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Ethnopharmacological Relevance: According to the Shen Nong Herbal Classic, Ginseng (Panax ginseng C.A. Meyer) is documented to possess life-prolonging effects and is extensively utilized in traditional Chinese medicine for the treatment of various ailments such as qi deficiency, temper deficiency, insomnia, and forgetfulness. Ginseng is commonly employed for replenishing qi and nourishing blood, fortifying the body and augmenting immunity; it has demonstrated efficacy in alleviating fatigue, enhancing memory, and retarding aging. Furthermore, it exhibits a notable ameliorative impact on age-related conditions including cardiovascular diseases and neurodegenerative disorders. One of its active constituents - ginsenoside Rg2 (G-Rg2) - exhibits potential therapeutic efficacy in addressing these ailments., Aim of the Review: The aim of this review is to explore the traditional efficacy of ginseng in anti-aging diseases and the modern pharmacological mechanism of its potential active substance G-Rg2, in order to provide strong theoretical support for further elucidating the mechanism of its anti-aging effect., Methods: This review provides a comprehensive analysis of the traditional efficacy of ginseng and the potential mechanisms underlying the anti-age-related disease properties of G-Rg2, based on an extensive literature review up to March 12, 2024, from PubMed, Web of Science, Scopus, Cochrane, and Google Scholar databases. Potential anti-aging mechanisms of G-Rg2 were predicted using network pharmacology and molecular docking analysis techniques., Results: In traditional Chinese medicine theory, ginseng has been shown to improve aging-related diseases with a variety of effects, including tonifying qi, strengthening the spleen and stomach, nourishing yin, regulating yin and yang, as well as calming the mind. Its potential active ingredient G-Rg2 has demonstrated significant therapeutic potential in age-related diseases, especially central nervous system and cardiovascular diseases. G-Rg2 exhibited a variety of pharmacological activities, including anti-apoptotic, anti-inflammatory and antioxidant effects. Meanwhile, the network pharmacological analyses and molecular docking results were consistent with the existing literature review, further validating the potential efficacy of G-Rg2 as an anti-aging agent., Conclusion: The review firstly explores the ameliorative effects of ginseng on a wide range of age-related diseases based on TCM theories. Secondly, the article focuses on the remarkable significance and value demonstrated by G-Rg2 in age-related cardiovascular and neurodegenerative diseases. Consequently, G-Rg2 has broad prospects for development in intervening in aging and treating age-related health problems., 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.)

Background: Carnosine, a natural bioactive dipeptide derived from meat muscle, possesses strong antioxidant properties. Dexamethasone, widely employed for treating various inflammatory diseases, raises concerns regarding its detrimental effects on bone health. This study aimed to investigate the protective effects of carnosine against dexamethasone-induced oxidative stress and bone impairment, along with its underlying mechanisms, utilizing chick embryos and a zebrafish model in vivo, as well as MC3T3-E1 cells in vitro., Results: Our findings revealed that carnosine effectively mitigated bone injury in dexamethasone-exposed chick embryos, accompanied by reduced oxidative stress. Further investigation demonstrated that carnosine alleviated impaired osteoblastic differentiation in MC3T3-E1 cells and zebrafish by suppressing the excessive production of reactive oxygen species (ROS) and enhancing the activity of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPX). Moreover, mechanistic studies elucidated that carnosine promoted the expression and nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2), thereby facilitating the transcription of its downstream antioxidant response elements, including heme oxyense-1 (HO-1), glutamate cysteine ligase modifier (GCLM), and glutamate cysteine ligase catalytic (GCLC) to counteract dexamethasone-induced oxidative stress., Conclusion: Overall, this study underscores the potential therapeutic efficacy of carnosine in mitigating oxidative stress and bone damage induced by dexamethasone exposure, shedding light on its underlying mechanism of action by activating the NRF2 signaling pathway. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Background: The present study explored the effects of pre-harvest methyl jasmonates spraying on the volatiles of 'Cabernet Gernischt' grapes through the lipoxygenase pathway. Headspace solid-phase microextraction combined with gas chromatography-mass spectrometry and an enzyme-linked immunosorbent assay were utilized to analyze volatile metabolites and key enzyme activities following methyl jasmonates application. Total RNA extraction and cDNA library construction were followed by transcriptome sequencing., Results: The application of 0.1 mmol L -1 methyl jasmonate and 5 mmol L -1 methyl dihydrojasmonate significantly increased the levels of C6 compounds in 'Cabernet Gernischt' berries, and also enhanced the utilization of unsaturated fatty acids as precursors in the lipoxygenase-hydroperoxides lyase pathway. The up-regulated expression of VvADH1, VvADH2, VvHPL and VvLOX2S genes led to modulations in enzyme activity, thereby enhancing the berries's aromatic profile. There was a significant correlation between linoleic and linolenic acids (i.e. the precursors of the lipoxygenase pathway) and the activities and metabolites of key enzymes., Conclusion: The optimal concentration of methyl jasmonates treatment favorably influences the accumulation of green leaf volatiles in 'Cabernet Gernischt' grape. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

The proteasome, an evolutionarily conserved proteolytic complex comprising the 20S core particle and 19S regulatory particles, performs both shared and distinct functions across various tissues and organs. Spermatogenesis, a highly complex developmental process, relies on proteasome activity at multiple stages to regulate protein turnover. In this study, we selected the 20S subunit PSMA1 and 19S regulatory subunit PSMD2 to investigate the potential functions of the proteasome in spermatogenesis. Using Psma1-EGFP and Psmd2-mCherry knock-in mouse models, we confirmed the expression of both subunits in all spermatogenic cell types, with pronounced presence in early germ cell development. To further clarify their functional significance, we specifically knocked out Psma1 and Psmd2 in germ cells. Deletion of either PSMA1 or PSMD2 led to disrupted spermatogenesis, characterized by the complete absence of sperm in the epididymis. Subsequent analysis indicated that loss of these proteasome components impaired meiotic initiation. Psma1 and Psmd2 knockout germ cells showed accumulation of DMRT1, a key regulator of mitosis-to-meiosis transition, leading to a reduction in STRA8 levels and consequent disruption of meiosis initiation. This study sheds light on the molecular mechanisms that govern meiotic initiation and identifies potential genes associated with male infertility.

tRNA-derived fragments (tRFs) are novel short noncoding RNAs that play pivotal roles in cell proliferation and survival. However, knowledge of the biological roles of tRFs in anterior cruciate ligament (ACL) cells is limited. Here, we intended to investigate the function of tRF-3031B in ACL cell. We used the tRF and tiRNA array to analyze tRF and tiRNA expression profiles in osteoarthritis (OA) ACL cells and normal ACL cells, and qRT-PCR and fluorescence in situ hybridization (FISH) were used to determine tRF-3031B expression. The results showed that tRF-3031B was expressed at low levels in OA ACL and Interleukin-1β (IL-1β) treated ACL cells. We found that RELA was the target of tRF-3031B. When ACL cells were transfected with tRF-3031B mimics, RELA expression was suppressed, whereas transfection with tRF-3031B inhibitors had the opposite effect. The rescue and dual-luciferase reporter assays showed that tRF-3031B silenced the RELA expression by binding to its untranslated region (3'-UTR). Hence, this study showed the novel function of tRF-3031B in regulating ACL cell proliferation and survival by targeting RELA, and these findings may offer a new direction for the study of ACL degeneration and pathophysiological of OA., 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 frequency of lymphocyte subsets and other laboratory indicators in paired cerebrospinal fluid (CSF) and peripheral blood (PB) samples from critically ill patients with intracerebral hemorrhage (ICH) who developed systemic inflammatory response syndrome (SIRS) following surgery., Introduction: Neuroinflammation and systemic inflammatory responses significantly contribute to secondary brain injury following ICH. Post-surgery SIRS is known to worsen clinical outcomes in ICH patients; however, the immune response in the CSF and PB has not been fully characterized. Understanding immunological changes in ICH patients with SIRS could lead to improved clinical management and prognostic outcomes., Methods: This study involved a retrospective analysis of data from patients with ICH who underwent surgery in the Neurological Intensive Care Unit (NICU) of Baoding No. 1 Hospital, Hebei Province, China, between January and July 2022. Patients were divided into SIRS and non-SIRS groups based on the clinical criteria. Demographic, clinical, and laboratory data, including lymphocyte subsets in CSF and PB, were collected and analyzed. This study compared lymphocyte subsets and other inflammatory markers between the SIRS and non-SIRS groups., Results: Patients with SIRS demonstrated higher systolic blood pressure (SBP) at admission, worse 90-day prognoses, elevated inflammatory markers, increased levels of complement proteins C3 and C4, and lower levels of immunoglobulin G (IgG) compared to patients without SIRS. Between 3-6 days post-surgery, SIRS patients showed higher percentages of CD3+T cells, CD4+T cells, and CD4+/CD8+ ratios in the CSF than non-SIRS patients. CD3+T cell percentages in the CSF were consistently higher than those in the PB and were independent of PB levels. In contrast, CD3-CD16+CD56+ natural killer (NK) cell percentages were lower in patients with SIRS. No significant differences in PB lymphocyte subsets were found between the two groups. A high CSF CD3+T cell percentage (≥85.68 %) was identified as the strongest predictor of critical ICH with SIRS after surgery, with an appropriate use criterion (AUC) of 0.7742, sensitivity of 77.42 %, specificity of 76.19 %, and 95 % CI of 0.6655-0.8829 (P < 0.0001)., Conclusion: Elevated levels of CD3+T lymphocytes in CSF are strongly associated with an increased risk of severe cerebral hemorrhage and SIRS following surgery. These findings suggest that monitoring CSF immune markers, particularly CD3+T lymphocytes, could serve as valuable predictors for the development of SIRS in critically ill ICH patients and inform post-surgical treatment strategies., 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.)

This study investigated mung bean protein hydrolysates (MBPH) produced using neutral protease, examining their physicochemical properties, stability, and lipid peroxidation inhibition capabilities. The research revealed that MBPH molecular weight ranged from 17 to 26 kDa and perform various functions, including catalytic, nutrient storage, and binding. Stability assessments showed that MBPH are stable at 45 °C and pH of 7.5 but are light-sensitive and unstable in solution or when combined with sugars. Additionally, increased concentrations of digestive enzymes reduce MBPH stability. Antioxidant tests in vitro and in Caenorhabditis elegans confirmed MBPH's ability to neutralizing radicals, enhance antioxidant enzyme activities, and reduce lipid peroxidation, thereby protecting against oxidative damage. Furthermore, in vivo experiments showed that MBPH extend the lifespan of worms and reduced their body lipid content, indicating potential benefits in mitigating cholesterol-related damage. This research demonstrates the potential of MBPH in inhibiting lipid peroxidation., 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 Ltd.)

Ethnopharmacological Relevance: Prostate cancer patients often suffer from depression during androgen deprivation therapy. Chaihu-Shugan-San (CSS) can prevent prostate cancer metastasis caused by chronic unpredictable mild stress (CUMS), but its active ingredients and molecular mechanism remain unelucidated., Aim of Study: This study aims to explore the potential targets and molecular mechanisms of CSS in the treatment of emotional stress-aggravated metastasis of prostate cancer., Results: Stress induces nuclear translocation of GR, initiating the transcription of PER1, which leads to an enhanced lipid metabolism and decreased secretion of α2M in BMDMs. CSS, a classical Traditional Chinese Medicine (TCM) formula for alleviating depression, can improve prostate cancer metastasis caused by CUMS. Of the active ingredients in CSS, kaempferol demonstrated the highest potency for enhancing α2M secretion in BMDMs and inhibiting prostate cancer cell migration. Kaempferol also inhibited nuclear translocation of GR and the GR/PER1 pathway in Per1-overexpressed BMDMs., Conclusions: These findings reveal that emotional stress-aggravated prostate cancer growth and metastasis rely on the GR/PER1 pathway and lipid metabolism, as the suppression of this pathway ultimately leads to an increase in α2M secretion in BMDMs and inhibition of PC-3 cell metastasis., Competing Interests: Declaration of competing interest I have nothing to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Aim: The acute pulmonary infectious disease caused by influenza viruses is known as influenza virus pneumonia (IVP). In recent years, Gegen Qinlian Decoction (GQD) has been widely used to treat pulmonary inflammation; however, the underlying mechanism of action of GQD in IVP remains unclear. This study aimed to elucidate the molecular mechanism through which GQD improved IVP., Materials and Methods: The efficacy of GQD was evaluated using classical pharmacodynamic indicators in a murine model of H1N1-induced IVP. Network pharmacology predicted the material basis of GQD in improving IVP, while metabonomics and 16 s rDNA sequencing assessed its regulation on small molecule metabolites and intestinal flora. Additionally, molecular biology techniques were used to investigate the molecular mechanism underlying the improvement of IVP by GQD., Results: The study results demonstrated that GQD exhibited a significant ameliorative effect on the inflammatory response in lung tissue of IVP mice. The potential pharmacological substances of GQD for improving IVP were identified by network pharmacology combined with ultra-high performance liquid chromatography/high-resolution time-of-flight mass spectrometry (UHPLC-HR-TOFMS) analysis, including puerarin, baicalin, berberine, and glycyrrhizin. Further analysis of biological processes and mechanisms of action predicted that GQD could improve IVP by inhibiting activation of inflammasomes, regulating the body's immune system, and intestinal microecology. Metabolomics and microbiomics findings revealed that GQD could bi-directionally regulate lipid and amino acid metabolites by increasing the abundance of beneficial bacteria like Akkermansia and Acetobacter, thereby maintaining host metabolic balance and immune homeostasis. RT-qPCR and immunohistochemistry results indicated that GQD improved IVP by inhibiting the complement C3/NLRP3 inflammasome pathway., Conclusion: The findings of this study confirmed that GQD effectively inhibited IVP by modulating the "gut microbiota-metabolomics-immune/inflammation" axis in the host, thereby establishing a solid immunological foundation for the clinical application of GQD., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Heterogeneities among tumor cells significantly contribute towards cancer progression and therapeutic inefficiency. Hence, understanding the nature of cancer through liquid biopsies and isolation of circulating tumor cells (CTCs) has gained considerable interest over the years. Microfluidics has emerged as one of the most popular platforms for performing liquid biopsy applications. Various label-free and labeling techniques using microfluidic platforms have been developed, the majority of which focus on CTC isolation from normal blood cells. However, sorting and profiling of various cell phenotypes present amongst those CTCs is equally important for prognostics and development of personalized therapies. In this review, firstly, we discuss the biophysical and biochemical heterogeneities associated with tumor cells and CTCs which contribute to cancer progression. Moreover, we discuss the recently developed microfluidic platforms for sorting and profiling of tumor cells and CTCs. These techniques are broadly classified into biophysical and biochemical phenotyping methods. Biophysical methods are further classified into mechanical and electrical phenotyping. While biochemical techniques have been categorized into surface antigen expressions, metabolism, and chemotaxis-based phenotyping methods. We also shed light on clinical studies performed with these platforms over the years and conclude with an outlook for the future development in this field.

Exploring the trend of long time-series ecological quality evolution and spatial differentiation of influencing factors in Guiyang is of great significance for realizing regional ecological protection and high-quality development strategies. Based on the 7-period Landsat remote sensing images from 1991 to 2020, the remote sensing ecological index （RSEI） of Guiyang from 1991 to 2020 was calculated using the GEE remote sensing big data platform, and a geodetector, Hurst index, and coefficient of variation with different random sampling quantities and classification strategies were used to analyze the evolutionary pattern of ecological quality, change trends, and spatial differentiation influencing factors. The results showed that ① The ecological quality of Guiyang in the past 30 years was mainly medium and good, showing a wave-like pattern of change, with the highest and lowest values occurring in 2020 （mean value 0.58） and 2010 （mean value 0.47）, respectively, and the overall trend of the RSEI in the past ten years was good, with a spatial trend of decreasing distribution from the northeast to the southwest. ② The domain of values of the coefficient of variation for the RSEI in Guiyang was in the range of （0-2）, of which 46.61% of the area was in high fluctuation change, and the overall volatility of the RSEI was large； the mean value of the Hurst index was 0.59, and the area greater than 0.5 accounted for 73.98%, most of which showed weak persistence, and the future trend of change was the same as that of the past 30 years. ③ Different classification methods and random samples affect the q -value results of the geodetector, but the trend of the size ordering of the explanatory power of different factors was generally consistent. Land use, nighttime lighting index, slope, and population density indicators had stronger explanatory power for RSEI spatial differentiation； factor interaction detection was two-factor enhancement and nonlinear enhancement； and the interaction between land use and other factors was most favorable for explaining RSEI spatial differentiation.

To compare the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) and rhG-CSF in the recovery of neutrophils after induction therapy in ALL patients, PEG-rhG-CSF was injected subcutaneously within 24 ~ 48 h after the end of intravenous infusion of daunorubicin/idarubicin during induction chemotherapy. In rhG-CSF group, patients were given rhG-CSF. The main outcome indexes were the incidence and duration of grade 4 chemotherapy-induced-neutropenia (CIN, ANC less than 0.5 × 10 9 /L), the incidence of severe agranulocytosis (ANC less than 0.2 × 10 9 /L). The incidence of grade 4 CIN in the PEG-rhG-CSF group was significantly lower than that in the rhG-CSF group (P = 0.007). There was no significant difference in the incidence of severe neutrophil deficiency and the median time of neutrophil deficiency in PEG-rhG-CSF group and rhG-CSF group. There was no significant difference in day 28 complete response (CR) rate of bone marrow cytology between the two groups (P = 0.985). Compared with rhG-CSF, PEG-rhG-CSF can reduce the incidence of agranulocytosis after induction chemotherapy in newly diagnosed ALL patients, without affecting the efficacy of chemotherapy. Meanwhile, it can reduce the pain of patients, with good safety and tolerance., Competing Interests: Declarations. Ethical approval: The retrospective, observational study was approved by the Ethics Committee of Qilu Hospital, Shandong University, and was conducted in accordance with the Declaration of Helsinki. All authors of this article agree to publish in your journal. Consent to participate: The Ethics Committee of Qilu Hospital approved waiving the need to obtain written informed consent from each participant. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Lactobacillus helveticus LZ-R-5 (R-5), a strain with high epithelial adhesion and bioactive exopolysaccharide production, was isolated from Tibetan kefir grains. This study investigated its potential to alleviate intestinal inflammation using a DSS-induced colitis model in BALB/c mice. We integrated microbial diversity and serological analyses to assess changes in gut flora and cytokines following the R-5 treatment. Pathological assessments showed that R-5 reduced crypt distortion in the proximal colon and mitigated hepatic immune challenges by enhancing gut barrier function. The increased relative expression of TGF-β1 and the downregulation of NLRP3-related inflammatory factors were conducive to preventing organ damage in the thymus and spleen of mice with colitis. Additionally, R-5 stimulated GPR43 expression and improved epithelial nutrition, promoting mucin production to prevent enterotoxin leakage. It also modulated the gut microbiota by suppressing Bacteroides and Erysipelatoclostridium, leading to a microbiota composition more akin to that of normal flora.

The integrative multiomics characterization of minute amounts of clinical tissue specimens has become increasingly important. Here, we present an approach called Integral-Omics, which enables sequential extraction of metabolites, lipids, genomic DNA, total RNA, proteins, and phosphopeptides from a single biopsy-level tissue specimen. We benchmarked this method with various samples, applied the workflow to perform multiomics profiling of tissues from six patients with colorectal cancer, and found that tumor tissues exhibited suppressed ferroptosis pathways at multiomics levels. Together, this study presents a methodology that enables sequential extraction and profiling of metabolomics, lipidomics, genomics, transcriptomics, proteomics, and phosphoproteomics using biopsy tissue specimens.

Bioenergy with carbon capture and storage (BECCS) is a key negative emission technology for climate mitigation. Some countries have made no commitment to carbon neutrality but are viewed as potential BECCS candidates (hereafter, non-CN countries). Here we analyze contributions of these countries to global climate mitigation with respect to BECCS using an Earth system model with explicit representations of bioenergy crops. Switchgrass cultivation in these non-CN countries can further remove atmospheric CO 2 by 9.1 ± 2.8 and 19.9 ± 5.2 PgC in the low-warming and overshot scenarios, resulting in an extra biogeochemical cooling effect of 0.01 ± 0.04 to 0.02 ± 0.06 °C. This cooling is largely counterbalanced by the biophysical warming, but the net effect is still an extra cooling. The non-CN countries play a more important role in the low-warming scenario than in the overshoot scenario, despite the inequality of temperature change among countries. Our study highlights the importance of a global system for climate mitigation., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Intracellular delivery of proteins has attracted significant interest in biological research and cancer treatment, yet it continues to face challenges due to the lack of effective delivery approaches. Herein, we developed an efficient strategy via cationic α-helical polypeptide-mediated anionic proprotein delivery. The protein was reversibly modified with adenosine triphosphate via dynamic covalent chemistry to prepare an anionic proprotein (A-protein) with abundant phosphate groups. A guanidyl-decorated α-helical polypeptide (LPP) was employed not only to encapsulate A-protein through electrostatic attraction and hydrogen bonding, forming stable nanocomplexes, but also to enhance cell membrane penetration due to its rigid α-helical conformation. Consequently, this strategy mediated the effective delivery of various proteins with different isoelectric points and molecular weights, including α-chymotrypsin, bovine serum albumin, ribonuclease A, cytochrome C , saporin, horseradish peroxidase, β-galactosidase, and anti-phospho-Akt, into cancer cells. More importantly, it enabled efficient delivery of CRISPR-Cas9 ribonucleoproteins to elicit robust polo-like kinase 1 genome editing for inhibiting cancer cell growth. This rationally designed protein delivery system may benefit the development of intracellular protein-based cancer therapy.

R2 retrotransposons can be harnessed to insert genes at targeted sites by all-RNA delivery, presenting a new technology for next-generation biotherapeutics. Here, we report a protocol for evaluating the gene integration activity of R2 retrotransposons in mammalian cells. We describe the construction of vectors separately expressing R2 protein and donor, the process of liposome transfection, and flow cytometry. This protocol provides a useful reporter system, which can be applied to evaluate the activity of other new retrotransposon systems. For complete details on the use and execution of this protocol, please refer to Chen et al. 1 ., Competing Interests: Declaration of interests Q.Z. is a member of the Cell advisory board., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Plants mount induced resistance and adult-plant resistance against different pathogens throughout the whole growth period. Rice production faces threats from multiple major diseases, including rice blast, sheath blight, and bacterial leaf blight. Here, we report that the miR172a-SNB-MYB30 module regulates both induced and adult-plant resistance to these three major diseases via lignification in rice. Mechanistically, pathogen infections induce the expression of miR172a, which downregulates the transcription factor SNB to release its suppression of MYB30, leading to an increase in lignin biosynthesis and disease resistance throughout the whole growth period. Moreover, expression levels of miR172a and MYB30 gradually increase and are consistently correlated with lignin contents and disease resistance during rice development, reaching a peak at full maturity, whereas SNB RNA levels are negatively correlated with lignin contents and disease resistance, indicating the involvement of the miR172a-SNB-MYB30 module in adult-plant resistance. The functional domain of SNB protein and its binding sites in the MYB30 promoter are highly conserved among more than 4000 rice accessions, while abnormal expression of miR172a, SNB, or MYB30 compromises yield traits, suggesting artificial selection of the miR172a-SNB-MYB30 module during rice domestication. Taken together, these results reveal a novel role for a conserved miRNA-regulated module that contributes significantly to induced and adult-plant resistance against multiple pathogens by increasing lignin accumulation, deepening our understanding of broad-spectrum resistance and adult-plant resistance., (Copyright © 2024 The Author. Published by Elsevier Inc. All rights reserved.)

Single-cell sequencing technology has enabled the discovery and characterization of subpopulations of immune cells with unique functions, which is critical for revealing immune responses under healthy or disease conditions. Efforts have been made to collect and curate single-cell RNA sequencing (scRNA-seq) data, yet an immune-specific single-cell multi-omics atlas with harmonized metadata is still lacking. Here, we present scImmOmics (https://bio.liclab.net/scImmOmics/home), a manually curated single-cell multi-omics immune database constructed based on high-quality immune cells with known immune cell labels. Currently, scImmOmics documents >2.9 million cell-type labeled immune cells derived from seven single-cell sequencing technologies, involving 131 immune cell types, 47 tissues and 4 species. To ensure data consistency, we standardized the nomenclature of immune cell types and presented them in a hierarchical tree structure to clearly describe the lineage relationships within the immune system. scImmOmics also provides comprehensive immune regulatory information, including T-cell/B-cell receptor sequencing clonotype information, cell-specific regulatory information (e.g. gene/chromatin accessibility/protein/transcription factor states within known cell types, cell-to-cell communication and co-expression networks) and immune cell responses to cytokines. Collectively, scImmOmics is a comprehensive and valuable platform for unraveling the heterogeneity and diversity of immune cells and elucidating the specific regulatory mechanisms at the single-cell level., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Introduction: Hyperglycemia and hyperlipidemia are the hallmarks of type 2 diabetes mellitus (T2DM). T2DM is a systemic metabolic disease caused by insulin resistance and malfunctioning pancreatic β-cells. Although ginseng (the roots of Panax ginseng C.A. Meyer) can be used to treat T2DM, the underlying mechanism is unclear., Objectives: To assess the role and mechanism of, γ-aminobutyric acid-fructosyl-glucose (GABAFG), a maillard reaction product of ginseng, in T2DM treatment., Methods: The metabolism of GABAFG in serum and tissues was analyzed via ultra-high performance liquid chromatography-Q exactive-mass spectrometry (UHPLC-QE-MS). The molecular mechanisms of GABAFG in pancreatic β-cells (in vivo and in vitro) were investigated via Western blotting, qPCR and immunofluorescence. In addition, the results were validated via high-throughput sequencing and serum metabolomics., Results: GABAFG alleviated the elevation of blood glucose and blood lipids in HFD/STZ-induced T2DM mice. Also, GABAFG reduced the insulin resistance-associated IRS-1 signaling axis in pancreatic β-cells in vitro. Mechanistically, GABAFG targeted the nuclear translocation of TFEB inhibited apoptosis of pancreatic β-cells by enhancing autophagolysosome function. In addition, GABAFG remodeled the gut microbiota. Specifically, GABAFG increased Akkermansia, decreased Romboutsia abundance, and decreased serum glycerophospholipid metabolism, thus alleviating T2DM-induced dyslipidemia., Conclusion: This is the first study to assess the pharmacological effects of ginseng-derived GABAFG in T2DM. Therefore, this study provides a new theoretical basis for understanding ginseng effect in metabolic 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 © 2025. Published by Elsevier B.V.)

Bacterial infections evoke considerable apprehension in orthopedics. Traditional antibiotic treatments exhibit cytotoxic effects and foster bacterial resistance, thereby presenting an ongoing and formidable obstacle in the realm of therapeutic interventions. Achieving bacterial eradication and osteogenesis are critical requirements for bone infection treatment. Herein, we design and fabricate a nanoenzyme-mimicking drug through the co-precipitation process, integrating MgFe layered double hydroxide with ascorbic acid (AA@LDH), to facilitate the simultaneous presence of these two unique functionalities. Within a bacterial acidic milieu, the degradation of the AA@LDH nanosystem prompts ascorbic acid to undergo a pro-oxidative transformation, generating an abundance of reactive oxygen species (ROS). These ROS overwhelm bacterial cellular processes, including nucleic acid replication, cell wall construction, virulence factor production, biosynthetic pathways, and energy generation. This disruption culminates in substantial bacterial mortality, as substantiated by RNA sequencing data. Hence, the AA@LDH nano system exhibits an in vitro antibacterial rate of approximately 100 % and 99 %, against S.aureus and E. coli, respectivaly. Additionally, the AA@LDH could directly accelerate osteogenic differentiation in vitro, evidenced by a 50 % increase in alkaline phosphatase activity and a 270 % improvement in extracellular matrix mineralization capability. Moreover, it enhances osteointegration process in vivo by favorably reshaping the osteogenic immune microenvironment. This innovative nanosystem for delivery offers new strategies that concurrently combat bacterial infections, mitigate inflammation, and induce tissue regeneration, marking a significant advancement in the realm of advanced materials and its applications., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Human embryonic stem cells (hESCs) possess the ability to differentiate into various cell types, which is intricately linked to fatty acid synthesis and metabolism. Fatty acid desaturase 2 (FADS2) plays important role in fatty acid metabolism. In this study, we elucidate that the inhibition of FADS2 by SC-26196 enhances hESC pluripotency by upregulating key pluripotency genes such as POU5F1, NANOG, and KLF5. Moreover, SC-26196 treatment alters the fatty acid metabolic profile of hESCs, decreasing the synthesis of saturated fatty acids (SFAs) while increasing the content of monounsaturated fatty acids (MUFAs). Meanwhile, transcriptomic and proteomic analyses revealed that under FADS2 inhibition, hESCs maintain pluripotency primarily through enhanced oxidative phosphorylation and modified fatty acid metabolism. Knockdown and overexpression experiments confirm that FADS2 is a crucial regulator of these metabolic processes, and is essential for sustaining hESCs pluripotency. Collectively, this study unveils the pivotal role of FADS2 in the metabolic regulation of hESCs and provide new insights into the mechanisms governing pluripotency., 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.)

Background: The primary objective of this study was to examine whether ARID1A mutations confer a fitness advantage to gastric cancer from an immunological perspective, along with elucidating the underlying mechanism. Additionally, we aimed to identify the clinical potential of combining epigenetic inhibitors with immune checkpoint inhibitors to improve the efficacy of immunotherapy for gastric cancer., Methods: The correlation between ARID1A gene expression and gastric cancer patient survival was analyzed using the GEO dataset GSE62254. The association between chemokines (CXCL9, CXCL10) and ARID1A was conducted using GSE15460 dataset. Real-time PCR was employed for gene expression analysis, while chromatin immunoprecipitation was used to identify transcriptional regulation on target genes. Protein expression and regulation were assessed through various techniques, including Western blot, ELISA, immunohistochemistry, and immunofluorescence. Chromatin DNA accessibility was determined through MNase digestions, transmission electron microscopy, and ChIP-seq. The impact of ARID1A expression and epigenetic inhibitors on tumor immunity in mice was assessed using flow cytometry., Results: ARID1A expression demonstrated a positive correlation with CD8 + T cell infiltration and clinical prognosis. The loss of ARID1A expression led to impaired Th1-type chemokines. Additionally, ARID1A depletion was associated with enhanced tumor growth and the absence of CD8 + T cells within the tumor microenvironment. The study revealed that ARID1A played a role in promoting histone acetylation and facilitating chromatin accessibility. Notably, the application of deacetylase inhibitors effectively reversed the effects of ARID1A depletion on tumor progression and significantly enhanced the efficacy of immunotherapy., Conclusion: Gastric cancer with ARID1A mutations modulates immune cell chemotaxis within the tumor microenvironment by influencing histone acetylation. Deacetylase inhibitors have the potential to alter the secretion of chemokines for tumor immune cells, consequently enhancing the effectiveness of immune checkpoint inhibitor therapy in ARID1A-mutated gastric cancer., Competing Interests: Declarations. Ethics approval and consent to participate: The clinical data collection was approved with written informed consent from gastric cancer patients. The study was reviewed and approved by the Ethics Committee of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. The approval number was [2015] IEC-J (075). Consent for publication: All the authors have read and approved the final manuscript. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Purpose: This study identified novel variants of the FSIP2 and SPEF2 genes in multiple morphological abnormalities of the sperm flagella (MMAF) patients and to investigate the potential effect of variations on male infertility and assisted reproductive outcomes., Methods: Whole-exome sequencing was performed in 106 Chinese MMAF patients. The discovered variants were evaluated in silico and confirmed by Sanger sequencing. A mini-gene assay and immunofluorescence staining were used to determine the effects on mRNA and protein. Assisted reproductive technology (ART) based on intracytoplasmic sperm injection (ICSI) and in vitro fertilization (IVF) was used for MMAF patients carrying novel variants., Results: Biallelic variants in FSIP2 or SPEF2 involving nineteen novel variations were found in eleven MMAF patients. These variations included fourteen missense variants, two nonsense variants, two frameshift variants, and a splicing variant. The FSIP2 protein was markedly reduced or mislocalized to the spermatozoa head. Two novel missense variants of SPEF2 reduced cell diameter. Eleven MMAF couples had 12 ICSI cycles and 2 IVF cycles. The 2PN fertilization rate, good-quality embryos rate, and clinical pregnancy rate were 80.1% (133/166), 74.4% (99/133), and 45.7% (16/35). Four of them have seven babies born., Conclusion: Our work revealed that missense variations of FSIP2 or SPEF2 might cause a milder spermatozoa damage. The infertility caused by FSIP2 and SPEF2 variants can be mitigated through ICSI or even IVF. The results of this study presented signs of the correlation of phenotype/genotype for the FSIP2 and SPEF2, which might provide a reference for clinical genetic and fertility consultation., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: A scarcity of data exists concerning atrial fibrillation (AF) during the perioperative stage of non-cardiothoracic surgery, particularly orthopedic surgery. In addition, given the frequency and significant impact of AF in the perioperative period, therefore our aim was to identify prognosis and predictors of elderly hip fracture patients with perioperative AF., Methods: An examination of hip fracture patients at the Third Hospital of Hebei Medical University, who had been hospitalized from January 2018 to October 2020 in succession, was conducted retrospectively. To determine independent risk factors for paroxysmal AF in elderly hip fracture patients, univariate and multivariate logistic regression analysis were employed. The Kaplan-Meier survival curve demonstrated the correlation between all-cause mortality in the non-AF, paroxysmal AF, and permanent AF groups. An assessment of the correlation between baseline factors, complications, and all-cause mortality was conducted through univariable and multivariable Cox proportional hazards analysis., Results: Enrolling 1,376 elderly patients with hip fractures, we found 1,189 in the non-AF group, 103 in the paroxysmal AF group, and 84 in the permanent AF group. Kaplan-Meier survival curves revealed a significantly lower overall survival rate in elderly hip fracture patients with AF, especially permanent AF. Based on COX regression analysis, we found that the main risk factors for all-cause death in elderly hip fracture patients with AF were concomitant pulmonary infection(HR 2.006,95%CI 1.019-3.949, P = 0.044), hyponatremia(HR 2.417,95%CI 1.177-4.961, P = 0.016), permanent AF(HR 2.806, 95%CI 1.036-4.198, P = 0.039). Independent risk factors for perioperative paroxysmal AF in elderly hip fracture patients were hypertension(OR 2.248, 95% CI 1.415-3.571, P = 0.001), COPD(OR 4.694, 95% CI 2.207-9.980, P < 0.001) and ACCI(OR 1.436, 95%CI 1.072-1.924, P = 0.015)., Conclusions: The mortality risk is high in elderly patients with hip fractures combined with AF. The independent risk factors for their death include permanent AF, pulmonary infection and hyponatremia. The independent risk factors for perioperative paroxysmal AF in elderly patients with hip fractures are ACCI, hypertension and COPD. we should identify risk factors and optimize the treatment plan at an early stage., Competing Interests: Declarations. Ethics approval and consent to participate: The ethics committee of the Third Hospital of Hebei Medical University gave their approval to this study protocol, in accordance with the Helsinki Declaration (approval number 2021–087-1) and an exemption from obtaining informed consent was granted due to the retrospective nature of the data collection. To ensure patient privacy, all data was anonymized before analysis. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Subarachnoid hemorrhage (SAH) remains a serious public health problem worldwide, especially in economically developed regions/countries. This study intends to thoroughly analyze the incidence, mortality, and disability-adjusted life years (DALYs) rate of SAH at the global, regional, and national levels. This study focused on the differences in SAH incidence between China and Japan from 1990 to 2019, and projected global, Chinese, and Japanese SAH incidence rates until 2030., Methods: Data on the disease burden owing to SAH from 1990 to 2019 were obtained from the Global Burden of Disease (GBD) Study 2019. linear regression analysis was used to calculate the estimated annual percentage change (EAPC) and linear regression method was used to calculate the average annual percentage change (AAPC). Bayesian age-period-cohort (BAPC) model was used to predict the disease burden from 2020 to 2030., Results: Globally, age-standardised incidence, mortality, and DALYs rates was declined from 1990 to 2019. In 1990-2019, the incidence of SAH decreased in China, while it increased in Japan, especially among middle-aged and elderly women. Projections suggest that the global incidence of SAH will decrease by 2.06% in 2030, with an increase of 6.24% in China and 13.82% in Japan, with the highest increase among Japanese women being 16.19%., Conclusions: Global SAH incidence, mortality, and DALYs rates declined over the 1990-2019 period, with regional/national SAH mortality and DALYs rates negatively correlated with socio-demographic index (SDI), while SAH incidence was positively correlated with SDI. The incidence of SAH decreased in China and increased in Japan during this period. The predictions show that over the next 10 years, while the incidence of SAH continues to decline globally, the incidence of SAH in China and Japan has increased. Thus, SAH remains a serious disease burden that requires early intervention targeting risk factors and populations at risk that may have increased because of economic development., Competing Interests: Declarations. Ethical approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The burgeoning volume of parameters in artificial neural network models has posed substantial challenges to conventional tensor computing hardware. Benefiting from the available optical multidimensional information entropy, optical intelligent computing is used as an alternative solution to address the emerging challenges of electrical computing. These limitations, in terms of device size and photonic integration scale, have hindered the performance of optical chips. Herein, an ultrahigh computing density optical tensor processing unit (OTPU), which is grounded in an individual microring resonator (MRR), is introduced to respond to these challenges. Through the independent tuning of multiwavelength lasers, the operational capabilities of an MRR are orchestrated, culminating in the formation of an optical tensor core. This design facilitates the execution of tensor convolution operations via the lightwave and microwave multidomain hybrid multiplexing in terms of the time, wavelength, and frequency of microwaves. The experimental results for the MRR-based OTPU show an extraordinary computing density of 34.04 TOPS/mm 2 . Additionally, the achieved accuracy rate in recognizing MNIST handwritten digits was 96.41%. These outcomes signify a significant advancement toward the realization of high-performance optical tensor processing chips., Competing Interests: Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s).)

With the rapid development of technology and the evolution of the global financial system, digital inclusive finance has become a new way to promote rural revitalization and rural residents' consumption with the power of financial technology. This study explores the relationship between digitally inclusive finance, rural revitalization, and rural residents' consumption. Based on the panel data of 30 provinces and cities in China from 2011 to 2021, this study empirically examines the impact of digitally inclusive finance on rural residents' consumption and the mediating and threshold effects of rural revitalization. The results reveal that digitally inclusive finance is conducive to the enhancement of rural residents' consumption, and rural revitalization acts as a mediator. Meanwhile, there is a nonlinear positive correlation between the impact of digitally inclusive finance and rural revitalization on rural residents' consumption, in which there is a double-threshold effect of digitally inclusive finance and rural revitalization in the lagged period. Based on the above findings, we believe that while promoting digitally inclusive finance, it is important to promote rural revitalization strategy in a timely manner, improve rural infrastructure, and continuously stimulate the impact of digitally inclusive finance on rural residents' consumption., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Li 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.)

Hydroxytyrosol, a fine chemical, is widely utilized in food and pharmaceutical industries. In this study, we constructed a pathway to produce hydroxytyrosol by co-expressing tyrosin-phenol lyase (TPL), L-amino acid dehydrogenase (aadL), α-keto acid decarboxylase (KAD), aldehyde reductase (yahK) and glucose dehydrogenase (gdh). We changed combinations between plasmids with different copy numbers and target genes, resulting in 84% increase in hydroxytyrosol production. The yield of hydroxytyrosol was further increased 89.3% by optimizing the temperature and pH. Finally, 55.3 mM hydroxytyrosol was produced within 14 h by fed-batch biotransformation. This study provides a novel approach for hydroxytyrosol production., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Biological neural circuits demonstrate exceptional adaptability to diverse tasks by dynamically adjusting neural connections to efficiently process information. However, current two-dimension materials-based neuromorphic hardware mainly focuses on specific devices to individually mimic artificial synapse or heterosynapse or soma and encoding the inner neural states to realize corresponding mock object function. Recent advancements suggest that integrating multiple two-dimension material devices to realize brain-like functions including the inter-mutual connecting assembly engineering has become a new research trend. In this work, we demonstrate a two-dimension MoS 2 -based reconfigurable analog hardware that emulate synaptic, heterosynaptic, and somatic functionalities. The inner-states and inter-connections of all modules co-encode versatile functions such as analog-to-digital/digital-to-analog conversion, and linear/nonlinear computations including integration, vector-matrix multiplication, convolution, to name a few. By assembling the functions to fit with different environment-interactive demanding tasks, this hardware experimentally achieves the reconstruction and image sharpening of medical images for diagnosis as well as circuit-level imitation of attention-switching and visual residual mechanisms for smart perception. This innovative hardware promotes the development of future general-purpose computing machines with high adaptability and flexibility to multiple tasks., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Patients with preoperative acute heart failure (AHF) after hip fracture in the elderly have a worse prognosis. We aim to investigate the characteristics, risk factors and postoperative complications of elderly patients with hip fracture complicated with preoperative AHF. We also looked at the effect of the severity of anemia at admission on the prognosis of the above people., Methods: A retrospective study of hip fracture patients (aged ≥ 65) admitted to the Department of Geriatric Orthopaedics, Third Hospital, Hebei Medical University, was conducted from January 2018 to October 2020. We used univariate and multivariate logistic regression to assess risk factors for preoperative AHF. The Kaplan-Meier survival curve shows the relationship between the severity of anemia on admission and all-cause mortality in elderly hip fracture patients with preoperative AHF., Results: Out of the 1092 patients, 503 had preoperative AHF and the incidence of it in hip fracture patients was 46.1%. Age, coronary artery disease, chronic atrial fibrillation, Age-Adjusted Charlson Comorbidity Index (ACCI), admission anemia, admission albumin < 40 g/dl, and admission C-reactive protein (CRP) were all significantly different between those with AHF and those without. Multivariate logistic regression analysis revealed that age ≥ 80 years (OR 1.740, 95% CI 1.309-2.313), coronary artery disease (OR 1.417, 95% CI 1.017-1.975), chronic atrial fibrillation (OR 4.010, 95% CI 1.757-9.152), admission anemia (OR 1.433, 95% CI 1.051-1.953) are the independent risk factors for preoperative AHF in elderly patients with hip fracture (p < 0.05). The HF group exhibited a higher incidence of postoperative complications, such as anemia, arrhythmia, NOAF (new-onset atrial fibrillation), AIS (acute ischemic stroke), electrolyte disturbance and hypoproteinemia. The moderate-to-severe anemia group had a higher incidence of postoperative complications, including deep vein thrombosis of the lower limbs, NOAF, and hypoproteinemia, as well as all-cause mortality., Conclusion: Older patients combined with admission anemia, coronary artery disease, chronic atrial fibrillation are more likely to have preoperative AHF after hip fracture. For such patients, early and effective identification and strengthening perioperative management can avoid the occurrence of adverse events. For patients with moderate and severe anemia at admission, timely intervention is recommended to reduce postoperative complications and mortality., Competing Interests: Declarations. Ethics approval and consent to participate: The research conducted at the third Hospital of Hebei Medical University was authorized by the institutional review board in accordance with Helsinki guidelines, and approval for waiving informed consent was granted. All data were anonymized before the analysis to safeguard patient privacy. Consent for publication: Not Applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The same cumulative carbon emission reduction target can correspond to multiple emission reduction pathways. This study explores how different coal power transition pathways with the same cumulative emissions reductions impact the transition costs, by assessing the dynamic transition processes for coal plants adopting multiple mitigation technologies concurrently or sequentially, such as flexibility operation, biomass and coal co-firing, carbon capture and storage, and compulsory retirement. We develop a plant-level dynamic optimization model and apply it to China's 4200+ coal plants. We find that under deep decarbonization, the majority of Chinese coal plants retrofit with multiple technologies to reduce emissions and retire naturally at lower costs while contributing to grid stability. Optimizing the pathway can potentially save over 700 billion U.S. Dollars for achieving the same target or increase cumulative emissions reduction from 30% to 50% at no additional cost. This analysis can help inform a cost-effective coal phase-out under China's carbon neutrality., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The photocatalytic conversion of lignin into value-added chemicals especially those functionalized molecules represent one of the most important strategies for sustainable and environmental-friendly development. Cleavage of C-C bonds in lignin under mild photocatalytic conditions for refining lignin into useful molecules is meaningful but challenging. Meanwhile, the assembly of diverse functional groups into active lignin fragments during the depolymerization is of great challenging. Herein, using cheap iron catalysts under visible light irradiation, the highly selective and efficient cleavage of C α -C β bond in lignin is realized via ligand-to-metal charge transfer (LMCT) and hydrogen atom transfer (HAT) processes. The subsequent divergent functionalization of generated lignin fragment-based radical intermediates enables an efficient formation of diverse functionalized molecules. This method is also effective for cleavage of C α -C β bond in native lignin, yielding two identified benzaldehyde monomers in a total yield of 8.7 wt %., (© 2024 Wiley-VCH GmbH.)

The advancement of interface engineering has demonstrated remarkable efficacy in overcoming the primary impediment associated with sluggish reaction kinetics in supercapacitor electrodes. In this investigation, we employed a facile co-precipitation method to synthesize NiCoMoO 4 /MXene heterostructures utilizing Ti 3 C 2 T x MXene nanosheets as carriers. This heterostructure inhibits the restacking of MXene nanosheets and simultaneously enhances the exposure of electrochemically active sites in NiCoMoO 4 nanorods, thereby mitigating the reduction in specific capacitance resulting from volumetric fluctuations. The NiCoMoO 4 /MXene electrode, possessing pseudo-capacitance properties, demonstrates an impressive level of specific capacitance, exceptional performance across various charging rates, and consistent behavior throughout repeated cycles. By optimizing the mass ratio, this electrode achieves a specific capacity of 1900 F/g under a current density of 1 A/g. Even after enduring 10,000 cycles at a significantly higher current density of 5 A/g, it still maintains an impressive retention rate of 94.73 %. Our density functional theory (DFT) calculations indicate that the enhanced electrochemical performance can be attributed to the improved electronic coupling within the NiCoMoO 4 /MXene heterostructure. The integration of NiCoMoO 4 /MXene cathode and activated carbon (AC) anode with an alkaline gel electrolyte containing potassium ferricyanide in flexible quasi-solid-state supercapacitors (FSSCs) results in exceptional electrochemical performance and flexibility. These FSSCs demonstrate a maximum energy density of 72.89 Wh kg -1 at a power density of 850 W kg -1 , while maintaining an impressive power output of 16,780 W kg -1 with an energy density of 37.28 Wh kg -1 . Based on these outstanding properties, it is evident that the NiCoMoO 4 /MXene heterojunction possesses significant advantages as electrode material for supercapacitors, and the fabricated FSSCs devices pave a new pathway for flexible electronic devices., 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 Inc. All rights reserved.)

Mumefural (MF), the primary functional ingredient of prunus mume extract that enhances blood fluidity, is produced by boiling the prunus mume juice for 24-48 h in a traditional one-step concentration process. Low MF yields and long processing time are two disadvantages of this process. This study introduced microwaves into the traditional one-step concentration process of prunus mume extract for increasing MF content. The best time for microwave treatment of prunus mume extract was concentrated to remove 93 %-95 % water. Results demonstrated that as microwave processing time increased, the content of reducing sugar, glucose, fructose, titratable acid content, and organic acids initially significantly increased (p < 0.05) and subsequently dramatically decreased (p < 0.05). Additionally, 5-Hydroxymethylfurfural (5-HMF) and MF showed a significant increase (p < 0.05) with the extension of microwave processing time. The MF generated by microwave for 0.5 min was equal to the concentration for 0.5 h. After 2 min microwave, the MF content in the prunus mume extract increased by fivefold compared to the sample without microwave treatment, and the maximum increase in MF was 3.19 g/kg. The two-step process consisted of concentration followed by microwave, which could shorten the concentration-time, promote the synthesis of MF, increase the content of MF, and provide a new idea for enterprises to improve the processing technology of prunus mume extract., 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.)

A comprehensive understanding of the dynamic changes in plasma cells (PCs) during inflammation remains elusive. In this study, we analyzed the distinct responses of PCs across different phases of inflammation in a dextran sodium sulfate (DSS)-induced mouse colitis model. Six-week-old male C57BL/6 mice were treated with 2.2 % DSS in distilled water for 5 days to induce colitis, and colonic tissues were collected at the peak of inflammation, during recovery, and at the end of the recovery phase. Single-cell RNA sequencing was performed to investigate temporal changes in the gut immune environment. PCs were categorized into six subsets, with Ube2c + PCs displaying notable alterations during various inflammatory phases. Genes such as Pycard, Gpx1, Lgals3, and Chchd10 were significantly expressed in Ube2c + PCs and appeared critical in resolving DSS-induced inflammation. Transcription factors (TFs), including Atf4, Cebpg, Jund, and Klf6, exhibited high regulatory activity in Ube2c + PCs across inflammatory stages. Additionally, we identified an interaction between Chchd10 and C1qbp in PCs, which stabilized C1qbp, reduced reactive oxygen species (ROS) production, and potentially enhanced PC survival and function under inflammatory conditions. This study highlights dynamic quasi-temporal gene expression and TF regulation in PCs during colitis, providing insights for future PC-targeted immunotherapy research., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: This study presents a novel technique for intraocular lens (IOL) fixation. The technique can be used on single-piece acrylic IOLs and can manage patients who are either with aphakia or with a dislocated IOL., Methods: One end of the Gore-Tex suture is tied into the optic-haptic junction of the IOL. Another end is fixated on the scleral wall. The single-sclerotomy and double-sclerotomy settings can be applied to different situations., Results: Twelve eyes received this procedure. After a follow-up period of up to 20 months, the IOLs were well centered., Conclusion: The technique is a reliable method for scleral fixation of IOLs, which can be applied to the widely used single-piece acrylic IOLs. In the authors' experience, it is reproducible and rarely causes complications.

Pulmonary fibrosis (PF) is a chronic, progressive and irreversible interstitial lung disease characterized by unremitting pulmonary myofibroblasts activation, extracellular matrix (ECM) deposition and inflammatory recruitment. PF has no curable medication yet. In this study we investigated the molecular pathogenesis and potential therapeutic targets of PF and discovered drug lead compounds for PF therapy. A murine PF model was established in mice by intratracheal instillation of bleomycin (BLM, 5 mg/kg). We showed that the protein level of pulmonary protein phosphatase magnesium-dependent 1A (PPM1A, also known as PP2Cα) was significantly downregulated in PF patients and BLM-induced PF mice. We demonstrated that TRIM47 promoted ubiquitination and decreased PPM1A protein in PF progression. By screening the lab in-house compound library, we discovered otilonium bromide (OB, clinically used for treating irritable bowel syndrome) as a PPM1A enzymatic activator with an EC 50 value of 4.23 μM. Treatment with OB (2.5, 5 mg·kg -1 ·d -1 , i.p., for 20 days) significantly ameliorated PF-like pathology in mice. We constructed PF mice with PPM1A-specific knockdown in the lung tissues, and determined that by targeting PPM1A, OB treatment suppressed ECM deposition through TGF-β/SMAD3 pathway in fibroblasts, repressed inflammatory responses through NF-κB/NLRP3 pathway in alveolar epithelial cells, and blunted the crosstalk between inflammation in alveolar epithelial cells and ECM deposition in fibroblasts. Together, our results demonstrate that pulmonary PPM1A activation is a promising therapeutic strategy for PF and highlighted the potential of OB in the treatment of the disease., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Terpene synthases (TPSs) are key enzymes in terpenoids synthesis of plants and play crucial roles in regulating plant defence against pests and diseases. Here, we report the functional characterization of OsTPS19 and OsTPS20, which were upregulated by the attack of brown planthopper (BPH). BPH female adults performed concentration-dependent behavioural responses to (S)-limonene showing preference behaviour at low concentrations and avoidance behaviour at high concentrations. Overexpression lines of OsTPS19 and OsTPS20, which emitted higher amounts of the monoterpene (S)-limonene, decreased the hatching rate of BPH eggs, reduced the lesion length of sheath blight caused by Rhizoctonia solani and bacterial blight caused by Xanthomonas oryzae. While knockout lines of OsTPS19 and OsTPS20, which emitted lower amounts of (S)-limonene, were more susceptible to these pathogens. Overexpression of OsTPS19 and OsTPS20 in rice plants had adverse effects on the incidence of BPH, rice blast, and sheath blight in the field and had no significant impacts on rice yield traits. OsTPS19 and OsTPS20 were found to be involved in fine-tuning the emission of (S)-limonene in rice plants and play an important role in defence against both BPH and rice pathogens., (© 2024 The Author(s). Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Background: Prior studies have investigated cardiac anatomy and clinical parameters as predictors for pulmonary vein and non-pulmonary vein triggers., Objective: We aimed to assess the link between the descending aorta to left inferior pulmonary vein (Dao-LIPV) distance and the occurrence of triggers and drivers in atrial fibrillation (AF) ablation procedures., Methods: Drug-refractory AF patients who underwent first-time index catheter ablation from January 2010 to December 2019 were retrospectively assembled. The Dao-LIPV distance was measured from preablation pulmonary vein computed tomography. Patients were assigned to groups on the basis of the presence of LIPV triggers or drivers. Multivariate logistic regression was used to identify risk factors., Results: A total of 886 consecutive patients with drug-refractory AF were studied, and 63 (7.1%) patients were identified to have LIPV triggers or drivers. The Dao-LIPV distance had a better predictive performance (area under the curve, 0.70) compared with persistent AF (area under the curve, 0.57). Multivariate logistic regression analysis showed that Dao-LIPV distance ≤2.5 mm (odds ratio, 3.96; 95% CI, 2.15-7.29; P < .001) and persistent AF (odds ratio, 1.73; 95% CI, 1.02-2.94]; P = .044) were independent predictors for the presence of LIPV triggers or drivers. A risk score model was established to predict the probability of LIPV triggers or drivers with persistent AF (10.2%), Dao-LIPV distance ≤2.5 mm (11.4%), and both (15.0%)., Conclusion: The proximity of the Dao-LIPV was correlated to the presence of LIPV triggers or drivers. We developed a risk score model indicating that persistent AF and Dao-LIPV distances ≤2.5 mm significantly increase the risk of LIPV triggers or drivers, aiding electrophysiologists in preparing for and performing catheter ablation more effectively., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Aims: This study aims to determine whether postpartum body mass index (BMI) trajectories and its time in target range (TTR) are associated with long-term type 2 diabetes risk in women with a history of gestational diabetes mellitus (GDM)., Materials and Methods: The present study included 1057 women with a history of GDM who participated in the Tianjin Gestational Diabetes Mellitus Prevention Program (TGDMPP). Oral glucose tolerance tests or physician-diagnosed information were used to diagnose type 2 diabetes after a median follow-up period of 8.47 years. Latent class modelling was applied to identify trajectories of BMI after delivery. TTR was defined as the proportion of time that BMI was within the standard range (18.5 ≤ BMI < 24.0 kg/m 2 ). The associations of BMI trajectories and TTR with type 2 diabetes risk were analysed using multivariable Cox modelling., Results: Five distinct trajectories of postpartum BMI were identified. Compared with low-stable class, the multivariable-adjusted hazard ratios of type 2 diabetes were 2.02 (95% confidence interval 0.99-4.10) for median-stable class, 3.01 (1.17-7.73) for high-stable class, 2.15 (0.63-7.38) for U-shape class and 7.15 (2.08-24.5) for inverse U-shape class (p for trend = 0.012), respectively. Multivariable-adjusted hazard ratios of type 2 diabetes associated with postpartum BMI TTR of 100%, >43.4%-<100%, >0%-≤43.4% and 0% were 1.00, 1.84 (0.72-4.73), 2.75 (1.23-6.15) and 2.31 (1.05-5.08) (p for trend = 0.039), respectively., Conclusions: Postpartum BMI trajectories of high-stable and inverse U-shape class as well as lower TTR were associated with an increased risk of type 2 diabetes among women with a history of GDM. Reducing BMI to a normal range in the early postpartum period and maintaining stable over time could attenuate the development of long-term type 2 diabetes., (© 2024 John Wiley & Sons Ltd.)

Aspongpyridiniums A-J (1-10), ten previously undescribed amino acid-derived pyridinium salts were isolated and identified from the n-BuOH fraction of the 50% MeOH extract of insect species Aspongopus chinensis, well-known for its use in traditional Chinese medicine for the treatment of pain, indigestion and kidney diseases. Their structures were determined by extensive spectroscopic data as well as electronic circular dichroism calculations and comparisons. Aspongpyridiniums A-J are structurally characterized by a unique 1,3,4-trisubstituted pyridinium skeleton with a variable functional group derived from an amino acid unit. In bioassays, Compounds 5 and 10 exhibited certain inhibitory activities against α-glucosidase, while 1-10 showed moderate to weak acetylcholinesterase inhibitory effects., 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 Ltd.)

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis during chronic stress is essential for depression neurobiology. As the latest member of the RFamide peptide family in mammals, pyroglutamylated RFamide peptide (QRFP) is closely implicated in neuroendocrine maintenance by activating G-protein-coupled receptor 103 (GPR103). We hypothesized that QRFP and GPR103 might contribute to chronic stress-induced depression by promoting corticotropin-releasing hormone (CRH) release from neurons in the paraventricular nucleus (PVN), and various methods were employed in this study, with male C57BL/6J mice adopted as the experimental subjects. Chronic stress induced not only depression-like behaviors but also significant enhancement in QRFP and GPR103 in the PVN. Genetic overexpression of QRFP/GPR103 and stereotactic infusion of QRFP-26/QRFP-43 peptide in the PVN all mimicked chronic stress that induced various depression-like phenotypes in naïve mice, and this was mediated by promoting CRH biosynthesis and HPA activity. In contrast, genetic knockdown of QRFP/GPR103 in the PVN produced notable antidepressant-like effects in mice exposed to chronic stress. Furthermore, genetic knockout of QRFP also protected against chronic stress in mice. In addition, both the C-terminal biological region of QRFP and the downstream PKA/PKC-CREB signaling coupled to GPR103 stimulation underlie the role of QRFP and GPR103 in depression. Collectively, QRFP and GPR103 in PVN neurons could be viable targets for novel antidepressants., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest for this study., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: Sitting Baduanjin exercises can be effective in treating mild cognitive impairment (MCI). However, evidence on effectiveness of sitting Baduanjin exercises is lacking. This study investigated the effects of sitting Baduanjin exercises on cognitive function, attention, and muscle strength in patients with MCI., Design: Quasi-experimental., Methods: The participants were assigned to the experimental ( n  = 12) or comparison group ( n  = 12). The experimental group performed sitting Baduanjin exercises three times weekly for 40-50 minutes per session for 12 weeks, while the comparison group maintained their usual routine and attended health-related education. The two groups' cognitive function and attention were assessed through a questionnaire and their muscle strength was measured at weeks 0, 9, and 13., Findings: The experimental group showed significant improvements in cognitive function, attention, and muscle strength in the right shoulder anterior flexor; however, the left shoulder anterior flexor group showed no obvious improvements., Conclusion: Sitting Baduanjin exercises feature simple actions, are convenient, and have positive effects on improving cognitive function, attention, and muscle strength in patients with MCI., Clinical Evidence: Baduanjin exercises are suitable for long-term community frontline care services. Early intervention with this exercise program may prevent healthy older people or those with health issues from progressing to dementia.

MS imaging (MSI) is a powerful technique for investigating the spatial distribution of metabolites in complex biological samples. However, due to the absence of liquid chromatography (LC) separation in routine MSI analysis, matrix effect is obvious and isomers identification remains challenging. To overcome these shortcomings of classical MSI tools (e.g., DESI-MSI and MALDI-MSI) for isomer differentiation and insufficient datapoints for quantification, online extraction-liquid chromatogram-hybrid triple quadrupole-time-of-flight mass spectrometry (OLE-LC-Qtof-MS) platform has been developed for spatial metabolome. As a proof-of-concept, two species flowers namely Forsythia viridissima (FV) and Jasminum nudiflorum (JN) that bloom in early spring were collected, dried, and cut into small pieces (1.0 mm × 1.0 mm). All pieces successively underwent OLE-LC-Qtof-MS measurements. As a result, 46 and 41 metabolites were observed and identified from FV and JN petals, respectively. Particularly, each compound corresponded to a chromatographic peak and isomeric differentiation was achieved amongst a set of chlorogenic acid derivatives. The peak areas of high intensity metabolites were aligned and combined within either species. The datasets were individually converted into heatmaps for all compounds, 87 ones in total, and each grid of any heatmap was assigned to the original location in the petal. Then, the spatial-resolved distribution style of each compound crossing the petal was reflected by the re-organized heatmap bearing the petal shape. As expected, regio-specific occurrence and accumulation were observed for several compounds, particularly among the chlorogenic acid isomers. Above all, OLE-LC-Qtof-MS is an alternative tool for spatial-resolved metabolome attributing to the advantages of isomeric separation and reliable quantification., 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: The aim of this study was to evaluate the effect of periodontal Porphyromonas gingivalis (P. gingivalis) infection on lung homeostasis and to explore the underlying mechanism., Designs: In in vivo experiments, twelve mice were divided into two groups. The P. gingivalis infection group received P. gingivalis around the maxillary second molar, and the control group was left untreated. After 12 weeks, the histopathological changes of the lung tissue and the autophagy and apoptosis in the lung tissue cells were detected. In in vitro experiments, alveolar epithelial cell A549 was co cultured with P. gingivalis and treated with autophagy inhibitor chloroquine (CQ). Western blot was then used to detect autophagic markers LC3 and P62, and mRFP-GFP-LC3 was used to observe autophagic flux. Cell viability and apoptosis were also detected., Results: For the in vivo experiments, pathological changes were observed in the lung tissue of the P. gingivalis infection group at 12 weeks, along with higher levels of autophagy and apoptosis in the lung tissue cells. For the in vitro experiments, infection of alveolar epithelial cells with P. gingivalis inhibited cell viability and promoted cell autophagy and apoptosis. Interestingly, we found that inhibiting P. gingivalis-activated autophagy significantly improved cell apoptosis and viability damage induced by P. gingivalis., Conclusion: Periodontal P. gingivalis infection can cause pathological changes and abnormal homeostasis in lung tissue, and the up-regulation of autophagy induced by P. gingivalis may play a synergistic role in this process., 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.)

Purpose: Upper tract urothelial carcinoma (UTUC) presents a higher incidence rate in Taiwan compared to Western societies. The aim of this study is to investigate the potential of metformin in improving survival outcomes for patients with UTUC in Taiwan., Material and Methods: This retrospective study included 940 patients with UTUC and type 2 diabetes from the Taiwan UTUC Collaboration Group, spanning 21 hospitals from July 1988 to September 2023. Patients were divided into two groups: those treated with metformin (n = 215) and those without metformin treatment (n = 725). Parameters analyzed included age, BMI, renal function, tumor grade and location, and pathological staging. Oncological outcomes measured were overall survival (OS), cancer-specific survival (CSS), and bladder recurrence-free survival (BRFS). Statistical analysis involved the use of Student's t-test, Mann-Whitney test, Chi-squared test, Fisher's exact test, and Cox proportional hazard regression., Results: Significant differences were observed between the two groups in BMI, preoperative creatinine, eGFR, tumor location, tumor laterality, tumor size, and pathological grade and T stage. Patients treated with metformin exhibited a lower risk of CSS (HR = 0.619; p = 0.018) and improved OS (HR = 0.713; p = 0.024), although no significant association was found with BRFS (HR = 1.034; p = 0.791). The protective effect of metformin on OS was particularly significant in patients with advanced T stage, metastasis, and high-grade tumors., Conclusion: The study suggests that metformin use in UTUC patients with diabetes is associated with improved OS and CSS but not BRFS. The underlying mechanisms warrant further investigation. Repurposing metformin, a well-established and safe drug, may develop new therapeutic strategies for UTUC., (© 2025 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

This study investigates the impact of neoadjuvant therapy (NT) on body composition and its correlation with long-term survival and other clinical outcomes in patients with advanced gastric cancer. We utilized Computed Tomography (CT) scans to measure body composition before and after NT, including Subcutaneous Adipose Tissue Index (SATI), Visceral Adipose Tissue Index (VATI), Skeletal Muscle Index (SMI), and Muscle Density (MA). We then analyzed the decrease in body composition in relation to tumor regression, inflammatory markers, nutritional scores, and long-term survival. Our findings reveal a negative correlation between the decrease in SATI and VATI after NT, and both tumor regression and nutritional score. Notably, patients who experienced a significant loss in SATI or VATI post-NT had shorter Recurrence-Free Survival (RFS) and Overall Survival (OS). Additionally, significant loss in SATI and VATI emerged as an independent risk factor for both RFS and OS. In conclusion, our study convincingly demonstrates that in patients with advanced gastric cancer, SATI and VATI decreases after NT and is negatively associated with tumor regression and nutritional score. A significant loss in SATI and VATI is a risk factor for shorter RFS and OS, thereby underscoring the importance of maintaining body composition during NT.