly reduced/reduced ejection fraction (HFmrEF/HFrEF) were performed. This work also assessed the effectiveness of combining FFA and NT-pro BNP biomarkers for risk stratification by calculating the concordance index (C-index). Results Among the 4,109 HF patients, FFA levels exceeding 0.4–0.42 mmol/L were associated with increased risks of the three outcomes. Patients in the highest FFA tertile faced greater risks than those in the lowest tertile. Adjusted hazard ratios were 1.32 (95% CI: 1.11–1.58) for CV death & HHP, 1.45 (95% CI: 1.16–1.82) for CV death, and 1.39 (95% CI: 1.15–1.68) for ACM, with a maximum follow-up of 8 years (median: 25 months). Subgroup analyses revealed that elevated FFA levels consistently predicted worse outcomes in both HFmrEF/HFrEF and HFpEF patients. The C-index for predicting outcomes was significantly greater when NT-pro BNP and FFA were combined than when NT-pro BNP was used alone (P

Abstract Background The Platelet to High-Density Lipoprotein cholesterol Ratio (PHR) is a novel indicator of inflammatory response and metabolic disorders, linked to various chronic diseases. This study aims to investigate the relationship between PHR and hypertension. Methods Data from the National Health and Nutrition Examination Survey (NHANES), collected across seven consecutive cycles from 2005 to 2018, were analyzed. The dataset included participants’ hypertension status as reported by a doctor, their use of antihypertensive medications, and the average of three blood pressure measurements to identify hypertensive adults, along with complete information for PHR calculation. PHR was calculated based on Platelet (PLT) count and High-Density Lipoprotein cholesterol (HDL-C) using the following formula: PHR = [PLT (1000 cells/µL) / HDL-C (mmol/L)]. A multivariable logistic regression model was employed to assess the association between PHR and hypertension, and subgroup analyses were conducted to explore potential influencing factors. Additionally, Restricted Cubic Spline (RCS) curves were applied for threshold effect analysis to describe nonlinear relationships. Results Higher PHR was associated with an increased prevalence of hypertension. After adjusting for various covariates, including race, education level, Family Poverty Income Ratio (PIR), smoking, alcohol consumption, sleep disturbances, waist circumference, diabetes, coronary heart disease, angina, heart attack, and stroke, the results remained significant (OR = 1.36; 95% CI, 1.32, 1.41, P

Abstract Chemotherapy resistance has been a great challenge in pancreatic ductal adenocarcinoma(PDAC) treatments. Current first-line chemotherapy regimens for PDAC include gemcitabine-based regimens such as AG regimen (albumin paclitaxel and gemcitabine), fluorouracil-based regiments such as FOLFIRINOX regimen ((5-fluorouracil5-FU), oxaliplatin, Irinotecan) and platinum-based regimens for patients with BRCA mutations. large amounts of work have been done on exploring the mechanism underlying resistance of gemcitabine-based and platinum-based regimens, while little research has been achieved on the mechanism of FOLFIRINOX regimens resistance. Hence, we identified Polypeptide N-Acetylgalactosaminyltransferase 5, (GALNT5) as a vital regulator and a potential therapeutic target in FOLFIRINOX regimens resistance. Colony formation assays and flow cytometry assays were performed to explore the roles of GALNT5 in cell proliferation and apoptosis in PDAC treated with FOLFIRINOX. IC50 alterations were calculated in GALNT5 knockdown and overexpressed cell lines. RNA-seq followed by GSEA (gene set enrichment analysis) was displayed to explore the potential mechanism. WB (western blotting), real-time PCR, and IF (immunofluorescence) were performed to validate relative pathways. The mouse orthotopic xenograft PDAC model was established to examine GALNT5 functions in vivo. GALNT5 was highly expressed in PDAC tissues and predicted poor prognosis in PDAC. Upregulation of GALNT5 in PDAC cells conferred FOLFIRINOX resistance on PDAC by inhibiting DNA damage. Moreover, GALNT5 interacted with MYH9, thus participating in the activation of the NOTCH pathways, resulting in hampering FOI-induced DNA damage. Functions of GALNT5 promoting FOLFIRINOX resistance were validated in vivo. In this study, we found that aberrantly overexpressed GALNT5 in PDAC took part in the activation of the NOTCH pathway by interacting with MYH9, thus inhibiting the DDR to achieve FOLFIRINOX resistance and causing poor prognosis. We identified GALNT5 as a potential therapeutic target for PDAC patients resistant to FOLFIRINOX chemotherapy.

Abstract Background Evidence for the relationship between individual and combined volatile organic compounds (VOCs) and cardiovascular disease (CVD) is limited. Besides, the mediating role of biological aging (BA) has not been studied. Therefore, this study aimed to examine the association between VOCs and CVD risk and to explore the mediating effects of BA. Methods Logistic regression models were used to investigate the relationships of metabolites of volatile organic compounds (mVOCs) and BA with CVD. In addition, weighted quantile sum (WQS) regression, adaptive elastic networks, and Environmental Risk Score (AENET-ERS) were utilized to assess overall associations of mixed VOCs co-exposure with CVD. Mediation analyses were used to identify potential mediating effects of BA. Results In the single-pollutant model, CYMA was shown to be associated with an increased risk of CVD. Additionally, we identified significantly positive associations between the WQS index and CVD (odds ratio (OR) = 1.292, 95% confidence interval (CI): 1.006, 1.660), and DHBMA had the greatest contribution for CVD (0.246). Furthermore, the AENET-ERS results showed that 8 mVOCs were significantly associated with CVD, and ERS was related to an elevated risk of CVD (OR = 1.538, 95%CI: 1.255, 1.884). Three BA indicators mediated the association of the mVOCs mixture with CVD, with mediating effect proportions of 11.32%, 34.34%, and 7.92%, respectively. Conclusion The risk of CVD was found to increase with both individual and combined exposure to VOCs. BA mediates the positive effects of VOCs on CVD, suggesting that this pathway may be one of the mechanisms of CVD.

Developing adaptive skills poses a significant challenge for children with autism spectrum disorder (ASD). Personal hygiene, including hand-washing, was particularly important during the Covid-19 pandemic. Video self-modeling (VSM) is an effective strategy for teaching adaptive skills due to its inherent individualization nature. However, the production and implementation of VSM face certain barriers. To address this issue, the present study employed an innovative approach termed iVSM, which utilizes the head-swapping technique to generate self-modeling videos. To evaluate the efficacy of iVSM in teaching hand-washing skills, a single-subject multiple probe design was employed across three preschool children with ASD. The findings indicated that all participants successfully acquired the targeted skill, with two of them achieving mastery following a single intervention session. The implications of these findings underscore the potential of this novel approach to strike a balance between individualization and feasibility, thereby enhancing the broader implementation of VSM within the context of inclusive education. Furthermore, future studies can focus on the comparative research and explore more applications.

Objective: To clarify the specific mechanisms of action of raw Phellodendron chinense Schneid. (RPC) and saltwater-processed PC (SPC) in the treatment of rats with a kidney-yin deficiency pattern (KYDP). Methods: Healthy rats were administered hydrocortisone to establish a KYDP model. The rats were divided into seven groups: blank control, model, positive control (Liuwei Dihuang pills), high-dose RPC, low-dose RPC, high-dose SPC, and low-dose SPC. Enzyme-linked immunosorbent assay was used to measure the levels of cAMP, cGMP, TRH, TSH, T3, T4, IFN-γ, TNF-α, and testosterone in the serum and the levels of Na+-K+-ATPase and Ca2+-Mg2+-ATPase in the liver. TRH mRNA expression in the rat hypothalamus was measured using RT-PCR. THRα1+2 protein expression in the hypothalamus of rats was measured using Western blot. Immunohistochemistry was performed to determine the expression levels of FAS, FasL, and TSHR. Flow cytometry was used to determine CD4+ and CD8+ T lymphocyte levels. Illumina MiSeq sequencing technology was used to evaluate the diversity of intestinal flora in KYDP rats. Results: The cAMP/cGMP ratio was significantly higher in the model group than in the blank control group (P = .048). Compared with the model group, after administration, the levels of the above-mentioned serum and liver indexes decreased, except that of testosterone. The CD4+/CD8+ ratio also decreased. Compared with the RPC group, the levels of T3, IFN-γ, FAS, FasL, and TSHR in the SPC group decreased whereas that of testosterone increased. Additionally, immune function and intestinal flora diversity improved in the SPC group. SPC proved to be more effective in improving liver energy metabolism in KYDP rats than RPC. Conclusion: SPC had a better therapeutic effect on KYDP than RPC. The underlying mechanism of action may be related to improvements in liver energy metabolism, immune function, and intestinal flora diversity.