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Hypoxic ischemic encephalopathy (HIE) is the leading cause of neonatal mortality and disability, but its treatment options are very limited and there is an urgent need to further improve treatment outcomes. The present study aims to reveal the therapeutic effects, action pattern, and potential mechanisms of Cerebroprotein hydrolysate-I (CH-I), a mixture of hydrolyzed peptides and amino acids, for the management of HIE. To simulate the complex pathogenesis of HIE more accurately, we innovatively constructed a "triple hit" neonatal HIE rat model. The efficacy of CH-1 was examined in this model, and it was found that CH-I treatment not only significantly improved the behavior and small molecule metabolism disorders of neonatal HIE rats, but also reduced intracerebral neuronal apoptosis, neuroinflammation, and oxidative stress levels. In addition, the neuroprotective effect of CH-I was also confirmed in the hypoxic oligodendrocyte precursor cell model. We innovatively found that CH-I could reverse myelin damage induced by HIE modeling via activating the Wnt/β-catenin signaling pathway. More importantly, a robust quantitative analysis assay for the main peptides in CH-I was developed based on LC-MS/MS system combining Skyline software. Then the pharmacokinetics of the main peptides was studied based on 'relative exposure approach' combining 'mixed calibration curves' strategy. The transient exposure of peptides in vivo indicated that CH-I should exert neuroprotective effects through the "hit and run" pattern., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Sepsis is a fatal consequence of compromised host immunity due to widespread infection. Its pathogenesis has recently been found to be associated with tetranectin (TN), a monocyte-produced plasma protein with a critical disease-associated epitope, P5-5. To develop a rapid and simple method for early monitoring of the disease in clinical settings, a purified monoclonal antibody (12F1 mAb) with high affinity for the human TN pathogenic epitope P5-5 was produced in this study. The linear range of the indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) based on the mAb to detect TN-P5-5 was 4.8-312 ng/mL, and the half-maximal inhibitory concentration (IC 50 ) was 26.99 ng/mL, with a limit of detection of 2.4 ng/mL. Furthermore, the average recovery of intra- and inter-assay were 103.253 ± 2.803 % and 107.778 ± 7.490 %, respectively. Importantly, the competitive ELISA method established using 12F1 revealed signals corresponding to disease severity in patients with sepsis. Furthermore, the specific in vivo recognition of a pathogenic epitope by mAbs can be extended to therapeutic applications. Collectively, the development of an epitope-specific mAb against disease-associated proteins could be utilized accurately and quantitatively for diagnosing and monitoring diseases in clinical blood samples., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Alzheimer's disease is one of at least 26 diseases characterized by tau-positive accumulation in neurons, glia or both. However, it is still unclear what modifications cause soluble tau to transform into insoluble aggregates. We previously performed genetic screens that identified tyrosine kinase 2 (TYK2) as a candidate regulator of tau levels. Here we verified this finding and found that TYK2 phosphorylates tau at tyrosine 29 (Tyr29) leading to its stabilization and promoting its aggregation in human cells. We discovered that TYK2-mediated Tyr29 phosphorylation interferes with autophagic clearance of tau. We also show that TYK2-mediated phosphorylation of Tyr29 facilitates pathological tau accumulation in P301S tau-transgenic mice. Furthermore, knockdown of Tyk2 reduced total tau and pathogenic tau levels and rescued gliosis in a tauopathy mouse model. Collectively, these data suggest that partial inhibition of TYK2 could thus be a strategy to reduce tau levels and toxicity., Competing Interests: Competing interests H.Y.Z. cofounded Cajal Neuroscience, is a director of the Regeneron Pharmaceuticals board and is on the scientific advisory board of Cajal Neuroscience, Lyterian and the Column Group. D.M.H. cofounded and is on the scientific advisory board of C2N Diagnostics. D.M.H. is on the scientific advisory board of Denali, Cajal Neuroscience and Genentech, consults for Asteroid Therapeutics, is an inventor of and has a patent on antitau antibodies that was licensed by Washington University to C2N Diagnostics. B.H. owns stock in Novartis; he serves on the scientific advisory board of Dewpoint and has an option for stock. He serves on a scientific advisory board or is a consultant for AbbVie, Alexion, Ambagon, Aprinoia Therapeutics, Arvinas, Avrobio, AstraZeneca, Biogen, BMS, Cure Alz Fund, Cell Signaling Technology, Dewpoint, Latus, Novartis, Pfizer, Sanofi, Sofinnova, Vigil, Violet, Voyager and WaveBreak. His laboratory is supported by research grants from the NIH, Cure Alzheimer’s Fund, Tau Consortium and the JPB Foundation, as well as a sponsored research agreement from Abbvie. The other authors declare no competing interests., (© 2024. The Author(s).)

The ongoing evolution and immune escape of SARS-CoV-2, alongside the potential threat of SARS-CoV-1 and other sarbecoviruses, underscore the urgent need for effective strategies against their infection and transmission. This study highlights the discovery of nanobodies from immunized alpacas, which demonstrate exceptionally broad and potent neutralizing capabilities against the recently emerged and more divergent SARS-CoV-2 Omicron subvariants including JD.1.1, JN.1, KP.3, KP.3.1.1, as well as SARS-CoV-1 and coronaviruses from bats and pangolins utilizing receptor ACE2. Among these, Tnb04-1 emerges as the most broad and potent, binding to a conserved hydrophobic pocket in the spike's receptor-binding domain, distinct from the ACE2 binding site. This interaction disrupts the formation of a proteinase K-resistant core, crucial for viral-cell fusion. Notably, intranasal administration of Tnb04-1 in Syrian hamsters effectively prevented respiratory infection and transmission of the authentic Omicron XBB.1.5 subvariant. Thus, Thb04-1 holds promise in combating respiratory acquisition and transmission of diverse sarbecoviruses., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Dong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Uneven energy distribution of femtosecond lasers presents a significant challenge for single-spot analysis, which often leads to concave ablation craters. This study assesses the performance of a femtosecond laser ablation system for in situ analysis using novel galvanometer scanners. A galvanometer rapidly moved the laser beam focus to create craters with a small beam spot. We first examined the inductively coupled plasma mass spectrometry (ICP-MS) signal sensitivity to laser parameters, establishing a strong linear correlation with the laser energy, repetition rate, scanning ablation area, and galvanometer scanning frequency. Elemental fractionation analysis of NIST SRM 610 suggests minimal bias, with fractionation indices of different elements approaching unity. Subsequently, the elemental concentration of six reference material glasses was measured by fsLA-ICP-MS to evaluate the elemental quantification capabilities of the Galvo-femtosecond laser (Galvo-fsLA). The laser's capability for in situ U-Pb dating was demonstrated by concordant U-Pb ages of five zircon reference materials that are highly consistent with the ID-TIMS ages reported previously. Finally, the reliability of the new Galvo-fsLA for isotope analysis was verified by the accurate determination of radiogenic Hf, Pb isotopes, and stable Cu isotopes, all agreeing well with their reference values within uncertainties. These assessments underscore the significant potential of Galvo-fsLA for enhanced accuracy and precision of single-spot in situ analysis.

To gain a deeper understanding of the ACE inhibition effect, the inhibitory effect of ACE-inhibiting peptide (ACEIP) FPPDVA's digestive products on ACE was further investigated. Two novel peptides, PD (IC 50 = 161.1 ± 1.10 μM) and DV (IC 50 = 66.51 ± 0.99 μM) were identified in the digestive products of FPPDVA using LC-MS/MS. The Peptide Mix (FPPDVA, PD, and DV) exhibited a remarkable synergistic effect on ACE inhibition by significantly enhancing it by up to 508% compared to the individual peptides alone. Furthermore, theoretical simulations suggest that the Peptide Mix synergistically inhibits ACE activity by forming more stable complexes with the active site of ACE, facilitated by an increased number of hydrogen bonds. Additionally, Lineweaver-Burk plot analysis and spectroscopic studies further verified the presence of these stable complexes. ITC results show that the combination of Peptides Mix and ACE is a spontaneous exothermic process driven by entropy. The study showed that FPPDVA has a stronger inhibitory effect on ACE after digestion, making it suitable as an antihypertensive peptide in functional foods.

N6-methyladenosine (m6A) RNA modification orchestrates cellular epitranscriptome through tuning the homeostasis of transcript stability, translation efficiency, and the transcript affinity toward RNA-binding proteins (RBPs). An aberrant m6A deposition on RNA can lead toward oncogenic expression profile (mRNA), impaired mitochondrial metabolism (mtRNA), and translational suppression (rRNA) of tumor suppressor genes. In addition, non-coding RNAs (ncRNAs), such as X-inactive specific transcript (XIST), miRNAs, and α-ketoglutarate-centric metabolic transcripts are also regulated by the m6A epitranscriptome. Notably, recent studies had uncovered a myriad of m6A-modified transcripts the center of hematopoietic stem cell (HSC) regulation, in which m6A modification act as a context dependent switch to the on and off of hematopoietic stem cell (HSC) maintenance, lineage commitment and terminal differentiation. In this review, we sequentially unfold the m6A mediated epithelial-to-hematopoietic transition in progenitor blood cell production, lymphocytic lineage expansion (T cells, B cells, NK cells, and non-NK ILCs), and the m6A crosstalk with the onco-metabolic prospects of leukemogenesis. Together, an encompassing body of evidence highlighted the emerging m6A significance in the regulation of HSC biology and leukemogenesis., (© 2024. The Author(s).)

Background: Pea protein isolate (PPI) is gaining increasing popularity in the food industry. It provides a diverse range of health benefits, such as hypoallergenic and gluten-free characteristics. However, the functional performance of PPI is hindered by its low solubility and poor stability. Therefore, in this article, PPI and dextran (DX) of different molecular weights were grafted to investigate the effects of grafting DX with different molecular weights on the interface properties and antioxidant properties of PPI. Additionally, the stability and digestive properties of the glycated PPI nanoemulsion system were explored., Results: The result showed that the grafting degree of PPI-DX conjugates (PPI-DC) decreased with an increase in the molecular weight of DX. Surface hydrophobicity, antioxidant activity and solubility of PPI-DC were significantly improved after grafting compared with PPI and PPI-DX mixtures (PPI-DM). Astaxanthin-loaded emulsions stabilized by grafted conjugates had smaller droplets and higher astaxanthin encapsulation rate compared to PPI emulsions. In vitro digestion demonstrated that the bioavailability of PPI-DC emulsions was higher than of PPI emulsion. Furthermore, after 24 days of storage, retention rate of astaxanthin-loaded emulsions prepared by conjugates remained above 70%, surpassing that of PPI emulsion., Conclusion: These results indicated that DX grafting can improve the emulsion properties of PPI. In addition, the DX with a molecular weight of 5 kDa showed the most significant improvement. This study contributes to the advancement of natural emulsifiers by modifying PPI through glycation, and furnishes a valuable reference for its utilization in functional foods. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

This study evaluated the safety, tolerability, pharmacodynamics, and pharmacokinetics of recombinant neorudin (EPR-hirudin [EH]) in patients with acute coronary syndrome (ACS), providing a basis for further therapeutic research. This open-label, single-center, nonrandomized, nonblinded, and noncontrolled trial categorized 24 patients with nonprogressive ACS who met the screening criteria into 3 groups. They received an intravenous injection of neorudin (0.4 mg/kg), followed by an intravenous drip at doses of 0.15, 0.30, and 0.45 mg/kg/h for 3 days in the low-, medium-, and high-dose groups, respectively. The safety, tolerability, pharmacodynamics, and pharmacokinetics of EH were assessed after treatment, indicating that neorudin was safe and well tolerated in nonprogressive ACS. No serious adverse events or clinical composite end points were observed. The activated partial thromboplastin time and thrombin time increased significantly and dose dependently following EH administration across all groups compared to pretreatment values. Conversely, thrombin activity significantly decreased after drug administration but returned to baseline levels shortly after drug withdrawal. Within the administered dose range, neorudin exposure increased with the dose, and its half-life was approximately 2 hours. Neorudin was found to be safe and tolerable for treating patients with nonprogressive ACS, demonstrating therapeutic efficacy at doses up to 0.45 mg/kg/h over a 3-day period., (© 2024 The Author(s). Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Environmental estrogens are currently a significant research topic, and poultry manure serves as a crucial source. This study investigated the degradation characteristics and effect mechanisms of six estrogens (E1, 17α-E2, 17β-E2, E3, 17α-EE2, and DES) during the aerobic composting of chicken manure. An orthogonal test comprising four factors (aeration rate, calcium-magnesium-phosphorus fertilizer (Ca-Mg-P fertilizer), coconut shell biochar, initial moisture content) and three levels of aerobic composting was conducted over a 45-day period to monitor the changes in estrogens and basic parameters. The results indicated that the factors influencing the estrogen degradation rate ranked as: initial moisture content (MC) > Ca-Mg-P fertilizer > aeration rate > coconut shell biochar. These factors significantly influenced the abundance of estrogen-degrading genera. Optimal composting conditions for estrogen degradation were identified as the addition of 10% coconut shell biochar, maintaining an initial moisture content of 60%, and using an aeration rate of 0.08 L min -1 ∙kg -1 DM (dry matter), with an average degradation rate of 86.88% for the six estrogens under these conditions. During the composting process under various treatments, five known estrogen-degrading genera were observed with high relative abundance (max 31.08%), and the predominant genera were Staphylococcus and Brachybacterium for 17α-E2, 17β-E2, E3, 17α-EE2, and DES, and Pusillimonas for E1. The composition of microbial community structure changed significantly, and the dominated environment factors effecting the composition and succession of these genera were carbon to nitrogen ratio (C/N) and MC. The research results can provide both a theoretical basis and practical reference for the effective degradation of estrogens during the composting of chicken manure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Cancer stem cells (CSCs) are a major hindrance to clinical cancer treatment. Owing to their high tumorigenic and metastatic potential, CSCs are vital in malignant tumor initiation, growth, metastasis, and therapeutic resistance, leading to tumorigenesis and recurrence. Compared with normal tumor cells, CSCs express high levels of surface markers (CD44, CD90, CD133, etc.) and activate specific signaling pathways (Wnt/β-catenin, Notch, and Hedgehog). Although Current drug delivery systems (DDS) precisely target CSCs, the heterogeneity and multidrug resistance of CSCs impede CSC isolation and screening. Conversely, hydrogel DDSs exhibit good biocompatibility and high drug delivery efficiency. Hydrogels are three-dimensional (3D) spatial structures for drug encapsulation that facilitate the controlled release of bioactive molecules. Hence, hydrogels can be loaded with drugs to precisely target CSCs. Their 3D structure can also culture non-CSCs and facilitate their transformation into CSCs. for identification and isolation. Given that their elastic modulus and stiffness characteristics reflect those of the cellular microenvironment, hydrogels can simulate extracellular matrix pathways and markers to regulate CSCs, disrupting the equilibrium between CSC and non-CSC transformation. This article reviews the CSC microenvironment, metabolism, signaling pathway, and surface markers. Additionally, we summarize the existing CSC targeting strategies and explore the application of hydrogels for CSC screening and treatment. Finally, we discuss potential advances in CSC research that may lead to curative measures for tumors through targeted and precise attacks on CSCs., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Progestins are crucial steroid hormones that have attracted wide attention due to their endocrine disrupting effects in fish. The aim of this study is to investigate the effects of long-term exposure to low concentrations of norgestrel (NGT) on the reproductive and thyroid endocrine systems of adult zebrafish. Adult zebrafish were exposed to 7 and 39 ng/L NGT for a duration of 90 days. The results revealed that exposure to 39 ng/L NGT led to a significant up-regulation of 3β-hydroxysteroid dehydrogenase (hsd3b) and 20β-hydroxysteroid dehydrogenase (hsd20b) genes in the ovary of female zebrafish. Additionally, there was a significant up-regulation of 11β-hydroxysteroid dehydrogenase 2 (hsd11b2) gene in the testis of male zebrafish. Furthermore, egg production decreased significantly, accompanied by notable alterations in the proportion of ovarian development stages, as well as reductions of sex hormone levels (E2, 11-KT, and T) in both females and males. However, long-term exposure to low concentrations of NGT did not lead to changes in thyroid hormone levels and thyroid histopathology in adult zebrafish. The overall results imply that environmental concentrations of NGT have a strong endocrine disrupting effect on the reproductive system of zebrafish, while the thyroid system is not sensitive to NGT exposure. The present study underscores the reproductive endocrine impacts of NGT and emphasizes the necessity for prolonged exposure at environmental concentrations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To assess the impact of multicomponent exercises on physical functions of frail elderly in communities, evaluating their effect on muscle strength, balance, and endurance, and their influence on quality of life., Method: PubMed, Embase, Cochrane, and Web of Science were searched to collect relevant randomized controlled trials. The search cutoff date was January 24, 2024. Included studies met pre-specified inclusion and exclusion criteria. Data analysis was performed using Revman 5.4 and Stata 15.0 software., Result: This analysis included 19 studies. After 12 weeks, the multicomponent exercises significantly enhanced participants' performance in various physical function assessments. Specifically, in the Timed Up and Go Test, the exercise group showed a significant reduction in time [SMD = -0.86 (95 % CI: -1.40 to -0.33)]. In the Short Physical Performance Battery, interventions shorter than 6 weeks significantly increased scores [SMD = 1.01 (95 % CI: 0.64 to 1.37)], and those longer than 6 weeks showed improvements [SMD = 0.53 (95 % CI: 0.26 to 0.80)]. Muscle strength also improved, with handgrip strength and knee extensor strength enhancements [SMD = 0.93 (95 % CI: 0.27 to 1.59); SMD = 0.72 (95 % CI: 0.24 to 1.20)]. However, there was no statistically significant difference in walking speed between the groups [SMD = 0.04 (95 % CI: -0.33 to 0.40)]., Conclusion: Although multicomponent exercises significantly improve muscle strength, balance, and endurance in frail elderly individuals, there is no conclusive evidence of their effect on enhancing quality of life or long-term health outcomes. Further research is needed to explore the specific impacts of different types and intensities of exercises on this population., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Study Design: This was a retrospective cohort radiographic study., Objective: To determine the age- and gender-related normative values and correlation of cervical sagittal parameters in asymptomatic Chinese adults, and to explore the changes and compensating mechanisms across different age groups., Methods: The asymptomatic subjects were divided into 6 groups according to age and then one-way analysis of variance was used to compare the multiple sets of cervical sagittal parameters among the different age groups. Independent t-tests were performed to compare the sagittal parameters among different gender and different cervical spine alignments. Relationships between each parameter were tested by Pearson's correlation. Linear regression analysis based on T1 slope (T1S) and C2 slope (C2S) was used to provide an equation to predict normal cervical alignment., Results: Mean values of each cervical sagittal parameter were presented based on age and gender. There were positive correlations between age and cervical lordosis (CL) (r = -.278, P < .001), T1S (r = .271, P < .001), cervical sagittal vertical axis (cSVA) (r = .218, P < .001), C2-C4 Cobb angle (r = -.283, P < .001), horacic inlet angle (TIA) (r = .443, P < .001), and neck tilt (NT) (r = .354, P < .001). Older groups (aged >50 years) had greater T1 Slope, C2S, and TIA. The C2-C4 Cobb angle maintained a steadily increasing trend and significantly increased in the older adult groups ( P < .05), while the C5-C7 Cobb angle was relatively constant. Mean values of parameters were larger in males ( P > .05). Linear regression analysis indicated a strong association between T1S and CL (R2 = .551, standard error 1.16°), T1S and C5-7 (R2 = .372; P < .001), and C2S and C2-4 (R2 = .309; P < .001)., Conclusions: Normative values of cervical sagittal parameters vary by age and sex. The CL, cSVA, and T1S, C2-4 Cobb angle changed with increasing age, and it can influence the recruitment of compensation mechanism. Normative CL of Chinese adults was predicted by the equation CL = T1S-14.7° ± 1.2°, which could serve as a reference when planning for cervical surgery., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Antibiotics and triazole fungicides coexist in varying concentrations in natural aquatic environments, resulting in complex mixtures. These mixtures can potentially affect aquatic ecosystems. Accurately distinguishing synergistic and antagonistic mixtures and predicting mixture toxicity are crucial for effective mixture risk assessment. We tested the toxicities of 75 binary mixtures of antibiotics and fungicides against Auxenochlorella pyrenoidosa. Both regression and classification models for these mixtures were developed using machine learning models: random forest (RF), k-nearest neighbors (KNN), and kernel k-nearest neighbors (KKNN). The KKNN model emerged as the best regression model with high values of determination coefficient (R 2  = 0.977), explained variance in prediction leave-one-out (Q 2 LOO  = 0.894), and explained variance in external prediction (Q 2 F1  = 0.929, Q 2 F2  = 0.929, and Q 2 F3  = 0.923). The RF model, the leading classifier, exhibited high accuracy (accuracy = 1 for the training set and 0.905 for the test set) in distinguishing the synergistic and antagonistic mixtures. These results provide crucial value for the risk assessment of mixtures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Entity alignment is a crucial task in knowledge graphs, aiming to match corresponding entities from different knowledge graphs. Due to the scarcity of pre-aligned entities in real-world scenarios, research focused on unsupervised entity alignment has become more popular. However, current unsupervised entity alignment methods suffer from a lack of informative entity guidance, hindering their ability to accurately predict challenging entities with similar names and structures. To solve these problems, we present an unsupervised multi-view contrastive learning framework with an attention-based reranking strategy for entity alignment, named AR-Align. In AR-Align, two kinds of data augmentation methods are employed to provide a complementary view for neighborhood and attribute, respectively. Next, a multi-view contrastive learning method is introduced to reduce the semantic gap between different views of the augmented entities. Moreover, an attention-based reranking strategy is proposed to rerank the hard entities through calculating their weighted sum of embedding similarities on different structures. Experimental results indicate that AR-Align outperforms most both supervised and unsupervised state-of-the-art methods on three benchmark datasets., Competing Interests: Declaration of competing interest All authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: To evaluate the different characteristics of oropharyngeal pH changes in patients with different laryngeal diseases., Methods: A retrospective analysis was performed. The clinical data of 262 patients were summarized. The patients were divided into 4 groups. Group 1 included 123 patients with suspected laryngopharyngeal reflux disease (LPRD). Group 2 included 45 patients with vocal cord polyps. Group 3 included 40 patients with vocal cord leukoplakia. Group 4 included 54 patients with laryngeal carcinoma. Their reflux symptom indexes (RSIs), reflux finding scores (RFSs), and Dx-pH monitoring results were compared., Results: In total, 235 patients had abnormal RSI/RFS, 90 patients had abnormal Ryan scores. The rate of abnormal RSI/RFS of Group 1 was significantly higher than that of Group 4 (P = .001). Significant differences of the rates of abnormal Ryan scores existed between Groups 2 and 4 (P = .021) and Groups 3 and 4 (P = .027). There were obvious differences in upright Ryan scores between Groups 1 and 2 (P = .013), Groups 1 and 3 (P = .002), Groups 2 and 4 (P = .046), and Groups 3 and 4 (P = .009). There were significant differences in time percentage of oropharyngeal pH of upright 5.5∼6.5 and supine 5.0∼6.5 between Groups 1 and 3 as well as Groups 1 and 4 (upright: Groups 1 and 3: P = .017; Groups 1 and 4: P = .019. Supine: Groups 1 and 3: P = .018; Groups 1 and 4: P = .023)., Conclusions: There were different oropharyngeal pH characteristics in patients with different laryngeal diseases, which indicated laryngopharyngeal reflux may play different roles in different diseases through various patterns. Patients with vocal cord polyps, vocal cord leukoplakia, and laryngeal carcinoma had more and different patterns of oropharyngeal pH change than patients with LPRD. Patients with vocal cord polyps and vocal cord leukoplakia had more severe acid oropharyngeal pH change episodes than patients with laryngeal carcinoma., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: MADS-box transcription factors have been shown to be involved in multiple developmental processes, including the regulation of floral organ formation and pollen maturation. However, the role of the MADS-box gene family in floral development of the alpine plant species Coptis teeta Wall, which is widely used in Traditional Chinese Medicine (TCM), is unknown., Results: Sixty-six MADS-box genes were identified in the C. teeta genome. These genes were shown to be unevenly distributed throughout the genome of C. teeta. The majority of which (49) were classified as type I MADS-box genes and were further subdivided into four groups (Mα, Mβ, Mγ and Mδ). The remainder were identified as belonging to the type II MADS-box gene category. It was observed that four pairs of segmental and tandem duplication had occurred in the C. teeta MADS-box gene family, and that the ratios of Ka/Ks were less than 1, suggesting that these genes may have experienced purifying selection during evolution. Gene expression profiling analysis revealed that 38 MADS-box genes displayed differential expression patterns between the M and F floral phenotypes. Sixteen of these MADS-box genes were further verified by RT-qPCR. The 3D structure of each subfamily gene was predicted, further indicating that MADS-box genes of the same type possess structural similarities to the known template., Conclusions: These data provide new insights into the molecular mechanism of dichogamy and herkogamy formation in C. teeta and establish a solid foundation for future studies of the MADS-box genes family in this medicinal plant species., (© 2024. The Author(s).)

Quantitative analysis of cell-free RNA (cfRNA) in plasma sample can be used for screening, diagnosing, and prognosticating of multiple diseases. Here, we report a quantitative CRISPR/Cas digital imaging platform (qCasdip) for the detection of various cfRNAs, including circular RNAs and miRNAs, in clinical samples at the attomolar (aM) level without the need for preamplification. Digital counting strategy provides qCasdip quantitative ability with a linear detection range of 10 2 -10 6 aM. Meanwhile, qCasdip demonstrated cfRNA profiling in clinical plasma samples, improving the diagnosis of breast cancer. These data highlight the potential of qCasdip to quantitatively assess the molecular patterns of specific cfRNA panels in plasma, thereby providing a novel liquid biopsy solution to enhance disease diagnosis.

Ethnopharmacological Relevance: China and India have unique traditional medicine systems with vast territory and rich medical resources. Traditional medicines in China include traditional Chinese medicine, Tibetan medicine, Mongolian medicine, Uyghur medicine, Dai medicine, etc. In the third national survey of Chinese medicine resources, 12694 medicinal materials were identified. Traditional medicines in India include Ayurveda, Unani, Siddha, Homoeopathy, etc. There are 7263 medicinal materials in India., Aim of the Study: To reveal the characteristics of medicinal materials between China and India respectively, and to compare the similarities and differences in terms of properties, tastes, medicinal parts and therapeutic uses and to promote the exchange of traditional medicine between China and India and the international trade of traditional medicine industry., Methods: The information of medicinal materials between China and India was extracted from The Chinese Traditional Medicine Resource Records and Pharmacopoeia of the People's Republic of China, as well as from 71 Indian herbal monographs. The information of each medicinal material, such as types, families, genera, properties, distribution, medicinal parts, efficacy, therapeutic uses, dosage form and dosage, was recorded in Excel for statistical analysis and visual comparison., Results: A total of 12694 medicinal materials in China and 5362 medicinal materials in India were identified. The medicinal materials were mostly distributed in Southwest China and northern India. Plants were the main sources of medicinal materials. The common medicinal parts in China were whole medicinal materials, roots and rhizomes, and India used more renewable fruits, seeds and leaves. They are commonly used in the treatment of digestive system diseases. There were 1048 medicinal materials used by both China and India, which were distributed in 188 families and 685 genera. The Chinese and Indian pharmacopoeias had a total of 80 species of medicinal materials used by both China and India., Conclusions: The characteristics of medicinal materials between China and India were somewhat different, which was conducive to provide a reference basis for traditional medicine in China or India to increase the medicinal parts and indications when using a certain medicinal material, as well as to expand the source of medicine and introduce new resources. However, there were certain similarities and shared medicinal materials, which can tap the potential of bilateral trade of medicinal materials between China and India, so as to promote the medical cultural exchange and economic and trade cooperation between the two countries., Competing Interests: Declaration of competing interest No conflict of interest exits in the submission of this manuscript, and all authors have read the manuscript and approve to publish. I would like to declare on behalf of my co-authors that the work described was review that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the manuscript that is enclosed., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Acetaminophen (APAP) induced liver injury (AILI) is a common cause of clinical hepatic damage and even acute liver failure. Our previous research has shown that Schisandra chinensis lignan extract (SLE) can exert a hepatoprotective effect by regulating lipid metabolism. Although polysaccharides from Schisandra chinensis (S. chinensis), like lignans, are important components of S. chinensis, their pharmacological activity and target effects on AILI have not yet been explored., Aim of the Study: This study aims to quantitatively reveal the role of SCP in the pharmacological activity of S. chinensis, and further explore the pharmacological components, potential action targets and mechanisms of S. chinensis in treating AILI., Materials and Methods: The therapeutic effect of SCP on AILI was systematically determined via comparing the efficacy of SCP and SLE on in vitro and in vivo models. Network pharmacology, molecular docking and multi-omics techniques were then used to screen and verify the action targets of S. chinensis against AILI., Results: SCP intervention could significantly improve AILI, and the therapeutic effect was comparable to that of SLE. Notably, the combination of SCP and SLE did not produce mutual antagonistic effects. Subsequently, we found that both SCP and SLE could significantly reverse the down-regulation of GPX4 caused by the APAP modeling, and then further improving lipid metabolism abnormalities., Conclusions: Hepatoprotective effects of SCP and SLE is most correlated with their regulation of GSH/GPX4-mediated lipid accumulation. This is the first exploration of the hepatoprotective effect and potential mechanism of SCP in treating AILI, which is crucial for fully utilizing S. chinensis and developing promising AILI therapeutic agents., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest, and all authors report no conflicts of interest in this work., (Copyright © 2024. Published by Elsevier B.V.)

Burnout, depression, anxiety, and stress negatively impact the well-being and retention of healthcare professionals. The interplay of these symptoms is understudied. Utilizing network analysis, this study examined the interrelationships among these symptom clusters in clinical therapists in China. An anonymous survey was conducted among clinical therapists from 41 tertiary psychiatric hospitals in China. Burnout was assessed using the Maslach Burnout Inventory-Human Service Survey (MBI-HSS), while symptoms of depression, anxiety, and stress were assessed via the Depression, Anxiety, and Stress Scale-21 (DASS-21). Analyses were performed to identify central symptoms and bridge symptoms of this network. A total of 419 participants were included in this survey. The prevalence rate for burnout, depression, anxiety, and stress was 19.8%, 22.2%, 17.9%, and 8.6%, respectively. Network analysis indicated that stress symptoms had the highest expected influence values, closely followed by emotional exhaustion from MBI-HSS. Notably, emotional exhaustion emerged as the strongest bridge of expected influence. The stability of the expected influence and bridge expected influence was robust, with coefficients at 0.75. The study's findings underscore the importance of recognizing the central symptoms and bridge symptoms, which could lead to more effective early detection and intervention for burnout, depression, anxiety, and stress among clinical therapists., (© 2024. The Author(s).)

Objective: To identify early changes in hippocampal quantitative parameters in multiple sclerosis (MS) patients using synthetic MRI, and to correlate these changes with clinical variables., Methods: 45 MS patients and 26 healthy controls (HCs) underwent synthetic MRI and 3D-T1 MRI. The hippocampus volumes were assessed by using voxel-based morphometry. Synthetic MRI parameters (T1, T2, and proton density (PD)) from hippocampus and its subfield were measured and compared, and their associations with the Expanded Disability Status Scale (EDSS), Symbol Digit Modalities Test (SDMT) scores were further investigated., Results: There was no significant difference in hippocampal volume between MS patients and HCs. Compared with HCs, the T1, T2 and PD values of hippocampus and its subfield increased in MS patients. T2 values showed positive correlation with EDSS and negative correlation with SDMT., Conclusions: Synthetic MRI can detect subtle quantitative changes of the hippocampus in MS patients with normal hippocampal volume. Specifically, Synthetic MRI parameters may apply as potentially effective imaging biomarker for hippocampus evaluation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We report a visible-light-driven, palladium-catalyzed 1,4-difluoromethylative functionalization of conjugated dienes using chlorodifluoromethane (ClCF 2 H, Freon-22) as a cost-effective difluoromethyl source. The excited palladium catalyst efficiently reduces the C-Cl bond, which generates a CF 2 H radical, followed by regioselective S N 2' substitution to afford 1,4-difunctionalized products. This versatile, redox-neutral method accommodates diverse nucleophiles and exhibits broad functional group compatibility, making it suitable for late-stage functionalization in drug discovery and offering a direct route to difluoromethylated molecules.

Recent documented infection with an endemic coronavirus (eCoV) associates with less severe coronavirus disease 2019 (COVID-19), yet the immune mechanism behind this protection has not been fully explored. We measured both antibody and T cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in SARS-CoV-2 naïve individuals classified into two groups, either with or without presumed recent eCoV infections. There was no difference in neutralizing antibodies and T cell responses against SARS-CoV-2 antigens between the two groups. SARS-CoV-2 naïve individuals with recent presumed eCoV infection, however, had higher levels of Fc receptor (FcR) binding antibodies against eCoV spikes (S) and SARS-CoV-2 S2. There was also a significant correlation between eCoV and SARS-CoV-2 FcR binding antibodies. Recent eCoV infection boosts cross-reactive antibodies that can mediate Fc effector functions, and this may play a role in the observed heterotypic immune protection against severe COVID-19., Competing Interests: The authors have declared that no conflict of interest exists.

A ferroelectric quantum spin Hall insulator (FEQSHI) exhibits coexisting ferroelectricity and time-reversal symmetry protected edge states, holding exciting prospects for inviting both scientific and application advances, particularly in two-dimensional systems. However, FEQSHI candidates that consist of only one constituent element are rarely reported. Here, we show that ψ-bismuthene, an allotrope of bilayer Bi (110), is a concrete example of a two-dimensional elemental FEQSHI. It is demonstrated that ψ-bismuthene possesses measurable ferroelectric polarization and nontrivial band gap with moderate switching barrier, making it highly suitable for the detection and observation of ferroelectric topologically insulating states. Additionally, the auxetic behavior, quantum transport properties and ferroelectric controllable persistent spin helix in ψ-bismuthene are also discussed. These findings make ψ-bismuthene promising for both fundamental physics and technological innovations.

Meiosis, a process unique to germ cells, involves formation and repair of double-stranded nicks in DNA, pairing and segregation of homologous chromosomes, which ultimately achieves recombination of homologous chromosomes. Genetic abnormalities resulted from defects in meiosis are leading causes of infertility in humans. Meiotic sex chromosome inactivation (MSCI) plays a crucial role in the development of male germ cells in mammals, yet its underlying mechanisms remain poorly understood. In this study, we illustrate the predominant presence of a protein known as glucose 6 phosphatase catalyzed 3 (G6PC3) in pachytene spermatocytes, with a high concentration in the sex body (XY body), suggesting its significant involvement in male germ cell development. By employing CRISPR-Cas9 technology, we generate mice deficient in the G6pc3 gene, resulting in complete meiotic arrest at the pachytene stage in spermatocytes and are completely sterile. Additionally, we observe abnormal XY body formation and impaired MSCI in G6pc3- knockout spermatocytes. These findings underscore G6pc3 as a new essential regulator that is essential for meiotic progression. G6PC3 is involved in spermatocyte during male spermatogenesis development by the maintenance of meiosis chromosome silencing.

Background and Purpose: Renal interstitial fibrosis is a frequent pathological manifestation of lupus nephritis (LN). tRNA halves (tiRNAs) are acquired from tRNA-derived small non-coding RNAs (sncRNAs) and are associated with fibrosis. Our previous study indicated enhanced tiRNA-Gly-GCC-002 (tiRNA002) levels in kidneys were positively related to LN-related fibrosis. However, the precise molecular mechanism remains unclear., Experimental Approach: The mimic and agomiR of tiRNA002 were introduced into tubular epithelial cells (TECs) and MRL/lpr mice by transfection. The levels of gene and protein expressions were quantified using real-time quantitative polymerase chain reaction (RT-qPCR), Western blot and immunofluorescence assays., Key Results: In TECs treated with LN serum, as well as in the kidneys of MRL/lpr mice, high levels of tiRNA002 directly influenced the epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) deposition. Furthermore, tiRNA002 overexpression promoted EMT in TECs and accelerated renal interstitial fibrosis in MRL/lpr mice via Smad signalling. The target gene of tiRNA002, FKBP prolyl isomerase 5 (FKBP5), improved Smad signalling by interacting with phosphorylated Smad2/3. Silencing FKBP5 alleviated LN serum- or tiRNA002-mimic-induced EMT in TECs. In addition, FKBP5 overexpression reversed the tiRNA002 knockdown-mediated reduction of EMT and ECM accumulation., Conclusions and Implications: These findings indicated that tiRNA002 is markedly increased in LN, which facilitates renal fibrosis by promoting EMT via FKBP5-mediated Smad signalling. Therefore, targeting tiRNA002 may be an innovative approach to treat renal interstitial fibrosis in LN., (© 2024 British Pharmacological Society.)

Herein, a pyrolysis-induced precursor transformation strategy has been proposed. Using pre-synthesized PDA-M as a precursor, the production of transition metal single atom catalysts (SACs) has been achieved, with compositional flexibility at high metal loadings. In particular, the Ni SAC sample has shown promising CO selectivity when evaluated for the electrochemical CO 2 reduction reaction, reaching 29.8 mA cm -2 CO partial current density and 90.3% CO faradaic efficiency at -1.05 V vs. RHE.

Background: Halo-pelvic traction (HPT) is acknowledged for enhancing pulmonary function and reducing neurological complications in severe and rigid scoliosis and kyphoscoliosis. While its role in improving coronal balance is established, its impact on sagittal kyphosis remains under-researched. This study aims to assess HPT's effects on sagittal alignment in these conditions., Methods: A retrospective review of 37 patients with severe and rigid scoliosis or kyphoscoliosis was conducted to evaluate HPT's efficacy. The analysis focused on the impact of HPT on coronal and sagittal parameters, pulmonary function tests (PFTs) and complications. Radiographic assessments included main cobb angle in coronal, sagittal major kyphosis., Results: HPT was applied for an average of 2.9 months, significantly reducing the primary coronal curve from 127.7°±30.3° to 74.9°±28.3° (P < 0.05), achieving a 41.3% correction rate. Sagittal kyphosis correction was more pronounced, with angles decreasing from 80.4°±26.4° to 41.3°±24.4° (P < 0.05), resulting in a 48.6% correction rate. Pulmonary function tests showed improvements in forced vital capacity (FVC) (from 1.32 ± 0.91 to 1.55 ± 0.83) and forced expiratory volume in 1 s (FEV1) (from 1.03 ± 0.76 to 1.28 ± 0.72), with percentage predicted values also increasing (FVC%: 40.4%±24.3-51.4%±23.1%; FEV1%: 37.8%±25.2-48.1%±22.7%; all P < 0.05)., Conclusion: HPT effectively reduces spinal deformity severity and improves pulmonary function in patients with severe and rigid scoliosis and kyphoscoliosis. Sagittal kyphosis correction was notably greater than coronal scoliosis correction. The correlation between PFT improvements and coronal curve adjustments suggests that correcting the coronal Cobb angle is pivotal for pulmonary function enhancement., (© 2024. The Author(s).)

Background: The existence and reasons for the weekend effect in patients with ischemic heart disease (IHD) were not yet fully identified. This study aimed to evaluate whether weekend admission was independently associated with in-hospital mortality and the possible mechanisms associated with the IHD patients., Methods: The study was a retrospective study, including IHD patients from 2015 to 2023. The International Classification of Diseases, tenth revision (ICD-10) codes were used to identify all admissions with a primary diagnosis of IHD. The sample was divided into weekday and weekend groups. We performed a multivariate logistic regression analysis and a mediation analysis to estimate the effect of weekend admission on hospital mortality., Results: A total of 18,906 IHD patients were included in the study, with an average age of 63.8 ± 12.7. Of these patients, 21.7% ( n  = 4,102) were admitted over the weekend. The in-hospital 30-days mortality rate was significantly higher among the patients admitted at weekends compared with those admitted at weekdays (2.0% vs. 1.1%). Respectively, the 30-day mortality rate of patients admitted on weekends was higher compared to patients admitted on weekdays among patients with surgical treatment (2.34% vs. 1.06%, OR = 1.75; 95% CI: 1.23-2.42) and with emergency admission (3.48% vs. 2.59%, OR = 1.56; 95% CI: 1.05-2.28). Mediation analyses showed that the surgical scheduling had significant mediated effects on the associations of admission time with mortality risk., Conclusions: IHD patients with a surgical therapy or admitted from emergency department had a significantly higher risk of mortality when admitted on weekends compared to weekdays. These findings have potential implications for resource allocation and redistribution of surgery to weekends in hospitals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Liu, Lin, Jia, Wu, Liu and Liang.)

With the advantages of a high specificity, a long half-life, and a high safety, the use of antibody biologic drugs, including camrelizumab, has been rapidly increasing in clinical practice. Camrelizumab, an immune checkpoint inhibitor and humanized monoclonal antibody, is used to treat several advanced solid cancers. Measuring its concentration supports personalized dosage adjustments, influences treatment decisions for patients, strengthens the control of disease activity through therapeutic drug monitoring, and helps evaluate and prevent drug interactions in combination therapy. Because antibodies are present in complex biological matrices, quantifying monoclonal antibody drugs is challenging, and must rely on precise, selective, and reliable analytical methods. In this study, a quadrupole time-of-flight mass spectrometry TripleTOF 6600+ (AB SCIEX, Framingham, MA, USA) system equipped with a Turbo V ion source was used for the qualitative analysis of monoclonal antibodies using the data-dependent acquisition (IDA) MS/MS mode, followed by quantitative analysis using a targeted MRMHR workflow. This method showed a good linear relationship within the range of 4-160 μg/mL, with a correlation coefficient of R 2 ≥ 0.996. It demonstrated an acceptable accuracy (88.95-101.18%) and precision (≤15%). Furthermore, the lower limit of quantification was found to be 4 μg/mL, with the lowest detection limit of 0.3217 μg/mL, indicating that this method is rapid, accurate, and reliable for the quantitative analysis of camrelizumab in human serum.

Cis-regulatory elements (CREs) are critical in regulating gene expression, and yet understanding of CRE evolution remains challenging. Here, we constructed a comprehensive single-cell atlas of chromatin accessibility in Oryza sativa, integrating data from 103,911 nuclei representing 126 discrete cell states across nine distinct organs. We used comparative genomics to compare cell-type resolved chromatin accessibility between O. sativa and 57,552 nuclei from four additional grass species (Zea mays, Sorghum bicolor, Panicum miliaceum, and Urochloa fusca). Accessible chromatin regions (ACRs) had different levels of conservation depending on the degree of cell-type specificity. We found a complex relationship between ACRs with conserved noncoding sequences, cell-type specificity, conservation, and tissue-specific switching. Additionally, we found that epidermal ACRs were less conserved compared to other cell types, potentially indicating that more rapid regulatory evolution has occurred in the L1-derived epidermal layer of these species. Finally, we identified and characterized a conserved subset of ACRs that overlapped the repressive histone modification H3K27me3, implicating them as potentially silencer-like CREs maintained by evolution. Collectively, this comparative genomics approach highlights the dynamics of plant cell-type-specific CRE evolution.

Background: Surgery for adnexal mass does occur in pregnant women and therefore the choice of surgery during pregnancy needs to be carefully considered and studied. This study aimed to evaluate the safety and feasibility of Laparo-endoscopic Single-site Surgery (LESS) for adnexal mass during pregnancy and investigate the perioperative condition, pregnancy complications, and obstetric outcomes of operative women during pregnancy., Methods: This study retrospectively collected medical records and surgery videos of 20 pregnant women who underwent LESS for adnexal mass between November 2019 and January 2022. Baseline characteristics, operative-related variables, and pregnancy outcomes were followed up., Results: LESS for adnexal mass was successfully performed in 20 pregnant women, with very satisfactory surgery outcomes reported in all cases. The average gestational age at operation was 15 +2  weeks (range, 5 +1 - 25 +4  weeks). The median operative time was 80.8 min (range, 40 -185 min) and the average operative bleeding was 28.0 ml (range, 10-50 ml). The average VAS of 24 h postoperatively was 1 (range, 0-2), and the average length of hospital stay was 5.15 days (range, 3-7 days). All these women delivered a healthy newborn at full term except 1 woman induced abortion for her own reasons at 16 +5  weeks gestational age (GA). The average GA of delivery was 39 +1  weeks (range, 37-40 +1  weeks), the average birth weight was 3228.95 g (range, 2740-3930 g), and the average Apgar score at 5 min was 9.95 (range, 9-10)., Conclusions: LESS for adnexal mass is safe and feasible for pregnant women., (© 2024. The Author(s).)

Objective: The aim of the study is to describe the season of RSV prevalence in China during the COVID-19 pandemic., Methods: This multicenter retrospective study analyzed the epidemiology of pediatric RSV infections and the possible factors contributing to its variations in China from January 1, 2019, to October 31, 2022., Results: A total of 872,565 children were included. During the pandemic, RSV detection rate increased across various regions, including South China, East China, Central China, and Northeast China. From 2019 to 2021, the detection rates of RSV showed an increasing trend among children aged <1 year, 1-2 years, and 3-5 years, but decreased in 2022. Among those tested positive for RSV, the proportion of children under 1 year old significantly decreased during the pandemic. The spring season of RSV in China in 2020 was shortened, and most regions experienced a summer season of RSV in 2021. This shift led to a year-round RSV outbreak throughout 2021. After April 2022, RSV positive rate significantly decreased, and no clear seasonal pattern was observed., Conclusion: Our study found that the COVID-19 pandemic has disrupted the seasonal pattern of RSV outbreaks in China, leading to increased RSV positive rate and off-season outbreaks., Competing Interests: Declaration of competing interest This project is supported in part by MSD R&D (CHINA) CO., LTD. We declare that we have no conflicts of interest related to this research work., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction. Negative changes in the microbial composition have been extensively studied in individuals with periodontal disease. Gap Statement. The changes in the oral microbiota after treating this disease are still unknown. Aim. We sought to elucidate the distinctive traits of salivary microbiota in individuals displaying healthy gums and those with severe periodontitis (SP) and examine the influence of periodontal therapy. Methodology. Periodontal pocket depths were examined to determine disease severity. The presence and quantity of oral Helicobacter pylori (associated with periodontal disease) were determined. Sequencing of 16S ribosomal DNA and bioinformatic analyses were performed to assess oral bacterial compositions in patients. Results. Sequencing analysis of 16S ribosomal DNA revealed a significant reduction in the abundance of operational taxonomic units (OTUs) and Chao1 and Abundance coverage-based estimator(ACE) indices in the oral cavities of individuals with SP compared to those of the healthy controls. However, these parameters showed significant recovery after appropriate treatment severe periodontitis after treatment (TSP). Additionally, the levels of harmful Bacillales and Spirochetes significantly increased, whereas the presence of beneficial Euryarchaeota significantly decreased in the SP group. The TSP group exhibited considerably augmented abundances of Burkholderiaceae and Veillonella, while noteworthy reductions in the pathogenic microbiota (Clostridia, Fusobacteria and Spirochaetes) were noticed compared to those of the SP group. Functionally, these modified OTUs were extensively implicated in 41 metabolic pathways. Conclusion. Our study demonstrates that nonsurgical periodontal therapy can effectively reduce the diversity of the oral microbiota, thereby potentially enhancing the treatment efficacy in patients with periodontal disease.

Traditional vaccines have played an important role in the prevention and treatment of infectious diseases, but they still have problems such as low immunogenicity, poor stability, and difficulty in inducing lasting immune responses. In recent years, the nucleic acid vaccine has emerged as a relatively cheap and safe new vaccine. Compared with traditional vaccines, nucleic acid vaccine has some unique advantages, such as easy production and storage, scalability, and consistency between batches. However, the direct administration of naked nucleic acid vaccine is not ideal, and safer and more effective vaccine delivery systems are needed. With the rapid development of nanocarrier technology, the combination of gene therapy and nanodelivery systems has broadened the therapeutic application of molecular biology and the medical application of biological nanomaterials. Nanoparticles can be used as potential drug-delivery vehicles for the treatment of hereditary and infectious diseases. In addition, due to the advantages of lung immunity, such as rapid onset of action, good efficacy, and reduced adverse reactions, pulmonary delivery of nucleic acid vaccine has become a hot spot in the field of research. In recent years, lipid nanocarriers have become safe, efficient, and ideal materials for vaccine delivery due to their unique physical and chemical properties, which can effectively reduce the toxic side effects of drugs and achieve the effect of slow release and controlled release, and there have been a large number of studies using lipid nanocarriers to efficiently deliver target components into the body. Based on the delivery of tuberculosis (TB) nucleic acid vaccine by lipid carrier, this article systematically reviews the advantages and mechanism of liposomes as a nucleic acid vaccine delivery carrier, so as to lay a solid foundation for the faster and more effective development of new anti-TB vaccine delivery systems in the future.

Abstract: The hypothalamic paraventricular nucleus (PVN) plays a central role in regulating cardiovascular activity and blood pressure. We administered hydroxylamine hydrochloride (HA), a cystathionine-β-synthase inhibitor, into the PVN to suppress endogenous hydrogen sulfide and investigate its effects on the mitogen-activated protein kinase (MAPK) pathway in high salt (HS)-induced hypertension. We randomly divided 40 male Dahl salt-sensitive rats into 4 groups: the normal salt (NS) + PVN vehicle group, the NS + PVN HA group, the HS + PVN vehicle group, and the HS + PVN HA group, with 10 rats in each group. The rats in the NS groups were fed a NS diet containing 0.3% NaCl, while the HS groups were fed a HS diet containing 8% NaCl. The mean arterial pressure was calculated after noninvasive measurement using an automatic sphygmomanometer to occlude the tail cuff once a week. HA or vehicle was infused into the bilateral PVN using Alzet osmotic mini pumps for 6 weeks after the hypertension model was successfully established. We measured the levels of H 2 S in the PVN and plasma norepinephrine using enzyme linked immunosorbent assay. In addition, we assessed the parameters of the MAPK pathway, inflammation, and oxidative stress through western blotting, immunohistochemical analysis, or real-time polymerase chain reaction. In this study, we discovered that decreased levels of endogenous hydrogen sulfide in the PVN contributed to the onset of HS-induced hypertension. This was linked to the activation of the MAPK signaling pathway, proinflammatory cytokines, and oxidative stress in the PVN, as well as the activation of the sympathetic nervous system., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Gastroesophageal reflux related chronic cough (GERC), is a common type of chronic cough. Drug treatment is the first choice. But some patients are tired of taking medicine everyday and some patients can not benefit from drugs. For these patients, fundoplication may be the most effective method. However, the importance of fundoplication in treating GERC is undervalued, and there is very few meta-analysis looking into the effect and safety of fundoplication in treating GERC. To solve this question, we performed this meta-analysis. The PRISMA strategy was used for this study. Our study was registered with PROSPERO (ID: CRD42021251072). We searched PubMed, Medline, Web of Science, and the Cochrane databases from 1990 to December of 2022. The meta-analysis was performed with Review Manager 5.4 and Stata 14. After selection and exclusion, 15 articles out of 672 were included. The meta-analysis showed that the cure rate of laparoscopic fundoplication in treating GERC was 58% (95%CI: 52%-65%), with I 2  = 45%; and the effective rate was 86% (95%CI: 80%-93%), with I 2  = 0%. Laparoscopic fundoplication is effective for the most of GERC patients; however, when the goal is to cure GERC completely, a relatively conservative attitude should be taken. In terms of safety, laparoscopic fundoplication is quite reliable offered by skilled surgeons., Competing Interests: Declaration of competing interest All authors have no conflicts of interest to declare., (Copyright © 2024 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

In the presence of a high magnetic field, quantum Hall systems usually host both even- and odd-integer quantized states because of lifted band degeneracies. Selective control of these quantized states is challenging but essential to understand the exotic ground states and manipulate the spin textures. Here we demonstrate the quantum Hall effect in Bi 2 O 2 Se thin films. In magnetic fields as high as 50 T, we observe only even-integer quantum Hall states, but there is no sign of odd-integer states. However, when reducing the thickness of the epitaxial Bi 2 O 2 Se film to one unit cell, we observe both odd- and even-integer states in this Janus (asymmetric) film grown on SrTiO 3 . By means of a Rashba bilayer model based on the ab initio band structures of Bi 2 O 2 Se thin films, we can ascribe the only even-integer states in thicker films to the hidden Rasbha effect, where the local inversion-symmetry breaking in two sectors of the [Bi 2 O 2 ] 2+ layer yields opposite Rashba spin polarizations, which compensate with each other. In the one-unit-cell Bi 2 O 2 Se film grown on SrTiO 3 , the asymmetry introduced by the top surface and bottom interface induces a net polar field. The resulting global Rashba effect lifts the band degeneracies present in the symmetric case of thicker films., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Reactive oxygen species (ROS) is a collective term for highly reactive oxygen derivatives, including singlet oxygen, hydroxyl radicals, superoxide anions, and hydrogen peroxide. In plants, ROS are produced in apoplasts, chloroplasts, mitochondria, and peroxisomes. Although ROS are toxic when their levels exceed a certain threshold, low-concentration ROS can serve as essential signaling molecules for plant growth and development, as well as plant responses to abiotic and biotic stresses. Various aspects of the role of ROS in plants have been discussed in previous reviews. In this review, we first summarize recent progress in the regulatory mechanisms of apoplastic ROS signaling and then propose its potential roles in plant defense against vascular pathogens to provide new ideas for the prevention and control of vascular diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Messenger RNA (mRNA) is an emerging class of therapeutic agents for treating a wide range of diseases. However, due to the instability and low cell transfection rate of naked mRNA, the expression of delivered mRNA in target cells or tissues in vivo requires delivery strategies. Biomimetic vectors hold advantages such as high biocompatibility, tissue specific targeting ability and efficient delivery mechanisms, potentially overcoming challenges faced by other delivery vectors. In this review, biomimetic vector-based mRNA delivery systems are summarized and discuss the possible challenges and prospects of such delivery systems, which may contribute to the progress and application of mRNA-based therapy in the biomedical field., (© 2024 Wiley‐VCH GmbH.)

Background: RhD variants are categorized into partial D, weak D, and DEL. The detection of DEL can only be achieved through the adsorption and elution method or molecular techniques. Here, we report a case of DEL phenotypes associated with a novel allele in a Chinese individual., Study Design and Methods: We used serological methods such as saline, indirect anti-human globulin, and adsorption-elution. The RHD genotype was determined by the PCR-sequence specific primer (PCR-SSP) method as well as the Sanger dideoxy sequencing., Results: RBCs of the sample were found to be DEL phenotype by serological testing, with negative reactions in the saline and indirect anti-human globulin tests while positive reactions by the absorption-elution method. The genotyping results revealed a hemizygous (RHD c .1127 T>G /RHD-). The novel allele sequence has been submitted to GenBank (Accession number: OR608456)., Conclusion: Our study demonstrates a case of a Chinese individual with DEL phenotype caused by a novel allele RHD c .1127 T > G. It expands the database of the DEL variant., Competing Interests: Conflict of interest The authors have disclosed no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Diabetic nephropathy (DN) is one of microvascular complication associated with diabetes. Circular RNAs (circRNAs) have been shown to be involved in DN pathogenesis. Hence, this work aimed to explore the role and mechanism of circ&#95;Arf3 in DN. Mouse mesangial cells (MCs) cultured in high glucose (HG) condition were used for functional analysis. Cell proliferation was determined using 5-ethynyl-2'-deoxyuridine (EdU) and cell counting kit-8 assays. Western blotting was used to measure the levels of proliferation indicator PCNA and fibrosis-related proteins α-smooth muscle actin (α-SMA), collagen I (Col I), fibronectin (FN), and collagen IV (Col IV). The binding interaction between miR-107-3p and circ&#95;Arf3 or Tmbim6 (transmembrane BAX inhibitor motif containing 6) was confirmed using dual-luciferase reporter and pull-down assays. Circ&#95;Arf3 is a stable circRNA, and the expression of circ&#95;Arf3 was decreased after HG treatment in MCs. Functionally, ectopic overexpression of circ&#95;Arf3 protected against HG-induced proliferation and elevation of fibrosis-related proteins in MCs. Mechanistically, circ&#95;Arf3 directly bound to miR-107-3p, and Tmbim6 was a target of miR-107-3p. Further rescue assay showed miR-107-3p reversed the protective action of circ&#95;Arf3 on MCs function under HG condition. Moreover, inhibition of miR-107-3p suppressed HG-induced proliferation and fibrosis, which were attenuated by Tmbim6 knockdown in MCs. CircRNA Arf3 could suppress HG-evoked mesangial cell proliferation and fibrosis via miR-107-3p/Tmbim6 axis, indicating the potential involvement of this axis in DN progression., (© 2024. The Author(s).)

In the [Bmim]Cl reaction medium, five different acidic ionic liquids were used as catalysts to study the effects of reaction time, reaction temperature, system water content, catalyst dosage, microwave power, and other factors on cellulose hydrolysis under microwave irradiation. The results showed that in the [Bmim]Cl reaction system, using N-methylpyrrolidone methylsulfonic acid salt as a catalyst, controlling the microwave reaction time at 10 min, reaction temperature at 130 °C, catalyst dosage at 1 g/g (cellulose), water addition at 0.756 μL/g ([Bmim]Cl), and microwave power at 480 W, resulted in the best cellulose hydrolysis effect with a glucose yield of 74.49%. Compared to conventional heating, the glucose yield increased by 24% and the hydrolysis time was reduced by 77%. Microwave irradiation significantly enhances the cellulose hydrolysis process in an ionic liquid medium.

Thought of as a metastasis-associated gene, however, NME/NM23 nucleoside diphosphate kinase 4 (NME4) has rarely been described in the context of the tumour microenvironment. To understand the immunological implications of NME4 in oesophageal squamous cell carcinoma (ESCC), we used multiplex immunohistochemistry to analyse the clinicopathological and prognostic importance of NME4 expression. Then, after establishing a syngeneic tumour model with a C57BL/6 mouse strain that can recapitulate the tumour microenvironment of humans, we examined the immunological involvement of NME4 expression. To explore the underlying molecular mechanism, via quantitative proteomics and protein microarray screening, we investigated the potential signalling pathways involved. The clinicopathological and prognostic importance of NME4 expression is limited in ESCC patients. In vivo, single-cell RNA sequencing showed that NME4 strikingly prevented CD8+ T cells from infiltrating the tumour microenvironment in murine ESCC. Mechanistically, we mapped out the NFκB2-CCL5 axis that was negatively controlled by NME4 in the murine ESCC cell line AKR. Collectively, these data demonstrated that regulation of NFκB2-CCL5 axis by NME4 prevents CD8+ T cells infiltration in ESCC., (© 2024 John Wiley & Sons Ltd.)

Pyroptosis, an inflammatory cell death, plays a pivotal role in activating inflammatory response, reversing immunosuppression and enhancing anti-tumor immunity. However, challenges remain regarding how to induce pyroptosis efficiently and precisely in tumor cells to amplify anti-tumor immunotherapy. Herein, a pH-responsive polydopamine (PDA) nanocluster, perfluorocarbon (PFC)@octo-arginine (R 8 )-1-Hexadecylamine (He)-porphyrin (Por)@PDA-gambogic acid (GA)-cRGD (R-P@PDA-GC), is rationally design to augment phototherapy-induced pyroptosis and boost anti-tumor immunity through a two-input programmed cascade therapy. Briefly, oxygen doner PFC is encapsulated within R 8 linked photosensitizer Por and He micelles as the core, followed by incorporation of GA and cRGD peptides modified PDA shell, yielding the ultimate R-P@PDA-GC nanoplatforms (NPs). The pH-responsive NPs effectively alleviate hypoxia by delivering oxygen via PFC and mitigate heat resistance in tumor cells through GA. Upon two-input programmed irradiation, R-P@PDA-GC NPs significantly enhance reactive oxygen species production within tumor cells, triggering pyroptosis via the Caspase-1/GSDMD pathway and releasing numerous inflammatory factors into the TME. This leads to the maturation of dendritic cells, robust infiltration of cytotoxic CD8 + T and NK cells, and diminution of immune suppressor Treg cells, thereby amplifying anti-tumor immunity., (© 2024 Wiley‐VCH GmbH.)

Vimentin has been considered a canonical marker of epithelial-mesenchymal transition (EMT) and is associated with tumor escape characterized by aberrant PD-L1 expression. However, whether there is a relationship between vimentin and PD-L1 in esophageal squamous cell carcinoma (ESCC) remains poorly understood. The immunological involvement of vimentin in ESCC was first analyzed by multiplex immunofluorescence staining in ESCC tissue microarray followed by a xenografted mouse model. In vivo, C57BL/6 mice were subcutaneously transplanted with AKR cells after stable silencing of vimentin. In vivo results showed that in addition to PD-L1 and PD-L2 expression, vimentin expression was inversely correlated with CD8+ T-cell infiltration. Mechanistically, vimentin can directly interact with PD-L1 and promote nuclear translocation of PD-L1 in AKR cells. In addition, SEMA6C, STC-2 and TRAILR2 were identified as cytokines modulated by vimentin. Blockade of STC-2 and TRAILR2 in co-culture with their own primary antibodies was shown to recruit more CD8+ T cells than controls. Together, these data strongly suggest targeting Vimenin to overcome the immune cycle in ESCC., Competing Interests: Declaration of competing interest The authors report that there are no competing interests to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: In recent years, 5-Methoxytryptophan (5-MTP) has been identified as an endothelial factor with vaso-protective and anti-inflammatory properties., Methods: In this prospective cohort study, a total of 407 patients with acute myocardial infarction (AMI) who underwent percutaneous coronary intervention (PCI) successfully were enrolled. A 1-year follow-up Kaplan-Meier survival analysis was used for evaluating the correlation between 5-MTP and major adverse cardiovascular event (MACE) while Cox proportional-hazards regression was used to identify predictive values of 5-MTP on MACE after AMI., Results: Increased 5-MTP level led to a significant downtrend in the incidence of MACE (All Log-rank p < 0.05). Thus, a high baseline 5-MTP could reduce the 1-year incidence of MACE (HR = 0.33, 95%Cl 0.17-0.64, p = 0.001) and heart failure (HF) (HR = 0.28, 95% Cl 0.13-0.62, p = 0.002). Subgroup analysis indicated the predictive value of 5-MTP was more significant in patients aged ≤ 65 years and those with higher baseline NT-proBNP, T2DM, STEMI, and baseline HF with preserved LVEF (HFpEF) characteristics., Conclusions: Plasma 5-MTP is an independent and protective early biomarker for 1-year MACE and HF events in patients with AMI, especially in younger patients and those with T2DM, STEMI, and baseline HFpEF characteristics., (© 2024. The Author(s).)

Backgroud/Objectives: Ferula spp. is an essential crop in Central Asia with pronounced economic benefits governed by its flowering process. However, the mechanisms of the flowering phenotype remain unclear. Methods: In this study, using F. sinkiangensis as a model plant, we integrated transcriptome, proteome, and metabolome analyses to compare the multilayer differences in leaves and roots of plants with flowering and unflowering phenotypes. Results: We found that several variations in the transcriptome, proteome, and metabolome were closely associated with flowering. The Photosynthesis and Phenylpropanoid biosynthesis pathways in plants with the flowering phenotype were more active. Additionally, three flowering genes, named FL2-FL4 , were upregulated in the leaves of flowering plants. Notably, six transcription factors were potentially responsible for regulating the expression of FL2-FL4 in the leaves to mediate flowering process of F. sinkiangensis . Moreover, genes relevant to Photosynthesis and Phenylpropanoid biosynthesis were also involved in regulating the expression of FL2-FL4 in flowering plants. Conclusions: The active regulation network together with Photosynthesis and Phenylpropanoid biosynthesis were essential for inducing the expression of flowering-related genes in leaves to promote the flowering process of F. sinkiangensis .