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For quality control improvement of medicine and food homology (MFH) health food, the concept of functional quality control and rapid screening strategy of functional compounds were proposed based on the dual identity characteristics. Taking Wuweisanqi Capsule as the research object, firstly, a modified method “syndrome correlation-network analysis” based on network pharmacology was used for analysis. Functions related targets were collected from common medical databases, while the clustering algorithm was used to extract the information of clinical records related to daily health care from traditional Chinese medicine (TCM) database to obtain the targets. The bioactive compounds and related targets were retrieved from the TCM Systems Pharmacology Database and Analysis Platform around the five materials included in formula. Protein-protein interaction (PPI) network and pathway enrichment analysis were performed on the intersection targets. According to the constructed formula material-compound-target-pathway network, the potential functional compounds were preliminarily identified. Secondly, key targets and compounds were analyzed by molecular docking to further screen functional compounds. Finally, combined with references, the screening and establishing determination methods of functional compounds containing total saponins, astragaloside IV, puerarin and schisandrin were finished. The rapid screening strategy adequately utilizes the advantage of TCM background for MFH health food and the effective extracting ability of massive data by the algorithm. It links three aspects of health food functions, formula materials and functional compounds, providing an efficient solution for the realization of function-formula-component integrated functional quality control, which has great application potential in health food industry.

Flow cytometry (FCM), characterized by its simplicity, rapid processing, multiparameter analysis, and high sensitivity, is widely used in the diagnosis, treatment, and prognosis of hematological malignancies. FCM testing of tissue samples not only aids in diagnosing and classifying hematological cancers, but also enables the detection of solid tumors. Its ability to detect numerous marker parameters from small samples is particularly useful when dealing with limited cell quantities, such as in fine-needle biopsy samples. This attribute not only addresses the challenge posed by small sample sizes, but also boosts the sensitivity of tumor cell detection. The significance of FCM in clinical and pathological applications continues to grow. To standardize the use of FCM in detecting hematological malignant cells in tissue samples and to improve quality control during the detection process, experts from the Cell Analysis Professional Committee of the Chinese Society of Biotechnology jointly drafted and agreed upon this consensus. This consensus was formulated based on current literature and clinical practices of all experts across clinical, laboratory, and pathological fields in China. It outlines a comprehensive workflow of FCM-based assay for the detection of hematological malignancies in tissue samples, including report content, interpretation, quality control, and key considerations. Additionally, it provides recommendations on antibody panel designs and analytical approaches to enhancing FCM tests, particularly in cases with limited sample sizes.

Abstract Prostate cancer (PCa) is a common form of malignancy among men. The associations between socioeconomic status (SES) indicators and PCa risks remain incompletely elucidated. Through two-sample Mendelian randomization (MR), this research seeks to assess the causal links between 4 genetically predicted SES indicators—average total household income before tax, the Townsend deprivation index at recruitment, unemployed status and college or university degree in the household—and PCa. Genetic variants were extracted from publicly available genome-wide association studies (GWAS) under stringent threshold as instrumental variables (IVs). We employed the inverse variance weighted (IVW), weighted median, weighted mode and MR-Egger to estimate the causal effect, with sensitivity analyses such as Cochran’s Q tests, MR-Egger, MR-PRESSO and leave-one-out performed to detect potential heterogeneity and pleiotropy. Our MR analysis revealed a causal association between unemployment and prostate cancer (OR: 3.07, 95%CI:1.12–8.42, P = 0.03). No causal associations were identified between other SES components and prostate cancer. The MR-PRESSO suggested 2 outliers in the association between college or university degree in household and prostate cancer, which rendered the association significant after outliers were removed. The heterogeneity and pleiotropy are unlikely to affect our causal estimate. Our results indicated that unemployment poses a potential risk factor for the incidence of PCa. The findings highlight the necessity for further exploration into the underlying etiology of PCa.

Abstract Esophageal squamous cell carcinoma (ESCC) is one of the most common digestive malignancies. Our previous studies revealed necroptosis-related lncRNA ENSG00000253385.1 was an independent prognostic factor for ESCC. However, the specific regulatory mechanisms are unknown. This study aimed to investigate the expression of the lncRNA ENSG00000253385.1 in ESCC tissues and its relationship with clinicopathological features and patient prognosis, and to explore its potential regulatory mechanism in ESCC cells. We detected the location of the lncRNA ENSG00000253385.1 in ESCC cells by fluorescence in situ hybridization (FISH). FISH and quantitative real-time polymerase chain reaction (qRT‒PCR) were used to detect gene expression in ESCC tissues and cells. Cell proliferation, migration and apoptosis were evaluated by CCK-8 assay, wound healing, transwell cell migration, invasion and flow cytometry assay. The levels of necroptosis-related protein were detected by western blot. The binding sites between miR-16-2-3p and lncRNA ENSG00000253385.1 or voltage-dependent anion channel 1 (VDAC1) were predicted by bioinformatics database and confirmed by dual luciferase reporter gene assay. Results revealed that the lncRNA ENSG00000253385.1 expression was higher in ESCC tissues than in the adjacent tissues. High lncRNA ENSG00000253385.1 expression, positive lymph node metastasis and clinical stage III were associated with poor overall survival (OS) in patients with ESCC, and were independent risk factors for prognosis of patients with ESCC. The lncRNA ENSG00000253385.1 was located in the cytoplasm. MiR-16-2-3p had a direct targeting regulatory relation ship with lncRNA ENSG00000253385.1 and VDAC1. MiR-16-2-3p inhibitor promoted proliferation, migration and invasion, and inhibited apoptosis of ESCC cells. Knockdown of the lncRNA ENSG00000253385.1 could inhibit the proliferation, migration and invasion, promote the apoptosis, and result in increases in the necroptosis-related proteins p-receptor-interacting protein kinase 3 (RIPK3)/RIPK3 and p-mixed lineaae kinase domain-like protein (MLKL)/MLKL and a decrease in the VDAC1 protein levels in ESCC cells, whereas miR-16-2-3p inhibition rescued these effects. Therefore, The lncRNA ENSG00000253385.1/ miR-16-2-3p/VDAC1 axis may be considered as a potential predictive biomarker and target for ESCC.

Abstract Background The Objective Structured Clinical Examination (OSCE) is a systematic and structured assessment tool that evaluates candidates’ professional medical skills in a simulated environment through a series of time-limited stations. The aim of this meta-analysis was to determine the optimal station number and duration time per station of OSCE to achieve good reliability. Methods A comprehensive search was conducted across PubMed and Embase from inception until August 2024, without language restrictions. Studies were included if they provided data on the station number and duration time of OSCE, along with Cronbach’s alpha. A random-effects model was used to pool the data. Results A total of 23 studies encompassing 26 Cronbach’s alpha were finally included. Cronbach’s alpha values ranged from 0.43 to 0.93, and 11 studies demonstrated good internal consistency (Cronbach’s alpha ≥ 0.8). The analysis indicated that a design of 5–10 stations, with each station lasting less than 10 min, yielded the best internal consistency (Cronbach’s alpha = 0.88, 95% CI: 0.86, 1.00). Conclusions This meta-analysis suggests that the station number of OSCE falling in between 5 and 10, with each station time lasting no more than 10 min are likely to yield good reliability and strong internal consistency.

Abstract Background The co-occurrence of Lemierre’s syndrome, primarily triggered by Fusobacterium necrophorum following oropharyngeal infection, with diabetic ketoacidosis (DKA) in diabetes mellitus (DM) patients, underscores a rare but life-threatening clinical scenario. Lemierre’s syndrome induced DKA is extremely rare, with only one case report in adult and no case yet reported in elderly. Case Presentation We reported a case of a 69-year-old female who presented with DKA triggered by deep neck space infection (DNSI), leading to rapid clinical deterioration within 6 h that necessitated high flow nasal cannula (HFNC) and antibiotic administration. Laboratory findings included leukocytosis, elevated serum C-reactive protein, hyperglycemia, ketonemia, and severe metabolic acidosis. Culture of the fluid from a neck mass puncture drainage and blood were positive for Klebsiella pneumoniae. The patient was further complicated by thrombosis of the left internal jugular vein with extension to the sigmoid and a neck abscess surrounding the carotid artery sheath, consistent with Lemierre’s syndrome. This condition was managed aggressively with fluid resuscitation, insulin therapy, surgical drainage, antibiotics, and anticoagulation led to a significant improvement in her condition. Following a 13-day hospitalization, there was significant clinical improvement, culminating in the patient’s discharge. Conclusions The case highlights the need for greater awareness and understanding of the interrelated and mutually promoting conditions of DKA and Lemierre’s syndrome among clinicians. Early recognition and treatment are crucial to prevent mortality in such complex cases.

Abstract Background Asthma is an airway inflammatory disease driven by multiple factors with a high incidence in children and adolescents. Environmental tobacco smoke exposure (TSE) and diet are inducing factors for asthma. The potential of omega-3 polyunsaturated fatty acids (PUFAs) to alleviate asthma symptoms by their anti-inflammatory effects has been explored. However, to date, no studies have explored the effect of dietary PUFAs intake on the asthma in children and adolescents exposed to tobacco smoke. Objective We aimed to examine the effect of dietary PUFAs intake on the current asthma in children and adolescents exposed to tobacco smoke. Methods Data of this cross-sectional were extracted from the National Health and Nutrition Examination Survey (NHANES) 2007–2018. Children and adolescents with serum cotinine concentration ≥ 0.05 ng/mL were defined to exposed to tobacco smoke. Dietary PUFAs intake information were obtained from 24 h recall interview. The weighted univariate and multivariate were utilized to explore the effect of PUFAs on the association of asthma and TSE, with adjusted odds ratios (AORs) and 95% confidence intervals (CIs). These moderating effects were further explored based on the age, gender and body mass index (BMI) and sedentary time. Results Totally, 7981 eligible children and adolescents were included, with the mean age of 11.96 ± 0.06 years old. Of whom, 1.024 (12.83%) had current asthma. After adjusted all covariates, we found children and adolescents with TSE had high occurrence of current asthma (AOR = 1.2, 95% CI 1.03–1.63); We also found omega-3 PUFAs intake (P for interaction = 0.010), not omega-6 PUFAs (P for interaction = 0.546), has a moderating effect on the association of TSE and current asthma. Moreover, we further observed that children and adolescents with TSE and low omega-3 PUFAs intake had high occurrence of current asthma (AOR = 1.58, 95% CI 1.19–2.10), while no significant association was found in children and adolescents with high omega-3 PUFAs intake (all P > 0.05). This moderating effect was more prominent in children and adolescents aged ≤ 12 years old (AOR = 1.62, 95% CI 1.06–2.47), girls (AOR = 2.14, 95% CI 1.15–3.98), overweight (AOR = 1.87, 95% CI 1.01–3.47) and sedentary time > 6 h (AOR = 1.96, 95% CI 1.00–3.86). Conclusion We found dietary omega-3 PUFAs plays a moderating effect on the association of asthma and TSE in children and adolescents, especially in children and adolescents aged ≤ 12 years, girls, overweight or sedentary time > 6 h. This moderating effect suggested higher omega-3 intake has potential benefits in decreasing the occurrence of asthma in children and adolescents who exposed to tobacco smoke.

Intracerebral hemorrhage (ICH) is associated with the highest rates of mortality and residual disability. To date, effective treatments to delay or prevent ICH are still lacking. Multiple forms of neuronal cell death have been discovered following ICH, including apoptosis, necrosis, autophagy, and ferroptosis. Aldo-keto reductase family 1 member C1 (AKR1C1) has been identified to act as a protective factor in ferroptosis. However, whether AKR1C1 was involved in the development of ICH was unknown. In this study, the left cerebral striatum of the Sprague-Dawley rat was injected with collagenase type IV to induce an in vivo model. Primary rat cortical neurons treated with oxygen hemoglobin (OxyHb) were applied to as an in vitro model. AKR1C1 was found to be downregulated and immunoreactivity colocalized with NeuN-positive neurons in the perihematomal region. Rats injected with lentiviral particles overexpressing AKR1C1 showed the reduction of cerebral hematoma and the remission of blood-brain barrier disruption. Moreover, AKR1C1 upregulation repressed cell apoptosis and ferroptosis induced by ICH through downregulating the expression of pro-apoptotic factors, inhibiting iron accumulation and lipid peroxidation, along with increasing the expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). The results of in vitro assays were consistent with results from the in vivo. Mechanistically, P53 overexpression augmented the cellular damage in OxyHb-stimulated neurons when AKR1C1 was overexpressed. Taken together, AKR1C1 improves ICH injury by inhibiting neuronal cell death via negatively regulating P53 expression and affecting the SLC7A11/GPX4 pathway.

Classifying household water-consumption behaviors is crucial for providing targeted suggestions for water-saving behaviors and enabling effective resource management and conservation. Although it is common knowledge that energy consumption is closely coupled with household water consumption, the effectiveness of energy consumption information in classifying household water-consumption behaviors remains unexplored. This study proposes a hybrid model of long short-term memory (LSTM) and random forest (RF) using water and electricity consumption as inputs to classify household water-consumption behaviors. Data from three households in Beijing collected from January to March 2020 were used for the case studies. The hybrid model achieved a macro F1 score of 0.89 at a 5-min resolution, outperforming the standalone LSTM and RF models. Additionally, the inclusivity of time-series electricity consumption improves the accuracy (F1 scores) of classifying bathing and laundry behaviors by 0.12 and 0.20, respectively. These findings underscore the scientific value of integrating electricity consumption as a proxy variable in water-consumption behavior classification models, demonstrating its potential to enhance accuracy while simplifying data acquisition processes. This study establishes a framework for demand-side water management aimed at empowering residents to understand their own water-energy consumption behavior patterns and engage in personalized water conservation efforts.

ObjectiveTo explore the recovery of upper limb motor function and the changes in cortical functional connectivity in patients with early subcortical small infarcts accompanied by severe upper limb motor dysfunction (PESSUM) after intermittent theta burst stimulation (iTBS) via functional near-infrared spectroscopy (fNIRS) and to explore the related mechanisms.MethodsWe enrolled 56 subcortical ischemic stroke patients with FMA-UE ≤28 and randomly assigned them to receive either genuine (TG, n = 29) or sham (CG, n = 23) iTBS plus standard rehabilitation over 8 days. fNIRS was used to monitor cerebral HbO, HbD, and HbT concentrations, and RSFC changes were analyzed. The FMA-UE and MBI scores were used to evaluate upper limb motor function and daily activities. Intergroup comparisons were conducted using independent samples t tests, whereas intragroup comparisons were performed using paired samples t tests or Mann–Whitney U tests. The trend of the RSFC changes was analyzed via repeated-measures Analysis of Variance (ANOVA).ResultsBoth groups showed significant improvements in FMA-UE and MBI scores postintervention (p

Chronic itch which is primarily associated with dermatologic, systemic, or metabolic disorders is often refractory to most current antipruritic medications, thus highlighting the need for improved therapies. Oxidative damage is a novel determinant of spinal pruriceptive sensitization and synaptic plasticity. The resolution of oxidative insult by molecular hydrogen has been manifested. Herein, we strikingly report that both hydrogen gas (2 %) inhalation and hydrogen-rich saline (5 mL/kg, intraperitoneal) injection prevent and alleviate persistent dermatitis-induced itch, diabetic itch and cholestatic itch. Hydrogen therapy reverses the decrease of spinal SIRT1 expression and antioxidant enzymes (SOD, GPx and CAT) activity after dermatitis, diabetes and cholestasis. Furthermore, hydrogen reduces spinal ROS generation, oxidation products (MDA, 8-OHdG and 3-NT) accumulation, β-catenin acetylation and dendritic spine density in persistent itch models. Spinal SIRT1 inhibition eliminates antipruritic and antioxidative effects of hydrogen, while SIRT1 agonism attenuates chronic itch phenotype, spinal β-catenin acetylation and mitochondrial damage. β-catenin inhibitors are effective against chronic itch via reducing β-catenin acetylation, blocking ERK phosphorylation and elevating antioxidant enzymes activity. Hydrogen treatment suppressed dermatitis and cholestasis mediated spontaneous excitatory postsynaptic currents in vitro. Additionally, hydrogen impairs cholestasis-induced the enhancement of cerebral functional connectivity between the right primary cingulate cortex and bilateral sensorimotor cortex, as well as bilateral striatum. Taken together, this study uncovers that molecular hydrogen protects against chronic pruritus and spinal pruriceptive sensitization by reducing oxidative damage via up-regulation of SIRT1-dependent β-catenin deacetylation in mice, implying a promising strategy in translational development for itch control.

Brain functional hypernetworks that can characterize the complex and multivariate interactions among multiple brain regions have been widely used in the diagnosis and prediction of brain diseases. However, there are few studies on the structure and dynamics of brain functional hypernetworks. Such studies can help to explore how the important functional features of brain functional hypernetworks characterize the working and pathological mechanisms of the human brain. Therefore, this article introduces the hypernetwork null model to analyze the dependencies between the features of interest. Specifically, first, based on the original brain functional hypernetwork, this article proposed the optimized hyper dK-series algorithm with hyperedges to construct null models that preserved the different node attributes and hyperedge attributes of the original brain functional hypernetwork, respectively. Next, based on the original hypernetwork model and the null model, multiple node attributes and hyperedge attributes were respectively introduced. Then, the level of similarity and correlation between the topological attributes of the original brain functional hypernetwork and the topological attributes of the brain functional hypernetwork null model were calculated to analyze the dependencies between the features of interest. The results showed that there were differences in the level of dependence between the features of interest. Node degree is the main dependency attribute for multiple metrics. Hyperedge degree, node degree-dependent redundancy coefficient, and hyperedge degree-dependent redundancy coefficient are partial dependency attributes for some metrics. The dependency attributes and level of dependency are the same for the hypernetwork clustering coefficients—HCC2 and HCC3. This indicates that the node degree is redundant with respect to other attributes, while the hyperedge degree, node degree-dependent redundancy coefficient, and hyperedge degree-dependent redundancy coefficient perhaps contain other topology information. In addition, there is redundancy between HCC2 and HCC3. Therefore, the effects of these redundant attributes need to be considered when performing network analysis.

Objective: This study aims to explore the effect of music therapy on improving the negative psychology of stroke rehabilitation patients with dysphagia. Methods: The medical records of 160 stroke rehabilitation patients with dysphagia admitted to Wuwei People’s Hospital from June 2020 to May 2021 were retrospectively analyzed. Based on the different clinical management programs, these patients were divided into the control group (n = 77, receiving routine clinical rehabilitation management) and the research group (n = 83, receiving routine clinical rehabilitation management + music therapy). The scores of the Standard Swallowing Assessment Scale (SSA), Patient Health Questionnaire-9 (PHQ-9), and the World Health Organization Five-item Well-Being Index (WHO-5), as well as the levels of dopamine (DA) and 5-hydroxy tryptamine (5-HT), of the two groups were compared. Results: After treatment, there was no significant difference in SSA scores between the two groups (P > 0.05). After the treatment, the PHQ-9 score of the research group was lower than that of the control group, whereas the WHO-5 score was significantly higher than that of the control group (P < 0.05). After the treatment, the levels of DA and 5-HT in the research group were significantly higher than those in the control group (P < 0.05). Conclusions: Music therapy for stroke rehabilitation patients with dysphagia can improve their negative emotions and quality of life to a certain extent, which may alleviate the condition of patients.

Abstract The eyes provide insights into psychology, potentially offering a distinctive perspective for psychological health profiles. However, there exist a notable deficiency in datasets that simultaneously encompass eye features and psychological assessments. To address this gap, our study presents a dataset that included Fundus Photography, Psychological Assessment, Retina Characteristics, and Multimodal Imaging (FPRM). FPRM dataset comprise fundus images at different wavelengths (548 nm and 605 nm), image of oxygen saturation for the retina and 8 specific retinal vessels, videos of retinal blood flow and pupillary light reflex, along with 61 items of multimodal quantitative measurement from 384 participants. Additionally, it features psychological assessments across five dimensions (geriatric depression, generalized anxiety disorder, insomnia, activities of daily living, and deterioration), accompanied by fundus photographs and 6 items of retina characteristics from 1683 participants. FPRM dataset is the first to integrate multimodal ophthalmic data and psychological assessments, not only advancing the development of machine learning applications but also facilitating in-depth research into the relationship between eye health and psychological health profiles.

Abstract Single B-cell antibody generation technology is an advanced method that offers several advantages, including rapid production, high efficiency, and high yield. The antibodies generated via this technique retain their natural conformation and are well suited for applications in pathogen diagnosis, disease treatment, and investigations of virus cross-species transmission mechanisms. Our study aimed to establish a platform for generating single B-cell antibodies specifically targeting the foot-and-mouth disease virus (FMDV) 146S antigen in mice. Female BALB/c mice were immunized with inactivated O-type FMDV 146S antigen, and spleen cells were collected for further analysis. Flow cytometric sorting was performed using a biotin-labeled O-type FMDV 146S antigen as a decoy to identify and select CD19 + /CD21/35 + /CD43-/IgM-/Biotin + antigen-specific individual B cells. The gene sequences encoding the variable regions of the heavy and light chains of the murine IgG antibodies were obtained via single-cell nested PCR amplification. Separate constructs were created for the heavy and light chain plasmids to ensure the proper expression of intact IgG antibodies. These plasmids were cotransfected into human embryonic kidney 293T (HEK293T) cells, leading to the successful production and purification of 15 specific monoclonal antibodies (mAbs), 10 which exhibited activity in ELISA tests, and six antibodies that displayed activity in IFA tests. These findings highlight the successful development of a method for generating mouse-derived single B-cell antibodies that target FMDV. This achievement provides a solid foundation for diagnostic techniques and the analysis of antigenic structural variations.

Abstract Since the Qin terracotta warriors were unearthed, polyamide 650 cross-linked E-44 epoxy resin binder has been employed to bond and restore them. In this paper, the chemical aging of the binders service in indoor natural environment during the past 30 years in the terracotta warriors was studied by means of infrared spectroscopy, X-ray photoelectron spectroscopy and thermogravimetric analysis. The results indicated that the binders did not emerge the characteristic peak of carbonyl stretching vibration at 1700 cm−1 in the IR spectra of all determined binders, and their thermal decomposition curves did not emerge any abnormal changes, and the thermal decomposition mainly occurred above 300 °C. There are evident ceramic grains attached to the surface of the binders being peeled off for sampling. These results that the binders service in the Qin terracotta warriors did not exhibit an observable chemical aging and still has strong adhesion. Generally, discrepancies were observed between natural aging and accelerated artificial aging due to the ineffectiveness of the latter to reproduce the effects of complex weather conditions. Compared to artificially accelerated aging, the evaluation results in a long-term natural aging of the binder which is used for restoration of the life-size Qin terracotta warriors, providing in the present investigation, are more reliable in terms of predicting the safety of restored terracotta warriors.

Carbon nanotubes (CNTs), members of the nanomaterial family, are increasingly being used in consumer products and extensively studied for various biomedical applications. Due to their benign elemental composition, large surface area, and chemical and biological activities, CNTs demonstrate great potential in cancer therapy, including drug delivery, imaging analysis, photothermal therapy, photodynamic therapy, and radiotherapy. However, there is still a major knowledge gap when it comes to transitioning from research to clinical applications. One of the important issues is that the biological toxicity of CNTs, especially in terms of carcinogenesis, and the underlying mechanisms are not fully understood. Therefore, a thorough evaluation of toxicity and the underlying mechanisms of carcinogenesis is essential to enable the wide application of CNTs. In this review, we summarize the recent progress of CNTs as multifunctional therapeutics in cancer therapy. Furthermore, a detailed discussion is provided on the carcinogenesis and potential mechanisms of CNTs. Finally, the review ends with further challenges and prospects for CNTs with the expectation of facilitating their broader utilization.

This study investigates the potential of fluorescence characteristics of dissolved organic matter (DOM) to identify sediment organic matter (OM) sources in shallow lakes. Spectral analyses were performed on water and alkali extractable organic matter (WEOM and AEOM) from Lake Taihu sediments. The lake was divided into seven distinct regions: R1 and R2 strongly influenced by inflowing rivers, R3 and R4 were characterized by submerged macrophytes, and R5-R7 were dominated by cyanobacterial blooms. The investigation illustrated that the highest values of water and alkali extractable organic carbon (WEOC and AEOC) were found in region R4. Specifically, the Humification Index (HIX) values consistently exceeded 2.0 in the northwest regions, contrasting with values predominantly below 1.0 in most southeastern regions. Moreover, the Fluorescence Index (FI) of WEOM in regions R5, R6 and R7 reached 2.10, markedly higher than the values observed in other regions. The horizontal distribution of the four spectrographic indices of AEOM exhibited partial similarity to the distribution pattern of WEOM. Although the WEOC content marginally trailed AEOC, there was a significant correlation between WEOM and AEOM in three indices including slope ratio (SR), HIX and FI. The identification of sources implied that organic matter in sediments of regions R1 and R2 originated from terrestrial sources, while regions R3 and R4 were largely derived from submerged macrophyte and the regions R5-R7 were notably impacted by cyanobacteria-derived organic matters. Notably, the identification results aligned perfectly with the distribution of inflowing rivers, cyanobacterial blooms and submerged macrophyte coverage within Taihu Lake, underscoring the potential use of dissolved organic matter's spectral characteristics for organic matter source analysis within sediments. Synopsis: This study identifies distinct sources and spatial distributions of organic matter in Lake Taihu's sediments, using fluorescence characteristics to highlight influences from terrestrial input, submerged macrophytes, and cyanobacterial blooms.

Objective Hematuria is one of the most common conditions in children, and increase the risk of chronic kidney disease. Persistent hematuria may be the earliest manifestation of type IV collagen-related nephropathy. Early diagnosis is essential for optimized therapy. Due to the invasive nature of kidney biopsy and the high cost of whole exome sequencing, its application in the diagnosis of isolated hematuria is rare. Hence, we performed noninvasive and convenient genetic testing approaches for type IV collagen-related nephropathy.Methods We used noninvasive oral mucosa sampling as an alternative method for DNA isolation for genetic testing and designed a panel targeting three type IV collagen nephropathy-related genes in children with hematuria. Children with persistent hematuria unaccompanied by clinically significant proteinuria or renal insufficiency who underwent genetic testing using a hematuria panel were enrolled.Results Thirty-seven of 112 (33.0%) patients were found to have a genetic variant in COL4A3/A4/A5. Pathogenic/likely pathogenic COL4A3/A4/A5 variants were identified in 17 of the 112 patients analyzed (15.2%), which were considered to explain their hematuria manifestations. In addition, variants of unknown significance (VUSs) were found in 17.8% (20/112) of patients. Furthermore, we observed a much greater COL4A3/A4/A5 variant detection rate in patients with a positive family history or more severe hematuria (RBC ≥ 20/HP) or with coexisting microalbuminuria (59.2% vs. 12.7%, p

Binding phospholipid is a simple, yet flexible, strategy for anchorage of bacterial effectors at cell membrane to manipulate host signaling responses. Phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-biphosphate are the only two phospholipid species known to direct bacterial effectors to establish inner leaflet localization at the plasma membrane. Here, selectivity of phosphatidic acid (PA) by bacterial effectors for the plasma membrane anchorage and its molecular entity was identified. C-terminal BID domain of Bartonella T4SS effectors (Beps) directed the plasma membrane localization of Beps in host cells through binding with PA. A hydrophobic segment of the 'HOOK' subdomain from BID is inserted into the bilayer to enhance the interaction of positively charged residues with the lipid headgroups. Mutations of a conserved arginine facilitating the electrostatic interaction, a conserved glycine maintaining the stability of the PA binding groove, and hydrophobic residues determining membrane insertion, prevented the anchorage of Beps at the plasma membrane. Disassociation from plasma membrane to cytosol attenuated the BepC capacity to induce stress fiber formation and cell fragmentation in host cells. The substitution of alanine with aspartic acid at the -1 position preceding the conserved arginine residue hindered BepD anchoring at the plasma membrane, a vital prerequisite for its ability to elicit IL-10 secretion in host macrophages. In conclusion, our findings reveal the PA-binding properties of bacterial effectors to establish plasma membrane localization and will shed light on the intricate mechanisms employed by bacterial effectors within host cells.

Hyperlipidemia, commonly referred to as dyslipidemia, is characterized by elevated serum cholesterol and/or triglyceride levels. This condition contributes significantly to the high mortality rates associated with cardiovascular diseases, posing a serious threat to global health. Although statins remain the predominant pharmacological treatment for hyperlipidemia, their associated side effects have led to a growing interest in alternative therapeutic approaches. Traditional Chinese Medicine (TCM) is exploring these alternatives, with the Erchen Decoction (ECD) emerging as a promising candidate. This review aims to summarize current clinical research, elucidate the mechanisms of action, and assess the compatibility of ECD in the management of hyperlipidemia. By doing so, we hope to provide valuable insights and references for clinical practice and future research.

BackgroundFluid-attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH) might be useful for predicting and functional outcome in ischemic stroke patients after endovascular thrombectomy (EVT), but its clinical benefit remains controversial. Thus, this study aimed to evaluate the association of FVH on prognosis in ischemic stroke patients who received EVT.MethodsPubMed, Embase, Cochrane Library, Web of Science, and Wanfang databases were searched for potentially eligible studies published up to March 2024. Pooled standard mean difference (SMD), risk ratios (RR) with 95% confidence intervals (CI) were employed to assess the association of FVH on prognosis in ischemic stroke patients who received EVT. All statistical analyses were conducted using STATA 12.0 software.ResultsA total of 10 studies were included in our study. The results indicated that higher FVH score were associated with better prognosis (SMD: 0.80, 95% CI 0.63–0.97). Moreover, the presence of FVH was significant associated with better functional outcome in ischemic stroke patients who received EVT (RR: 0.68, 95% CI, 0.58–0.79).ConclusionThe current meta-analysis suggests that FVH is related the prognosis of ischemic stroke patients after EVT.

PurposeThis study aimed to evaluate the comparative reproductive outcomes of ovarian stimulation combined with intrauterine insemination using partner’s sperm (OS-IUI) in eumenorrheic and normogonadotropic oligomenorrheic women.MethodA retrospective cohort study was conducted, including 3833 couples who underwent 5920 cycles of OS-IUI between June 2013 and March 2019. Participants were stratified into two cohorts based on menstrual regularity: eumenorrheic and normogonadotropic oligomenorrheic. The primary outcome measured was the live birth rate (LBR) per cycle and cumulative LBR per couple. Secondary outcomes encompassed the clinical pregnancy rate (CPR) per cycle, miscarriage rate, and multiple pregnancy rate. Propensity score matching (PSM) was utilized to balance maternal baseline characteristics.ResultsPrior to PSM, significant differences in CPR, LBR and cumulative LBR were observed between eumenorrheic and oligomenorrheic women, favoring the latter (CPR: 11.16% vs. 18.75%; LBR: 9.02% vs. 14.96%; cumulative LBR: 13.60% vs. 24.25%, P < 0.001). These differences persisted post-PSM (CPR: 9.74% vs. 19.29%; LBR: 7.30% vs. 16.29%; cumulative LBR 7.76% vs. 19.90%, P

Quantum cascade lasers (QCLs) in the mid-infrared (MIR) hold significant potential for widespread applications in both military and civilian contexts. However, the utility of present single-chip QCLs is hampered by issues such as low output power and subpar beam quality. This study addresses these limitations by employing spectral beam combining (SBC) based on a diffraction grating, with an aim to enhance both power and beam quality of MIR QCLs. Coaxial power synthesis of three single-chip QCLs (around 4.75 μm) is achieved experimentally, importantly, the beam quality did not decrease after combining, essentially maintaining the same quality as before combining. It is proposed that there are four main factors affecting the combining efficiency, namely operating optical power (or driving current) of the chips, individual differences in QCL chips, diffraction grating, and reflectivity of feedback mirror, and their effects on the combining efficiency are discussed separately. This study confirms that SBC is an effective way to obtain high-power and high-beam quality MIR QCL sources, and lays a research foundation for more beam spectral combining.

Spinal cord injury (SCI) is a severe traumatic disease for which no satisfying treatment is available. The severe inflammatory reactions and poor endogenous regenerative capacity cause difficulty in functional recovery. Neural stem cells (NSCs) transplantation is currently a promising treatment for repairing SCI. However, there is a lack of effective ways to improve the survival rates of NSCs and promote the neuron differentiation rates of NSCs. Conductive hydrogel can mimic environment which is suitable for neurodevelopment. Low-frequency pulsed electromagnetic fields (LPEMFs) have the advantages of safety, non invasiveness, and tissue repair, making it a potential method of repairing SCI. In this study, an injectable, self-healing magnetic, and conductive hydrogel was synthesized to carry out NSCs with LPEMFs for repairing SCI. In vitro experiments, under the treatment of LPEMFs and conductive hydrogel, the microglia tend to polarize into M2 phenotype, rather than M1 phenotype. Meanwhile, NSCs tend to differentiate into neuronal direction. In SCI model, conductive hydrogel loaded with NSCs combined with LPEMFs can promote functional recovery, through reducing inflammation and promoting neuron differentiation of NSCs. This study provides a novel NSCs transplantation strategy combined with physical interventions for SCI treatment, which brings a new desire to repair SCI.

Hepatocyte transplantation (HTx) has been a novel cell-based therapy for severe liver diseases, as the donor livers for orthotopic liver transplantation are of great shortage. However, HTx has been confronted with two main hurdles: limited high-quality hepatocyte sources and low cell engraftment and repopulation rate. To cope with, researchers have investigated on various strategies, including small molecule drugs with unique advantages. Small molecules are promising chemical tools to modulate cell fate and function for generating high quality hepatocyte sources. In addition, endothelial barrier, immune responses, and low proliferative efficiency of donor hepatocytes mainly contributes to low cell engraftment and repopulation rate. Interfering these biological processes with small molecules is beneficial for improving cell engraftment and repopulation. In this review, we will discuss the applications and advances of small molecules in modulating cell differentiation and reprogramming for hepatocyte resources and in improving cell engraftment and repopulation as well as its underlying mechanisms.

Abstract Background Palliative care and the integration of health and social care have gradually become the key direction of development to address the aging of the population and the growing burden of multimorbidity at the end of life in the elderly. Aims To explore the benefits/effectiveness of the availability and stability of palliative care for family members of terminally ill patients in an integrated institution for health and social care. Methods This prospective observational study was conducted at an integrated institution for health and social care. 230 patients with terminal illness who received palliative care and their family members were included. Questionnaires and scales were administered to the family members of patients during the palliative care process, including quality-of-life (SF-8), family burden (FBSD, CBI), anxiety (HAMA), and distress (DT). We used paired t-tests and correlation analyses to analyze the data pertaining to our research questions. Results In the integrated institution for health and social care, palliative care can effectively improve quality of life, reduce the family’s burden and relieve psychological impact for family members of terminally ill patients. Palliative care was an independent influencing factor on the quality of life, family burden, and psychosocial status. Independently of patient-related and family-related factors, the results are stable and widely applicable. Conclusion The findings underline the availability and stability of palliative care and the popularization of an integrated service model of health and social care for elder adults.

Abstract Background Immunotherapies effectively treat human malignancies, but the low response and resistance are major obstacles. Neoantigen is an emerging target for tumor immunotherapy that can enhance anti-tumor immunity and improve immunotherapy. Aberrant alternative splicing is an important source of neoantigens. HNRNPA1, an RNA splicing factor, was found to be upregulated in the majority of tumors and play an important role in the tumor immunosuppressive microenvironment. Methods Whole transcriptome sequencing was performed on shHNRNPA1 SKOV3 cells and transcriptomic data of shHNRNPA1 HepG2, MCF-7M, K562, and B-LL cells were downloaded from the GEO database. Enrichment analysis was performed to elucidate the mechanisms underlying the activation of anti-tumor immunity induced by HNRNPA1 knockdown. mRNA alternative splicing was analyzed and neoantigens were predicted by JCAST v.0.3.5 and Immune epitope database. The immunogenicity of candidate neoantigens was calculated by Class I pMHC Immunogenicity and validated by the IFN-γ ELISpot assay. The effect of shHNRNPA1 on tumor growth and immune cells in vivo was evaluated by xenograft model combined with immunohistochemistry. Results HNRNPA1 was upregulated in a majority of malignancies and correlated with immunosuppressive status of the tumor immune microenvironment. Downregulation of HNRNPA1 could induce the activation of immune-related pathways and biological processes. Disruption of HNRNPA1 resulted in aberrant alternative splicing events and generation of immunogenic neoantigens. Downregulation of HNRNPA1 inhibited tumor growth and increased CD8+ T cell infiltration in vivo. Conclusion Our study demonstrated that targeting HNRNPA1 could produce immunogenic neoantigens that elicit anti-tumor immunity by inducing abnormal mRNA splicing. It suggests that HNRNPA1 may be a potential target for immunotherapy.

Background: The paclitaxel liposome formulation, encapsulating paclitaxel within a phospholipid bilayer, addresses the insolubility of traditional paclitaxel formulations, thereby reducing toxicity without compromising its antitumor efficacy. Methods: This multicenter, open-label, non-inferiority randomized controlled trial (ChiCTR2000038555) evaluates the efficacy and safety of paclitaxel liposome in comparison to the standard regimen of paclitaxel combined with carboplatin (PLC vs. PC) as first-line therapy in patients with epithelial ovarian cancer. Results: An analysis of median progression-free survival (PFS) revealed non-inferior outcomes between 263 patients in the PLC group and 260 patients in the PC group (32.3 vs. 29.9 months, hazard ratio [HR], 0.89 [95% CI, 0.64−1.25]), using a non-inferior margin of 1.3. Although the overall incidence of treatment-related adverse events was comparable between groups, the PLC group experienced significantly fewer non-hematologic toxicities than those treated with the PC regimen. Conclusion: The findings affirm the non-inferiority of paclitaxel liposome compared to the combination of paclitaxel and carboplatin regarding therapeutic efficacy, with an enhanced safety profile marked by reduced non-hematologic toxicities.

Abstract Background Tumor-infiltrating lymphocyte (TIL) therapy has been restricted by intensive lymphodepletion and high-dose intravenous interleukin-2 (IL-2) administration. To address these limitations, we conducted preclinical and clinical studies to evaluate the safety, antitumor activity, and pharmacokinetics of an innovative modified regimen in patients with advanced gynecologic cancer. Methods Patient-derived xenografts (PDX) were established from a local recurrent cervical cancer patient. TILs were expanded ex vivo from minced tumors without feeder cells in the modified TIL therapy regimen. Patients underwent low-dose cyclophosphamide lymphodepletion followed by TIL infusion without intravenous IL-2. The primary endpoint was safety; the secondary endpoints included objective response rate, duration of response, and T cell persistence. Results In matched patient-derived xenografts (PDX) models, homologous TILs efficiently reduced tumor size (p

Abstract To study the total particulate matter (TPM) in flue gas emitted by coking plants, a sampling system that could be used to collect filterable particulate matter (FPM) and condensable particulate matter (CPM) was designed and developed based on Method 202 recommended by the U.S. Environmental Protection Agency in 2017 and HJ 836-2017 issued by China. Using this system, FPM and CPM in flue gas emitted by four coking furnaces named A, B, C, and D were tested in China. Further, 9 water-soluble ions, 20 elements, and organic matter present in the CPM were simultaneously examined to determine their formation mechanisms. Statistical data suggested that the FPM emission level in the coking flue gas was low and the average mass concentration was less than 10 mg/m3. However, with high CPM and TPM emission levels, the TPM mass concentrations of A, B, C, and D were 130 ± 11.1, 84.4 ± 6.36, 35.1 ± 17.0, and 63.8 ± 13.0 mg/m3, respectively. The main component of TPM was CPM, and the average mass concentration of CPM accounted for 98%, 95%, 68%, and 95% of TPM in furnaces A, B, C, and D, respectively. Water-soluble ions were the important components of CPM, and the total concentration of water-soluble ions accounted for 70%, 87%, 42%, and 66% of CPM in furnaces A, B, C, and D, respectively. Toxic and harmful heavy metals, such as Mn, Cr, Ni, Cu, Zn, As, Cd, and Pb, were detected in CPM. The formation mechanism of CPM was analyzed in combination with flue-gas treatment. It was shown that the treatment process “activated carbon– flue-gas countercurrent-integrated purification technology + ammonia spraying” used in furnaces A and B was less effective in removing CPM, water-soluble ions, metals, and compounds than that of “selective catalytic reduction denitrification + limestone–gypsum wet desulfurization (spraying NaOH solution)” in furnaces C and D. Hence, different flue-gas treatment technologies and operation levels played vital roles in the formation, transformation, and removal of CPM from flue-gas. Organic components in CPM discharged from furnace A were determined via gas chromatography–mass spectrometry, and the top 15 organic components in CPM were obtained using the area normalization method. N-alkanes accounted for the highest proportion, followed by esters and phenols, and most of them were toxic and harmful to humans and ecosystems. Therefore, advanced CPM treatment technologies should be developed to reduce atmospheric PM2.5 and its precursors to improve ambient air quality in China.

Abstract During spaceflight, the cardiovascular system undergoes remarkable adaptation to microgravity and faces the risk of cardiac remodeling. Therefore, the effects and mechanisms of microgravity on cardiac morphology, physiology, metabolism, and cellular biology need to be further investigated. Since China started constructing the China Space Station (CSS) in 2021, we have taken advantage of the Shenzhou-13 capsule to send human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) to the Tianhe core module of the CSS. In this study, hPSC-CMs subjected to space microgravity showed decreased beating rate and abnormal intracellular calcium cycling. Metabolomic and transcriptomic analyses revealed a battery of metabolic remodeling of hPSC-CMs in spaceflight, especially thiamine metabolism. The microgravity condition blocked the thiamine intake in hPSC-CMs. The decline of thiamine utilization under microgravity or by its antagonistic analog amprolium affected the process of the tricarboxylic acid cycle. It decreased ATP production, which led to cytoskeletal remodeling and calcium homeostasis imbalance in hPSC-CMs. More importantly, in vitro and in vivo studies suggest that thiamine supplementation could reverse the adaptive changes induced by simulated microgravity. This study represents the first astrobiological study on the China Space Station and lays a solid foundation for further aerospace biomedical research. These data indicate that intervention of thiamine-modified metabolic reprogramming in human cardiomyocytes during spaceflight might be a feasible countermeasure against microgravity.

Abstract Background Congenital anomalies of the kidney and urinary tract (CAKUT) are prevalent birth defects. Although pathogenic CAKUT genes are known, they are insufficient to reveal the causes for all patients. Our previous studies indicated GEN1 as a pathogenic gene of CAKUT in mice, and this study further investigated the correlation between GEN1 and human CAKUT. Methods In this study, DNA from 910 individuals with CAKUT was collected; 26 GEN1 rare variants were identified, and two GEN1 (missense) variants in a non-CAKUT group were found. Mainly due to the stability results of the predicted mutant on the website, in vitro, 10 variants (eight CAKUT, two non-CAKUT) were selected to verify mutant protein stability. In addition, mainly based on the division of the mutation site located in the functional region of the GEN1 protein, 8 variants (six CAKUT, two non-CAKUT) were selected to verify enzymatic hydrolysis, and the splice variant GEN1 (c.1071 + 3(IVS10) A > G) was selected to verify shear ability. Based on the results of in vitro experiments and higher frequency, three sites with the most significant functional change were selected to build mouse models. Results Protein stability changed in six variants in the CAKUT group. Based on electrophoretic mobility shift assay of eight variants (six CAKUT, two non-CAKUT), the enzymatic hydrolysis and DNA-binding abilities of mutant proteins were impaired in the CAKUT group. The most serious functional damage was observed in the Gen1 variant that produced a truncated protein. A mini-gene splicing assay showed that the variant GEN1 (c.1071 + 3(IVS10) A > G) in the CAKUT group significantly affected splicing function. An abnormal exon10 was detected in the mini-gene splicing assay. Point-mutant mouse strains were constructed (Gen1: c.1068 + 3 A > G, p.R400X, and p.T105R) based on the variant frequency in the CAKUT group and functional impairment in vitro study and CAKUT phenotypes were replicated in each. Conclusion Overall, our findings indicated GEN1 as a risk factor for human CAKUT.

Abstract The unsustainable and widespread utilization of fossil fuels continues to drive the rapid depletion of global supplies. Biodiesel has emerged as one of the most promising alternatives to conventional diesel, leading to growing research interest in its production. Microbes can facilitate the de novo synthesis of a type of biodiesel in the form of fatty acid methyl esters (FAMEs). In this study, Saccharomyces cerevisiae metabolic activity was engineered to facilitate enhanced FAME production. Initially, free fatty acid concentrations were increased by deleting two acetyl-CoA synthetase genes (FAA1, FAA4) and an acyl-CoA oxidase gene (POX1). Intracellular S-adenosylmethionine (SAM) levels were then enhanced via the deletion of an adenosine kinase gene (ADO1) and the overexpression of a SAM synthetase gene (SAM2). Lastly, the S. cerevisiae strain overproducing free fatty acids and SAM were manipulated to express a plasmid encoding the Drosophila melanogaster Juvenile Hormone Acid O-Methyltransferase (DmJHAMT). Using this combination of engineering approaches, a FAME concentration of 5.79 ± 0.56 mg/L was achieved using these cells in the context of shaking flask fermentation. To the best of our knowledge, this is the first detailed study of FAME production in S. cerevisiae. These results will provide a valuable basis for future efforts to engineer S. cerevisiae strains for highly efficient production of biodiesel.

IntroductionRepetitive transcranial magnetic stimulation (rTMS) can improve post stroke motor function. However, there is little research on targets. The purpose of this study is to investigate the effects of rTMS therapy with different targets on post stroke motor function and neural plasticity.MethodsFifty-four subjects were randomly divided into M1 (Primary motor area) group, SMA (supplementary motor area) group and Sham group, and were given 10 Hz on the affected M1 area, SMA area and sham stimulation rTMS. The primary outcomes included Fugl-Meyer Assessment Upper Extremity Scale (FMA-UE), Fugl-Meyer Assessment Lower Extremity Scale (FMA-LE) and Berg balance scale (BBS). Secondary outcomes: amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo) and functional connectivity (FC) were analyzed by functional magnetic resonance imaging (fMRI) to evaluate brain functional activation and functional connectivity changes.ResultsThe 2-way repeated-measures ANOVA revealed a significant group × time interaction (F = 23.494, p

Background: Previous studies have shown that necroptosis-related long noncoding RNA (lncRNA) risk models can be used to predict prognosis and immune infiltration in patients with esophageal cancer. However, further analysis of the regulatory mechanisms of necroptosis-related lncRNAs used in risk models remains to be conducted. The purpose of the present study was to identify valuable necroptosis-related lncRNAs in esophageal cancer and to verify their molecular and cellular functions. Methods: Esophageal cancer data were downloaded from The Cancer Genome Atlas (TCGA). The expression of eight genes (LINC00299, AC090912.2, AC244197.2, AL158166.1, AC079684.1, AP003696.1, AC079684.1 and AP003696.1) in the necroptosis-related lncRNA risk model, their relationships with clinicopathological stage, and their diagnostic receiver operating characteristic (ROC) curves were analyzed. The prognostic value of these lncRNAs for overall survival (OS) and disease specific survival (DSS) was analyzed, and time-dependent ROC curves were generated. The AP003696.1 target gene (lncRNA ENSG00000253385.1) was further investigated through immune infiltration analysis, Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) enrichment analyses, and gene coexpression analysis. Finally, in vitro functional assays based on lncRNA ENSG00000253385.1 were conducted to explore its regulatory role in esophageal cancer. Results: A bioinformatics approach was used to study the eight genes in the necroptosis-related lncRNA risk model. AP003696.1 (lncRNA ENSG00000253385.1) was highly expressed in esophageal cancer tissues, and its high expression was correlated with poor OS and DFdS. Both univariate and multivariate Cox regression analyses revealed that lncRNA ENSG00000253385.1 is an independent prognostic factor. The lncRNA ENSG00000253385.1 gene was demonstrated to play a definite role in the invasion of esophageal cancer immune cells and in signaling pathways in these cells. In vitro cell functional assays revealed that lncRNA ENSG00000253385.1 expression was elevated in the KYSE150 and KYSE410 esophageal cancer cell lines. Small interfering RNA (siRNA)-mediated silencing of lncRNA ENSG00000253385.1 significantly inhibited the proliferation, migration, and invasion of KYSE150 and KYSE410 cells, as well as promoted their apoptosis. Conclusions: The ENSG00000253385.1 gene may be a key gene in the occurrence, development, and prognosis of esophageal cancer. These findings provide new ideas and references for the screening of therapeutic targets, as well as the development of targeted drugs, for esophageal cancer treatment.

BackgroundAberrant lipid metabolism is intricately linked to the development of endometrial cancer, and statin lipid-lowering medications are regarded as promising adjunctive therapies for future management of this malignancy. This study employed Mendelian randomization (MR) to explore the causal association between lipid traits and endometrial cancer while assessing the potential impact of drug targets on lower lipids on endometrial cancer.MethodTwo-sample Mendelian randomization was employed to probe the causal association between lipid traits and endometrial carcinoma. Drug-target Mendelian randomization was also utilized to identify potential drug-target genes for managing endometrial carcinoma. In instances where lipid-mediated effects through particular drug targets were notable, the impacts of these drug targets on endometrial carcinoma risk factors were investigated to bolster the findings.ResultNo causal association between genetically predicted lipid traits (LDL-C, TG, TC, and HDL-C) and EC was found in two-sample Mendelian randomization. In drug target Mendelian randomization, genetic modeling of apolipoprotein B (APOB) (OR [95%CI]=0.31, [0.16-0.60]; p=4.73e-04) and cholesteryl ester transfer protein (CETP) (OR [95%CI]=1.83, [1.38-2.43]; p=2.91e-05) genetic mimicry was associated with non-endometrioid carcinoma.ConclusionThe results of our MR study revealed no causal association between genetically predicted lipid traits (LDL-C, TG, TC, and HDL-C) and EC. Among the six lipid-lowering drug targets, we observed a significant association between lower predicted APOB levels and higher CETP levels with an increased risk of endometrioid carcinoma. These findings provide novel insights into the importance of lipid regulation in individuals with endometrial carcinoma, warranting further clinical validation and mechanistic investigations.

BackgroundIn the general population, primary human papillomavirus (HPV) testing is advocated for cervical cancer (CC) screening. HPV E6/E7 mRNA (Aptima HPV, AHPV) assays have garnered considerable traction due to their higher specificity when compared with HPV DNA assays. Here, we investigated age-specific primary AHPV screening assays and different triage strategies versus cytology to identify the best approach.MethodsBetween April 2018 and December 2021, we recruited female participants from 34 communities across Liaoning province and Qingdao City, China. Primary cervical screening protocols included liquid-based cytology (LBC) and AHPV assays, with females positive for any assays undergoing colposcopy. Genotyping (AHPV-GT) was conducted on all HPV-positive samples. Our primary outcomes were the identification of age-specific detection rates, colposcopy referral rates, and sensitivity and specificity values for high-grade squamous intraepithelial lesions or worse (HSIL+). AHPV and different triage strategy performances were also examined across different age cohorts.ResultsOur investigation included 9911 eligible females. Age-specific abnormal cytology rates were in the 6.1%–8.0% range, and were highest in 45–54-year olds. When compared with 35–44-or 45–54-year olds, HPV prevalence was highest in 55–64-year olds (12.2% or 11.6% vs.14.1%, P = 0.048 and P = 0.002, respectively). In 35–44-year olds, AHPV sensitivity for detecting HSIL+ was 96.6 (95% confidence interval [CI]: 89.7–100) - significantly higher than LBC sensitivity (65.5 [95% CI: 48.3–82.8], P < 0.001). When compared with LBC, HSIL+ detection rates by AHPV-GT using reflex LBC triage increased by 31.5% (9.6‰ vs. 7.3‰), and colposcopy referral rates decreased by 16.4% (5.1% vs. 6.1%). In 45–54-year olds, HSIL+ detection rates for AHPV-GT using reflex LBC triage were lower than LBC rates (6.2‰ vs. 6.6‰). In 55–64-year olds, AHPV sensitivity (97.2 [95% CI: 91.7–100.0]) was higher than LBC sensitivity (66.7 [95% CI: 50.0–80.6], P = 0.003). The area under the curve (AUC) value was not significantly different between AHPV-GT with reflex LBC triage and LBC (0.845 [95% CI: 0.771–0.920] vs. 0.812 [95% CI: 0.734–0.891], P = 0.236).ConclusionsPrimary AHPV screening using different triage strategies were different across different age cohorts. Thus, AHPV may be an appropriate primary screening method for 35–44 and 55–64 year old females, while AHPV-GT with reflex LBC triage may be more apt for 35–44 year old females.

The Gulong shale demonstrates high clay content and pronounced thin laminations, with limited vertical variability in log curves, complicating lithofacies classification. To comprehend the distribution and compositional features of lithofacies in the Gulong shale for optimal sweet spot selection and reservoir stimulation, this study introduced a lithofacies classification scheme and a log-based lithofacies evaluation method. Specifically, the ΔlgR method was utilized for accurately determining the total organic carbon (TOC) content; a multi-mineral model based on element-to-mineral content conversion coefficients was developed to enhance mineral composition prediction accuracy, and the microresistivity curve variations derived from formation micro-image (FMI) log were used to compute lamination density, offering insights into sedimentary structures. Using this method, integrating TOC content, sedimentary structures, and mineral compositions, the Qingshankou Formation is classified into four lithofacies and 12 sublithofacies, displaying 90.6% accuracy compared to core description outcomes. The classification results reveal that the northern portion of the study area exhibits more prevalent fissile felsic shales, siltstone interlayers, shell limestones, and dolomites. Vertically, the upper section primarily exhibits organic-rich felsic shale and siltstone interlayers, the middle part is characterized by moderate organic quartz-feldspathic shale and siltstone/carbonate interlayers, and the lower section predominantly features organic-rich fissile felsic/clayey felsic shales. Analyzing various sublithofacies in relation to seven petrophysical parameters, oil test production, and fracturing operation conditions indicates that the organic-rich felsic shales in the upper section and the organic-rich/clayey felsic shales in the lower section possess superior physical properties and oil content, contributing to smoother fracturing operation and enhanced production, thus emerging as dominant sublithofacies. Conversely, thin interlayers such as siltstones and limestones, while producing oil, demonstrate higher brittleness and pose great fracturing operation challenges. The methodology and insights in this study will provide a valuable guide for sweet spot identification and horizontal well-based exploitation of the Gulong shale.

Tissue-resident memory T (TRM) cells infiltrating solid tumors could influence tumor progression and the response to immune therapies. However, the proportion and prognostic value of TRM cells in the bone marrow (BM) of patients with acute myeloid leukemia (AML) are unclear. In this study, we used flow cytometry to assay the phenotype of 49 BM samples from patients newly diagnosed with AML (ND-AML). We found that the BM CD8+ effector memory (TEM) cells highly expressed CD69 (CD8+ TRM-like T cells), and their percentage was significantly increased in patients with ND-AML compared with that in healthy individuals (HI). The high percentage of CD8+ TRM-like subset was associated with poor overall survival in our ND-AML cohort. The Kaplan–Meier Plotter database verified a significantly reduced survival rate among patients with high expression of CD8+ TRM-like T cell characteristic genes (CD8A, CD69, and TOX), especially the M4 and M5 subtypes. Phenotypic analysis revealed that the BM CD8+ TRM-like subpopulation exhibited exhausted T cell characteristics, but its high expression of CD27 and CD28 and low expression of CD57 suggested its high proliferative potential. The single-cell proteogenomic dataset confirmed the existence of TRM-like CD8+ T cells in the BM of patients with AML and verified the high expression of immune checkpoints and costimulatory molecules. In conclusion, we found that the accumulation of BM CD8+ TRM-like cells could be an immune-related survival prediction marker for patients with AML.

Thermal action is a crucial process in laser processing. The classical Fourier heat conduction theory, which assumes an infinite speed of heat propagation, is commonly applied to describe steady-state and mild transient thermal processes. However, under the influence of ultra-short pulse lasers, such as those with picosecond and femtosecond durations, the heat propagation speed within the material is finite and deviates from Fourier’s law. This article addresses the unique characteristics of heat conduction in materials subjected to ultra-short pulse laser exposure by integrating Fourier’s law with the Gaussian distribution of the actual pulse laser output power density and the material’s optical absorption properties. It introduces a time variable to establish a time-dependent heat conduction equation. This equation is numerically analyzed using a difference algorithm. Based on this, simulation and experimental studies on the processing of dental hard tissues with a 1064 nm ps laser were conducted. The results show that the experimental processing depths were slightly larger than the simulation results, which may be due to damage to the dental hard tissues and the thermomechanical effects during processing. The results offer a technical reference for adjusting laser parameters in the ultra-short pulse laser processing technique.

BackgroundThis study aimed to measure the accuracy of optical coherence tomography (OCT) in the early diagnosis of high-grade cervical lesions and assess its diagnostic value in the triage of high-risk HPV infection.MethodFrom Jan 2019 to Jan 2021, women who visited the gynecology clinics of 2 hospitals for colposcopy were invited to participate in this study. Women aged 35 to 64 years old who were sexually active and had an intact cervix with a diameter of more than or equal to 2 cm were included in this study. Additionally, individuals with abnormal cytology, positive HPV test results, or other clinically suspicious symptoms or signs were referred. All participants were examined before colposcopy using OCT. Biopsy and/or ECC were conducted under colposcopy. We used the results of histopathology as the gold standard and assessed the accuracy of OCT.ResultsOverall, 883 women were included in the analysis. Approximately 13.25% of women were ASCUS+ in cytological assessments, and 22.31% were positive for high-risk HPV. Nearly 15.18% of women were positive in OCT. Of them, 27 women were diagnosed with CIN2, and 33 were diagnosed with CIN3+ lesions. Among HPV-positive women, the detection rates for CIN2+ and CIN3+ were much lower for those who were negative in OCT, compared with NILM cytology (CIN2+: 20.0% vs. 30.0%, P=0.002, and CIN3+: 18.2% vs. 27.3%, P=0.013). Among women who were positive for HPV16/18, the detection rate for CIN2+ was much lower for negative OCT, compared with NILM cytology (8.3% vs.15.0%, P=0.005). Compared to HPV and cytological tests, HPV combined with OCT had higher specificity for detecting CIN2+ and CIN3+ (96.1% vs. 93.2%, P=0.002; 93.8% vs. 91.3%, P=0.013). OCT triage after HPV genotyping had the highest AUC for detecting CIN2+ and CIN3+ cases among patients with high-risk HPV infection (0.921, 0.920).ConclusionOCT is an accurate test for the early diagnosis of high-grade cervical lesions and has great diagnostic value in the triage of patients with high-risk HPV infection.

Abstract Objective The present research aimed to explore the dynamic change of the neutrophil‐to‐lymphocyte ratio (NLR) and its relationship with functional outcome following an acute ischemic stroke (AIS), whether receiving intravenous thrombolysis (IVT) or not. Methods We retrospectively analyzed data that were prospectively acquired from patients with AIS treated with IVT or not. For patients receiving IVT, the NLR was based on a blood test performed prior to IVT (d0) and at different time points after disease onset (d1, d3, d7). In addition, in the non‐IVT group, the NLR was obtained at different time points after disease onset (d1, d3, d7). Follow‐ups were performed 3 months after onset via telephone. In addition, a good outcome was defined as a modified Rankin scale (mRS) ≤1; a poor outcome means 2 ≤ mRS ≤ 6. Results A total of 204 AIS patients were included in this study. The NLR presented a dynamic change as it increased to its peak at day 1 and gradually declined to its baseline at day 7, no matter whether patients were receiving IVT or not. Patients with poor outcomes have a higher NLR at various time points. The results of multivariate logistic regression analysis demonstrated that the National Institutes of Health Stroke Scale (NIHSS), NLR d1, NLR d3, and NLR d7 were independently associated with functional outcomes. The area under the receiver operating characteristic curve of NLR in predicting outcomes was as follows: NLR d3 demonstrated robust predictive power within the IVT therapy cohort, whereas NLR d7 was predictive in the non‐IVT cohort. However, the most potent predictor emerged as the combination of NIHSS and NLR. Conclusion NLR has the potential to predicate diagnosis for AIS, especially when combined with the NIHSS score.

BackgroundIt is unclear whether patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are allowed variable low levels of alcohol. This study aimed to evaluate the effect of mild-moderate alcohol consumption on the biochemical and histological characteristics of patients with MASLD.MethodsAlcohol consumption was assessed in 713 patients with steatotic liver disease (SLD) who underwent liver biopsy. Non-drinking, mild-moderate drinking, and excessive drinking were defined as 0 g/day, 1-20 g/day for women and 0 g/day, 1-30 g/day for men, respectively. Liver biopsies were scored according to the NASH CRN system.ResultsA total of 713 participants (median age 39.0 years and 77.1% male) with biopsy-proven SLD were enrolled, including 239 nondrinkers, 269 mild-moderate drinkers and 205 excessive drinkers. Excessive drinking was associated with increased risks for lobular inflammation and liver fibrosis compared to nondrinkers and mild-moderate drinkers. Compared with non-drinkers, mild-moderate drinkers had significantly lower odds for steatosis (OR = 0.60, 95% CI = 0.38–0.93, p = 0.025), hepatocellular ballooning (OR = 0.52, 95% CI = 0.29–0.91, p = 0.020) and fibrosis (OR = 0.50, 95% CI = 0.31–0.81, p = 0.005). However, in non-excessive drinkers with type 2 diabetes mellitus (T2DM), there was no association between mild-moderate alcohol consumption and liver fibrosis (OR = 0.562, 95% CI = 0.207–1.530, p = 0.257).ConclusionsMild-moderate alcohol consumption might be protective against liver fibrosis in MASLD patients, which is modified by the presence of T2DM. However, further longitudinal studies are needed to determine the effect of ongoing alcohol consumption on disease severity.

Digital soil mapping relies on statistical relationships between soil profile observations and environmental covariates at the sample locations. However, inherent limitations of legacy soil profiles, such as inaccurate georeferencing, could frequently introduce location errors into these soil profiles that affect the quality of digital soil mapping. To address this challenge, this study focuses on reducing the location error of legacy soil profiles and evaluating the resulting impact on digital soil mapping. We improved the agreement between the detailed descriptive information of legacy soil profiles and the relatively accurate environmental covariates (such as elevation, slope, and land use) to reduce the location errors of the legacy soil profiles. Quantile regression forest models were constructed to predict soil properties and their uncertainty using legacy soil profiles before and after location error correction. Our results demonstrate that for the majority of soil variables, correcting positional errors in legacy soil profiles to some extent enhances the accuracy of the digital soil mapping. The largest improvement was found for soil organic carbon at 0–5 cm depth interval, with 21 % increase of MEC. The impact of reduced location error is particularly noteworthy in regions characterized by complex terrain. In addition, the details of the predicted maps of legacy soil profiles were improved after correcting for positional errors, which better represent the spatial variation of soil properties across China. Besides, we also found that elevation was the primary controlling factor for correcting location error of legacy soil profiles. This research presents a step towards producing high-resolution and high-quality spatial soil datasets, which can provide essential support for soil management and ensure future soil security.

Abstract Estimating household water consumption can facilitate infrastructure management and municipal planning. The relatively low explanatory power of household water consumption, although it has been extensively explored based on various techniques and assumptions regarding influencing features, has the potential to be enhanced based on the water-energy nexus concept. This study attempts to explain household water consumption by establishing estimation models, incorporating energy-related features as inputs and providing strong evidence of the need to consider the water-energy nexus to explain water consumption. Traditional statistical (OLS) and machine learning techniques (random forest and XGBoost) are employed using a sample of 1320 households in Beijing, China. The results demonstrate that the inclusion of energy-related features increases the coefficient of determination (R 2) by 34.0% on average. XGBoost performs the best among the three techniques. Energy-related features exhibit higher explanatory power and importance than water-related features. These findings provide a feasible modelling basis and can help better understand the household water-energy nexus.