Background Gestational weight gain is closely related to maternal and infant health outcomes. Pregnant women are simultaneously exposed to four metals—lithium (Li), vanadium (V), uranium (U), and bismuth (Bi)—through inhalation of fine particulate matter and consumption of contaminated food and water. Existing studies suggest that exposure to these metals may be associated with gestational weight gain. However, no study has yet explored the complex relationships between exposure to mixtures of these four metals and weight gain at different stages of pregnancy. Objective To investigate the associations between mixed exposure to Li, V, U, and Bi in early pregnancy and the average weekly gestational weight gain during both early pregnancy and mid-to-late pregnancy. Methods This prospective study recruited eligible women in early pregnancy from an obstetrics clinic of a tertiary hospital in Jinan, China, between September 2021 and July 2023. Pre-pregnancy weight, current weight (at 11⁺⁰ to 13⁺⁶ weeks of gestation), and spot urine samples (≥5.0 mL) were collected at enrollment. Urinary concentrations of Li, V, Bi, and U were determined using inductively coupled plasma mass spectrometry. Participants were followed up in late pregnancy (≥28 weeks of gestation) to collect information on physical activity via questionnaire; weight measurements at the last antenatal visit (35⁺⁰ to 37⁺⁶ weeks of gestation) were obtained from the hospital information system. After adjusting for covariates, multiple linear regression and generalized additive models were used to assess the associations of individual metals with weekly weight gain in early pregnancy and in mid-to-late pregnancy. Bayesian kernel machine regression (BKMR) and quantile-based g-computation (Qgcomp) were applied to evaluate the joint effects of the metal mixture exposure on weekly weight gain at the two gestational stages. Results A total of 313 pregnant women were included. The geometric means of urinary Li, V, U, and Bi concentrations were 37.07, 0.20, 0.06, and 0.04 μg·L⁻¹, respectively; after creatinine adjustment, the corresponding values were 46.82, 0.25, 0.07, and 0.05 μg·g⁻¹ (Cr). The mean weekly gestational weight gain was (0.19±0.25) kg in early pregnancy and (0.53 ± 0.18) kg in mid-to-late pregnancy. Both multiple linear regression and generalized additive models showed that urinary V concentration was positively associated with average weekly gestational weight gain in early pregnancy, while no significant associations were found for other metals or for gestational weight gain in mid-to-late pregnancy. In the BKMR model with early-pregnancy weight gain as the outcome, V had the strongest association [posterior inclusion probability (PIP)=0.773]. When other metals were fixed at their medians, V showed a positive non-linear association with the outcome. A significant single-metal effect of V and its interaction with Li were observed. Compared with the 50th percentile of the metal mixture, the average weekly weight gain in early pregnancy increased by 0.016 (95%CI: 0.003, 0.029) and 0.018 (95%CI: 0.001, 0.036) at the 60th and 65th percentiles, respectively; conversely, at the 25th percentile, it decreased by 0.026 (95%CI: 0.002, 0.050). Overall, the joint effect of the metal mixture on early- pregnancy weight gain showed an upward trend. In the BKMR model for mid-to-late pregnancy gestational weight gain, all PIPs were<0.5, and no significant single-metal effects, interactions, or joint effects were identified. Qgcomp results confirmed a positive association between the metal mixture and early-pregnancy weight gain (b=0.031, 95%CI: 0.010, 0.051; P<0.01), with V contributing the highest positive weight (0.71). No significant association was found for weight gain in mid-to-late pregnancy (b=0.007, P=0.339). Conclusion Higher levels of co-exposure to the Li, V, Bi, and U metal mixture during early pregnancy may be associated with increased average weekly weight gain in early pregnancy. Among these metals, V exhibits a predominant role and appears to interact with Li. No association is observed between early-pregnancy metal mixture exposure and average weekly gestational weight gain in mid-to-late pregnancy. These findings suggest that monitoring and managing metal exposure during early pregnancy may be crucial for the rational regulation of gestational weight gain.

The inference of tissue origin of body fluid stains is crucial for case investigation and court proceedings.However,traditional methods for identification of body fluid stains,such as morpho-logical,chemical,and immunoassay identifications have certain limitations,and there is an urgent need for more efficient methods for confirmatory experiments.In recent years,the rapid development of tran-scriptomics technology has provided new means for the identification of tissue origin of body fluid stains.Different types of RNA in the transcriptome have their own advantages.This paper elaborates in detail on the application of different types of RNA,such as mRNA,miRNA,circRNA,lncRNA,piRNA and microbial transcriptomics in body fluid identification,and summarizes their respective ad-vantages and limitations,in order to provide a reference for related research.

Objective:To explore the characteristics of potential categories of chronic disease co-morbid patients' learned helplessness, and to analyze the differential characteristics of different categories of chronic disease co-morbid patients.Methods:Convenience sampling method was used to select patients with chronic disease co-morbidities who attended The NO.1 People's Hospital of Xiangyang, Hubei University of Medicine, from June to December 2023 as survey respondents. General information questionnaire, Learned Helplessness Scale, Health Questionnaire Somatic Symptom Cluster Scale, Kessler Psychological Distress Scale, and Comprehension Social Support Scale were used for the cross-sectional survey. The potential profile of learned helplessness, and the influencing factors of potential categories of learned helplessness was analyzed.Results:A total of 810 patients with chronic co-morbidities were investigated. There were 453 males and 357 females, aged (65.03±10.89) years old. The learned helplessness of these patients was categorized into three different potential categories, which were named as low-level learned helplessness group, medium-level learned helplessness group, high-level learned helplessness, accounting for 17.5% (142/810), 23.5% (190/810), and 59.0% (478/810), respectively. Compared with the low-level learned helplessness group, the probability of belonging to the medium-level learned helplessness group and high-level learned helplessness group was higher for patients with chronic co-morbidities with more severe physical symptoms ( OR=1.456, 1.391, both P<0.01). Compared with the low-level learned helplessness group, the probability of belonging to the medium-level learned helplessness group and high-level learned helplessness group was higher for patients with chronic co-morbidities with more severe the psychological distress ( OR=1.359, 1.917, both P<0.01). Compared with the low-level learned helplessness group, the probability of belonging to the medium-level learned helplessness group and high-level learned helplessness group was higher for patients with chronic co-morbidities with lower levels of social support ( OR=0.928, 0.874, both P<0.01). Compared with the low-level learned helplessness group, patients with a duration of illness >5 years were used as controls, patients with a duration of illness 2-5 years were more likely to belong to the medium-level learned helplessness group and high-level learned helplessness group ( OR=74.586, 62.620, both P<0.01). Compared with the low-level learned helplessness group, patients with neutral personalities were compared, patients with extroverted personalities had a lower probability of belonging to the medium-level learned helplessness group ( OR=0.105, P<0.05), while patients with introverted personalities had a lower probability of belonging to the medium-level learned helplessness group and high-level learned helplessness group ( OR=0.052, 0.046, both P<0.01). Conclusions:Patients with chronic disease co-morbidities have higher levels of learned helplessness during disease treatment and have more distinctive categorical characteristics. Healthcare professionals should adopt targeted nursing interventions according to different categories of chronic disease co-morbid patients to reduce the level of learned helplessness.

Objective:To explore the relationship between autistic trait and pain empathy among college students, as well as the mediating role of personal pain perception.Methods:From October to December 2023, a cross-sectional survey was conducted among 1 195 college students using the autism spectrum quotient, pain sensitivity questionnaire, fear of pain questionnaire, pain catastrophizing scale and empathy for pain scale.SPSS 27.0 software was used for descriptive statistics and correlation analysis.A structural equation model was constructed using Mplus 8.3 to examine the mediating effect of personal pain perception, which was composed of pain sensitivity, fear and catastrophizing cognition.Results:Autistic trait(22.00(18.00, 26.00))was significantly positively correlated with pain sensitivity (55.00(43.00, 70.00)), fair of pain (69.00(60.00, 78.00)), and pain catastrophizing cognition (16.00(8.00, 23.00)) ( r=0.112, 0.154, 0.204, all P<0.001).Autistic trait was also significantly positively correlated with affective distress(62.00(46.00, 80.00), r=0.162, P<0.001) and vicarious pain (14.00(8.00, 20.00), r=0.096, P<0.001) of pain empathy.Pain sensitivity, fear of pain and pain catastrophizing cognition were significantly positively correlated with affective distress( r=0.244, 0.332, 0.375, all P<0.001) and vicarious pain ( r=0.210, 0.232, 0.285, all P<0.001) of pain empathy.The effects of autistic trait on affective distress and vicarious pain dimensions of pain empathy were fully mediated by personal pain perception, with the mediating effects of 0.115( P<0.001, 95% CI=0.073-0.165) and 0.085( P<0.001, 95% CI=0.053-0.124). Conclusions:The autistic trait of college students can predict the affective distress and vicarious pain of pain empathy indirectly through personal pain perception.

Objective:To construct a sizeable naive human Fab phage display antibody library to screen high-affinity specific antibodies in vitro. Methods:Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of 126 healthy individuals, subsequently reverse-transcribed into cDNA, and used as a template. PCR amplification was performed to obtain the V H from IgG, IgM and light chain κ, λ, separately, with the initial PCR products serving as templates for a second round of PCR. Overlap extension PCR was employed to generate fragments of the κ and λ light chains. These fragments were ligated with the phage vector pNC3, which harbors the variable region 1 of the heavy chain, to construct a recombinant phage plasmid. This plasmid was then electroporated into competent Escherichia Coli TG1 cells to establish a naive human Fab phage display antibody library. One hundred clones were randomly selected for identification and sequencing, and antibody gene polymorphisms were analyzed using the IMGT database and MAFFT software. Recombinant α-hemolysin from Staphylococcus aureus was utilized to screen Fab antibody fragments through biopanning of the antibody library, followed by random selection of phage ELISA-identified clones. The positive clones (antigen A450∶blank control A450≥2.1) were sequenced. Results:Two large naive Fab phage display antibody libraries were successfully constructed, in which the capacity of κ and λ chain antibody libraries were 1.25×10 11 and 1.54×10 11, respectively. The titers for two antibody libraries were 6.04×10 13 CFU/ml and 3.50×10 13 CFU/ml. The positive transformation insertion rates for κ and λ chain antibody libraries were 96% (96/100) and 100% (100/100), respectively. Sequence analysis revealed that all antibody sequences were unique. The amino acid sequences in the skeletal region were relatively conserved. In contrast, significant variations in the length of the complementarity determining region (CDR) were found, and the diversity of amino acid sequence of the complementary determining region was high, especially the CDR3. Analysis using the IMGT database indicated that the sequences exhibited a broad distribution across variable-diversity-joining gene families. After six rounds of panning, specific phage antibodies enrichment targeting α-hemolysin were achieved. A total of 142 monoclonal antibodies were sequenced, yielding 8 distinct Fab antibody sequences. Conclusion:This study successfully constructed two naive human Fab phage display antibody libraries with large capacity and good diversity, which can be used for screening human antibodies for serum epidemiology.

Genetic transformation is a fundamental tool in molecular biology research of medicinal plants. Tailoring transgenic technologies to each distinct medicinal plant would necessitate a substantial investment of time and effort. Here, we present a simple hairy root transformation method that does not require sterile conditions, utilizing Agrobacterium rhizogenes strain K599 and the visible RUBY reporter system. Transgenic hairy roots were obtained for six tested medicinal plant species, roots or rhizomes of which have recognized medicinal value, spanning four botanical families and six genera (Platycodon grandiflorus, Atractylodes macrocephala, Scutellaria baicalensis, Codonopsis pilosula, Astragalus membranaceus, and Glycyrrhiza uralensis). Furthermore, two previously identified Glycyrrhiza uralensis UGTs that convert liquiritigenin into liquiritin in heterologous systems were studied in planta using the method. Our results indicate that overexpression of GuUGT1 but not GuUGT10 and Cas9-mediated knockout of GuUGT1 profoundly influenced the accumulation of liquiritin and isoliquiritin in licorice roots. Therefore, the method described here represents a simple, rapid and widely applicable hairy root transformation method that enables fast gene functional study in medicinal plants.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

Hepatocellular carcinoma (HCC) expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming. Aldolase A (ALDOA) plays a prominent role in glycolysis; however, little is known about its role in HCC development. In the present study, we aim to explore how ALDOA is involved in HCC proliferation. HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout, which is consistent with ALDOA overexpression encouraging HCC proliferation. Mechanistically, ALDOA knockout partially limits the glycolytic flux in HCC cells. Meanwhile, ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase; ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function. A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun, and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells. In HCC patients, the expression level of ALDOA was correlated with the phosphorylation level of c-Jun (Thr93) and poor prognosis. Remarkably, hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models, and the knockdown of A ldoa strikingly decreased HCC development in vivo. Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription, opening additional avenues for anti-cancer therapies.

Objective:To explore the current status of quality of life of rheumatoid arthritis (RA) patients and its influencing factors based on the health ecology model (HEM) , and to provide a scientific basis for the development of health education programs for RA patients.Methods:From November 2023 to April 2024, 230 RA patients in the Department of Rheumatology and Immunology, General Hospital of Ningxia Medical University, were selected for the study using convenience sampling method. Patients were surveyed using the General Information Questionnaire, Quality of Life Instruments for Chronic Diseases in RA (QLICD-RA) , Health Literacy Management Scale, Social Support Rate Scale, Brief Illness Perception Questionnaire, 8-item Morisky Medication Adherence Scale, Pain Catastrophizing Scale, Chronic Disease Self-Management Study Measures, Fear of Progression Questionnaire-Short Form, Tampa Scale for Kinesiophobia and Visual Analogue Scale. Pearson and Spearman correlation was used to analyze the correlation between quality of life and health literacy, social support, disease perception, self-management behaviors, fear of disease progression, fear of exercise, medication adherence, pain catastrophizing, and pain in RA patients. Multiple linear regression was used to analyze the factors influencing the quality of life of RA patients.Results:A total of 230 questionnaires were distributed and 228 valid questionnaires were recovered, with a valid recovery rate of 99.13% (228/230) . The total QLICD-RA score of 228 RA patients was (137.53±27.57) . Duration of disease, disease perception, pain, pain catastrophizing, self-management behavior, joint deformity, morning stiffness duration, gastrointestinal response, sleep, social support, and main economic sources were the factors influencing the quality of life of RA patients ( P<0.05) , explaining 83.6% of the total variance. Conclusions:The quality of life of RA patients is moderate, and its influencing factors are distributed at all levels of HEM. Healthcare professionals can optimize the health education program for the main influencing factors of each layer, focusing on guiding patients to correctly understand the disease, stimulating the subjective initiative of patients, enhancing the ability of patients to actively manage the disease, and improving the quality of life of patients.