Predictive value of the early postoperative hemoglobin-to-red blood cell distribution width ratio for acute kidney injury in elderly intertrochanteric fracture patients.

BACKGROUND: Hemoglobin-to-red blood cell distribution width ratio (HRR) had great predictive value for the prognosis of malignant tumors and cardiovascular disease. However, its predictive value for the occurrence of acute kidney injury (AKI) in elderly intertrochanteric fracture patients remains unclear. This study aims to analyze the correlation between the early postoperative HRR and the risk of postoperative AKI in elderly intertrochanteric fracture patients. METHODS: We reviewed the medical records of 307 elderly intertrochanteric fracture patients in this single-center retrospective cohort study. We performed univariate analysis on the relevant parameters, and parameters with significant differences were included in the following logistic regression model for multivariate analysis. Then, we used a receiver operating characteristic (ROC) curve to evaluate the predictive value of the early postoperative HRR level for AKI in elderly intertrochanteric fracture patients. Patients were divided into a high HRR group and a low HRR group according to the cutoff point determined by ROC curve analysis. Subsequently, the relevance between postoperative HRR and AKI was further determined using propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). RESULTS: The area under the curve of the early postoperative HRR for predicting postoperative AKI was 0.714 (95% CI: 0.618-0.809). The cutoff value was 5.44. The sensitivity was 72.7%, and the specificity was 70.8%. Patients were divided into low HRR (⩽ 5.44) and high HRR (> 5.44) groups according to the cutoff value. PSM and IPTW analysis indicated that the risk of AKI in the low HRR group was significantly higher than that in the high HRR group in both the matched cohort (OR = 6.914, 95% CI: 1.714-46.603, p = 0.016) and the weighted group (OR = 2.784, 95% CI: 1.415-5.811, p = 0.040). CONCLUSIONS: Early postoperative HRR is an accurate, accessible, and economical blood test parameter that can predict the risk of postoperative AKI in elderly patients with femoral intertrochanteric fracture.

Natural Gastrointestinal Stable Pea Albumin Nanomicelles for Capsaicin Delivery and Their Effects for Enhanced Mucus Permeability at Small Intestine.

Natural nanodelivery systems are highly desirable owing to their biocompatibility and biodegradability. However, these delivery systems face challenges from potential degradation in the harsh gastrointestinal environment and limitations imposed by the intestinal mucus barrier, reducing their oral delivery efficacy. Here, gastrointestinal stable and mucus-permeable pea albumin nanomicelles (PANs) with a small particle size (36.42 nm) are successfully fabricated via pre-enzymatic hydrolysis of pea albumin isolate (PAI) using trypsin. Capsaicin (CAP) is used as a hydrophobic drug model and loaded in PAN with a loading capacity of 20.02 µg/mg. PAN exhibits superior intestinal stability, with a 40% higher CAP retention compared to PAI in simulated intestinal digestion. Moreover, PAN displays unrestricted movement in intestinal mucus and can effectively penetrate it, since it increases the mucus permeability of CAP by 2.5 times, indicating an excellent ability to overcome the mucus barrier. Additionally, PAN enhances the cellular uptake and transcellular transport of CAP with endoplasmic reticulum/Golgi and Golgi/plasma membrane pathways involved in the transcytosis and exocytosis. This study suggests that partially enzymatically formed PAN may be a promising oral drug delivery system, effectively overcoming the harsh gastrointestinal environment and mucus barrier to improve intestinal absorption and bioavailability of hydrophobic bioactive substances.

Glycyrrhizic acid alleviates concanavalin A-induced acute liver injury by regulating monocyte-derived macrophages.

Autoimmune hepatitis (AIH) is characterized by persistent liver inflammation induced by aberrant immune responses. Glycyrrhizic acid (GA), a prominent bioactive ingredient of licorice, has shown potential as a safe and effective treatment for AIH. However, the immune regulatory mechanism by which GA exerts its therapeutic effect on AIH remains elusive. In this study, we found that GA intervention significantly alleviated ConA-induced acute liver injury in mice. Cytometry by time-of-flight (CyTOF) analysis revealed that GA increased the abundance of anti-inflammatory F4/80loCD11bhiMHCIIhi MoMF-1 and decreased the abundance of pro-inflammatory F4/80loCD11bhiiNOShi MoMF-3. Multiplex immunofluorescence demonstrated the infiltration of MoMFs in liver tissues. Single-cell RNA sequencing (scRNA-seq) analysis indicated that GA facilitated the immune activation in MoMFs, regulated gene expression of diverse cytokines secreted by MoMFs, and played a role in shaping the immune microenvironment. By integrating the results of CyTOF with scRNA-seq, our study comprehensively elucidates the immune landscape of ConA-induced liver injury following GA intervention, advancing the understanding of GA's mechanism of action. However, it is important to note that some single-cell data in this study remain raw and require further processing and annotation. Our findings suggest that GA alleviates ConA-induced acute liver injury by regulating the function of MoMFs, opening potential avenues for AIH treatment and management, and providing a theoretical basis for the design of novel MoMFs-centered immunotherapies.

miR-1915-3p regulates megakaryocytic and erythroid differentiation by targeting SOCS4.

BACKGROUND: Proper control of the lineage bias of megakaryocytic and erythroid progenitor cells (MEPs) is of significant importance, the disorder of which will lead to abnormalities in the number and function of platelets and erythrocytes. Unfortunately, the signaling pathways regulating MEP differentiation largely remain to be elucidated. This study aimed to analyze the role and the underlying molecular mechanism of miR-1915-3p in megakaryocytic and erythroid differentiation. METHODS: We utilized miRNA mimics and miRNA sponge to alter the expression of miR-1915-3p in megakaryocytic and/or erythroid potential cells; siRNA and overexpression plasmid to change the expression of SOCS4, a potential target of miR-1915-3p. The expression of relevant surface markers was detected by flow cytometry. We scanned for miR-1915-3p target genes by mRNA expression profiling and bioinformatic analysis, and confirmed the targeting by dual-luciferase reporter assay, western blot and gain- and lost-of-function studies. One-way ANOVA and t-test were used to analyze the statistical significance. RESULTS: In this study, overexpression or knockdown of miR-1915-3p inhibited or promoted erythroid differentiation, respectively. Accordingly, we scanned for miR-1915-3p target genes and confirmed that SOCS4 is one of the direct targets of miR-1915-3p. An attentive examination of the endogenous expression of SOCS4 during megakaryocytic and erythroid differentiation suggested the involvement of SOCS4 in erythroid/megakaryocytic lineage determination. SOCS4 knockdown lessened erythroid surface markers expression, as well as improved megakaryocytic differentiation, similar to the effects of miR-1915-3p overexpression. While SOCS4 overexpression resulted in reversed effects. SOCS4 overexpression in miR-1915-3p upregulated cells rescued the effect of miR-1915-3p. CONCLUSIONS: miR-1915-3p acts as a negative regulator of erythropoiesis, and positively in thrombopoiesis. SOCS4 is one of the key mediators of miR-1915-3p during the differentiation of MEPs.

Concurrent chemoradiotherapyof different radiation doses and different irradiation fields for locally advanced thoracic esophageal squamous cell carcinoma: A randomized, multicenter, phase III clinical trial.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). However, the optimal radiotherapy regimen, particularly in terms of total dose and planned range of irradiation field, remains unclear. This phase III clinical trial aimed to compare the survival benefits between different radiation doses and different target fields. METHODS: This trial compared two aspects of radiation treatment, total dose and field, using a two-by-two factorial design. The high-dose (HD) group received 59.4 Gy radiation, and the standard-dose (SD) group received 50.4 Gy. The involved field irradiation (IFI) group and elective nodal irradiation (ENI) group adopted different irradiation ranges. The participants were assigned to one of the four groups (HD+ENI, HD+IFI, SD+ENI and SD+IFI). The primary endpoint was overall survival (OS), and the secondary endpoints included progression-free survival (PFS). The synergy indexwas used to measure the interaction effect between dose and field. RESULTS: The interaction analysis did not reveal significant synergistic effects between the dose and irradiation field. In comparison to the target field, patients in IFI or ENI showed similar OS (hazard ratio [HR] = 0.99, 95% CI: 0.80-1.23, p = 0.930) and PFS (HR = 1.02, 95% CI: 0.82-1.25). The HD treatment did not show significantly prolonged OS compared with SD (HR = 0.90, 95% CI: 0.72-1.11, p = 0.318), but it suggested improved PFS (25.2 months to 18.0 months). Among the four groups, the HD+IFI group presented the best survival, while the SD+IFI group had the worst prognosis. No significant difference in the occurrence of severe adverse events was found in dose or field comparisons. CONCLUSIONS: IFI demonstrated similar treatment efficacy to ENI in CCRT of ESCC. The HD demonstrated improved PFS, but did not significantly improve OS. The dose escalation based on IFI (HD+IFI) showed better therapeutic efficacy than the current recommendation (SD+ENI) and is worth further validation.

Shared molecular signatures between systemic lupus erythematosus and osteoporosis.

This study explores the molecular interplay between systemic lupus erythematosus (SLE) and osteoporosis (OP), aiming to uncover shared gene signatures and pathways for better treatment approaches. Leveraging microarray data from the Gene Expression Omnibus (GEO) database, we employed weighted gene coexpression network analysis to identify coexpression modules in SLE and OP, with subsequent protein-protein interaction analysis clarifying the connections among shared genes. Key genes were pinpointed using CytoHubba and random forest algorithms, validated across independent GEO datasets, and further analyzed through gene set enrichment analysis (GSEA) and immune infiltration studies. We discovered two highly correlated modules in SLE and OP, isolating 30 shared genes and identifying GBP1, SOCS1, IFI16, and XAF1 as central to both conditions. Notably, XAF1 and GBP1 mRNA levels were significantly elevated in the peripheral blood of SLE patients compared with healthy and RA counterparts, underscoring their potential as biomarkers. GSEA and immune infiltration analyses indicated pronounced immune and inflammatory responses, especially in interferon signaling pathways, implicating these core-shared gene networks in the diseases' pathogenesis. The findings highlight the involvement of GBP1, SOCS1, IFI16, and XAF1 in SLE with concurrent OP and suggest that targeting immune and inflammatory responses, particularly through interferon pathways, may offer therapeutic promise for these intertwined conditions.

Disturbance alters soil organic carbon content and stability in Carex tussock wetland, Northeast China.

With the intensification of climate change and human activities, wetland ecosystem and their carbon pool function have been seriously compromised. To determine the soil organic carbon pool composition and stability response to wetland disturbance, three disturbed (grazing, mowing, invasion) and two undisturbed Carex tussock wetlands were investigated in Momoge Wetland, northeast China. The results showed that the disturbance significantly reduced the soil organic carbon content under hummock, but effectively promoted organic carbon storage in surface soil in hummock interspace. In disturbed wetlands, relative abundance of aromatic-C, asymmetric aliphatic-C, polysaccharide-C and clay minerals, and organic carbon stability significantly declined. Furthermore, asymmetric aliphatic-C and polysaccharide-C were the most important organic carbon chemical components affecting SOC stability under hummock and in hummock interspace. Disturbance facilitated the effects of pH, TP and minerals on organic carbon stability, with pH being the most important. These findings improved our understanding of the composition and stability of carbon pools in disturbed wetlands.

New insights into N2O emission and electron competition under different chemical oxygen demand to nitrogen ratios in a biofilm system.

Nitrous oxide (N2O) is a greenhouse gas that could accumulate during the heterotrophic denitrification process. In this study, the effects of different chemical oxygen demand to nitrogen ratio (COD/N) on N2O production and electron competition was investigated. The electron competition was intensified with the decrease of electron supply, and Nos had the best electron competition ability. The model simulation results indicated that the degradation of NOx-Ns was a combination of diffusion and biological degradation. As reaction proceeding, N2O could accumulate inside biofilm. A thinner biofilm and a longer hydraulic retention time (HRT) might be an effective way to control N2O emission. The application of mathematical model is an opportunity to gain deep understanding of substrate degradation and electron competition inside biofilm.

Incidental Learning of Collocations Under Different Input Modes and the Mediating Role of Perceptual Learning Style.

This study investigated how input modes (reading vs. listening) and learners' perceptual learning style (visual vs. auditory) affected the incidental learning of collocations. A total of 182 college students were first assigned to either a visual or auditory group based on their performance on a perceptual learning style questionnaire. Each style group was subsequently subdivided into three groups who were exposed to a series of texts containing unfamiliar collocation items under one of the input conditions: written input, aural input, or no input. Results of the study indicated that both written and aural input led to gains in collocational knowledge, and aural input was more effective than written input. Furthermore, the study provided empirical evidence that there was a moderating role of perceptual learning style on incidental collocation learning. The auditory learners under aural input showed the highest rate of collocation learning among all treatment subgroups.

Anionic Surfactant-Tailored Interfacial Microenvironment for Boosting Electrochemical CO2 Reduction.

Both the catalyst and electrolyte deeply impact the performance of the carbon dioxide reduction reaction (CO2RR). It remains a challenge to design the electrolyte compositions for promoting the CO2RR. Here, typical anionic surfactants, dodecylphosphonic acid (DDPA) and its analogues, are employed as electrolyte additives to tune the catalysis interface where the CO2RR occurs. Surprisingly, the anionic surfactant-tailored interfacial microenvironment enables a set of typical commercial catalysts for the CO2RR to deliver a significantly enhanced selectivity of carbon products in both neutral and acidic electrolytes. Mechanistic studies disclose that the DDPA addition restructures the interfacial hydrogen-bond environment via increasing the weak H-bonded water, thus promoting the CO2 protonation to CO. Specifically, in an H-type cell, the Faradaic efficiency of CO increases from 70 to 98% at -1.0 V versus the reversible hydrogen electrode. Furthermore, in a flow cell, the DDPA-containing electrolyte maintains over 90% FECO from 50-400 mA cm-2. Additionally, this electrolyte modulation strategy can be extended to acidic CO2RR with a pH of 1.5-3.5.

HEARTSVG: a fast and accurate method for identifying spatially variable genes in large-scale spatial transcriptomics.

Identifying spatially variable genes (SVGs) is crucial for understanding the spatiotemporal characteristics of diseases and tissue structures, posing a distinctive challenge in spatial transcriptomics research. We propose HEARTSVG, a distribution-free, test-based method for fast and accurately identifying spatially variable genes in large-scale spatial transcriptomic data. Extensive simulations demonstrate that HEARTSVG outperforms state-of-the-art methods with higher F 1 scores (average F 1 Score=0.948), improved computational efficiency, scalability, and reduced false positives (FPs). Through analysis of twelve real datasets from various spatial transcriptomic technologies, HEARTSVG identifies a greater number of biologically significant SVGs (average AUC = 0.792) than other comparative methods without prespecifying spatial patterns. Furthermore, by clustering SVGs, we uncover two distinct tumor spatial domains characterized by unique spatial expression patterns, spatial-temporal locations, and biological functions in human colorectal cancer data, unraveling the complexity of tumors.

Unmet Needs for Ancillary Services by Provider Type Among People With Diagnosed Human Immunodeficiency Virus.

Background: Unmet needs for ancillary services are substantial among people with human immunodeficiency virus (PWH), and provider type could influence the prevalence of unmet needs for these services. Methods: Data from a national probability sample of PWH were analyzed from the Centers for Disease Control and Prevention's Medical Monitoring Project. We analyzed 2019 data on people who had ≥1 encounter with a human immunodeficiency virus (HIV) care provider (N = 3413) and their care facilities. We assessed the proportion of needs that were unmet for individual ancillary services, overall and by HIV care provider type, including infectious disease (ID) physicians, non-ID physicians, nurse practitioners, and physician assistants. We calculated prevalence differences (PDs) with predicted marginal means to assess differences between groups. Results: An estimated 98.2% of patients reported ≥1 need for an ancillary service, and of those 46% had ≥1 unmet need. Compared with patients of ID physicians, needs for many ancillary services were higher among patients of other provider types. However, even after adjustment, patients of non-ID physicians had lower unmet needs for dental care (adjusted PD, -5.6 [95% confidence interval {CI}, -9.9 to -1.3]), and patients of nurse practitioners had lower unmet needs for HIV case management services (adjusted PD, -5.4 [95% CI, -9.4 to -1.4]), compared with patients of ID physicians. Conclusions: Although needs were greater among patients of providers other than ID physicians, many of these needs may be met by existing support systems at HIV care facilities. However, additional resources may be needed to address unmet needs for dental care and HIV case management among patients of ID physicians.

"Top-down" overexpression optimization of butelase-1 in Escherichia coli and its application in anti-tumor peptides.

Butelase-1, the fastest known Asn/Asp-specific peptide ligase capable of catalyzing peptide ligation and cyclization, holds promising application prospects in the fields of food and biology. However, limited research exists on its recombinant expression and potential applications in peptide drugs. In this study, the activity of recombinantly-produced butelase-1 was enhanced by co-expressing it with a molecular chaperone in the SHuffle T7 strain. By introducing single or multiple synonymous rare codons at the beginning of the coding regions of beta-strand or alpha-helix, in combination with ribosomal binding site engineering, the activity of butelase-1 could be further improved. Consequently, the butelase-1 with a specific activity of 386.93 U/mg and a catalytic efficiency of 11,048 M-1 s-1 was successfully prepared in E. coli, resulting in a total activity of 8183.54 U/L and a yield of about 100 mg/L. This optimized butelase-1 was then used to efficiently cyclize the redesigned anti-cancer peptide lunasin, leading to enhanced bioavailability and anti-cancer effects. Overall, this study not only provided valuable biotechnology strategies for improving the recombinant expression of butelase-1 but also demonstrated a successful application for enhancing the biological efficacy of anti-cancer peptides.

Exploring the Potential of Probiotics and Prebiotics in Major Depression: From Molecular Function to Clinical Therapy.

Major depressive disorder (MDD) represents a complex and challenging mental health condition with multifaceted etiology. Recent research exploring the gut-brain axis has shed light on the potential influence of gut microbiota on mental health, offering novel avenues for therapeutic intervention. This paper reviews current evidence on the role of prebiotics and probiotics in the context of MDD treatment. Clinical studies assessing the effects of prebiotic and probiotic interventions have demonstrated promising results, showcasing improvements in depression symptoms and metabolic parameters in certain populations. Notably, prebiotics and probiotics have shown the capacity to modulate inflammatory markers, cortisol levels, and neurotransmitter pathways linked to MDD. However, existing research presents varied outcomes, underscoring the need for further investigation into specific microbial strains, dosage optimization, and long-term effects. Future research should aim at refining personalized interventions, elucidating mechanisms of action, and establishing standardized protocols to integrate these interventions into clinical practice. While prebiotics and probiotics offer potential adjunctive therapies for MDD, continued interdisciplinary efforts are vital to harnessing their full therapeutic potential and reshaping the landscape of depression treatment paradigms.

Hierarchical Robust Generalized Nash Equilibrium Seeking of High-Order Uncertain Nonlinear Systems.

This article investigates the distributed generalized Nash equilibrium (GNE) seeking problem of noncooperative games (NGs) for high-order strict-feedback nonlinear multiagent systems (MASs). In particular, the feasible action set of each agent is not only subject to local set and inequality constraints but also coupled through an equality constraint with other agents. This constraint structure is more general and covers most of the constraints in the GNE seeking literature. To accomplish the concerned GNE seeking objective, we propose a novel hierarchical GNE seeking approach in this article to decouple the distributed GNE seeking algorithm design into two layers. First, we construct a distributed primary-dual GNE estimator to generate virtual reference signals that converge to the GNE. Then, with the output of the estimator as the reference signal, we develop an adaptive tracking controller to solve the resultant tracking problems under output constraints. To overcome the negative effects of the disturbances, novel compensating terms associated with smooth functions and positive integrable time-varying functions are incorporated in the controller design, which thereby realizes the exact GNE seeking in the presence of nonvanishing mismatched disturbances. At last, an example is given to support the theoretical analysis of the proposed algorithms.

Cortical functional mechanisms in emotional cognitive tasks in first-episode, drug-naïve with major depressive disorder: A fNIRS study.

BACKGROUND: Previous research has revealed that patients with major depressive disorder (MDD) have negative biases in various aspects of information processing, and these biases are mainly manifested in recognizing facial expressions. However, the link between this emotional cognitive inhibition and neural activation mechanisms in cortical brain regions remains poorly understood. Therefore, this study employed functional near-infrared spectroscopy (fNIRS) to explore the potential impaired regions and neural mechanisms associated with facial emotion cognition in MDD patients. METHODS: 37 MDD patients and 34 healthy controls (HC) were recruited to participate in three sets of cognitive tasks for emotion recognition, and the cortical activation in the brain was synchronously recorded using multi-channel fNIRS. RESULTS: During tasks requiring the motions identification of sad versus happy emotional states, MDD patients exhibit altered activation in both the left frontopolar cortex (FPC) and the right dorsolateral prefrontal cortex (DLPFC). Notably, the FPC demonstrates a higher level of internal coherence and broader correlation with other cortical areas. Moreover, MDD patients showed lower accuracy in distinguishing emotional cues associated with sadness versus those associated with neutral and happy emotions. LIMITATIONS: The study had a relatively small sample size, and it specifically examined only three prevalent facial expressions. CONCLUSION: Facial expression recognition in MDD patients is characterized by negative cognitive interpretation of expressions, which are associated with various cortical altered activations. Neuroimaging further suggests that the cognitive inhibition of emotion signal recognition in everyday interpersonal interactions in MDD patients may primarily be influenced by activation in the left FPC.

Extracellular vesicle surface display enhances the therapeutic efficacy and safety profile of cancer immunotherapy.

Immunotherapy has emerged as a mainstay in cancer therapy, yet its efficacy is constrained by the risk of immune-related adverse events. In this study, we present a nanoparticle-based delivery system that enhances the therapeutic efficacy of immunomodulatory ligands while concurrently limiting systemic toxicity. We demonstrate that extracellular vesicles (EVs), lipid bilayer enclosed particles released by cells, can be efficiently engineered via inverse electron demand Diels-Alder (iEDDA)-mediated conjugation to display multiple immunomodulatory ligands on their surface. Display of immunomodulatory ligands on the EV surface conferred substantial enhancements in signaling efficacy, particularly for tumor necrosis factor receptor superfamily (TNFRSF) agonists, where the EV surface display served as an alternative FcγR-independent approach to induce ligand multimerization and efficient receptor crosslinking. EVs displaying a complementary combination of immunotherapeutic ligands were able to shift the tumor immune milieu toward an anti-tumorigenic phenotype and significantly suppress tumor burden and increase survival in multiple models of metastatic cancer to a greater extent than an equivalent dose of free ligands. In summary, we present an EV-based delivery platform for cancer immunotherapeutic ligands that facilitates superior anti-tumor responses at significantly lower doses with fewer side effects than is possible with conventional delivery approaches.

Unraveling host-pathogen dynamics in a murine Model of septic peritonitis induced by vancomycin-resistant Enterococcus faecium.

Vancomycin-resistant Enterococcus faecium (E. faecium) infection is associated with higher mortality rates. Previous studies have emphasized the importance of innate immune cells and signalling pathways in clearing E. faecium, but a comprehensive analysis of host-pathogen interactions is lacking. Here, we investigated the interplay of host and E. faecium in a murine model of septic peritonitis. Following injection with a sublethal dose, we observed significantly increased murine sepsis score and histological score, decreased weight and bacterial burden, neutrophils and macrophages infiltration, and comprehensive activation of cytokine-mediated signalling pathway. In mice receiving a lethal dose, hypothermia significantly improved survival, reduced bacterial burden, cytokines, and CD86 expression of MHC-II+ recruited macrophages compared to the normothermia group. A mathematical model constructed by observational data from 80 animals, recapitulated the host-pathogen interplay, and further verified the benefits of hypothermia. These findings indicate that E. faecium triggers a severe activation of cytokine-mediated signalling pathway, and hypothermia can improve outcomes by reducing bacterial burden and inflammation.

Antimicrobial drugs for Parkinson's disease: Existing therapeutic strategies and novel drugs exploration.

Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by loss of dopaminergic neurons in the substantia nigra, as well as the abnormal accumulation of misfolded α-synuclein. Clinically, PD is featured by typical motor symptoms and some non-motor symptoms. Up to now, although considerable progress has been made in understanding the pathogenesis of PD, there is still no effective therapeutic treatment for the disease. Thus, exploring new therapeutic strategies has been a topic that needs to be addressed urgently. Noteworthy, with the proposal of the microbiota-gut-brain axis theory, antimicrobial drugs have received significant attention due to their effects on regulating the intestinal microbiota. Nowadays, there is growing evidence showing that some antimicrobial drugs may be promising drugs for the treatment of PD. Data from pre-clinical and clinical studies have shown that some antimicrobial drugs may play neuroprotective roles in PD by modulating multiple biochemical and molecular pathways, including reducing α-synuclein aggregation, inhibiting neuroinflammation, regulating mitochondrial structure and function, as well as suppressing oxidative stress. In this paper, we summarized the effects of some antimicrobial drugs on PD treatment from recent pre-clinical and clinical studies. Then, we further discussed the potential of a few antimicrobial drugs for treating PD based on molecular docking and molecular dynamics simulation. Importantly, we highlighted the potential of clorobiocin as the therapeutic strategy for PD owing to its ability to inhibit α-synuclein aggregation. These results will help us to better understand the potential of antimicrobial drugs in treating PD and how antimicrobial drugs may alleviate or reverse the pathological symptoms of PD.

Trifolium repens L. recruits root-associated Microbacterium species to adapt to heavy metal stress in an abandoned Pb-Zn mining area.

Root-associated microbiota provide great fitness to hosts under environmental stress. However, the underlying microecological mechanisms controlling the interaction between heavy metal-stressed plants and the microbiota are poorly understood. In this study, we screened and isolated representative amplicon sequence variants (strain M4) from rhizosphere soil samples of Trifolium repens L. growing in areas with high concentrations of heavy metals. To investigate the microecological mechanisms by which T. repens adapts to heavy metal stress in abandoned mining areas, we conducted potting experiments, bacterial growth promotion experiments, biofilm formation experiments, and chemotaxis experiments. The results showed that high concentrations of heavy metals significantly altered the rhizosphere bacterial community structure of T. repens and significantly enriched Microbacterium sp. Strain M4 was demonstrated to significantly increased the biomass and root length of T. repens under heavy metal stress. Additionally, L-proline and stigmasterol could promote bacterial growth and biofilm formation and induce chemotaxis for strain M4, suggesting that they are key rhizosphere secretions of T. repens for Microbacterium sp. recruitment. Our results suggested that T. repens adapted the heavy metal stress by reshaping rhizosphere secretions to modify the rhizosphere microbiota.