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Heavy metals are a growing threat to human health due to the resulting damage to the ecology; the removal of heavy metals by lactic acid bacteria (LAB) has been a focus of many studies. In this study, 10 LAB strains were evaluated for their ability to absorb and tolerate lead. Lactobacillus plantarum YW11 was found to possess the strongest ability of lead absorbing and tolerance, with the rate of absorption as high as 99.9% and the minimum inhibitory concentration of lead on YW11 higher than 1000 mg/L. Based on the isobaric tags for relative and absolute quantitation (iTRAQ) proteomics analysis of YW11, a total of 2009 proteins were identified both in the lead-treated strain and the control without the lead treatment. Among these proteins, 44 different proteins were identified. The abundance of 25 proteins increased significantly, and 19 proteins decreased significantly in the treatment group. These significantly differential abundant proteins are involved in the biological processes of amino acid and lipid metabolism, energy metabolism, cell wall biosynthesis, and substance transport. This study contributed further understanding of the molecular mechanism of L. plantarum in the binding and removal of lead to explore its potential application in counteracting heavy metal pollution of environment, food, and other fields.

Fear extinction alone does not erase the original fear memory. Interventions that enhance extinction can be beneficial for the treatment of fear-related disorders. Repetitive transcranial magnetic stimulation has been shown to improve memory performance. The present study examined the effects of intermittent theta-burst stimulation (iTBS) on fear extinction and the return of fear memory in humans. Ninety-one young healthy volunteers underwent 3 experiments using a randomized controlled experimental design. Participants first acquired fear conditioning, after which they received 30 Hz iTBS before and after extinction training. The iTBS was applied to 1 of 2 targets: the left dorsolateral prefrontal cortex (dlPFC) and the vertex (control). Fear responses were measured 24 hours later and 1 month later. During the spontaneous recovery and reinstatement tests, iTBS of the left dlPFC before and after extinction significantly reduced fear response, whereas iTBS of the vertex had no effect on fear memory performance. This combined approach had a relatively long-lasting effect (i.e., at least 1 month). We did not explore the effect of iTBS of the dlPFC on the expression of fear without extinction training. The neural mechanisms of iTBS with fear extinction to inhibit the fear response are unclear. Our results are preliminary and should be interpreted with caution. The present results showed that 30 Hz iTBS of the left dlPFC enhanced retention of fear extinction. Our study introduces a new intervention for fear memory and suggests that the left dlPFC may be a treatment target for fear-related disorders.

As an important class of microorganisms, filamentous fungi have crucial roles in protein secretion, secondary metabolite production and environmental pollution control. However, characteristics such as apical growth, heterokaryon, low homologous recombination (HR) efficiency and the scarcity of genetic markers mean that the application of traditional gene editing technology in filamentous fungi faces great challenges. The introduction of the RNA-mediated CRISPR/Cas (clustered regularly interspaced short palindromic repeat/CRlSPR-associated protein) system in filamentous fungi in recent years has revolutionized gene editing in filamentous fungi. In addition, the continuously expressed CRISPR system has significantly improved the editing efficiency, while the optimized sgRNA design and reduced cas9 concentration have effectively reduced the off-target effect, further enhancing the safety and reliability of the technology. In this review, we systematically analyze the molecular mechanism and regulatory factors of CRISPR/Cas9, focus on the optimization of its expression system and the improvement of the transformation efficiency in filamentous fungi, and reveal the core regulatory roles of HR and non-homologous end-joining (NHEJ) pathways in gene editing. Based on the analysis of various filamentous fungi applications, this review reveals the outstanding advantages of CRISPR/Cas9 in the enhancement of protein secretion, addresses the reconstruction of secondary metabolic pathways and pollutant degradation in the past decade, and provides a theoretical basis and practical guidance for the optimization of the technology and engineering applications.

Background This study aims to develop an AI-powered platform using Mel-spectrogram analysis and convolutional neural networks (CNN) to automate the severity assessment of unilateral vocal fold paralysis (UVCP) through voice analysis, providing an objective basis for individualized clinical treatment plans. Methods To accurately identify the severity of UVCP, this study developed the CNN model TripleConvNet. Voice samples were collected from 131 healthy individuals and 292 confirmed UVCP patients from the Eye and ENT Hospital of Fudan University. Based on vocal fold compensation function, the patients were divided into three groups: decompensated (84 cases), partially compensated (98 cases), and fully compensated (110 cases). Using Mel-spectrograms and their first- and second-order differential features as inputs, the TripleConvNet model classified patients by severity and was systematically evaluated for its performance in UVCP severity grading tasks. Results TripleConvNet achieved a classification accuracy of 74.3% in distinguishing between healthy voices and the UVCP decompensated, partially compensated, and fully compensated groups. Conclusion This study demonstrates the potential of deep learning-based non-invasive voice analysis for precise grading of UVCP severity. The proposed method offers a promising clinical tool to assist physicians in disease assessment and personalized treatment planning.

Hepatocellular carcinoma (HCC) is an aggressive malignancy without effective therapeutic approaches. Here, we evaluate the tumor-intrinsic mechanisms that attenuate the efficacy of immune checkpoint inhibitor (ICI) that is observed in patients with advanced HCC who progress on first-line tyrosine kinase inhibitor (TKI) therapy. Upregulation of AXL observed in sorafenib- and lenvatinib-resistant HCCs is correlated with poor response towards TKI and ICI treatments. AXL upregulation protects sorafenib-resistant HCC cells from oxidative stress, mitochondrial damage, and accompanying immunogenic cell death through suppressed tumor necrosis factor-α (TNF-α) and STING-type I interferon pathways. Pharmacological inhibition of AXL abrogates the protective effect and re-sensitizes TKI-resistant HCC tumors to anti-PD-1 treatment. We suggest that targeting AXL in combination with anti-PD-1 may provide an alternative treatment scheme for HCC patients who progress on TKI treatment.

Purpose Human Herpesvirus 6 (HHV‐6) infections are primarily observed in immunocompromised individuals, such as those with acquired immunodeficiency syndrome or organ transplant recipients. However, its role as a pathogen in immunocompetent adults remains debated. We aimed to explore the clinical significance of HHV‐6 in immunocompetent individuals by presenting a case of HHV‐6‐associated meningitis with concurrent lymphadenitis. Method We describe a case of an immunocompetent adult presenting with recurrent fever and headaches. Finding Diagnostic evaluations included next‐generation sequencing analysis identified HHV‐6 in both cerebrospinal fluid specimens and lymphoid tissue samples. The patient demonstrated complete clinical resolution following a 14‐day course of ganciclovir therapy. Conclusion This case underscores the need to consider HHV‐6 infection in immunocompetent adults presenting with meningitis of unknown etiology. Early detection and targeted antiviral therapy may lead to favorable clinical outcomes Human Herpesvirus‐6 infectious meningitis with lymphadenitis in an immunocompetent adult. CSF: cerebrospinal fluid; NGS: next‐generation sequencing; HHV‐6: Human herpes virus‐6

The biological functions of the circadian clock on growth and development have been well elucidated in model plants, while its regulatory roles in crop species, especially the roles on yield-related traits, are poorly understood. In this study, we characterized the core clock gene CIRCADIAN CLOCK-ASSOCIATED 1 (CCA1) homoeologs in wheat and studied their biological functions in seedling growth and spike development. TaCCA1 homoeologs exhibit typical diurnal expression patterns, which are positively regulated by rhythmic histone modifications including histone H3 lysine 4 trimethylation (H3K4me3), histone H3 lysine 9 acetylation (H3K9Ac), and histone H3 lysine 36 trimethylation (H3K36me3). TaCCA1s are preferentially located in the nucleus and tend to form both homo- and heterodimers. TaCCA1 overexpression ( TaCCA1- OE) transgenic wheat plants show disrupted circadian rhythmicity coupling with reduced chlorophyll and starch content, as well as biomass at seedling stage, also decreased spike length, grain number per spike, and grain size at the ripening stage. Further studies using DNA affinity purification followed by deep sequencing [DNA affinity purification and sequencing (DAP-seq)] indicated that TaCCA1 preferentially binds to sequences similarly to “evening elements” (EE) motif in the wheat genome, particularly genes associated with photosynthesis, carbon utilization, and auxin homeostasis, and decreased transcriptional levels of these target genes are observed in TaCCA1- OE transgenic wheat plants. Collectively, our study provides novel insights into a circadian-mediated mechanism of gene regulation to coordinate photosynthetic and metabolic activities in wheat, which is important for optimal plant growth and crop yield formation.

Exploring a new method of pharyngoplasty surgery, which uses CO2 laser to dislocate the mucosa and then covers the wound with mucosal flap complementary sutures, successfully preventing postoperative pharyngeal stenosis. Exploring a new method of pharyngoplasty surgery, which uses CO2 laser to dislocate the mucosa and then covers the wound with mucosal flap complementary sutures, successfully preventing postoperative pharyngeal stenosis.

Background Among the largest and most diverse transcription factor families in plants, basic leucine zipper (bZIP) family participate in regulating various processes, including floral induction and development, stress and hormone signaling, photomorphogenesis, seed maturation and germination, and pathogen defense. Although common wheat ( Triticum aestivum L.) is one of the most widely cultivated and consumed food crops in the world, there is no comprehensive analysis of bZIPs in wheat, especially those involved in anther development. Previous studies have demonstrated wheat, T. urartu , Ae. tauschii , barley and Brachypodium are evolutionarily close in Gramineae family, however, the real evolutionary relationship still remains mysterious. Results In this study, 187 bZIP family genes were comprehensively identified from current wheat genome. 98, 96 and 107 members of bZIP family were also identified from the genomes of T.urartu , Ae.tauschii and barley, respectively. Orthology analyses suggested 69.4 % of TubZIPs were orthologous to 68.8 % of AetbZIPs and wheat had many more in-paralogs in the bZIP family than its relatives. It was deduced wheat had a closer phylogenetic relationship with barley and Brachypodium than T.urartu and Ae.tauschii . bZIP proteins in wheat, T.urartu and Ae.tauschii were divided into 14 subgroups based on phylogenetic analyses. Using Affymetrix microarray data, 48 differentially expressed TabZIP genes were identified to be related to anther development from comparison between the male sterility line and the restorer line. Genes with close evolutionary relationship tended to share similar gene structures. 15 of 23 selected TabZIP genes contained LTR elements in their promoter regions. Expression of 21 among these 23 TabZIP genes were obviously responsive to low temperature. These 23 TabZIP genes all exhibited distinct tissue-specific expression pattern. Among them, 11 TabZIP genes were predominantly expressed in anther and most of them showed over-dominance expression mode in the cross combination TY806 × BS366. Conclusions The genome-wide identification provided an overall insight of bZIP gene family in wheat and its relatives. The evolutionary relationship of wheat and its relatives was proposed based on orthology analyses. Microarray and expression analyses suggested the potential involvement of bZIP genes in anther development and facilitated selection of anther development related gene for further functional characterization.

Introduction This study protocol specifies the primary research line and theoretical framework of the 2023 Survey of the Psychology and Behavior of the Chinese Population. It aims to establish a consistent database of Chinese residents' psychological and behavioral surveys through multi‐center and large‐sample cross‐sectional surveys to provide robust data support for developing research in related fields. It will track the public's physical and psychological health more comprehensively and systematically. Methods The study was conducted from June 20, 2023 to August 31, 2023, using stratified and quota sampling methods. A total of 150 cities across 800 communities/villages were surveyed, selected from China (Despite extensive coordination, we have been unable to contact our counterparts in the Taiwan region of China to obtain relevant statistical data). The questionnaires were distributed to the public one‐on‐one and face‐to‐face by trained surveyors. The questionnaires included basic information about the individual, personal health status, basic information about the family, the social environment in which the individual lives, psychological condition scales, behavioral level scales, other scales, and attitudes towards topical social issues. Supervisors conducted quality control during the distribution process and returned questionnaires, logically checked and cleaned for data analysis. Discussion Data collection has been finished, and scientific outputs based on this data will support the development of health promotion strategies in China and globally. In the aftermath of the pandemic, it will guide policymakers and healthcare organizations to improve their existing policies and services to maximize the physical and mental health of the Chinese population. Trial Registration This study was filed in the National Health Security Information Platform (Record No.: MR‐37‐23‐017876) and officially registered in the China Clinical Trials Registry (Registration No.: ChiCTR2300072573).