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Abstract China has implemented the “tiered medical services” policy since 2015, while there is a paucity of data evaluating the the current status of chronic obstructive pulmonary disease (COPD) management under the system. Characteristics and treatments from 11,905 COPD patients in 88 hospitals across different tiers in China were included and analyzed. We assessed the statistical significance of differences by one way analysis of variance (ANOVA) for continuous variables and with the chi-squared test for categorical variables. Patients in primary hospitals (Tier1) exhibited heightened exposure to risk factors including smoking, household biofuel, and family history of respiratory diseases, and displayed elevated COPD assessment test (CAT) and modified Medical Research Council (mMRC) dyspnea scale scores, and worse lung function, in comparison to tertiary (Tier3) hospitals (P

Abstract Long non-coding RNA (lncRNA) plays important roles in animals and plants. In filamentous fungi, however, their biological function in infection stage has been poorly studied. Here, we investigated the landscape and regulation of lncRNA in the filamentous plant pathogenic fungus Botrytis cinerea by strand-specific RNA-seq of multiple infection stages. In total, 1837 lncRNAs have been identified in B. cinerea. A large number of lncRNAs were found to be antisense to mRNAs, forming 743 sense-antisense pairs, of which 55 antisense lncRNAs and their respective sense transcripts were induced in parallel as the infection stage. Although small RNAs were produced from these overlapping loci, antisense lncRNAs appeared not to be involved in gene silencing pathways. In addition, we found the alternative splicing events occurred in lncRNA. These results highlight the developmental stage-specific nature and functional potential of lncRNA expression in the infection stage and provide fundamental resources for studying infection stage-induced lncRNAs.

Abstract Background Recognition of carbapenem-resistant gram-negative bacteria (CR-GNB) carriage is frequently delayed, which increases the risk of subsequent infection and transmission. Previously, we developed a scoring system to identify CR-GNB carriage upon intensive care unit (ICU) admission. Although the ICU-CARB score showed satisfactory performance, it has not been externally validated. In this study, therefore, we externally validated the ICU-CARB score. Methods In the previous article, we introduced a risk-scoring system that incorporated seven key variables: neurological disease, high-risk department history, length of stay ≥ 14 days, ICU history, invasive mechanical ventilation, gastrointestinal tube placement, and carbapenem usage. To externally validate the ICU-CARB score, we conducted a study involving patients admitted to the ICUs of four tertiary hospitals between January 2021 and December 2023. Patients from three hospitals were grouped into Cohort I (n = 815) and those from the fourth hospital into Cohort II (n = 1602). Model calibration, discrimination, and performance were then assessed. Results A total of 2417 patients were included, among which 289 (12%) carried CR-GNB upon ICU admission. Neurological disease, high-risk department history and length of stay ≥ 14 days were still 3 most important contributing factors in the scoring system. The ICU-CARB score exhibited high calibration, with an area under the receiver operating characteristic curve of 0.825 (95% confidence interval [CI], 0.778–0.873) for Cohort I and 0.823 (95% CI, 0.791–0.855) for Cohort II. The ICU-CARB score showed a highly positive association with CR-GNB carriage in both cohort I (C = 0.315; P

Piwi-interacting RNAs (piRNAs) are a class of small non-coding RNAs (ncRNAs) that plays important roles in many biological processes and major cancer diagnosis and treatment, thus becoming a hot research topic. This study aims to provide an in-depth review of computational piRNA-related research, including databases and computational models. Herein, we perform literature analysis and use comparative evaluation methods to summarize and analyze three aspects of computational piRNA-related research: (i) computational models for piRNA-related molecular identification tasks, (ii) computational models for piRNA–disease association prediction tasks, and (iii) computational resources and evaluation metrics for these tasks. This study shows that computational piRNA-related research has significantly progressed, exhibiting promising performance in recent years, whereas they also suffer from the emerging challenges of inconsistent naming systems and the lack of data. Different from other reviews on piRNA-related identification tasks that focus on the organization of datasets and computational methods, we pay more attention to the analysis of computational models, algorithms, and performances that aim to provide valuable references for computational piRNA-related identification tasks. This study will benefit the theoretical development and practical application of piRNAs by better understanding computational models and resources to investigate the biological functions and clinical implications of piRNA.

Abstract With the rapid aging of populations and advancements in information technology, the development of intelligent elder-care service platforms (IESPs) has gained momentum. This paper examines the feasibility and strategies for constructing an IESP. Unlike commercial internet platforms, IESP facilitates transactions in elderly care services, which are quasi-public goods requiring government guidance and multi-stakeholder collaboration. Utilizing value co-creation theory, this study constructs a tripartite evolutionary game model involving a digital technology company, a social organization, and an elderly care service provider to analyze factors influencing stakeholder behavior. The findings reveal that sustained value co-creation is influenced by platform revenue, participation costs, reputation effects, and government subsidies. To optimize outcomes, the government should balance stakeholder interests, ensure reasonable profits for the digital company and social organization, and reduce participation costs through grassroots mobilization, data support, and subsidies for digital transformation. Strengthening reputation management and standardizing service evaluations are also crucial for achieving system equilibrium.

Abstract Based on the experimentally reported stable and conductive two-dimensional covalent organic frameworks with copper phthalocyanine (CuPc) as building block and cyan substituted phenyl as connector (CuCOF-CN) as an electrocatalyst for CO2 reduction reaction (RR), first principle calculations were performed on CuCOF-CN and its analog with the CN being replaced by H (CuCOF). Comparatively studied on the crystal structures, electronic properties, and CO2RR performance of the two catalysts found that CuCOF has reduced crystal unit size, more positive charge on Cu and CuPc segments, smaller band gap, and lower reaction barrier for CO2 RR than CuCOF-CN. CuCOF is proposed to be good potential electrocatalyst with good environment friendliness. The substituent effect and structure-property-performance relationship would help for designing and fabricating new electrocatalysts.

Background: To evaluate the effectiveness and safety of the Shenfu injection (SFI) combined with standard bundle treatment in septic patients with hypoperfusion. Method: This study was a multi-center, randomized, open-label, controlled trial conducted in four teaching hospitals in China. The septic patients with hypoperfusion and traditional Chinese medicine (TCM) syndrome with Yang-Qi deficiency were enrolled from January 2019, through September 2020. Eligible patients were randomly allocated in a 1:1 ratio to either receive 60 mL of SFI infusion per day plus standard treatment (SFI group) or standard bundle treatment alone (control group). The primary outcome was 28-day all-cause mortality. Secondary outcomes were 90-day all-cause mortality time to weaning from mechanical ventilation, time to weaning from vasopressors, time to discharge from the ICU and hospital, and laboratory results after randomization. Results: A total of 188 patients completed the trail. This study revealed that the results of the SFI group and the control groups were not statistically significant in 28-day all-cause mortality (10.6% vs. 20.2%, respectively; P=0.106). The infusion of SFI was associated with a significant reduction in the duration of vasopressor use (median=4.0 days, interquartile range [IQR]: 2.0 days–6.0 days vs. median=5.0 days, IQR: 3.0 days–8.0 days, respectively; P=0.043). Patients in the SFI group had statistically greater reductions in plasma lactate levels compared with those in the control group at the first 12 h (median=1.1 mmol/L, IQR: 0.3–2.0 mmol/L vs. median=0.0 mmol/L, IQR: −0.2 to 0.8 mmol/L, respectively; P

Abstract The ongoing epidemic of flaviviruses worldwide has underscored the importance of studying flavivirus vector competence, considering their close association with mosquito vectors. Tembusu virus is an avian-related mosquito-borne flavivirus that has been an epidemic in China and Southeast Asia since 2010. However, the reason for the outbreak of Tembusu virus in 2010 remains unclear, and it is unknown whether changes in vector transmission played an essential role in this process. To address these questions, we conducted a study using Culex quinquefasciatus as a model for Tembusu virus infection, employing both oral infection and microinjection methods. Our findings confirmed that both vertical and venereal transmission collectively contribute to the cycle of Tembusu virus within the mosquito population, with persistent infections observed. Importantly, our data revealed that the prototypical Tembusu virus MM_1775 strain exhibited significantly greater infectivity and transmission rates in mosquitoes than did the duck Tembusu virus (CQW1 strain). Furthermore, we revealed that the viral E protein and 3′ untranslated region are key elements responsible for these differences. In conclusion, our study sheds light on mosquito transmission of Tembusu virus and provides valuable insights into the factors influencing its infectivity and transmission rates. These findings contribute to a better understanding of Tembusu virus epidemiology and can potentially aid in the development of strategies to control its spread.

Abstract Background Social participation is an important index of rehabilitation and social reintegration in patients after total knee arthroplasty (TKA). However, most existing studies focus on improving patients’ functioning and activities, with only a few examining the social participation among patients after TKA. Therefore, the study aims to investigate the heterogeneity of social participation in patients three months after TKA and analyze subgroup influencing factors, to promote functional exercise and postoperative follow-up in specific patients. Methods This cross-sectional study recruited 255 patients who underwent TKA in a Tertiary Hospital in Jinan City, China, from March to July 2022. Three months after having undergone TKA, participants’ data were collected using the Numeric Pain Rating Scale, the Chinese version of the Tampa Scale of Kinesiophobia, the 10-item Kessler Psychological Distress Scale, Hospital for Special Surgery Knee-rating Scale, and Impact on Participation and Autonomy Questionnaire. Latent profile analysis was used to identify categories of patients’ social participation. Multiple logistic regression analysis was used to analyze the influencing factors of the different subgroups. Results Three months after TKA, the patients were divided into three subgroups: low social participation group (17.9%), moderate social participation group (40.8%), and high social participation group (41.3%). The vast majority of patients who underwent TKA exhibited moderate-to-high level of social participation. The multiple logistic regression analysis results showed that age, degree of pain, knee function, and kinesiophobia were the influencing factors of the potential profiles of social participation in patients three months after TKA (p

Chinese jujube (CJ) is a nutritious food. Its authenticity has received increasing attention. This research utilized computer vision, ultrafast gas-phase electronic nose, and GC–MS technologies to collect jujube samples from various regions in China, including Xinjiang, Gansu, Shaanxi, Henan, Shandong, and Hebei. Multidimensional trait data, encompassing spectra, texture, and odour, were gathered. By employing multivariate statistical methods, 46 trait characteristic factors (VIP > 1, P

Abstract Meiosis in males is a critical process that ensures complete spermatogenesis and genetic diversity. However, the key regulators involved in this process and the underlying molecular mechanisms remain unclear. Here, we report an essential role of the m6A methyltransferase METTL16 in meiotic sex chromosome inactivation (MSCI), double‐strand break (DSB) formation, homologous recombination and SYCP1 deposition during male meiosis. METTL16 depletion results in a significantly upregulated transcriptome on sex chromosomes in pachytene spermatocytes and leads to reduced DSB formation and recombination, and increased SYCP1 depositioin during the first wave of spermatogenesis. Mechanistically, in pachytene spermatocytes, METTL16 interacts with MDC1/SCML2 to coordinate DNA damage response (DDR) and XY body epigenetic modifications that establish and maintain MSCI, and in early meiotic prophase I, METTL16 regulates DSB formation and recombination by regulating protein levels of meiosis‐related genes. Furthermore, multi‐omics analyses reveal that METTL16 interacts with translational factors and controls m6A levels in the RNAs of meiosis‐related genes (e.g., Ubr2) to regulate the expression of critical meiotic regulators. Collectively, this study identified METTL16 as a key regulator of male meiosis and demonstrated that it modulates meiosis by interacting with MSCI‐related factors and regulating m6A levels and translational efficiency (TE) of meiosis‐related genes.

BackgroundRespiratory syncytial virus (RSV) is a major cause of severe health problems in newborns and young children. The protective role and limitations of serum maternal RSV antibodies in infants under 3 months remain controversial.MethodsA two-center prospective study from 2020 to 2023 recruited infants (n=286) admitted to the respiratory departments of two children’s hospitals in southwestern and southeastern China during RSV epidemic. These infants were hospitalized with lower respiratory tract infections (LRTI). We evaluated the relationship between serum RSV Prefusion (Pre-F), postfusion (Post-F) IgG levels, subtype neutralizing antibodies, and the incidence of RSV infection, as well as the relationship between these maternal antibodies and severity of disease. Since this prospective study only included data from RSV epidemic, we retrospectively reviewed medical records from the Children’s Hospital of Chongqing Medical University for the years 2019 to 2023 (n=3467) to analyze population characteristics during both RSV epidemic and non-epidemic periods, using the same inclusion and exclusion criteria.ResultThere were no significant differences in RSV Pre-F IgG, Post-F IgG, or RSV A or B neutralizing antibody levels between the RSV infected and non-infected groups during the epidemic. While RSV Pre-F IgG antibody was inversely correlated with disease severity, RSV Post-F IgG, and RSV A and B neutralizing antibodies did not show a similar correlation across the three illness severity categories. Additionally, there were no differences in age, gender, or illness severity distribution among hospitalized patients during epidemic and non-epidemic periods.ConclusionSerum maternal antibody levels offer insufficient protection against RSV-associated LRTI in hospitalized infants aged 28 to 90 days.

Due to the structural diversity and rapid prevalence of synthetic cannabinoids (SCs) in the market, the information linking the chemical structure of SCs to their toxicity remains scant, despite emerging in the 1970s. In the present study, we aimed to investigate the toxicity and underlying mechanisms of indole SCs JWH-018 and JWH-019 in mice (C57BL/6, male, 6–8 weeks old), zebrafish (AB strain, male, 4–5 months old) and modified human embryonic kidney (HEK) 293 T cells, using behavioral, pharmacokinetic, pharmacological approaches, and molecular docking. JWH-018 induced time- and dose-dependent cannabinoid-like effects in mice (administration dosages: 0.02, 0.1, and 0.5 mg/kg, i.p.), and yielded dose-dependent anxiogenic effects and lower aggression behavior in zebrafish (administration dosages: 0.01, 0.05, and 0.25 µg/g, i.p.), unlike JWH-019. These effects were blocked by the selective cannabinoid receptor 1 (CB1R) antagonist AM251. JWH-018, but not JWH-019, activated the CB1R-dependent extracellular signal-regulated kinase 1 and 2 (ERK1/2) pathway in vivo and in vitro. Molecular docking identified essential residues PHE268, PHE170, and TRP279 within CB1R as pivotal contributors to enhancing receptor-ligand associations. While both drugs had a similar binding pattern with shared linker binding pockets in CB1R, there were still differences in their spatial conformation. These findings shed light on the molecular pharmacology and activation mechanism of SCs for CB1R and should guide further research into the mechanisms underlying their deleterious effects in humans.

Background:. The repair of skin defect wounds is a long-term goal of clinical pursuit. Currently, free or pedicled skin flap transplantation is commonly used to repair skin defects. However, these methods may lead to complications such as flap necrosis, thrombosis, scarring, diminished sensation, and pigmentation in both the donor and recipient areas. Since its introduction in 1976, skin stretching techniques were widely used for minor skin and soft-tissue defects in the surgical field. Methods:. A narrative review was conducted to identify relevant articles about the skin stretching techniques for promoting wound healing. We searched the Web of Science and PubMed databases for all articles containing different combinations of “skin stretch techniques” and “wound repair,” “skin defects,” and “tissue expansion.” Results:. Through the screening of 500 articles, 84 representative and persuasive articles were selected in this review. These studies collectively demonstrate the technique’s effectiveness in reducing wound size, facilitating primary closure, and improving cosmetic outcomes. Reported complications were generally minor, including transient erythema and mild discomfort, with rare instances of skin necrosis. Conclusions:. Skin stretch techniques emerge as a promising approach for managing large-area wounds, offering the advantage of achieving primary healing without compromising surrounding healthy tissue. However, to optimize its clinical application, further research is warranted, particularly in addressing challenges related to precise stretching and infection management.

Hysteroscopic myomectomy is widely used to treat submucosal myomas. However, performing hysteroscopic surgery on certain type II (and even type III) or large myomas remains challenging. High-intensity focused ultrasound (HIFU) has recently emerged as a promising alternative for treating various gynecologic conditions. Studies have shown that following HIFU ablation, not only is the myoma volume reduced, but the intramural portion of the myoma may also protrude into the uterine cavity. This reclassification or ‘degradation’ of the myoma could facilitate the resection of difficult type II and III myomas during hysteroscopy, ultimately reducing the complexity of the procedure and improving surgical safety.

BackgroundNuclear protein in testis (NUT) cancers, also known as midline cancers, tends to occur in organs near the midline, such as the nasal sinuses and mediastinum. NUT carcinoma is very rare and has a poor prognosis.Case descriptionWe report the case of a 44-year-old female patient with sinonasal NUT carcinoma who presented with a soft tissue mass in the left frontal sinus, ethmoid sinus, and left nasal cavity on computed tomography; the tumor was poorly demarcated from the left rectus medialis. After discussion with a multidisciplinary team with expertise on head and neck tumors, the patient was considered inoperable, and definitive concurrent chemoradiotherapy (CCRT) was recommended. The patient underwent CCRT followed by three cycles of consolidation chemotherapy with albumin-bound paclitaxel and nedaplatin. Subsequently, the patient underwent 16 cycles of consolidation therapy with the programmed death–1 (PD-1) inhibitor tislelizumab. The immune-related adverse events included grade 2 hypothyroidism. After CCRT, consolidation chemotherapy, and consolidation immunotherapy, the patient achieved a favorable outcome. The patient survived for 31 months, and there were no signs of recurrence or metastasis during follow-up.ConclusionAt present, there is no clear consensus on the consolidation treatment plan after CCRT for sinonasal NUT cancer. We used consolidation immunotherapy for the first time and achieved good efficacy, providing an innovative and promising treatment plan for refractory sinonasal NUT cancer.

Purpose Immune checkpoint inhibitors (ICIs) and target therapy have provided the clinical efficacy for improving the clinical progression-free survival (PFS) and overall survival (OS) for patients with renal cell carcinoma (RCC). There has been little report of an surrogate salvage treatment for those failure of both ICIs and target. An innovation therapeutic model named SHAPE-T (synchronized hyperthermia with ex vivo autologous progenitor expanded T cells) was applied to previously heavily treated metastatic RCC (mRCC). The safety and clinical response with a three-year follow-up were filed.Materials and methods This was N-of-1 clinical study describing such mRCC case with ECOG 3-4 score was treated by SHAPE-T. The peripheral blood apheresis was completed to produce ACT in vitro periodically .The nonimplantable in-depth hyperthermia device where the intratumor temperature could reach 42.5 C was performed for the average of 45 min, twice per week. One cycle ACT constituted three infusions of RetroNectin activated killer (RAK)cells at each 28 days interval. One SHAPE-T therapeutic schema included two cycles of 42.6 billion of RAKs plus 10 times of hyperthermia. The primary endpoints were PFS and OS. The clinical safety and efficacy of treatment cycles of infused T cells and therapeutic cycle were recorded.Results The enrolled patient was successfully recovered to complete response with OS exceeded 40 months. The ECOG performance recovered and sustained to score 0. There were less adverse reactions associated with SHAPE-T.Conclusions The intractable and progressive mRCC could be salvaged by SHAPE-T. This was the first case that provide the insights into the importance of the SHAPE-T.

Hypervirulent Klebsiella pneumoniae isolates have been increasingly reported worldwide, especially hypervirulent drug-resistant variants owing to the acquisition of a mobilizable virulence plasmid by a carbapenem-resistant strain. This pLVPK-like mobilizable plasmid encodes various virulence factors; however, information about its genetic stability is lacking. This study aimed to investigate the type II toxin-antitoxin (TA) modules that facilitate the virulence plasmid to remain stable in K. pneumoniae. More than 3,000 TA loci in 2,000 K. pneumoniae plasmids were examined for their relationship with plasmid cargo genes. TA loci from the RES-Xre family were highly correlated with virulence plasmids of hypervirulent K. pneumoniae. Overexpression of the RES toxin KnaT, encoded by the virulence plasmid-carrying RES-Xre locus knaAT, halts the cell growth of K. pneumoniae and E. coli, whereas co-expression of the cognate Xre antitoxin KnaA neutralizes the toxicity of KnaT. knaA and knaT were co-transcribed, representing the characteristics of a type II TA module. The knaAT deletion mutation gradually lost its virulence plasmid in K. pneumoniae, whereas the stability of the plasmid in E. coli was enhanced by adding knaAT, which revealed that the knaAT operon maintained the genetic stability of the large virulence plasmid in K. pneumoniae. String tests and mouse lethality assays subsequently confirmed that a loss of the virulence plasmid resulted in reduced pathogenicity of K. pneumoniae. These findings provide important insights into the role of the RES-Xre TA pair in stabilizing virulence plasmids and disseminating virulence genes in K. pneumoniae.

This study is to investigate the therapeutical effect and mechanisms of human-derived adipose mesenchymal stem cells (ADSC) in relieving adriamycin (ADR)-induced nephropathy (AN). SD rats were separated into normal group, ADR group, ADR+Losartan group (20 mg/kg), and ADR + ADSC group. AN rats were induced by intravenous injection with adriamycin (8 mg/kg), and 4 d later, ADSC (2 × 105 cells/mouse) were administrated twice with 2 weeks interval time (i.v.). The rats were euthanized after the 6 weeks’ treatment. Biochemical indicators reflecting renal injury, such as blood urea nitrogen (BUN), neutrophil gelatinase alpha (NGAL), serum creatinine (Scr), inflammation, oxidative stress, and pro-fibrosis molecules, were evaluated. Results demonstrated that we obtained high qualified ADSCs for treatment determined by flow cytometry, and ADSCs treatment significantly ameliorated renal injuries in DN rats by decreasing BUN, Scr and NGAL in peripheral blood, as well as renal histopathological injuries, especially protecting the integrity of podocytes by immunofluorescence. Furthermore, ADSCs treatment also remarkably reduced the renal inflammation, oxidative stress, and fibrosis in DN rats. Preliminary mechanism study suggested that the ADSCs treatment significantly increased renal neovascularization via enhancing proangiogenic VEGF production. Pharmacodynamics study using in vivo imaging confirmed that ADSCs via intravenous injection could accumulate into the kidneys and be alive at least 2 weeks. In a conclusion, ADSC can significantly alleviate ADR-induced nephropathy, and mainly through reducing oxidative stress, inflammation and fibrosis, as well as enhancing VEGF production.

The ionicity of ionic solids is typically characterized by the electronegativity of the constituent ions. Electronegativity measures the ability of electron transfer between atoms and is commonly considered under ambient conditions. However, external stresses profoundly change the ionicity, and compressed ionic compounds may behave differently. Here, we focus on silver halides, with constituent ions from one of the most electropositive metals and some of the most electronegative nonmetals. Using first-principles calculations, we find that the strengths of the ionic bonds in these compounds change greatly under pressure owing to downshifting of the Ag 4d-orbital. The center of this orbital is lowered to fill the antibonding state below the Fermi level, leading to chemical decomposition. Our results suggest that under pressure, the orbital energies and correspondingly the electronegativities still tune the ionicity and control the electron transfer, ionicity, and reactivity of both the metal and the nonmetal elements. However, the effects of orbital energies start to become dominant under pressure, causing substantial changes to the chemistry of ionic compounds and leading to an unusual phenomenon in which elements with substantial electronegativity differences, such as Ag and Br, do not necessarily form ionic compounds, but remain in their elemental forms.

ObjectiveThe study aimed to compare the efficacy and safety of different noninvasive ventilation (NIV) modalities as primary respiratory support following extubation in Neonatal Respiratory Distress Syndrome (NRDS).MethodsA search was conducted in PubMed, Embase, Cochrane, Web of Science, China National Knowledge Network (CNKI), Wanfang database, VIP, and Chinese Biomedical Literature databases with a search time limit of April 2024 for the year of construction, and included randomized controlled clinical trials of different modes of noninvasive respiratory support after extubation in NRDS. The primary outcome indicators were the need for re-tracheal intubation within 72 h of extubation on noninvasive ventilatory support and carbon dioxide retention (PCO2) 24 h after extubation. Secondary outcome indicators included the incidence of bronchopulmonary dysplasia (BPD), nasal injury, pneumothorax, intraventricular hemorrhage (IVH) or periventricular white matter softening (PVL), retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), and mortality rate. A systematic review and network meta-analysis of the literature was performed by two investigators who screened, extracted, and evaluated the quality of the data. A systematic review and network meta-analysis were then performed using R software.ResultsA total of 23 studies involving 2,331 neonates were analyzed. These studies examined four noninvasive respiratory modalities: continuous positive airway pressure ventilation (NCPAP), noninvasive intermittent positive pressure ventilation (NIPPV), bi-level positive airway pressure ventilation (N-BiPAP), and noninvasive high-frequency oscillatory ventilation (NHFOV). Results indicated that NHFOV, NIPPV, and N-BiPAP were significantly more effective than NCPAP in reducing the risk of reintubation (all P

Abstract Woven coronary artery (WCA) is a rare anomaly and its etiology remains speculative. Both congenital and acquired factors are considered to be concerned with the pathogenesis. In a 35-year-old man, the tissue characteristics of WCA were evaluated by optical coherence tomography. Serial coronary angiography indicated that acquired factor is the cause, and thrombus recanalization is the most likely pathological mechanism.

Abstract The technology of building a retaining roadway along goaf or a protecting roadway with a small coal pillar has been developed and applied for many years, and a satisfactory supporting effect has been obtained in medium–thick coal seam and thin coal seam mining. However, the gob-side roadway or small coal pillar mining in a thick coal seam is still subjected to technical problems occasioned by factors such as high roadway, high support pressure beside roadway, and waste of coal resources. To solve these problems, the author proposes an innovative technology of coal-free mining: the technology of driving roadway along goaf with a flexible formwork pre-cast wall. The article utilizes the 3503 and 3505 working faces of Wangzhuang Coal Industry Group as the research background, and comprehensively introduces the principle of the technology and the overburden rock movement law. Through theoretical calculations and numerical simulations, the support resistance and support parameters of flexible formwork pre-cast walls have been determined and successfully performed in industrial practice. The results indicate that the combination of the flexible mould pre-cast wall coal pillar-free mining technology and roof cutting process is more conducive to the maintenance of the roadway in the lower working face, and effectively reduces the stress and deformation of the surrounding rock. The roof and floor of the drivage roadway move, and the deformation of the two sides is small; furthermore, the overall roadway retention effect is satisfactory, which meets the requirements of mining in the lower working face. The coal pillar pertaining to the 20 m section of the 5 m high mining height face was recovered for Wangzhuang Coal Mine, and the recovery rate of the coal resources and the driving speed of the roadway were improved. The proposed method can be popularised and applied in this mine and even in the mining of 15# large-height coal seams in the two cities.

Abstract Background The mitosis-to-meiosis switch during spermatogenesis requires dynamic changes in gene expression. However, the regulation of meiotic transcriptional and post-transcriptional machinery during this transition remains elusive. Results We report that methyltransferase-like protein 16 (METTL16), an N6-methyladenosine (m6A) writer, is required for mitosis-to-meiosis transition during spermatogenesis. Germline conditional knockout of Mettl16 in male mice impairs spermatogonial differentiation and meiosis initiation. Mechanistically, METTL16 interacts with splicing factors to regulate the alternative splicing of meiosis-related genes such as Stag3. Ribosome profiling reveals that the translation efficiency of many meiotic genes is dysregulated in METTL16-deficient testes. m6A-sequencing shows that ablation of METTL16 causes upregulation of the m6A-enriched transcripts and downregulation of the m6A-depleted transcripts, similar to Meioc and/or Ythdc2 mutants. Further in vivo and in vitro experiments demonstrate that the methyltransferase activity site (PP185-186AA) of METTL16 is necessary for spermatogenesis. Conclusions Our findings support a molecular model wherein the m6A writer METTL16-mediated alternative splicing and translation efficiency regulation are required to control the mitosis-to-meiosis germ cell fate decision in mice, with implications for understanding meiosis-related male fertility disorders.

Abstract While many countries employed digital contact tracing to contain the spread of SARS-CoV-2, the contribution of cospace-time interaction (i.e., individuals who shared the same space and time) to transmission and to super-spreading in the real world has seldom been systematically studied due to the lack of systematic sampling and testing of contacts. To address this issue, we utilized data from 2230 cases and 220,878 contacts with detailed epidemiological information during the Omicron outbreak in Beijing in 2022. We observed that contact number per day of tracing for individuals in dwelling, workplace, cospace-time interactions, and community settings could be described by gamma distribution with distinct parameters. Our findings revealed that 38% of traced transmissions occurred through cospace-time interactions whilst control measures were in place. However, using a mathematical model to incorporate contacts in different locations, we found that without control measures, cospace-time interactions contributed to only 11% (95%CI: 10%–12%) of transmissions and the super-spreading risk for this setting was 4% (95%CI: 3%–5%), both the lowest among all settings studied. These results suggest that public health measures should be optimized to achieve a balance between the benefits of digital contact tracing for cospace-time interactions and the challenges posed by contact tracing within the same setting.

Abstract Background Childbirth pain is a physiological phenomenon during the delivery process, the intense pain of childbirth could bring harmful effects to pregnant women and their babies. Assessment of childbirth pain is the first step in childbirth pain intervention. Some pain assessment scales have shortcomings such as interfering in the birthing process and affecting pain perception during delivery, while the Rating Scale of Pain Expression during Childbirth (ESVADOPA) could be used as an auxiliary scale to compensate for these shortcomings. The purpose of this study was to introduce the ESVADOPA and adapt it among Chinese pregnant women to check on the psychometric properties of the translated version of ESVADOPA. Methods A new translation model based on Brislin’s classical back translation model was used to translate and cross-cultural adapt the ESVADOPA. During June 2021 and June 2022, pregnant women at Shandong Provincial Hospital Affiliated to Shandong First Medical University were invited. In the stage of translation and cross-culturally adaptation, 18 midwives and 30 pregnant women were invited to participate in the first round of pre-experiment. And in the second round of pre-experiment, 15 midwives and 20 pregnant women were invited to participate. The Chinese version of ESVADOPA was tested on a group of pregnant women (N = 487). Construct validity was evaluated by exploratory factor analysis, confirmatory factor analysis and criterion-related validity. Reliability was assessed by Cronbach’s α coefficient, McDonald Omega, Spearman-Brown split-half reliability and Guttman split-half reliability. Results The item statistical analysis and construct validity resulted in six items and one factor that explained 61.064% of the total variance. Confirmatory factor analysis showed that the data fit the one-factor structure. Criterion-related validity indicated that the scale is significantly and positively correlated with the Numeric Rating Scale (NRS). Cronbach’s α coefficient, McDonald Omega, Spearman-Brown split-half reliability, and Guttman split-half reliability of the Chinese version of ESVADOPA were 0.868, 0.896, 0.845, 0.842, respectively. Conclusion The Chinese version of the ESVADOPA with good reliability and validity data could be used to assess the pain rating of pregnant women during childbirth without interfering in the birthing process.

Abstract Background The aim of this study is to assess the efficacy of a multiparametric ultrasound imaging omics model in predicting the risk of postoperative recurrence and molecular typing of breast cancer. Methods A retrospective analysis was conducted on 534 female patients diagnosed with breast cancer through preoperative ultrasonography and pathology, from January 2018 to June 2023 at the Affiliated Cancer Hospital of Xinjiang Medical University. Univariate analysis and multifactorial logistic regression modeling were used to identify independent risk factors associated with clinical characteristics. The PyRadiomics package was used to delineate the region of interest in selected ultrasound images and extract radiomic features. Subsequently, radiomic scores were established through Least Absolute Shrinkage and Selection Operator (LASSO) regression and Support Vector Machine (SVM) methods. The predictive performance of the model was assessed using the receiver operating characteristic (ROC) curve, and the area under the curve (AUC) was calculated. Evaluation of diagnostic efficacy and clinical practicability was conducted through calibration curves and decision curves. Results In the training set, the AUC values for the postoperative recurrence risk prediction model were 0.9489, and for the validation set, they were 0.8491. Regarding the molecular typing prediction model, the AUC values in the training set and validation set were 0.93 and 0.92 for the HER-2 overexpression phenotype, 0.94 and 0.74 for the TNBC phenotype, 1.00 and 0.97 for the luminal A phenotype, and 1.00 and 0.89 for the luminal B phenotype, respectively. Based on a comprehensive analysis of calibration and decision curves, it was established that the model exhibits strong predictive performance and clinical practicability. Conclusion The use of multiparametric ultrasound imaging omics proves to be of significant value in predicting both the risk of postoperative recurrence and molecular typing in breast cancer. This non-invasive approach offers crucial guidance for the diagnosis and treatment of the condition.

The development of engineered or modified autologous stem cells is an effective strategy to improve the efficacy of stem cell therapy. In this study, the stemness and functionality of adipose stem cells derived from type 1 diabetic donors (T1DM-ASC) were enhanced by treatment with Cu(II)-baicalein microflowers (Cu-MON). After treatment with Cu-MON, T1DM-ASC showed enhanced expression of the genes involved in the cytokine-cytokine receptor interaction pathway and increased cytokine secretion. Among the top 13 differentially expressed genes between T1DM-ASC and Cu-MON-treated T1DM-ASC (CMTA), some genes were also expressed in HUVEC, Myoblast, Myofibroblast, and Vascular Smooth Muscle cells, inferring the common role of these cell types. In vivo experiments showed that CMTA had the same therapeutic effect as adipose-derived stem cells from non-diabetic donors (ND-ASC) at a 15% cell dose, greatly reducing the treatment cost. Taken together, these findings suggest that Cu-MON promoted angiogenesis by promoting the stemness and functionality of T1DM-ASC and influencing multiple overall repair processes, including paracrine effects.

Polymyxins are the last line of defense against multidrug-resistant (MDR) Gram-negative bacterial infections. However, this last resort has been threatened by the emergence of superbugs carrying the mobile colistin resistance gene-1 (mcr-1). Given the high concentration of matrix metalloproteinase 3 (MMP-3) in bacterial pneumonia, limited plasma accumulation of colistin (CST) in the lung, and potential toxicity of ionic silver (Ag+), we designed a feasible clinical transformation platform, an MMP-3 high-performance lung-targeted bio-responsive delivery system, which we named “CST&Ag@CNMS”. This system exhibited excellent lung-targeting ability (>80% in lungs), MMP-3 bio-responsive release property (95% release on demand), and synergistic bactericidal activity in vitro (2–4-fold minimum inhibitory concentration reduction). In the mcr-1+ CST-resistant murine pneumonia model, treatment with CST&Ag@CNMS improved survival rates (70% vs. 20%), reduced bacteria burden (2–3 log colony-forming unit [CFU]/g tissue), and considerably mitigated inflammatory response. In this study, CST&Ag@CNMS performed better than the combination of free CST and AgNO3. We also demonstrated the superior biosafety and biodegradability of CST&Ag@CNMS both in vitro and in vivo. These findings indicate the clinical translational potential of CST&Ag@CNMS for the treatment of lung infections caused by CST-resistant bacteria carrying mcr-1.

Abstract As an alternative to antibiotics in response to antimicrobial-resistant infections, bacteriophages (phages) are garnering renewed interest in recent years. However, the massive preparation of phage is restricted using traditional pathogens as host cells, which incurs additional costs and contamination. In this study, an opportunistic pathogen, Klebsiella pneumoniae used to convert glycerol to 1,3-propanediol (1,3-PDO), was reused to prepare phage after fermentation. The phage infection showed that the fed-batch fermentation broth containing 71.6 g/L 1,3-PDO can be directly used for preparation of phage with a titer of 1 × 108 pfu/mL. Then, the two-step salting-out extraction was adopted to remove most impurities, e.g. acetic acid (93.5%), ethanol (91.5%) and cells (99.4%) at the first step, and obtain 1,3-PDO (56.6%) in the top phase as well as phage (97.4%) in the middle phase at the second step. This integrated process provides a cheap and environment-friendly manner for coproduction of 1,3-PDO and phage. Graphical abstract

Abstract Background The absence of heterozygosity (AOH) is a kind of genomic change characterized by a long contiguous region of homozygous alleles in a chromosome, which may cause human genetic disorders. However, no method of low-pass whole genome sequencing (LP-WGS) has been reported for the detection of AOH in a low-pass setting of less than onefold. We developed a method, termed CNVseq-AOH, for predicting the absence of heterozygosity using LP-WGS with ultra-low sequencing data, which overcomes the sparse nature of typical LP-WGS data by combing population-based haplotype information, adjustable sliding windows, and recurrent neural network (RNN). We tested the feasibility of CNVseq-AOH for the detection of AOH in 409 cases (11 AOH regions for model training and 863 AOH regions for validation) from the 1000 Genomes Project (1KGP). AOH detection using CNVseq-AOH was also performed on 6 clinical cases with previously ascertained AOHs by whole exome sequencing (WES). Results Using SNP-based microarray results as reference (AOHs detected by CNVseq-AOH with at least a 50% overlap with the AOHs detected by chromosomal microarray analysis), 409 samples (863 AOH regions) in the 1KGP were used for concordant analysis. For 784 AOHs on autosomes and 79 AOHs on the X chromosome, CNVseq-AOH can predict AOHs with a concordant rate of 96.23% and 59.49% respectively based on the analysis of 0.1-fold LP-WGS data, which is far lower than the current standard in the field. Using 0.1-fold LP-WGS data, CNVseq-AOH revealed 5 additional AOHs (larger than 10 Mb in size) in the 409 samples. We further analyzed AOHs larger than 10 Mb, which is recommended for reporting the possibility of UPD. For the 291 AOH regions larger than 10 Mb, CNVseq-AOH can predict AOHs with a concordant rate of 99.66% with only 0.1-fold LP-WGS data. In the 6 clinical cases, CNVseq-AOH revealed all 15 known AOH regions. Conclusions Here we reported a method for analyzing LP-WGS data to accurately identify regions of AOH, which possesses great potential to improve genetic testing of AOH.

ABSTRACT About 35% of grassland in Sanjiangyuan area of China has degenerated into black‐soil mountain. Artificial grassland is considered to be an effective measure to alleviate the severely degraded grassland in the alpine region of the three rivers and has been widely used. However, the pattern, potential function, and changes of carbon and nitrogen contents of soil microorganisms in degraded grassland in Heimushan by planting artificial grassland are still unclear. In this study, mixed‐sown artificial alpine grassland (AG) was the focus of our study, whereas degraded black‐soil mountain grassland (BG) and natural alpine grassland (NG) served as controls. Illumina 16S and ITS gene sequence analyses were used to analyze the community structure of the soil bacteria and fungi. The functional groups of NG, AG, and BG were predicted using the FAPROTAX and FUNGuild databases. In addition, the levels of soil carbon, nitrogen, and soil enzyme activities were evaluated. The results indicated a significant increase in the aboveground biomass of BG due to the planting artificial grassland. Moreover, the contents of total carbon (TC), total nitrogen (TN), ammonium nitrogen (NH4+−N), microbial biomass carbon (MBC), microbial biomass nitrogen (MBN), and leucine aminopeptidase (LAP) increased in the soil. Planting artificial grasslands changed the composition of bacterial and fungal communities. Among these, the bacterial community was more sensitive to planting artificial grasslands. The relative abundance of bacterial functional groups involved in carbon and nitrogen cycling changed significantly, suggesting that bacteria may play a role in regulating nutrient cycling during artificial grassland planting. Soil TC, TN, LAP, and NH4+−N affected the microbial community structure related to carbon and nitrogen. NH4+−N and β‐1,4‐glucosidase were carbon and nitrogen factors, respectively, that affected functional changes in fungi. These results indicate that planting artificial grasslands can effectively enhance the productivity of degraded black‐soil mountain and regulate soil microbial communities and soil physical and chemical properties.

IntroductionSemen Cuscutae is a traditional Chinese medicine (TCM) that tonifies the kidneys and prevents miscarriage. According to Chinese medicine theory, kidney deficiency is one of the main causes of recurrent spontaneous abortion (RSA). The previous studies showed that raw product of Semen Cuscutae (SP) and Semen Cuscutae processed with salt solution (YP) have ameliorative effects on RSA, and that YP is superior to SP. However, the active components of YP to ameliorate RSA remain unclear and require further studies. The objective of this study is to investigate the active components of YP in ameliorating RSA.MethodsFirst, a rat model of RSA was established using hydroxyurea in combination with mifepristone. Aqueous decoction of YP was given by gavage to rats. Second, pregnant rats were sampled on days 5, 7, 9, 10 and 12 during the modelling period. The content of Hyperin (HY), astragalin (AS) and kaempferol-3-O-β-D-glucuronide (KA) in blood and liver, heart, spleen, lung and kidney tissues were detected by liquid chromatography-mass spectrometry (LC-MS). The pharmacodynamic indicators including progesterone (P), chorionic gonadotropin β (β-HCG), estradiol (E2), tumor necrosis factor-α (TFN-α), interleukin 4 (IL-4), and tryptophan (TRP) were measured by enzyme-linked immunosorbent assay (ELISA) Pearson's correlation analysis and grey relational analysis were used to establish the relationship between the pharmacodynamic indexes and chemical constituents.ResultsThe pharmacokinetic results showed that the area under curve (AUC) value of KA was the largest. The tissue distribution results showed that astragalin was widely distributed in liver, heart, spleen, lung and kidney in the RSA model rats, while HY was detected only in the uterus, and KA was detected only in the kidney. The pearson correlationl analysis showed that KA was significantly and positively correlated with the contents of E2, P, β-HCG and TRP. Both AS and HY were significantly negatively correlated with the content of TNF-α, respectively.DiscussionThis study reveals the pharmacokinetics and tissue distribution of KA, AS and HY in rats with RSA. It was elucidated that all three were involved in the regulation of progesterone levels and immune function. It initially revealed the mechanism of action of YP in enhancing the improvement of RSA, and it provided a theoretical basis for the quality assessment of YP.

Abstract Inflammatory bowel disease (IBD) is a chronic and unspecific inflammatory disorder of the gastrointestinal tract, and current treatment options often fail to maintain long‐term remission. Studies have shown that propionate level is reduced in fecal samples from patients with IBD. Propionate can ameliorate IBD through intestinal epithelial cells and immune regulation, but its effects on the inflammatory microenvironment and macrophage differentiation have not been widely studied. To address this, we constructed an engineered propionate‐producing probiotic (EcNP3) to achieve sustained restoration of propionate levels in the gut and increase its bioavailability. DSS‐induced experimental intestinal inflammation model was used to evaluate the effect of EcNP3 on improving the intestinal mucosal barrier and increasing the proportion of anti‐inflammatory macrophages. It was found that EcNP3 exhibited a restorative effect on the depletion of peritoneal anti‐inflammatory macrophages (F4/80hiCD11bhi) and significantly improved the expression level of IL‐10. Simultaneously, the expression of IL‐1β, IL‐6, and CXCL1 was downregulated while inhibiting apoptosis of tissue‐resident macrophages ex vivo. Further investigation revealed that EcNP3 regulates IL‐10 expression through G protein‐coupled receptor 43 and histone deacetylase. Furthermore, EcNP3 significantly inhibited the protein expression of HDAC1 and promoted the histone acetylation level of cells. Finally, EcNP3 significantly improved DSS‐induced colitis in mice by increasing mucus production and reducing inflammatory infiltration. Our results suggest that the engineered live biotherapeutic product EcNP3 is a safe and potently efficacious treatment for IBD, which defines a novel strategy in IBD therapy through macrophage IL‐10 signaling.

Temporal lobe epilepsy (TLE) stands as the predominant adult focal epilepsy syndrome, characterized by dysfunctional intrinsic brain dynamics. However, the precise mechanisms underlying seizures in these patients remain elusive. Our study encompassed 116 TLE patients compared with 51 healthy controls. Employing microstate analysis, we assessed brain dynamic disparities between TLE patients and healthy controls, as well as between drug-resistant epilepsy (DRE) and drug-sensitive epilepsy (DSE) patients. We constructed dynamic functional connectivity networks based on microstates and quantified their spatial and temporal variability. Utilizing these brain network features, we developed machine learning models to discriminate between TLE patients and healthy controls, and between DRE and DSE patients. Temporal dynamics in TLE patients exhibited significant acceleration compared to healthy controls, along with heightened synchronization and instability in brain networks. Moreover, DRE patients displayed notably lower spatial variability in certain parts of microstate B, E and F dynamic functional connectivity networks, while temporal variability in certain parts of microstate E and G dynamic functional connectivity networks was markedly higher in DRE patients compared to DSE patients. The machine learning model based on these spatiotemporal metrics effectively differentiated TLE patients from healthy controls and discerned DRE from DSE patients. The accelerated microstate dynamics and disrupted microstate sequences observed in TLE patients mirror highly unstable intrinsic brain dynamics, potentially underlying abnormal discharges. Additionally, the presence of highly synchronized and unstable activities in brain networks of DRE patients signifies the establishment of stable epileptogenic networks, contributing to the poor responsiveness to antiseizure medications. The model based on spatiotemporal metrics demonstrated robust predictive performance, accurately distinguishing both TLE patients from healthy controls and DRE patients from DSE patients.

Background: Paraquat (PQ) is a widely used herbicide that poisons human by accident or intentional ingestion. PQ poisoning causes systemic inflammatory response syndrome (SIRS) resulting in acute lung injury (ALI) with an extremely high mortality rate. Blood trematode Schistosoma japonicum-produced cystatin (Sj-Cys) is a strong immunomodulatory protein that has been experimentally used to treat inflammation related diseases. In this study, Sj-Cys recombinant protein (rSj-Cys) was used to treat PQ-induced lung injury and the immunological mechanism underlying the therapeutic effect was investigated. Methods: PQ-induced acute lung injury mouse model was established by intraperitoneally injection of 20 mg/kg of paraquat. The poisoned mice were treated with rSj-Cys and the survival rate was observed up to 7 days compared with the group without treatment. The pathological changes of PQ-induced lung injury were observed by examining the histochemical sections of affected lung tissue and the wet to dry ratio of lung as a parameter for inflammation and edema. The levels of the inflammation related cytokines IL-6 and TNF-α and regulatory cytokines IL-10 and TGF-β were measured in sera and in affected lung tissue using ELISA and their mRNA levels in lung tissue using RT-PCR. The macrophages expressing iNOS were determined as M1 and those expressing Arg-1 as M2 macrophages. The effect of rSj-Cys on the transformation of inflammatory M1 to regulatory M2 macrophages was measured in affected lung tissue in vivo (EKISA and RT-PCR) and in MH-S cell line in vitro (flow cytometry). The expression levels of TLR2 and MyD88 in affected lung tissue were also measured to determine their role in the therapy of rSj-Cys on PQ-induced lung injury. Result: We identified that treatment with rSj-Cys significantly improved the survival rate of mice with PQ-induced lung injury from 30 % (untreated) to 80 %, reduced the pathological damage of poisoning lung tissue, associated with significantly reduced levels of proinflammatory cytokines (IL-6 from 1490 to 590 pg/ml, TNF-α from 260 to 150 pg/ml) and increased regulatory cytokines (IL-10 from360 to 550 pg/ml, and TGF-β from 220 to 410 pg/ml) in both sera (proteins) and affected lung tissue (proteins and mRNAs). The polarization of macrophages from M1to M2 type was found to be involved in the therapeutic effect of rSj-Cys on the PQ-induced acute lung injury, possibly through inhibiting TLR2/MyD88 signaling pathway. Conclusions: Our study demonstrated the therapeutic effect of rSj-Cys on PQ poisoning caused acute lung injury by inducing M2 macrophage polarization through inhibiting TLR2/MyD88 signaling pathway. The finding in this study provides an alternative approach for the treatment of PQ poisoning and other inflammatory diseases.

Colon cancer (CC) is one of the most common gastrointestinal malignancies. Effectiveness of the existing therapies is limited. Immunotherapy is a promising complementary treatment approach for CC. Major histocompatibility complex class I-related protein A and B (MICA/B) are ligands for NK cells. Shedding of MICA/B from the surface of tumor cells by cleavage of MICA/B at the membrane proxial region in MICA/B α3 structural domain is one of immune evasion strategies leading to escape of cancer cells from immunosurveillance. In this study, we generated a panel of MICA/B monoclonal antibodies (mAbs) and identified one of mAbs, mAb RDM028, that had high binding affinity to MICA/B and recognized a site on MICA/B α3 structural domain that is critically important for cleavage of MICA/B. Our study has further demonstrated that RDM028 augmented the surface expression of MICA/B on HCT-116 human CC cells by inhibiting the MICA/B shedding resulting in the enhanced cyotoxicity of NK cells against HCT-116 human CC cells and mediated anti-tumor activity in nude mouse model of colon cancer. These results indicate that mAb RDM028 could be explored for developing as an effective immuno therapy against CC by targeting the MICA/B α3 domain to promot immunosurveillance mediated by MICA/B-NKG2D interaction.

Abstract This study aims to investigate the role and mechanism of tubiquitin-conjugating enzyme E2 C (UBE2C) in acute myeloid leukemia (AML). Initially, UBE2C expression in leukemia was analyzed using the Cancer Genome Atlas database. Further, we silenced UBE2C expression using small-hairpin RNA (sh-RNA). UBE2C expression was detected via the quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blot analysis. Apoptotic events and reactive oxygen species (ROS) levels were detected by flow cytometry. A xenograft model of leukemia cells were established, and the protein levels of UBE2C, KI-67, and cleaved-caspase 3 were detected by immunohistochemistry. We reported an overexpression of UBE2C in leukemia patients and cell lines (HL60, THP-1, U937, and KG-1 cells). Moreover, a high expression level of UBE2C was correlated with a dismal prognosis in AML patients. UBE2C knockdown inhibited the viability and promoted apoptosis in AML cells by regulating the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Furthermore, UBE2C knockdown increased cellular Fe2+ and ROS levels, and enhanced erastin-induced ferroptosis in a proteasome-dependent manner. UBE2C knockdown also suppressed the tumor formation of AML cells in the mouse model. In summary, our findings suggest that UBE2C overexpression promotes the proliferation and inhibits ferroptosis in AML cells by activating the PI3K/AKT pathway.

In response to problems of poor sampling quality, low sensitivity, and high demand for medical personnel regarding the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) oropharyngeal (OP) swab sampling used in China, we aimed to evaluate the diagnostic performance and acceptability of saliva-based nucleic acid amplification tests (NAATs) in China. The results showed that, using nasopharyngeal (NP) swab results as the gold standard, the overall sensitivities for saliva specimens and OP swabs were 93.3 % and 85.0 %, the specificities were 92.6 % and 93.8 %, respectively. The results of an acceptability survey showed that the scores for saliva, OP, and NP samples were 9.46 ± 1.69, 8.11 ± 2.42, and 4.58 ± 3.82 out of 10, respectively, with significant differences among the three groups (P

Abstract Background The situation of mental health and discipline behaviors of left-behind children’s caregivers were not optimistic in rural China. Caregivers’ depression might increase the risk of using violent discipline. However, the specific ways in which depressive symptoms impact violent discipline have rarely been explored in rural areas. This study aims to assess the prevalence of violent discipline among left-behind children under 6 years of age in rural China and explore the potential mechanisms of how caregivers’ depressive symptoms affect violent discipline. Methods We enrolled a total of 396 pairs of left-behind children and their caregivers in our study, which was conducted in 5 counties of Hebei, Henan, Jiangxi, Guizhou, and Sichuan provinces in China. The depressive symptoms of caregivers were measured by using Zung Self-rating Depression Scale (ZSDS) and violent discipline was assessed by the Child Discipline Module of Multiple Indicator Cluster Surveys (MICS). A self-designed questionnaire was utilized to measure caregiver’s parenting attitude. Based on the cross-sectional data, controlling for potential confounders, structural equation modeling (SEM) was used to assess the direct and indirect effects of the mediation models by applying the weighted least squares with mean and variance adjusted (WLSMV) estimate. Results The prevalence of violent discipline, psychological aggression, and physical punishment was 72.7%, 59.3%, and 60.4% respectively of left-behind children under 6 years of age. According to the results of SEM, parenting attitude acted as a suppressor, suppressing the association between caregivers’ depressive symptoms and physical punishment/psychological aggression/violent discipline. The caregivers’ depressive symptoms positively influenced all the outcome variables by affecting parenting attitudes (p = 0.002, p = 0.013, p = 0.002). Conclusions The presence of depressive symptoms in caregivers increases the use of violent discipline through negative parenting attitudes. The mental health status of primary caregivers of left-behind children in rural China needed emphasis and improvement.

Abstract In the present study, a novel coordination polymer (CP) based on Ni(II), namely, [Ni(L)(D-CAM)(H2O)]n (1) (H2D-CAM = (1R,3S)-1,2,2-trimethylcyclopentane-1,3-dicarboxylic acid and L = 3,6-bis(benzimidazol-1-yl)pyridazine), has been produced successfully through applying a mixed ligand synthesis method via reacting Ni(NO3)2·6H2O with 3,6-bis(benzimidazol-1-yl)pyridazine ligand in the presence of a carboxylic acid co-ligand. Hyaluronic acid (HA) and carboxymethyl chitosan (CMCS) are representatives of natural polysaccharides and have good biocompatibility. Based on the chemical synthesis method, HA/CMCS hydrogel was successfully prepared. SEM showed that the lyophilized gel presented a typical macroporous structure with three-dimensional connected pores, which had unique advantages as a drug carrier. Using paclitaxel as a drug model, we further synthesized a novel paclitaxel-loaded metal gel and evaluated its therapeutic effect on cervical cancer. Finally, novel drugs from the reinforcement learning simulation are suggested to have better biological activity against ovarian cancer due to low affinity energy and stronger interaction strength towards the protein receptor.

Abstract Objective This study aimed to investigate the association between the triglyceride-glucose (TyG) index in early pregnancy and the development of gestational diabetes mellitus (GDM) in the second trimester. The primary objectives were to evaluate the predictive potential of the TyG index for GDM, determine the optimal threshold value of the TyG index for GDM assessment, and compare the predictive performance of the TyG index alone versus its combination with maternal age and pre-pregnancy body mass index on GDM. Moreover, the study explored the association between the TyG index in early pregnancy and the risk of other pregnancy-related complications (PRCs), such as placental abruption and gestational hypertension. Patients and methods This prospective cohort study recruited 1,624 pregnant women who underwent early pregnancy antenatal counseling and comprehensive assessments with continuous monitoring until delivery. To calculate the TyG index, health indicators, including maternal triglycerides and fasting plasma glucose, were measured in early pregnancy (

Abstract The root system is important for the growth and development of spinach. To reveal the temporal variability of the spinach root system, root traits of 40 spinach accessions were measured at three imaging times (20, 30, and 43 days after transplanting) in this study using a non-destructive and non-invasive root analysis system. Results showed that five root traits were reliably measured by this system (RootViz FS), and two of which were highly correlated with manually measured traits. Root traits had higher variations than shoot traits among spinach accessions, and the trait of mean growth rate of total root length had the largest coefficients of variation across the three imaging times. During the early stage, only tap root length was weakly correlated with shoot traits (plant height, leaf width, and object area (equivalent to plant surface area)), whereas in the third imaging, root fresh weight, total root length, and root area were strongly correlated with shoot biomass-related traits. Five root traits (total root length, tap root length, total root area, root tissue density, and maximal root width) showed high variations with coefficients of variation values (CV ≥ 0.3, except maximal root width) and high heritability (H2 > 0.6) among the three stages. The 40 spinach accessions were classified into five subgroups with different growth dynamics of the primary and lateral roots by cluster analysis. Our results demonstrated the potential of in-situ phenotyping to assess dynamic root growth in spinach and provide new perspectives for biomass breeding based on root system ideotypes.

The production performance and rumen bacterial diversity were compared for different silage-based diets supplemented with common concentrate or bio-concentrate to develop an alternative of common concentrate for fatten cattle feeding. The daily gain of fattening cattle was increased by 0. 99 kg and 1.04 kg, respectively, when fed with single corn silage or mixed silage-based diet supplemented with bio-concentrate. There was no significant difference in water loss rate and cooked meat rate among groups (P>0.05), but the tenderness of beef in the bio-concentrate group was significantly higher than that in the common concentrate group (P

Autonomous electric vehicle (AEV) services leverage advanced autonomous driving and electric vehicle technologies to provide innovative, driverless transportation solutions. The biggest challenge faced by AEVs is the limited number of charging stations and long charging times. A critical challenge is maximizing passenger travel satisfaction while reducing the AEV idle time. This involves coordinating passenger transport and charging tasks via leveraging the information from charging stations, passenger transport, and AEV data. There are four important contributions in this paper. Firstly, we introduce an integrated scheduling model that considers both passenger transport and charging tasks. Secondly, we propose a multi-level differentiated charging threshold strategy, which dynamically adjusts the charging threshold based on both AEV battery levels and the availability of charging stations, reducing competition among vehicles and minimizing waiting times. Thirdly, we develop a rapid strategy to optimize the selection of charging stations by combining geographic and deviation distance. Fourthly, we design a new evolutionary algorithm to solve the proposed model, in which a buffer space is introduced to promote diversity within the population. Finally, experimental results show that compared to the existing state-of-the-art scheduling algorithms, the proposed algorithm shortens the running time of scheduling algorithms by 6.72% and reduces the idle driving time of AEVs by 6.53%, which proves the effectiveness and efficiency of the proposed model and algorithm.

Background: Despite the administration of timely reperfusion treatment, patients with acute myocardial infarction have a high mortality rate and poor prognosis. The potential impact of intraluminal imaging guidance, such as optical coherence tomography (OCT), on improving patient outcomes has yet to be conclusively studied. Therefore, we conducted a retrospective cohort study to compare OCT-guided primary percutaneous coronary intervention (PCI) versus angiography-guided for patients with ST-segment elevation myocardial infarction (STEMI). Methods: This study enrolled 1396 patients with STEMI who underwent PCI, including 553 patients who underwent OCT-guided PCI and 843 patients who underwent angiography-guided PCI. The clinical outcome was a composite of cardiovascular death, myocardial infarction, admission due to heart failure, stroke, and unplanned revascularization at the 4-year follow-up. Results: The prevalence of major adverse cardiovascular events in OCT-guided group was not significantly lower compared to those without OCT guidance after adjustment (unadjusted hazard ratio (HR), 1.582; 95% confidence interval (CI), 1.300–1.924; p < 0.001; adjusted HR, 1.095; adjusted 95% CI, 0.883–1.358; p = 0.409). The prevalence of cardiovascular death was significantly lower in patients with OCT guidance compared to those without before and after adjustment (unadjusted HR, 3.303; 95% CI, 2.142–5.093; p < 0.001; adjusted HR, 2.025; adjusted 95% CI, 1.225–3.136; p = 0.004). Conclusions: OCT-guided primary PCI used to treat STEMI was associated with reduced long-term cardiovascular death.

The carbothermic reduction of ilmenite concentrate was performed with the addition of calcium carbonate (CaCO3) as an additive. The effects of roasting temperature and CaCO3 content on calcium titanate (CaTiO3) formation and metallic iron reduction were investigated. The Rietveld method was employed for qualitative and quantitative analysis of roasting products. It was found that as the temperature increased from 1000 °C to 1400 °C, the calcium titanate content increased from 21.95% to 83.02%. Similarly, as the CaCO3 content increased, the calcium titanate content rose from 0% to 83.11%, while the metallic iron content increased from 4.52% to 10.37%. SEM-EDS analysis suggested that adding CaCO3 during the carbothermic reduction of ilmenite promoted the aggregation and growth of metallic iron particles. The roasting products obtained under optimal conditions were subjected to three-stage grinding and three-stage magnetic separation. The final metallic iron product had a grade of 90.01% and a recovery rate of 91.32%. The calcium titanate product contained 55.43% TiO2, with a titanium recovery rate of 85.90%. Rietveld results indicated that the calcium titanate product had a high purity, with a content of 90.87%. This study effectively improved the comprehensive utilization of titanium and iron resources in ilmenite.

With the introduction of advanced Fiber Bragg Grating (FBG) technology, Fabry–Pérot (FP) interferometers have become widely used in fiber-optic ultrasound detection. In these applications, the slope of the reflectance is a critical factor influencing detection results. Due to the intensity limitations of the laser source in fiber-optic ultrasound detection, the reflectance of the FBG is generally increased to enhance the signal-to-noise ratio (SNR). However, increasing reflectance can cause the reflectance curve to deviate from a sinusoidal shape, which in turn affects the slope of the reflectance and introduces greater errors. This paper first investigates the relationship between the transmission curve of the FP interferometer and reflectance, with a focus on the errors introduced by simplified assumptions. Further research shows that in sensors with asymmetric reflectance slopes, their transmittance curves deviate significantly from sinusoidal signals. This discrepancy highlights the importance of achieving symmetrical slopes to ensure consistent and accurate detection. To address this issue, this paper proposes an innovative method to adjust the rear-end reflectance of the FP interferometer by combining stress modulation, UV adhesive, and a high-reflectivity metal disk. Additionally, by adjusting the rear-end reflectance to ensure that the transmittance curve approximates a sinusoidal signal, the symmetry of the slope is maintained. Finally, through practical ultrasound testing, by adjusting the incident wavelength to the positions of slope extrema (or zero) at equal intervals, the expected ultrasound signals at extrema (or zero) can be detected. This method converts the problem of approximating a sinusoidal signal into a problem of the slope adjustment of the transmittance curve, making it easier and more direct to determine its impact on detection results. The proposed method not only improves the performance of fiber-optic ultrasound sensors but also reduces costs, paving the way for broader applications in medical diagnostics and structural health monitoring.