Search

LC3-associated phagocytosis (LAP) is a distinct type of autophagy that involves the sequestration of extracellular material by phagocytes. Beyond the removal of dead cells and cellular debris from eukaryotic cells, LAP is also involved in the removal of a variety of pathogens, including bacteria, fungi, and viruses. These events are integral to multiple physiological and pathological processes, such as host defense, inflammation, and tissue homeostasis. Dysregulation of LAP has been associated with the pathogenesis of several human diseases, including infectious diseases, autoimmune diseases, and neurodegenerative diseases. Thus, understanding the molecular mechanisms underlying LAP and its involvement in human diseases may provide new insights into the development of novel therapeutic strategies for these conditions. In this review, we summarize and highlight the current consensus on the role of LAP and its biological functions in disease progression to propose new therapeutic strategies. Further studies are needed to illustrate the precise role of LAP in human disease and to determine new therapeutic targets for LAP-associated pathologies., (© 2024 Federation of American Societies for Experimental Biology.)

Backgroud: Intrauterine Adhesions (IUA) is a common gynecological disease which is seriously endangers the reproductive function of women without any ideal treatment. Some researchers found Menstrual Blood-derived Mesenchymal Stem Cells (MenSCs) can repair of damaged endometrium, however, has not been fully clarified. This study aims to evaluate the therapeutic effects of MenSCs in IUA and the repair mechanism in vivo., Methods: This study is Laboratory-based study. To evaluate the therapeutic effects of MenSCs in IUA, We cultivated MenSCs, established mouse endometrial injury model, observed the uterine morphology and degree of endometrial fibrosis and compared the expression of CXC chemokine ligand-13 (CXCL13)、CXC chemokine receptor-5 (CXCR5)、Plasmin Activating Inhibitor-1(Pai-1), Transforming Growth Faction-β1(TGF- β1) and Matrix Metalloproteinase-9 (Mmp-9) among each groups. GraphPad Prism 8.0 was used for statistical processing. Data were expressed as mean ± SD. Statistical comparisons among groups were performed with one-way ANOVA. P < 0.05 were considered statistically significant., Results: We successfully cultured and identified MenSCs and established mice model of uterine adhesion. After treatment with MenSCs, endometrial morphology of mice was partially restored, endometrial thickness was increased, and glands were multipiled. The concentrations of CXCL13 and CXCR5 were significantly increased by immunofluorescence detection compared with the control group. The results of RT-qPCR showed that the expressions of Pai-1 and Mmp-9 were significantly lower than those of the control group., Conclusions: MenSCs may reduce endometrial fibrosis and the down-regulating expression of Pai-1、Mmp-9 and CXCL13-CXCR5 axis were involved in the process of MenSCs repaired IUA., (© 2024. The Author(s).)

Background: Pancreatic cancer is a malignant tumor of the digestive tract with a high mortality rate. Erianin has antitumor activity, but the regulatory targets and mechanism of action in pancreatic cancer are unclear. The objective of this study was to evaluate the anti-pancreatic cancer activity of Erianin and explore its underlying mechanisms., Methods: A network pharmacology approach was used to investigate the mechanism of action of Erianin in pancreatic cancer cells. Cell proliferation was analyzed using CCK8, colony-formation, and EdU proliferation assays. Cell migration was evaluated through wound healing and transwell assays, as well as determination of the protein expression levels of EMT markers and β-catenin. Apoptosis and the cell cycle were measured using flow cytometry and JC-1 staining, respectively. The protein expression levels of p-Rb, CyclinB1, P21, Cleaved-PARP, and Cleaved-Caspase3 were assessed using western blotting. RNA sequencing (RNA-seq) and bioinformatics analyses were performed to elucidate the mechanism underlying the action of Erianin in pancreatic cancer. Western blotting was used to examine the expression levels of key proteins in the AKT, JNK, and p38 MAPK signaling pathways. Molecular docking and CETSA were used to test hypotheses. The tumor-suppressive ability of Erianin in vivo was assessed using a tumor-bearing assay in nude mice., Results: Network pharmacology revealed that Erianin inhibited pancreatic cancer through multiple pathways. Erianin significantly inhibited pancreatic cancer cell proliferation and migration while promoting intracellular ROS and inducing apoptosis. Mechanistically, Erianin inhibited pancreatic cancer cell proliferation by regulating the AKT/FOXO1 and ASK1/JNK/p38 MAPK signaling pathways. In vivo experiments showed that Erianin inhibited subcutaneous tumor growth and promoted tumor tissue apoptosis in nude mice., Conclusions: The component-target-pathway network revealed that Erianin exerted anti-cancer effects through multiple components, targets, and pathways. Erianin inhibited the proliferation and migration of pancreatic cancer cells and induced apoptosis through the AKT/FOXO1 and ASK1/JNK/p38 MAPK signaling pathways. These results indicate that Erianin is a promising agent for pancreatic cancer treatment., (© 2024. The Author(s).)

Depression is high in prevalence rate, recurrence rate and disability rate. Acupuncture is effective on depression. The paper reviewed the regulatory effect of acupuncture on five prominent signaling pathways, i.e. mitogen activated protein kinase (MAPK), Wnt/β-catenin, Notch, adenyl ate cyclase/cyclic adenosine phosphate/protein kinase (AC/cAMP/PKA) and NO/cyclic guanosine monophosphate (cGMP)； and elaborated the structure of each signaling pathway, the association with depression onset, and the relevant research progress of acupuncture in treatment of depression. In view of the regulation of signal pathways, acupuncture can up-regulate AC/cAMP/PKA and extracellular signal-regulated kinase (ERK), promote the expression of neurotrophic factors or Bcl-2, prevent from and repair neuronal damage, advance neurogenesis and improve synaptic plasticity； it can modulate the Wnt/β-catenin and Notch signal pathways to protect neurons and increase cell proliferation； and down-regulate JNK and up-regulate NO/cGMP signal pathways to inhibit stress that leads to abnormal apoptosis of neurosis and attenuate neurotoxicity and neuronal damage so that anti-depression of acupuncture is obtained. This review provides a new approach to the mechanism research of acupuncture in treatment of depression through regulating the relevant single pathways.

Phenols, parabens, and phthalates are commonly found in consumer products, yet there is limited research on their individual and combined effects on depressive symptoms, particularly regarding the role of inflammation in these associations. This study aimed to evaluate these effects and explore potential molecular mechanisms, with a focus on inflammation as a mediator. We conducted a cross-sectional analysis involving 2766 adult participants from the National Health and Nutrition Examination Survey (NHANES) 2013-2016. Urine samples were analyzed for 15 chemicals, including 3 phenols, 2 parabens, and 10 phthalates. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9). Statistical analyses included linear regression, restricted cubic splines, Bayesian Kernel Machine Regression and quantile g-computation models to investigate the relationships between chemical exposures and depressive symptoms. Additionally, mediation analysis was employed to explore the potential role of inflammation (immune cells, CRP, NLR) in these associations. The underlying molecular mechanisms were analyzed using bioinformatic approaches. Notably, BPA, MECPP, MEHHP, MiBP and MBP were found to be positively associated with depressive symptoms among females. Besides, BPA was the most significant positive contributor to the effect in the context of the chemical mixture, while the overall mixture effect was relatively weak. Furthermore, WBC were found to mediate a marginal portion (4 %) of the potential effects of MBP on depressive symptoms. The 15 genes identified are primarily involved in neurotransmission, mood regulation, and stress response. Further research is needed to elucidate the mechanisms underlying the observed associations., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Graphene quantum dots (GQDs) have garnered significant attention across numerous fields due to their ultrasmall size and exceptional properties. However, their extensive applications may lead to environmental exposure and subsequent uptake by humans. Yet, conflicting reports exist regarding the potential toxicity of GQDs based on experimental investigations. Therefore, a comprehensive understanding of GQD biosafety requires further microscopic and molecular-level investigations. In this study, we employed molecular dynamics (MD) simulations to explore the interactions between GQDs and graphene oxide quantum dots (GOQDs) with a protein model, the human intestinal fatty acid binding protein (HIFABP), that plays a crucial role in mediating the carrier of fatty acids in the intestine. Our MD simulation results reveal that GQDs can be adsorbed on the opening of HIFABP, which serves as an entrance for the fatty acid molecules into the protein's interior cavity. This adsorption has the potential to obstruct the opening of HIFABP, leading to the loss of its normal biological function and ultimately resulting in toxicity. The adsorption of GQDs is driven by a combination of van der Waals (vdW), π-π stacking, cation-π, and hydrophobic interactions. Similarly, GOQDs also exhibit the ability to block the opening of HIFABP, thereby potentially causing toxicity. The blockage of GOQDs to HIFABP is guided by a combination of vdW, Coulomb, π-π stacking, and hydrophobic interactions. These findings not only highlight the potential harmful effects of GQDs on HIFABP but also elucidate the underlying molecular mechanism, which provides crucial insights into GQD toxicology., (© 2024. The Author(s).)

In this study, a sustained-release paliperidone (PAL) patch was developed using a combination of ion-pair strategy and percutaneous permeation enhancers (PPEs). The ion-pair strategy was used to improve drug-adhesive miscibility and control drug release. PPEs were used to break SC barrier function to facilitate drug skin permeation. The in vitro skin permeation experiments using single-factor experiments and Box-Behnken design gave the optimized formulation, a 55 μm adhesive thickness patch with 7 % (w/w) PAL-LA (Lauric acid), 9.7 % (w/w) Plurol® Oleique CC 497 (POCC). Moreover, the pharmacokinetic study confirmed its potential in sustained-release transdermal patch with longer MRT 0-t (18.35 ± 3.11 h) and higher BA (63.14 %) than the gavage group (C max  = 6.64 ± 2.61 μg/mL, MRT 0-t  = 2.88 ± 1.06 h, BA = 45.70 %) without significant increasing C max . The mechanism study revealed that forming ion-pairs effectively modulated drug's physicochemical properties and doubly ionic H-bond strength to improve drug miscibility in patches. To summarize, a sustained-release patch of PAL was successfully developed, which provided a strategy for sustained-release patches with good drug-polymer miscibility, drug controlled-release, and feasible drug utilization features., 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.)

Mineral-microbe interactions in the Earth's Critical Zone significantly influence elemental biogeochemical cycling and energy flow processes. This study addresses the key scientific question of how semiconducting minerals drive microbial nitrogen cycling. In the red soil environment, the presence of semiconducting minerals enhances the denitrification process mediated by facultative microorganisms (Pseudomonas aeruginosa PAO1) with denitrifying activity. Compared to darkness, light significantly enhanced the synergistic denitrification kinetic process of red soil and Pseudomonas aeruginosa PAO1 (1.87 times). Cyclic voltammetry shows that the P. aeruginosa PAO1-red soil synergistic system exhibits distinct redox peaks under light. The constant potential current curve and electrochemical impedance spectroscopy measurements reveal a high photocurrent density (1.0 μA/cm 2 ) and minimal polarization resistance (102 Ω) under this condition. These findings confirm that the sunlight-red soil-P. aeruginosa PAO1 synergistic process has excellent electron generation and migration capacity, active redox reactions, and good electron compatibility. Additionally, the photoelectrons of semiconductive minerals in red soil profoundly impact the metabolic processes of microbial denitrification functional genes. Using real-time polymerase chain reaction (qPCR) gene array technology, the abundance of nitrogen metabolism functional genes in P. aeruginosa PAO1 increased by 200 % during the light-red soil synergistic process. Notably, denitrification-related genes (ureC, nirS1, gdhA, and nosZ2) were significantly upregulated. This study confirms that semiconducting minerals are involved in the nitrogen cycle pathway of microbial denitrification and supplements the theory of mineral-microbial synergistic element biogeochemical cycling in the natural environment., 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.)

Humans are often exposed to complex mixtures of multiple pollutants rather than a single pollutant. However, the combined toxic effects and the molecular mechanism of PFOS and BaP remain poorly understood. In this study, two typical environmental pollutants, perfluorooctane sulfonate acid (PFOS) and benzo [a]pyrene (BaP), were selected to investigate their combined neurotoxic effects on rat C6 glioma cells at environmentally relevant concentrations. The results showed that coexposure to low-dose PFOS and BaP induced greater toxicity (synergistic effect) than did single exposure. PFOS-BaP coexposure had stronger toxic effects on inducing oxidative stress and promoting early apoptosis. Targeted metabolomics confirmed that increased levels of the neurotransmitters 5-hydroxytryptophan, dopamine, tryptophan and serotonin disturb the phenylalanine, tyrosine and tryptophan biosynthesis pathways. Mechanistically, exposure to a low-dose PFOS-BaP binary mixture induces steroid hormone synthesis disorder through the activation of Cyp1a1 and Hsd17b8 (steroid hormone synthesis genes) and Dhcr24 and Dhcr7 (cholesterol synthesis genes). These findings are useful for comprehensively and systematically elucidating the biological safety of PFOS-BaP and its potential threats to human health., 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.)

Fibrosis, an aberrant reparative response to tissue injury, involves a disruption in the equilibrium between the synthesis and degradation of the extracellular matrix, leading to its excessive accumulation within normal tissues, and culminating in organ dysfunction. Manifesting in the terminal stages of nearly all chronic ailments, fibrosis carries a high mortality rate and poses a significant threat to human health. Heme oxygenase-1 (HO-1) emerges as an endogenous protective agent, mitigating tissue damage through its antioxidant, anti-inflammatory, and antiapoptotic properties. Numerous studies have corroborated HO-1's potential as a therapeutic target in anti-fibrosis treatment. This review delves into the structural and functional attributes, and the upstream and downstream pathways of HO-1. Additionally, the regulatory networks and mechanisms of HO-1 in cells associated with fibrosis are elucidated. The role of HO-1 in various fibrosis-related diseases is also explored. Collectively, this comprehensive information serves as a foundation for future research and augments the viability of HO-1 as a therapeutic target for fibrosis., (© 2024 Wiley Periodicals LLC.)

Monascus species are capable of producing various active metabolites, including monacolin K (MK) and pigments. Studies have shown that the overexpression of the mok I gene from the MK synthesis gene cluster in Monascus species can significantly increase MK production; however, the molecular mechanism has not yet been fully elucidated. Therefore, this study focused on the mok I gene of Monascus pilosus to construct overexpression strains of the mok I gene, resulting in high-yield MK production. Sixteen positive transformants were obtained, seven of which produced 9.63% to 41.39% more MK than the original strain, with no citrinin detected in any of the transformants. The qRT-PCR results revealed that the expression levels of mok I in the transformed strains TI-13, TI-24, and TI-25 increased by more than 50% compared to the original strain at various fermentation times, with the highest increase being 10.9-fold. Furthermore, multi-omics techniques were used to analyze the molecular mechanisms underlying enhanced MK production in transformed strains. The results indicated that mok I overexpression may enhance MK synthesis in M. pilosus by regulating the expression of key genes (such as MAO , HPD , ACX , and PLC ) and the synthesis levels of key metabolites (such as delta-tocopherol and alpha-linolenic acid) in pathways linked to the biosynthesis of cofactors, the biosynthesis of unsaturated fatty acids, tyrosine metabolism, ubiquinone and other terpenoid-quinone biosynthesis, alpha-linolenic acid metabolism, and glycerophospholipid metabolism. These findings provide a theoretical basis for further study of the metabolic regulation of MK in Monascus species and for effectively enhancing their MK production.

Collagen peptides have been reported to display various bioactivities and high bioavailability. Recently, increasing evidence has revealed the excellent wound-healing activity of collagen peptides, but their molecular mechanisms remain incompletely elucidated. This review systematically evaluates the therapeutic efficacy of collagen peptides from diverse sources based on various wound models. Furthermore, the structure-activity relationships of collagen peptides and wound-healing mechanisms are discussed and summarized. Characterized by their low molecular weight and abundant imino acids, collagen peptides facilitate efficient absorption by the body to deliver nutrition throughout the wound-healing process. The specific mechanism of collagen peptide for wound healing is mainly through up-regulation of related cytokines and participation in the activation of relevant signaling pathways, such as TGF-β/Smad and PI3K/Akt/mTOR, which can promote cell proliferation, angiogenesis, collagen synthesis and deposition, re-epithelialization, and ECM remodeling, ultimately achieving the effect of wound healing. Collagen peptides can offer a potential therapeutic approach for treating incision and excision wounds, mucosal injuries, burn wounds, and pressure ulcers, improving the efficiency of wound healing by about 10%-30%. The present review contributes to understanding of the wound-healing potential of collagen peptides and the underlying molecular mechanisms.

Intestinal mucositis (IM) is one of the most serious side effects of the chemotherapeutic agent irinotecan (CPT-11). Astragalus membranaceus-Pueraria lobata decoction is from the ancient medical book Zhengzhihuibu, has been reported to be used for the treatment of diabetes and hypertension. However, the beneficial effect and mechanism of AP on chemotherapy intestinal mucositis (CIM) remain largely unknown. This study aimed to investigate the efficacy and mechanism of Astragalus membranaceus-Pueraria lobata decoction (AP) in treating CIM. The beneficial effect and mechanism of AP on chemotherapy intestinal mucositis (CIM) were detected using Drosophila model, and combination with RT qPCR, transcriptomics. AP supplementation could significantly alleviate the CPT-11-induced body injury in Drosophila, such as increasing the survival rate, recovering the impaired digestion, improving the movement, and repairing the reproduction and developmental processes. Administration of AP remarkably alleviated the IM caused by CPT-11, including inhibiting the excretion, repairing the intestinal atrophy, improving the acid-base homeostasis imbalance, and inhibiting the disruption of intestinal structure. Mechanistic studies revealed that the protective role of AP against CPT-11 induced intestinal injury was regulated mainly by inhibiting immune-related Toll and Imd pathways, and enhancing the antioxidant capacity. Taken together, these results suggest that AP may be a novel agent to relieve CIM., (© 2024 Federation of American Societies for Experimental Biology.)

The concurrent environmental contamination by nanoplastics (NPs) and norfloxacin (NOR) is a burgeoning concern, with significant accumulations in various ecosystems and potential ingress into the human body via the food chain, posing threats to both public health and ecological balance. Despite the gravity of the situation, studies on the co-exposure contamination effects of these substances are limited. Moreover, the response mechanisms of key functional proteins to these pollutants are yet to be fully elucidated. In this work, we conducted a comprehensive assessment of the interaction mechanisms of NPs and NOR with lysozyme under both single and co-exposure condition, utilizing dynamic light scattering, ζ-potential measurements, multi-spectroscopy methods, enzyme activity assays and molecular docking, to obtain a relationship between the compound effects of NPs and NOR. Our results indicate that NPs adsorb NOR on their surface, forming more stable aggregates. These aggregates influence the conformation, secondary structure (α-Helix ratio decreased by 3.1 %) and amino acid residue microenvironment of lysozyme. And changes in structure affect the activity of lysozyme (reduced by 39.9 %) with the influence of composited pollutants exerting stronger changes. Molecular simulation indicated the key residues Asp 52 for protein function located near the docking site, suggesting pollutants preferentially binds to the active center of lysozyme. Through this study, we have found the effect of increased toxicity on lysozyme under the compounded conditions of NPs and NOR, confirming that the increased molecular toxicity of NPs and NOR is predominantly realized through the increase in particle size and stability of the aggregates under weak interactions, as well as induction of protein structural looseness. This study proposes a molecular perspective on the differential effects and mechanisms of NPs-NOR composite pollution, providing new insights into the assessment of in vitro responses to composite pollutant exposure., 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.)

Aging is an unavoidable process marked by numerous physiological and psychological changes that profoundly impact overall health and quality of life. As the global population ages, there is a growing interest in non-pharmacological therapies that can mitigate the adverse effects of aging and promote longevity. This narrative review explores the broad spectrum of non-pharmacological mechanisms offering anti-aging benefits, with a special emphasis on holistic practices such as yoga, meditation, and lifestyle interventions. These therapies influence critical biological processes, including reducing oxidative stress, modulating chronic inflammation, enhancing immune function, and preserving telomere length-key markers of cellular aging. Additionally, these practices contribute to improved cardiovascular health, musculoskeletal strength, and mental well-being, fostering a comprehensive approach to healthy aging. Yoga, for instance, combines physical postures, breath control, and meditation to enhance physical flexibility, mental clarity, and emotional balance. Meditation practices are shown to reduce stress and improve cognitive function, further supporting healthy aging. Lifestyle modifications, such as diet and regular physical activity, complement these therapies by promoting overall vitality and reducing the risk of age-related diseases. This review underscores the potential of integrating these non-pharmacological strategies into daily routines to enhance resilience against aging, improve quality of life, and extend healthspan. Furthermore, it highlights the need for continued research to fully elucidate the mechanisms by which these therapies exert their anti-aging effects and to develop evidence-based guidelines for their implementation., Competing Interests: Declaration of competing interest The author declares no conflicts of interests., (Copyright © 2024. Published by Elsevier Inc.)

Systems-wide understanding of gene expression profile regulating flower colour formation in Rhododendron simsii Planchon is insufficient. In this research, integration analysis of ribonucleic acid (RNA)omics and microRNAome were performed to reveal the molecular mechanism of flower colour formation in three R. simsii varieties with red, pink and crimson flowers, respectively. Totally, 3129, 5755 and 5295 differentially expressed gene (DEG)s were identified through comparative transcriptome analysis between 'Red variety' and 'Pink variety' (1507 up-regulated and 1622 down-regulated), 'Red variety' and 'Crimson variety' (2148 up-regulated 3607 down-regulated), as well as 'Pink variety' and 'Crimson variety' (2089 up-regulated and 3206 down-regulated), which were involved in processes of 'catalytic activity', 'binding', 'metabolic process' and 'cellular process', as well as pathways of 'metabolic pathways', 'biosynthesis of secondary metabolites', 'plant-pathogen interaction' and 'phenylpropanoid biosynthesis'. A total of 215 miRNAs, containing 153 known miRNAs belonging to 57 families and 62 novel miRNA, were involved in flower colour formation. In particular, 55 miRNAs were significantly differently expressed. Based on miRNA-mRNA regulatory network, ath-miR5658 could affect the synthesis of pelargonidin, cyanidin and delphinidin through downregulating accumulation of anthocyanidin 3-O-glucosyltransferase; ath-miR868-3p could regulate isoflavonoid biosynthesis through downregulating expression of CYP81E1/E7; ath-miR156g regulated the expression of flavonoid 3',5'-hydroxylase; and ath-miR829-5p regulated flavonol synthasein flavonoid biosynthesis process. This research will provide important roles in breeding new varieties with rich flower colour., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Annals of Botany Company.)

Zearalenone (ZEA) is a mycotoxin produced by Fusarium spp. fungi and is widely found in moldy corn, wheat, barley, and other grains. ZEA is distributed to the whole body via blood circulation after metabolic transformation in animals. Through oxidative stress, immunosuppression, apoptosis, autophagy, and mitochondrial dysfunction, ZEA leads to hepatitis, neurodegenerative diseases, cancer, abortion, and stillbirth in female animals, and decreased sperm motility in male animals. In recent years, due to the influence of climate, storage facilities, and other factors, the problem of ZEA pollution in global food crops has become particularly prominent, resulting in serious problems for the animal husbandry and feed industries, and threatening human health. Resveratrol (RSV) is a natural product with therapeutic activities such as anti-inflammatory, antioxidant, and anticancer properties. RSV can alleviate ZEA-induced toxic effects by targeting signaling pathways such as NF-κB, Nrf2/Keap1, and PI3K/AKT/mTOR via attenuating oxidative damage, inflammatory response, and apoptosis, and regulating cellular autophagy. Therefore, this paper provides a review of the protective effect of RSV against ZEA-induced toxicity and its molecular mechanism, and discusses the safety and potential clinical applications of RSV in the search for natural mycotoxin detoxification agents.

Multiple morphological abnormalities of the sperm flagella (MMAF) is a specific form of severe flagellar or ciliary deficiency syndrome. MMAF is characterized by primary infertility with abnormal morphology in the flagella of spermatozoa, presenting with short, absent, bent, coiled, and irregular flagella. As a rare disease first named in 2014, studies in recent years have shed light on the molecular defects of MMAF that comprise the structure and biological function of the sperm flagella. Understanding the molecular genetics of MMAF may provide opportunities for the development of diagnostic and therapeutic strategies for this rare disease. This review aims to summarize current studies regarding the molecular pathogenesis of MMAF and describe strategies of genetic counseling, clinical diagnosis, and therapy for MMAF.

Microplastics (MPs) are widely used and disposed of indiscriminately, posing a potential threat to aquatic life. Herein, Asian seabass (Lates calcarifer) fingerlings were exposed to various concentrations (1, 10 and 100 ppt or g/kg) of dietary polyethylene MPs for 16 days. The results indicated a significant increase in mortality among the fish fed with dietary MPs compared to the control. Furthermore, histological analysis of the liver revealed moderate-to-severe morphological alterations, hepatocyte necrosis and vacuolisation as the concentration gradient of MPs increased. The severity of the alterations was highest at a concentration of 100 ppt, indicating a direct correlation between MP and liver damage. In addition, RNA sequencing and Gene Ontology term enrichment analysis revealed that a total of 4137 genes were significantly differentially expressed, with 1958 upregulated and 2179 downregulated genes. The significantly enriched terms included 'oxidoreductase activity', 'endocytosis', 'mitochondrial', 'immune system process' and 'lipid catabolic process'. Moreover, the Kyoto Encyclopaedia of Genes and Genomes enrichment analysis demonstrated that dietary MPs triggered oxidative stress, immune response and adaptive mechanism pathways in fish. Thus, MPs can induce metabolic disorders in L. calcarifer, highlighting their potential threat to aquatic organisms., 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.)

Pb(II) sequestration in extracellular polymers-biochar composites (EPS-BC) was explored using macroscopic models and microscopic technology. The results showed that the actual adsorption capacity of EPS-BC was 52.2% lower than the calculated capacity based on adsorption onto pure components due to the interaction of polysaccharide and amide group in extracellular polymers with biochar, which masked the reactive sites related to Pb(II) in EPS-BC. The bond of Pb-O (40.8%) and Pb-OOC (31.5%) mainly contributed to Pb(II) speciation on the EPS-BC surfaces. Furthermore, each Pb atom coordinated with 6O atoms in the first shell and with 0.5C atoms in the second shell, indicating that the carboxyl group in composite was complexed with Pb(II) as a monodentate inner-sphere structure. The findings provide an in-depth understanding of the adsorption mechanism of heavy metals by extracellular polymers coupled with biochar at molecular scale, guiding bioremediation with respect to heavy metal contamination., 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.)

Chlorimuron-ethyl is a selective pre- and post-emergence herbicide, which is widely used to control broad-leaved weeds in soybean fields. However, herbicide residues have also increased as a result of the pervasive use of chlorimuron-ethyl, which has become a significant environmental concern. Consequently, the removal of chlorimuron-ethyl residues from the environment has garnered significant attention in recent decades. A variety of technologies have been developed to address this issue, including adsorption, aqueous chlorination, photodegradation, Fenton, photo-Fenton, ozonation, and biodegradation. After extensive studies, the biodegradation of chlorimuron-ethyl by microorganisms has now been recognized as an efficient and environmentally friendly degradation process. As research has progressed, a number of microbial strains associated with chlorimuron-ethyl degradation have been identified, such as Pseudomonas sp., Klebsiella sp., Rhodococcus sp., Stenotrophomonas sp., Aspergillus sp., Hansschlegelia sp., and Enterobacter sp. In addition, the enzymes and genes responsible for chlorimuron-ethyl biodegradation are also being investigated. These degradation genes include sulE, pnbA, carE, gst, Kj-CysJ, Kj-eitD-2267, Kj-kdpD-226, Kj-dxs-398, Kj-mhpC-2096, and Kj-mhpC-2289, among others. The degradation enzymes associated with chlorimuron-ethyl biodegradation includes esterases (SulE, PnbA, and E3), carboxylesterase (CarE), Cytochrome P450, flavin monooxygenase (FMO), and glutathione-S-transferase (GST). Regrettably, few reviews have focused on the microbial degradation and molecular mechanisms of chlorimuron-ethyl. Therefore, this review covers the microbial degradation of chlorimuron-ethyl and its degradation pathways, the molecular mechanism of the microbial degradation of chlorimuron-ethyl, and the outlook on the practical application of the microbial degradation of sulfonylurea herbicides are all covered in this review's overview of previous studies into the degradation of chlorimuron-ethyl., 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.)

(2,3)-Butanediol dehydrogenases (BDHs) are widely utilized for the stereoselective interconversion between α-hydroxy ketones and vicinal diols to produce various functional building blocks. In this study, to enhance the specific activity towards (R)-phenyl-1,2-ethanediol (1a) for 2-hydroxyacetophenone (1b), the substrate-binding pocket of a Bacillus subtilis BDH (BsBDHA) was refined through site-directed mutagenesis. Based on molecular docking simulations, 14 residues were identified and subjected to alanine scanning mutagenesis. After screening, two residues, His 42 and Gly 292 , were singled out for partial site-saturation mutagenesis. The results revealed that BsBDHA H42A and BsBDHA G292A displayed high activities of 3.21 and 1.97 U/mg, respectively. Employing combinatorial mutagenesis, a superior mutant, BsBDHA I49L/V266L/G292A , was developed, exhibiting significantly enhanced specific activity and catalytic efficiency towards (R)-1a, achieving 14.81 U/mg and 4.47 mM -1  s -1 , respectively, which were 27.4- and 55.9-fold higher than those of BsBDHA. Further substrate spectrum analysis revealed that the superior mutant displayed increased specific activities for (R)-2a-6a by 1.4- to 10.3-fold. The integration of BsBDHA I49L/V266L/G292A into a three-enzymatic cascade for the synthesis of 1b effectively elevated the yield from 58.1 to 82.4%. Molecular mechanism analysis indicated that the mutation-induced changes in intermolecular forces resulted in a higher frequency of reactive conformations for (R)-1a in BsBDHA I49L/V266L/G292A compared to BsBDHA., 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.)

Ependymal cells are arranged along the inner surfaces of the ventricles and the central canal of the spinal cord, providing anatomical, physiological and immunological barriers that maintain cerebrospinal fluid (CSF) homeostasis. Based on this, studies have found that alterations in gene expression, cell junctions, cytokine secretion and metabolic disturbances can lead to dysfunction of ependymal cells, thereby participating in the onset and progression of central nervous system (CNS) infections. Additionally, ependymal cells can exhibit proliferative and regenerative potential as well as secretory functions during CNS injury, contributing to neuroprotection and post-injury recovery. Currently, studies on ependymal cell primarily focus on the basic investigations of their morphology, function and gene expression; however, there is a notable lack of clinical translational studies examining the molecular mechanisms by which ependymal cells are involved in disease onset and progression. This limits our understanding of ependymal cells in CNS infections and the development of therapeutic applications. Therefore, this review will discuss the molecular mechanism underlying the involvement of ependymal cells in CNS infections, and explore their potential for application in clinical treatment modalities., (© 2024. The Author(s).)

The oxalate-carbonate pathway (OCP) involves degradation of soil oxalate to carbonate. To exploit and manage this natural mineralization of assimilated atmospheric CO 2 into stable carbonates, improved understanding of this complex biotransformation process is needed. A strain of oxalate-degrading bacteria, Azospirillum sp. OX-1, was isolated from soil, and its secondary products of calcium oxalate degradation were analyzed and characterized using SEM, XRD, TG/DTG-DTA and FTIR-spectroscopy. The molecular mechanism of calcium oxalate degradation was also analyzed using proteomics. The results showed, for the first time, that OX-1 could not only degrade calcium oxalate to calcium carbonate, but also that the process was accompanied by synthesis of methane. Proteomic analysis demonstrated that OX-1 has a dual enzyme system for calcium oxalate degradation, using formyl-CoA transferase (FRC) and thiamine pyrophosphate (ThDP)-dependent oxalyl-CoA decarboxylase (OXC) to form calcium carbonate. Up-regulated expression of enzymes related to methane synthesis was also detected during calcium oxalate degradation. Since methane is also a potent greenhouse gas, these new results suggest that the utility of exploiting the OCP to reduce atmospheric CO 2 must be re-evaluated and that further studies should be conducted to reveal how widespread the methane producing capacity of strain OX-1 is in other bacteria and soil environments., (© 2024. The Author(s).)

Background: Chronic Pulmonary Heart Disease (CPHD) significantly impacts global health, especially among middle-aged and older adults. In China, the Traditional Chinese Medicine (TCM) technique of Resolving Phlegm and Activating Blood (RPAB) is widely used to treat CPHD, although high-quality evidence supporting its efficacy remains limited., Objectives: The purpose of this study was to rigorously assess the clinical efficacy of RPAB for CPHD and elucidate the mechanisms underlying its primary herbal components., Methods: Through a detailed search of literature in both Chinese and English and strict inclusion and exclusion criteria, 18 randomized controlled trials (RCTs) were selected for meta-analysis. We identified RPAB's core herbal combinations using association rule analysis. This method statistically analyzes the frequency and correlation of herbal medicine usage. We then analyzed the chemical components of these combinations and investigated their potential intervention mechanisms on CPHD through network pharmacology., Results: The combination of RPAB with Western medicine was superior to Western medicine alone in improving blood gas analysis and pulmonary function and reducing plasma viscosity in CPHD patients. The core herbal combination identified was Astragalus membranaceus (Fisch.) Bunge, Ligusticum chuanxiong Hort. ex S. H. Qiu & al., and Stellaria alsine Grimm (ALS). This combination targeted 588 therapeutic and 27 core targets. It influenced ten core compounds across 34 pathways, primarily through the chemokine signaling pathway and the JAK-STAT signaling pathway., Conclusion: RPAB with Western medicine significantly improves CPHD treatment outcomes. The study highlights the therapeutic potential of the ALS combination, which operates through multiple pathways to remodel pulmonary arteries, decrease inflammation, and lessen oxidative stress. These insights support the clinical application of RPAB in CPHD treatment and open new avenues for research and therapeutic development., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Neuroinflammation hallmarks the pathology of depression although the etiological complexity has not yet been resolved. Previous studies demonstrate that bacterial lipopolysaccharide induces depressive-like behaviors by activating RagA-mTOR-p70S6K signaling pathway. The current project aims to investigate whether and how brain-specific RagA overexpression triggers depressive-like behaviors in mice. Full-length RagA cDNA is cloned into the mammalian expression vector under the control of brain specific promoter, and subsequently overexpressed in the brain of mouse embryos. Indeed, RagA transgenic mice exhibit depressive-like behaviors and memory impairments. RNA-seq profiling of the prefrontal cortex (PFC) transcriptome highlights adenosine A2a receptor (ADORA2A) as a key differentially expressed gene (DEG). Western blotting confirms that ADORA2A and phospho-p70S6K are markedly elevated in RagA transgenic mice. Behavioral assessments demonstrate that ADORA2A inhibitor istradefylline markedly attenuates depressive-like behaviors. Further metabolomics reveals that N-acetylserotonin and several depression-related metabolites are downregulated while proteomic profiling showed that OLIG1 and other proteins are significantly regulated in RagA transgenic mice. Collectively, RagA overexpression alters the expression patterns of signaling proteins and the metabolism of depression-associated metabolites. RagA may cause depressive-like behaviors in mice via activating p70S6K/ADORA2A signaling pathway. Thus, RagA-p70S6K-ADORA2A signaling pathway may be a target for the development of new antidepressant therapies., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Cationic and anionic castor oil-based waterborne polyurethanes (C-WPU/A and C-WPU/C) have great potential for development in agriculture. However, it is still unclear whether these polyurethanes are harmful or toxic to soil fauna. Based on multilevel toxicity endpoints and transcriptomics, we investigated the effects of C-WPU/A and C-WPU/C on earthworms (Eisenia fetida). The acute toxicity results showed that C-WPU/A was highly toxic to the earthworms, whereas C-WPU/C was nearly nontoxic. C-WPU/A significantly affected the body weight, burrowing ability and cocoon production rate of earthworms compared to C-WPU/C. After exposure to C-WPU/A, the results showed accumulation of reactive oxygen species (ROS), abnormal peroxidase activity, and increased malondialdehyde levels. Additionally, more serious histopathological damage was observed in earthworms, such as epidermal damage, vacuolization, longitudinal muscle disorganization, and shedding of intestinal epidermal cells. At the cellular level, C-WPU/A induced more severe lysosomal damage, DNA damage and apoptosis than C-WPU/A. C-WPU/A made more differentially expressed genes and considerably more enriched pathways at the transcriptional level than C-WPU/C. These pathways are largely involved in cell membrane signaling, detoxification, and apoptosis. These results provide an important reference for elucidating the selective toxicity mechanisms of C-WPU/A and C-WPU/C in earthworms., 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.)

Here, we subjected the marine copepod Tigriopus japonicus to environmentally-relevant concentrations of microplastics (MPs) and mercury (Hg) for three generations (F0-F2) to investigate their physiological and molecular responses. Hg accumulation and phenotypic traits were measured in each generation, with multi-omics analysis conducted in F2. The results showed that MPs insignificantly impacted the copepod's development and reproduction, however, which were significantly compromised by Hg exposure. Interestingly, MPs significantly increased Hg accumulation and consequently aggravated this metal toxicity in T. japonicus, demonstrating their carrier role. Multi-omics analysis indicated that Hg pollution produced numerous toxic events, e.g., induction of apoptosis, damage to cell/organ morphogenesis, and disordered energy metabolism, ultimately resulting in retarded development and decreased fecundity. Importantly, MPs enhanced Hg toxicity mainly via increased oxidative apoptosis, compromised cell/organ morphogenesis, and energy depletion. Additionally, phosphoproteomic analysis revealed extensive regulation of the above processes, and also impaired neuron activity under combined MPs and Hg exposure. These alterations adversely affected development and reproduction of T. japonicus. Overall, our findings should offer novel molecular insights into the response of T. japonicus to long-term exposure to MPs and Hg, with a particular emphasis on the carrier role of MPs on Hg toxicity., 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.)

The functions of major latex proteins (MLPs) in plant defense and stress responses have been widely documented; however, their roles in HT stress response in soybeans have not been elucidated. This study investigated the role of GmMLP34, a member of the major latex protein (MLP) family, in the response of soybeans to HT stress. Transcriptome analysis of HT-resistant (JD21) and HT-sensitive (HD14) soybean leaves under HT stress (43.40 ± 1.70 °C) and field conditions revealed differential expression of GmMLP34. Further examination across different HT-resistant varieties showed that GmMLP34 was down-regulated in the leaves of 6 HT-resistant varieties (85.7 %) and up-regulated in the leaves of 6 HT-sensitive varieties (85.7 %) under the HT treatment (45 °C for 3 h). The results of this study indicate that ectopic expression of the GmMLP34 gene in Arabidopsis led to a significant decrease in the survival rate of seedling when compared to the wild type (WT) under HT stress conditions of 37/28 °C (day/night) for 5 d, Moreover, the results indicated a significant decrease in primary root length and lateral root number under 45 °C/3 h HT stress followed by 12 h room temperature recovery. Additionally, the levels of abscisic acid (ABA), and flavonoids, and the activity of the peroxidase (POD) enzyme in the antioxidant system was decreased, while the activity of the superoxide dismutase (SOD) enzyme increased in GmMLP34-overexpressing transgenic Arabidopsis thaliana. The expression levels of the HT-response genes AtCHS1 and AtCHI2-A, were significantly down-regulated, whereas that of AtGBP1 was significantly up-regulated. These results suggest that GmMLP34 negatively regulates the response of Arabidopsis thaliana to HT stress by modulating flavonoid synthesis, hormone synthesis, and the antioxidant enzyme system. These findings provide theoretical information for the genetic improvement of HT tolerance in soybean and contribute to the understanding of the molecular mechanisms underlying plant responses to abiotic stress., 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.)

The mechanism of arsenic resistance in bacteria is under studied and still lacks a clear understanding despite of wide research work. The advanced technologies can help in analysing the arsenic bioremediating bacteria at a molecular level. With this line of idea, highly efficient arsenic bioremediating S. maltophilia was subjected to extensive analysis to understand the mechanism of arsenic resistance and bioremediation. The cell surface analysis revealed that S. maltophilia induces only slight changes in cell surface in the presence of arsenic. Whereas, TEM analysis has indicated the bioaccumulation of arsenic in S. maltophilia. Also, arsenic was found to generate ROS in a concentration dependant manner, and in response, S. maltophilia activated SOD, catalase, thioredoxin reductase etc. to manage oxidative stress which is very much crucial in managing arsenic toxicity. S. maltophilia was found to possess genes such as arsC, aoxB, aoxC and aioA. These genes are involved in arsenic reduction and oxidation. Transcriptomics and proteomics analysis have shown that S. maltophilia detoxifies arsenic by upregulating ars operon, arsH, BetB etc. which are responsible for arsenic reduction, efflux methylation, oxidation etc. A detailed molecular mechanism of arsenic bioremediation in S. maltophilia was put forth., Competing Interests: Declaration of competing interest Authors declare no competing interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Fibrosis is a tissue damage repair response caused by multiple pathogenic factors which could occur in almost every apparatus and leading to the tissue structure damage, physiological abnormality, and even organ failure until death. Up to now, there is still no specific drugs or strategies can effectively block or changeover tissue fibrosis. JNKs, a subset of mitogen-activated protein kinases (MAPK), have been reported that participates in various biological processes, such as genetic expression, DNA damage, and cell activation/proliferation/death pathways. Increasing studies indicated that abnormal regulation of JNK signal pathway has strongly associated with tissue fibrosis., Aim of Review: This review designed to sum up the molecular mechanism progresses in the role of JNK signal pathway in organ fibrosis, hoping to provide a novel therapy strategy to tackle tissue fibrosis., Key Scientific Concepts of Review: Recent evidence shows that JNK signaling pathway could modulates inflammation, immunoreaction, oxidative stress and Multiple cell biological functions in organ fibrosis. Therefore, targeting the JNK pathway may be a useful strategy in cure fibrosis., 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. Production and hosting by Elsevier B.V.)

The delivery of ultra-high dose rates of radiation, called flash irradiation or flash-RT, has emerged as a new modality of radiotherapy shaking up the paradigm of proportionality of effect and dose whatever the method of delivery of the radiation. The hallmark of flash-RT is healthy tissue sparing from the side effects of radiation without decrease of the antitumor efficiency in animal models. In this review we will define its specificities, the molecular mechanisms underlying the flash effect and the ongoing developments to bring this new modality to patient treatment., (Copyright © 2024 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Feed efficiency (FE) is an important economic factor in poultry production, and feed conversion ratio (FCR) is one of the most widely used measures of FE. Factors associated with FCR include genetics, the environment, and other factors. However, the mechanisms responsible for FCR in chickens are still less well appreciated. In this study, we examined the pattern changes of FCR, then delved into understanding the mechanisms behind these variations from both genetic and environmental perspectives. Most interestingly, the FCR at the front section of henhouse exhibited the lowest value. Further investigation revealed that laying rate in the high FCR (HFCR) group was lower than that in the low FCR (LFCR) group (P < 0.05). Cortisol, total antioxidant capacity (TAOC), and IgG levels in the LFCR group were significantly lower than those in the HFCR group (P < 0.05), while BUN level was significantly higher than that in the HFCR group (P < 0.05). We identified a total of 67 and 10 differentially expressed genes (DEGs) associated with FCR in ovarian and small intestine tissues, respectively. Functional enrichment analysis of DEGs revealed that they might affect FCR by modulating genes associated with salivary secretion, ferroptosis, and mineral absorption. Moreover, values for relative humidity (RH), air velocity (AV), PM 2.5 , ammonia (NH 3 ), and carbon dioxide (CO 2 ) in the LFCR group were significantly lower than those in the HFCR group (P < 0.05). Conversely, value for light intensity (LI) in the LFCR group was significantly higher than that in the HFCR group (P < 0.05). Correlation analysis revealed a positive correlation between FCR and RH, AV, PM 2.5 , NH 3 , and CO 2 , and a negative correlation with LI. Finally, the FCR prediction model was successfully constructed based on multiple environmental variables using the random forest algorithm, providing a valuable tool for predicting FCR in chickens., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The dose effect of radiation has long been a topic of concern, but the molecular mechanism behind it is still unclear. In this study, dried pea seeds were irradiated with 252 Cf fission neutron source. Through analyzing the transcriptome and proteome of M 1 generation pea (Pisum sativum L.) leaves, we studied the molecular rule and mechanism of neutron dose effect. Our results showed three important rules of global gene expression in the studied dose range. The rule closely related to the neutron absorbed dose at the transcription and translation levels is: the greater the difference in neutron absorbed dose between two radiation treatment groups, the greater the difference in differential expression between the two groups and the control group. We also obtained important sensitive metabolic pathways of neutron radiation, as well as related key genes. Furthermore, the overall molecular regulation mechanism of dose effect was revealed based on the main functional items obtained. Our research results can be applied to appropriate radiation dose estimation and agricultural production practice., Competing Interests: Declaration of competing interest No conflicts of interest exist., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The aim of this work was to investigate the therapeutic effect of modified Shisiwei Jianzhong Decoction (SJD) on aplastic anemia (AA) and its potential pharmacological mechanism from the perspective of mitophagy. A comprehensive approach combining network pharmacology, mendelian randomization, molecular docking and animal experiments was applied to evaluate the properties of SJD against AA. By integrating multiple databases, it was determined that SJD exerted its therapeutic effect on AA by targeting three key targets [mammalian target of rapamycin (MTOR), poly(ADP-ribose) polymerase 1 (PARP1) and Sirtuin 1 (SIRT1)] through four core compounds (quercetin, resveratrol, genistein and curcumin). Mendelian randomization analysis identified MTOR as a risk factor for AA occurrence while PARP1 was a protective factor. Results of animal experiments showed that SJD improved peripheral blood counts and promoted the proliferation of hematopoietic stem cells. Mechanistically, SJD, especially at high dose, played a therapeutic role in AA by activating mitophagy-related proteins PTEN induced kinase 1 (PINK1)/Parkin and inhibiting the phosphatidylinositol 3-kinase (PI3K)/protein kinase (AKT)/MTOR pathway. This study revealed for the first time the core chemical composition of SJD and its pharmacological effects against AA, which can restore hematopoietic function by activating mitophagy. The results provide inspiration for the clinical application of traditional Chinese medicine in AA treatment., (© 2024 John Wiley & Sons Ltd.)

The dried rhizomes of Paris yunnanensis Franch. have been extensively utilized in traditional Chinese medicine as hemostatic, antitumor, and antimicrobial agents. An examination of classical texts and renowned Chinese medical formulations showcased its efficacy in acne treatment. Presently, there is a significant scarcity of Paris resources. Consider directing attention towards the non-medicinal parts of Paris to mitigate the strain on medicinal resources within this realm. To address these resource limitations, this study investigated the bioactivity and pharmacodynamics of the above-ground parts of Paris (AGPP). A synergistic approach integrating network pharmacology, molecular docking (in silico validation), and animal experimentation (in vivo validation) was employed to elucidate the potential mechanisms underlying the efficacy of AGPP against acne vulgaris in this study. The active constituents in AGPP extracts were identified via UHPLC-Q-Orbitrap HRMS analysis, with their targets extracted for network pharmacological analysis. KEGG pathway analysis unveiled potential therapeutic mechanisms, validated through molecular docking and rat auricular acne model experiments. Comprehensive chemical characterization revealed fifty constituents, including steroidal saponins, flavonoids, amino acids, organic acids, phytohormones, phenolic acids, and alkaloids. Diosgenin, Quercetin, Kaempferol, Ecdysone, and α-linolenic acid were identified as main constituents with acne-treating potential. Core targets included SRC, MAPK3, and MAPK1, with key signaling pathways implicated. Histologically, AGPP mitigated acne-induced follicular dilatation and inflammation, inhibiting inflammatory cytokine production (IL-6, IL-1β, TNF-α). This study offers insight into AGPP's mechanism for acne treatment, laying groundwork for Paris development and drug discovery., Competing Interests: Declaration of competing interest The authors declare that they have no competing personal or financial interests., (Copyright © 2024. Published by Elsevier B.V.)

Portal hypertensive gastropathy (PHG) is a serious complication and the most common gastric mucosal injury amongst patients afflicted with cirrhotic or non-cirrhotic portal hypertension (PHT). The pathogenesis of PHG is not completely understood and is likely to be complex. The roles of portal hypertension pressure, parenchymal liver disease, Child-Pugh classification, variceal pressure and Helicobacter pylori infection in the development of PHG are controversial. Splanchnic blood flow, the distribution of mucosal blood, vascular ectasia, local disturbances, inflammatory cell infiltration and increased cytokine production have also been examined to elucidate the underlying mechanisms of PHG. Moreover, various other elements, including prostaglandin E 2 (PGE 2 ), endothelin-1 (ET-1), tumour necrosis factor-α (TNF-α), Fas ligand (FasL)/Fas, nitric oxide (NO), oxygen free radicals and vascular endothelial growth factor (VEGF), have also been revealed to participate in the pathogenesis of PHG. This review provides an overview of the risk factors, classification and potential molecular processes involved in PHG, followed by a concise summary of our and other studies. This review aims to integrate information to deepen our understanding of the interplay between different signalling pathways involved the pathogenesis of PHG and provides insights into how these signalling pathways are regulated to control the development of PHG., 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 Masson SAS. All rights reserved.)

Lycium barbarum L. is of great significance medicinal and edible plant, which is native to N. & Central China. The extensive health benefits of L. barbarum have earned it great respect in traditional medicine for centuries. Lycium barbarum polysaccharides (LBPs) being recognized as one of the most crucial bioactive compounds found within this plant, with it exhibit a diverse range of pharmacological activities and nutritional functions, thereby generating substantial market demand and broad application prospects. To gain a more comprehensive understanding of LBPs, the review discussed the extraction, purification and structural-property relationships of these compounds. In addition, this review provides a comprehensive summary of the potential mechanisms underlying various biological activities attributed to LBPs, including immune modulation, antioxidant effects, neuroprotection, hepatoprotection, and antitumor properties. The application status and the future research directions of LBPs were subsequently presented. This review will establish a robust foundation and serve as an invaluable resource for future research and advancements in the field of LBPs., 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.)

Biotechnology provides alternatives for regenerative medicine with more controllable functions. Herein, the polypeptides encoded with human collagen I amino-acid sequences were studied for the first time to modulate biomimetic hydroxyapatite (HAP). With a length of 50-100 nm and a width of 20-30 nm, the HAP crystal formed was plate-like. The interaction of the human collagen sequence polypeptide on the (001), (100), and (211) crystal faces of HAP crystal had been studied using Molecular Dynamics (MD) simulations, respectively. Based on MD simulations, van der Waals forces and hydrogen bonds are the main interactions between polypeptides and HAP through the -NH 2 , -CH 2 -, -OH, and -COOH, respectively. According to the calculated results, der Waals forces might be the main interaction. The human collagen sequence polypeptides exhibited the highest adsorption energy on the (001) plane of HAP, significantly higher than any of the adsorption energy on the (100) and (211) planes. Therefore, the growth of the (001) would be inhibited, which kept accurate with the result of images from the Transmission Electron Microscope (TEM). Study results provide a basis for rational designing of peptides with human collagen sequences to regenerate hard tissues., 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.)

Algal polysaccharide is an important food functional factor with diverse bioactive and low toxicity. Previous studies have confirmed Caulerpa chemnitzia polysaccharides (CRVP) have immunomodulatory activity, but the immunomodulatory mechanism of CRVP in macrophages has not been thoroughly explored yet. In our research, we found that CRVP has outstanding immunomodulatory activity in macrophages, which is reflected in promoting cell proliferation, upregulating cytokines (IL-1β, IL-6, and TNF-α) expression, and increasing NO and ROS levels. Additionally, the result of joint analysis of untargeted metabolomics showed metabolism played a major role in the immunomodulatory of CRVP and suggested succinic acid was a key metabolite. Further verification indicated that the accumulation of succinic acid in macrophages after administered with CRVP, induced the down-regulation of prolyl hydroxylase domain 2 (PHD2) and up-regulation of hypoxia-inducible factor-1α (HIF-1α), thereby enhancing IL-1β expression. Together, the immunomodulatory activity of CRVP in macrophages via succinate/PHD2/HIF-1α/IL-1β pathway., 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. All authors state that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Glaucoma, as an ischemia-reperfusion (I/R) injury disease, leading irreversible blindness through the loss of retinal ganglion cells (RGCs), mediated by various pathways. Resveratrol (Res) is a polyphenolic compound that exerts protective effects against I/R injury in many tissues. This article aimed to expound the underlying mechanisms through which Res protects RGCs and reduces visual dysfunction in vivo. An experimental glaucoma model was created using 6-8-week wild-type male C57BL/6J mice. Res was injected intraperitoneally for 5 days. The mice were then grouped according to the number of days after surgery and whether Res treatment was administered. We applied the Brn3a-labeled immunofluorescence staining and flash electroretinography (ERG) to assess the survival of RGCs and visual function. The expression of components of the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome, the interleukin-1-beta (IL-1β), and vital indicators of kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme-oxygenase 1 (HO-1) pathway at the protein and RNA levels were detected respectively. The survival of RGCs was reduced after surgery compared to controls, whereas Res application rescued RGCs and improved visual dysfunction. In conclusion, our results discovered that Res administration showed neuroprotective effects through inhibition of the NLRP3 inflammasome pathway and activation of Keap1/Nrf2/HO-1 pathway. Thus, we further elucidated the potential of Res in glaucoma therapy., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

AIDS is a serious disease with impaired immune function caused by human immunodeficiency virus (HIV) infection. The treatment of AIDS has always been the focus of global scientific research, and Tat protein is a key regulatory protein in the process of HIV infection. Its high expression is closely related to virus replication, disease progression, etc. The aim of this study is to explore the molecular mechanism of regulating Tat protein expression by using network pharmacology based traditional Chinese medicine for calming the liver and detoxifying. 129 AIDS patients were enrolled in the study and randomly divided into HAART combined with PGJDP treatment and HAART alone treatment groups. The virological response rate, immunological response status (CD4 + T cell level, CD4/CD8) and incidence of abnormal liver function were observed before and 48 weeks after treatment. Using the TCMSP database to obtain the chemical components and targets of the main traditional Chinese medicine components in PGJDP, clinical results indicate that the combination of HAART and PGJDP treatment can improve the virological response rate (P > 0.05); Increase the number of CD4 + T lymphocytes (P > 0.05); Significantly increased CD4/CD8 ratio (P < 0.01); Simultaneously, it significantly reduced the incidence of liver dysfunction (P < 0.01). After screening and analysis, the Chinese herbal medicine for calming liver and detoxifying has the potential to significantly regulate the expression of Tat protein. These Chinese herbal compounds can reduce the expression of Tat protein by affecting key pathways and regulating the expression of related genes, which has potential therapeutic effects on the treatment of AIDS., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Crocin, a natural bioactive compound derived from saffron (Crocus sativus) and other Crocus genera, has gained significant attention recently due to its potential therapeutic properties. The multifaceted nature of crocin's biological effects has piqued the interest of researchers and health enthusiasts, prompting further investigations into its mechanisms of action and therapeutic applications. This review article comprehensively explores the emerging evidence supporting crocin's role as a promising ally in protecting against metabolic disorders. The review covers the molecular mechanisms underlying crocin's beneficial effects and highlights its potential applications in preventing and treating diverse pathological conditions. Understanding the mechanisms through which crocin exerts its protective effects could advance scientific knowledge and offer potential avenues for developing novel therapeutic interventions. As we uncover the potential of crocin as a valuable ally in the fight against disorders, it becomes evident that nature's palette holds remarkable solutions for enhancing our health., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The molecular mechanism of the formation of protein corona by the interaction of gold nanorods (AuNRs) with fibrinogen and transferrin was studied by spectroscopic methods and molecular docking. Studies have shown that AuNRs can be used as quencher to quench the fluorescence of fibrinogen/transferrin. The quenching mechanism mainly comes from static quenching. Fibrinogen has two different binding sites on the longitudinal and the transverse plane of AuNRs respectively, while transferrin has only one binding site on the surface of AuNRs. The adsorption process conforms to Freundlich adsorption isotherm and the pseudo-second-order reaction. The chemisorption is the rate-limiting step. Fibrinogen/transferrin may be a component of the "hard corona" because they bind AuNRs with high binding affinity. The formation of protein corona leads to a decrease in the hydrophobicity of the microenvironment around transferrin tryptophan (Trp) residues and an increase in the hydrophobicity of the microenvironment around fibrinogen/transferrin tyrosine (Tyr) residues, affecting the tertiary and secondary structure of fibrinogen/transferrin. Molecular docking can clearly see the specific amino acid residues of fibrinogen and transferrin adsorbed on AuNRs, and verify the experimental results., 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.)

The connections between cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) is critical in cancer initiation, progression, metastasis, and therapy resistance, making it a focal point in cancer theragnosis. This review provides a panorama of associations and regulation pathways between CSCs and EMT, highlighting their significance in cancer. The molecular mechanisms underlined EMT are thoroughly explored, including the involvement of key transcription factors and signaling pathways. In addition, the roles of CSCs and EMT in tumor biology and therapy resistance, is further examined in this review. The clinical implications of CSCs-EMT interplay are explored, including identifying mesenchymal-state CSC subpopulations using advanced research methods and developing targeted therapies such as inhibitors and combination treatments. Overall, understanding the reciprocal relationship between EMT and CSCs holds excellent potential for informing the development of personalized therapies and ultimately improving patient outcomes., 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. The reviewer declared a shared parent affiliation with the authors JW, YL, ZC, LZ, SF, YL, YP to the handling editor at the time of review., (Copyright © 2024 Lei, Teng, Koya, Liu, Chen, Zeng, Chen, Fang, Wang, Liu and Pan.)

The therapy for breast cancer (BC), to date, still needs improvement. Apart from traditional therapy methods, biological therapy being explored opens up a novel avenue for BC patients. Integrin β1 (ITGβ1), one of the largest subgroups in integrin family, is a key player in cancer evolution and therapy. Recent researches progress in the relationship of ITGβ1 level and BC, finding that ITGβ1 expression evidently concerns BC progression. In this chapter, we outline diverse ITGβ1-based mechanisms regarding to the promoted effect of ITGβ1 on BC cell structure rearrangement and malignant phenotype behaviors, the unfavorable patient prognosis conferred by ITGβ1, BC therapy tolerance induced by ITGβ1, and lastly novel inhibitors targeting ITGβ1 for BC therapy. As an effective biomarker, ITGβ1 undoubtedly emerges one of targeted-therapy opportunities of BC patients in future. It is a necessity focusing on scientific and large-scale clinical trials on the validation of targeted-ITGβ1 drugs for BC patients., (© 2024. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

Aim: To delineate the RNA-5-methylcytosine (m5C) modification of breast cancer brain metastasis (BCBM). Methods: Methylated RNA immunoprecipitation next-generation sequencing (MeRIP-seq) was performed to obtain RNA-m5C patterns of BCBM. Results: 1048 hypermethylation and 1866 hypomethylation m5C peaks were identified in BCBM compared with those in breast cancer. The most significant m5C hypermethylated genes included ENG, SHANK1, IGFN1, EVL and MMP9, whereas the most significant m5C hypomethylated genes included AREG, SAA2, TP53I11, KRT7 and LCN2. MeRIP-qPCR data were concordant with the corresponding MeRIP-seq results in terms of the observed m5C levels. Conjoint analysis identified 190 hyper-up genes characterized by concurrent m5C hypermethylation and up-regulation, alongside 284 hypo-down genes exhibiting both m5C hypomethylation and down-regulation. Conclusion: This study presents the first comprehensive analysis of RNA-m5C modification in BCBM.

Lung cancer remains an intractable malignancy worldwide, prompting novel therapeutic modalities. Pyroptosis, a lethal form of programmed cell death featured by inflammation, has been involved in cancer progression and treatment response. Simultaneously, non-coding RNA has been shown to have important roles in coordinating pattern formation and oncogenic pathways, including long non-coding RNA (lncRNAs), microRNA (miRNAs), circular RNA (circRNAs), and small interfering RNA (siRNAs). Recent studies have revealed that ncRNAs can promote or inhibit pyroptosis by interacting with key molecular players such as NLRP3, GSDMD, and various transcription factors. This dual role of ncRNAs offers a unique therapeutic potential to manipulate pyroptosis pathways, providing opportunities for innovative cancer treatments. In this review, we integrate current research findings to propose novel strategies for leveraging ncRNA-mediated pyroptosis as a therapeutic intervention in lung cancer. We explore the potential of ncRNAs as biomarkers for predicting patient response to treatment and as targets for overcoming resistance to conventional therapies., 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 GmbH. All rights reserved.)

Wheat is the most widely grown crop in the world; its production is severely disrupted by increasing water deficit. Plant roots play a crucial role in the uptake of water and perception and transduction of water deficit signals. In the past decade, the mechanisms of drought tolerance have been frequently reported; however, the transcriptome and metabolome regulatory network of root responses to water stress has not been fully understood in wheat. In this study, the global transcriptomic and metabolomics profiles were employed to investigate the mechanisms of roots responding to water stresses using the drought-tolerant (DT) and drought-susceptible (DS) wheat genotypes. The results showed that compared with the control group, wheat roots exposed to polyethylene glycol (PEG) had 25941 differentially expressed genes (DEGs) and more upregulated genes were found in DT (8610) than DS (7141). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the DEGs of the drought-tolerant genotype were preferably enriched in the flavonoid biosynthetic process, anthocyanin biosynthesis and suberin biosynthesis. The integrated analysis of the transcriptome and metabolome showed that in DT, the KEGG pathways, including flavonoid biosynthesis and arginine and proline metabolism, were shared by differentially accumulated metabolites (DAMs) and DEGs at 6 h after treatment (HAT) and pathways including alanine, aspartate, glutamate metabolism and carbon metabolism were shared at 48 HAT, while in DS, the KEGG pathways shared by DAMs and DEGs only included arginine and proline metabolism at 6 HAT and the biosynthesis of amino acids at 48 HAT. Our results suggest that the drought-tolerant genotype may relieve the drought stress by producing more ROS scavengers, osmoprotectants, energy and larger roots. Interestingly, hormone signaling plays an important role in promoting the development of larger roots and a higher capability to absorb and transport water in drought-tolerant genotypes.