Distributions of candidate vaccine Targets, virulence Factors, and resistance features of invasive group B Streptococcus using Whole-Genome Sequencing: A Multicenter, population-based surveillance study.

BACKGROUND: Group B Streptococcus (GBS) is a leading cause of morbidity and mortality in young infants worldwide. This study aimed to investigate candidate GBS vaccine targets, virulence factors, and antimicrobial resistance determinants. METHODS: We used whole-genome sequencing to characterize invasive GBS isolates from infants < 3 months of age obtained from a multicenter population-based study conducted from 2015 to 2021 in China. RESULTS: Overall, seven serotypes were detected from 278 GBS isolates, four (Ia, Ib, III, V) of which accounted for 97.8 %. We detected 30 sequence types (including 10 novel types) that were grouped into six clonal complexes (CCs: CC1, CC10, CC17, CC19, CC23 and CC651); three novel ST groups in CC17 were detected, and the rate of CC17, considered a hyperinvasive neonatal clone complex, was attached to 40.6 % (113/278). A total of 98.9 % (275/278) of isolates harbored at least one alpha-like protein gene. All GBS isolates contained at least one of three pilus backbone determinants and the pilus types PI-2b and PI-1 + PI-2a accounted for 79.8 % of the isolates. The 112 serotype III/CC17 GBS isolates were all positive for hvgA. Most of the isolates (75.2 %) were positive for serine-rich repeat glycoprotein determinants (srr1or srr2). Almost all isolates possessed cfb (99.6 %), c1IE (100 %), lmb (95.3 %) or pavA (100 %) gene. Seventy-seven percent of isolates harboured more than three antimicrobial resistance genes with 28.4 % (79/278) gyrA quinoloneresistancedeterminants mutation, 83.8 % (233/278) carrying tet cluster genes and 77.3 % (215/278) carrying erm genes which mediated fluoroquinolone, tetracycline and clindamycin resistance, respectively." CONCLUSIONS: The findings from this large whole-genome sequence of GBS isolates establish important baseline data required for further surveillance and evaluating the impact of future vaccine candidates.

Heavy Metal Removal from Wastewater Using Poly(Gamma-Glutamic Acid)-Based Hydrogel.

The removal of toxic heavy metal ions from wastewater is of great significance in the protection of the environment and human health. Poly(gamma-glutamic acid) (PGA) is a non-toxic, biodegradable, and highly water-soluble polymer possessing carboxyl and imino functional groups. Herein, water-insoluble PGA-based hydrogels were prepared, characterized, and investigated as heavy metal adsorbents. The prepared hydrogels were recyclable and exhibited good adsorption effects on heavy metal ions including Cu2+, Cr6+, and Zn2+. The effects of adsorption parameters including temperature, solution pH, initial concentration of metal ions, and contact time on the adsorption capacity of the hydrogel for Cu2+ were investigated. The adsorption was a spontaneous and exothermic process. The process followed the pseudo-first-order kinetic model and Langmuir isotherm model, implying a physical and monolayer adsorption. The adsorption mechanisms investigation exhibited that Cu2+ adsorbed on the hydrogel via electrostatic interactions with anionic carboxylate groups of PGA in addition to the coordination interactions with the -NH groups. Importantly, the PGA hydrogel exhibited good reusability and the adsorption capability for Cu2+ remained high after five consecutive cycles. The properties of PGA hydrogel make it a potential candidate material for heavy metal ion removal in wastewater treatment.

Cuproptosis in glioblastoma: unveiling a novel prognostic model and therapeutic potential.

Glioblastoma, a notably aggressive brain tumor, is characterized by a brief survival period and resistance to conventional therapeutic approaches. With the recent identification of "Cuproptosis," a copper-dependent apoptosis mechanism, this study aimed to explore its role in glioblastoma prognosis and potential therapeutic implications. A comprehensive methodology was employed, starting with the identification and analysis of 65 cuproptosis-related genes. These genes were subjected to differential expression analyses between glioblastoma tissues and normal counterparts. A novel metric, the "CP-score," was devised to quantify the cuproptosis response in glioblastoma patients. Building on this, a prognostic model, the CP-model, was developed using Cox regression techniques, designed to operate on both bulk and single-cell data. The differential expression analysis revealed 31 genes with distinct expression patterns in glioblastoma. The CP-score was markedly elevated in glioblastoma patients, suggesting an intensified cuproptosis response. The CP-model adeptly stratified patients into distinct risk categories, unveiling intricate associations between glioblastoma prognosis, immune response pathways, and the tumor's immunological environment. Further analyses indicated that high-risk patients, as per the CP-model, exhibited heightened expression of certain immune checkpoints, suggesting potential therapeutic targets. Additionally, the model hinted at the possibility of personalized therapeutic strategies, with certain drugs showing increased efficacy in high-risk patients. The CP-model offers a promising tool for glioblastoma prognosis and therapeutic strategy development, emphasizing the potential of Cuproptosis in cancer treatment.

The Effects of a Healthy Lifestyle on Depressive Symptoms in Older Chinese Adults: The Mediating Role of Psychological Resilience.

Objectives This study aimed to validate the interrelationships and potential pathways of influence between healthy lifestyles, psychological resilience, and depressive symptoms in the Chinese elderly population. Methods We utilized data from the Chinese Elderly Health Influential Factors Tracking Survey 2018 and included 9448 samples for the study after screening according to the qualifying conditions. The interrelationships among healthy lifestyles, psychological resilience and depressive symptoms were analyzed using stepwise regression, and the robustness of mediation effects was assessed using Sobel and Bootstrap test. Results Among Chinese older adults, healthy lifestyles were negatively associated with depressive symptoms (ß = -0.310, 95% CI: -0.405, -0.215), positively associated with psychological resilience (ß = 0.137, 95% CI:0.071, 0.023), and psychological resilience was negatively associated with depressive symptoms (ß = -1.014, 95% CI: -1.037, -0.990). Conclusions Psychological resilience partially mediated the association between healthy lifestyles and depressive symptoms, with the mediating effect accounting for 44.8% of the total effect. Our study contributes to the understanding of the relationship between healthy lifestyles and depressive symptoms in the elderly population and emphasizes the important role of psychological resilience. It is recommended that the government and policymakers improve depressive symptoms among older adults through comprehensive measures such as promoting healthy lifestyles and education, providing psychological support services, and creating a favorable environment.

Multidimensional Frailty Instruments Can Predict Acute Exacerbations Within One Year in Patients with Stable Chronic Obstructive Pulmonary Disease: A Retrospective Longitudinal Study.

Background: Chronic obstructive pulmonary disease (COPD) is closely associated with frailty, and prevention of acute exacerbations is important for disease management. Moreover, COPD patients with frailty experience a higher risk of acute exacerbations. However, the frailty instruments that can better predict acute exacerbations remain unclear. Purpose: (1) To explore the factors influencing frailty and acute exacerbations in stable COPD patients, and (2) quantify the ability of multidimensional frailty instruments to predict acute exacerbations within 1 year. Patients and methods: In this retrospective longitudinal study, stable COPD patients were recruited from the outpatient department of Sichuan Provincial People's Hospital from July 2022 to June 2023. COPD patients reviewed their frailty one year ago and their acute exacerbations within one year using face-to-face interviews with a self-developed frailty questionnaire. Frailty status was assessed using the Frailty Index (FI), frailty questionnaire (FRAIL), and Clinical Frailty Scale (CFS). One-way logistic regression was used to explore the factors influencing frailty and acute exacerbations. Multivariate logistic regression was used to establish a prediction model for acute exacerbations, and the accuracy of the three frailty instruments was compared by measuring the area under the receiver operating characteristic curve (AUC). Results: A total of 120 individuals were included. Frailty incidence estimates using FI, FRAIL, and CFS were 23.3%, 11.7%, and 15.8%, respectively. The three frailty instruments showed consistency in COPD assessments (P<0.05). After adjusting for covariates, frailty reflected by the FI and CFS score remained an independent risk factor for acute exacerbations. The CFS score was the best predictor of acute exacerbations (AUC, 0.764 (0.663-0.866); sensitivity, 57.9%; specificity, 80.0%). Moreover, the combination of CFS plus FRAIL scores was a better predictor of acute exacerbations (AUC, 0.792 (0.693-0.891); sensitivity, 86.3%; specificity, 60.0%). Conclusion: Multidimensional frailty assessments could improve the identification of COPD patients at high risk of acute exacerbations and facilitate targeted interventions to reduce acute exacerbations in these patients.

Developing a machine learning model for accurate nucleoside hydrogels prediction based on descriptors.

Supramolecular hydrogels derived from nucleosides have been gaining significant attention in the biomedical field due to their unique properties and excellent biocompatibility. However, a major challenge in this field is that there is no model for predicting whether nucleoside derivative will form a hydrogel. Here, we successfully develop a machine learning model to predict the hydrogel-forming ability of nucleoside derivatives. The optimal model with a 71% (95% Confidence Interval, 0.69-0.73) accuracy is established based on a dataset of 71 reported nucleoside derivatives. 24 molecules are selected via the optimal model external application and the hydrogel-forming ability is experimentally verified. Among these, two rarely reported cation-independent nucleoside hydrogels are found. Based on their self-assemble mechanisms, the cation-independent hydrogel is found to have potential applications in rapid visual detection of Ag+ and cysteine. Here, we show the machine learning model may provide a tool to predict nucleoside derivatives with hydrogel-forming ability.

Analysis of preoperative and postoperative depression and anxiety in patients with osteochondral lesions of the talus.

Purpose: This study aims to investigate the psychological status of patients with Hepple V osteochondral lesions of the talus (OLT) and evaluate the effect of autologous osteoperiosteal transplantation (AOPT) on their psychological well-being. Methods: Fifty patients with Hepple V OLT who underwent AOPT at the Comprehensive Foot and Ankle Surgery Ward of Xi'an Honghui Hospital from November 2021 to May 2023 were included in this study. The patients were divided into two groups based on the presence or absence of preoperative symptoms of anxiety/depression. Group A comprised patients with preoperative symptoms, while Group B included patients without such symptoms. Preoperative and final follow-up assessments included the Hospital Anxiety and Depression Scale for evaluating anxiety and depression, the visual analogue scale for pain assessment, and the American Orthopaedic Foot and Ankle Society scores for assessing ankle and hindfoot function. Results: Among the 50 Hepple V OLT patients who obtained complete follow-up, twenty-four had preoperative symptoms of anxiety/depression, with an incidence rate of up to 48%. Patients in Groups A and B showed significant improvement in all evaluation indexes after AOPT compared to the preoperative period, but the overall prognosis of Group A was poorer than that of Group B. Conclusion: AOPT can effectively improve patients' pain, functional activities, and psychological status, and there is a significant correlation between patients' preoperative psychological status and prognosis.

Resveratrol Delays Diabetic Cardiomyopathy Fibrosis by Regulating Mitochondrial Autophagy.

Objective: To explore whether resveratrol can postpone the fibrosis associated with diabetic cardiomyopathy (DCM) by modulating the mitochondrial autophagy response through the AMPK/SIRT1-mediated IRE1α/PINK signaling pathway. Methods: A DCM mouse model was established using a high-sugar high-fat diet and streptozotocin. Resveratrol was administered to a subset of the DCM mouse models for comparison. Echocardiography, Masson staining, TNUEL assay, and transmission electron microscopy were employed to evaluate the cardiac status, myocardial fibrosis, myocardial cell apoptosis, and morphological changes of myocardial cells and their internal mitochondria in each group of mice. Western blot staining was performed on myocardial tissues to assess the protein expression levels of p-AMPK, SIRT1, SIRT3, p22, GP91, p-IRE1α, XBP1s PINK, Parkin, LC3I, and Beclin. Mouse myocardial cells were cultured in vitro and intervened with a high-sugar high-fat diet, resveratrol, and GSK690693 (an AMPK inhibitor) to observe the protein expression levels of p-AMPK, p22, XBP1s, and PINK in mouse myocardial cells in each group. Results: Results from echocardiography, Masson staining, TNUEL assay, and transmission electron microscopy showed that resveratrol administration alleviated cardiac damage, myocardial fibrosis, myocardial cell apoptosis, and mitochondrial autophagy in DCM mice. Resveratrol administration promoted the expression of phosphorylated AMP-activated protein kinase (p-AMPK), sirtuin 1 (SIRT1), and sirtuin 3 (SIRT3) in the myocardial tissue of mice, while lowering the elevated protein expression levels of p22 subunit (p22), guanine nucleotide-binding protein q polypeptide 1 (GP91), phosphorylated inositol-requiring enzyme 1 alpha (p-IRE1α), X-box binding protein 1 spliced form (XBP1s), PTEN-induced putative kinase 1 (PINK), Parkin, microtubule-associated proteins light chain 3 isoform I (LC3I), and Beclin (Bcl-2 interacting protein) caused by DCM. GSK690693 (an AMPK inhibitor) suppressed the expression of p-AMPK, SIRT1, and SIRT3 and enhanced the protein expression of p22, XBP1s, and PINK. Conclusion: Resveratrol postpones dilated cardiomyopathy fibrosis by regulating the mitochondrial autophagy response through the AMP-activated protein kinase (AMPK)/silent mating type information regulation 2 homolog 1 (SIRT1)-mediated inositol-requiring enzyme 1 alpha (IRE1α)/PTEN-induced putative kinase 1 (PINK) signaling pathway.

The Idesia polycarpa genome provides insights into its evolution and oil biosynthesis.

The deciduous tree Idesia polycarpa can provide premium edible oil with high polyunsaturated fatty acid contents. Here, we generate its high-quality reference genome, which is ∼1.21 Gb, comprising 21 pseudochromosomes and 42,086 protein-coding genes. Phylogenetic and genomic synteny analyses show that it diverged with Populus trichocarpa about 16.28 million years ago. Notably, most fatty acid biosynthesis genes are not only increased in number in its genome but are also highly expressed in the fruits. Moreover, we identify, through genome-wide association analysis and RNA sequencing, the I. polycarpa SUGAR TRANSPORTER 5 (IpSTP5) gene as a positive regulator of high oil accumulation in the fruits. Silencing of IpSTP5 by virus-induced gene silencing causes a significant reduction of oil content in the fruits, suggesting it has the potential to be used as a molecular marker to breed the high-oil-content cultivars. Our results collectively lay the foundation for breeding the elite cultivars of I. polycarpa.

A double-layer thin oral film for wet oral mucosa adhesion and efficient treatment of oral ulcers.

Oral ulceration (OU), a prevalent oral mucosal condition causing significant pain and hindering eating and speaking, adversely impacts the patient's quality of life. Topical medications are preferred for their minimal side effects and convenient administration. However, existing formulations generally present discomfort and insufficient drug retention due to the thick formulations and poor adhesion, which considerably restrict their therapeutic effectiveness. In this study, a thin and lightweight double-layer oral film based on FDA approved excipients with excellent adhesion under wet oral conditions and outstanding biocompatibility is successfully developed by a simple method. It consists of an adhesive layer for anchoring in situ to delivery drugs and a hydrophobic layer to isolate the saliva for unidirectional drug delivery. The double-layer oral film with extremely thin appearance (only 0.11 mm thick) offers excellent adhesion (up to 150 min on an SD rat oral ulceration), which was also matched with its drug release time (87.47% release in 2 h). Animal experiments confirmed that the double-layer oral film carrying dexamethasone sodium phosphate achieved satisfactory efficacy in the SD rat oral ulcer model. Hence, this biologically friendly double-layer thin oral film holds great promise for clinical application in topical drug therapy for oral mucosal conditions.

Living Synthelectronics: A New Era for Bioelectronics Powered by Synthetic Biology.

Bioelectronics, which converges biology and electronics, has attracted great attention due to their vital applications in human-machine interfaces. While traditional bioelectronic devices utilize nonliving organic and/or inorganic materials to achieve flexibility and stretchability, a biological mismatch is often encountered because human tissues are characterized not only by softness and stretchability but also by biodynamic and adaptive properties. Recently, a notable paradigm shift has emerged in bioelectronics, where living cells, and even viruses, modified via gene editing within synthetic biology, are used as core components in a new hybrid electronics paradigm. These devices are defined as "living synthelectronics," and they offer enhanced potential for interfacing with human tissues at informational and substance exchange levels. In this Perspective, the recent advances in living synthelectronics are summarized. First, opportunities brought to electronics by synthetic biology are briefly introduced. Then, strategic approaches to designing and making electronic devices using living cells/viruses as the building blocks, sensing components, or power sources are reviewed. Finally, the challenges faced by living synthelectronics are raised. It is believed that this paradigm shift will significantly contribute to the real integration of bioelectronics with human tissues.

GhCOL2 Positively Regulates Flowering by Activating the Transcription of GhHD3A in Upland Cotton (Gossypium hirsutum L.).

Plants have evolved sophisticated signaling networks to adjust flowering time, ensuring successful reproduction. Two crucial flowering regulators, FLOWERING LOCUS T (FT) and CONSTANS (CO), play pivotal roles in regulating flowering across various species. Previous studies have indicated that suppressing Gossypium hirsutum CONSTANS-LIKE 2 (GhCOL2), a homolog of Arabidopsis CO, leads to delayed flowering in cultivated cotton. However, the underlying regulatory mechanisms remain unknown. In this study, a yeast one-hybrid and dual-LUC expression assays were used to elucidate the molecular mechanism through which GhCOL2 regulates the transcription of GhHD3A. RT-qPCR was used to examine the expression of GhCOL2 and GhHD3A. Our findings reveal that GhCOL2 directly binds to CCACA cis-elements and atypical CORE (TGTGTATG) cis-elements in the promoter regions of HEADING DATE 3 A (HD3A), thereby activating GhHD3A transcription. Notably, GhCOL2 and GhHD3A exhibited high expression levels in the adult stage and low levels in the juvenile stage. Interestingly, the expression of GhCOL2 and GhHD3A varied significant between the two cotton varieties (Tx2094 and Maxxa). In summary, our study enhances the understanding of the molecular mechanism by which cotton GhCOL2-GhHD3A regulates flowering at the molecular level. Furthermore, it contributes to a broader comprehension of the GhCOL2-GhHD3A model in G. hirsutum.

Carbon Nanofibrous Aerogels Derived from Electrospun Polyimide for Multifunctional Piezoresistive Sensors.

The fabrication of carbon aerogels with ultralow density, high electrical conductivity, and ultraelasticity still remains substantial challenges. This study utilizes electrospun polyimide aerogel as the source to fabricate flexible carbon nanofibrous aerogel (PI-CNA) capable of multifunctional applications. The lightweight PI-CNA based piezoresistive sensor shows a wide linear range (0-217 kPa), rapid response/recovery time, and fatigue resistance (12,000 cycles). More importantly, the superior pressure sensing enables the PI-CNA for all-range healthcare sensing, including pulse monitoring, physiological activity detection, speech recognition, and gait recognition. Moreover, the EMI SE and the A coefficient of the PI-CNA reach 45 dB and 0.62, respectively, indicating the outstanding absorption dominated EMI shielding effects due to the multiple reflections and absorption. Furthermore, PI-CNA exhibits satisfying Joule heating performance up to 120 °C with rapid response time (10-30 s) under low supply voltages (1.5-5 V) and possesses sufficient heating reliability and repeatability in long-term repeated heating/cooling cycles. The fabricated PI-CNA shows significant potential applications in wearable technologies, energy conversion, electronic skin, and artificial intelligence.

Flexible and stretchable implantable devices for peripheral neuromuscular electrophysiology.

The peripheral nervous and muscular system, a cornerstone of human physiology, plays a pivotal role in ensuring the seamless functioning of the human body. This intricate network, comprising nerves and muscles extending throughout the body, is essential for motor control, sensory feedback, and the regulation of autonomic bodily functions. The qualified implantable peripheral interface can accurately monitor the biopotential of the target tissue and conduct treatment with stimulation, enhancing the human-machine interaction and new achievements in disease cure. Implantable electrodes have revolutionized the field of neuromuscular interfaces, offering precise bidirectional communication between the neuromuscular system and external devices. They enable natural control for individuals with limb loss, bridging the gap between mind and machine and aiding neuromuscular rehabilitation. In research and medical diagnostics, implantable electrodes provide invaluable tools for studying neuromuscular function and the development of therapies. However, traditional rigid electrodes face challenges due to the dynamic nature of the peripheral neuromuscular system. Flexible and stretchable devices show immense promise in accommodating dynamic alterations, offering adaptability, and accurate monitoring of electrophysiological signals. This review delves into the challenges associated with the peripheral interface, primarily focusing on monitoring and stimulation. It then provides a summary of common materials and structural design optimizations, discusses technologies for enhancing interface adhesion and surface functionalization, and explores encapsulation methods for implanted devices. Recent advancements in energy supply and the applications of implantable, flexible, and stretchable devices are also comprehensively reviewed, with due consideration given to ethical concerns and signal analysis. The promising directions are finally presented to provide enlightenment for high-performance sensor-tissue interfaces in the future, which will promote profound progress in clinical and human-machine interaction research. Flexible and stretchable devices are at the forefront of healthcare, with the potential to transform the treatment of neuromuscular disorders and enhance human augmentation, blurring the lines between natural and artificial limbs. They represent a promising avenue for the future, with exciting applications in healthcare, science, and technology, promising to bring us closer to the seamless integration of human and machine in the realm of neuromuscular interfaces.

Food Security and Health Outcomes following Gray Divorce.

The study evaluates the immediate and long-term consequences of gray divorce (i.e., marital dissolution after age 50) for the food security, depression, and disability of older Americans. Staggered Difference-in-Difference models were fitted to a nationally representative longitudinal sample of adults aged ≥ 50 years from the Health and Retirement Study, 1998-2018. Food insecurity and disability increase in the year of gray divorce and remain significantly elevated for up to six years or more following the event, consistent with the chronic strain model of gray divorce. Gray divorce has particularly adverse consequences for the food security of older women, while no gender differences were observed for disability. Increasing trends in gray divorce have important negative implications for food security and health of older Americans, particularly women, who appear to be less prepared to financially withstand a marital collapse in older age. Targeted policies to provide nutrition assistance and support in reemployment might be necessary to reduce the burden of food insecurity in the wake of gray divorce among women.

Aß-binding with alcohol dehydrogenase drives Alzheimer's disease pathogenesis: A review.

Although Alzheimer's disease (AD) characterized with senile plaques and neurofibrillary tangles has been found for over 100 years, its molecular mechanisms are ambiguous. More worsely, the developed medicines targeting amyloid-beta (Aß) and/or tau hyperphosphorylation did not approach the clinical expectations in patients with moderate or severe AD until now. This review unveils the role of a vicious cycle between Aß-derived formaldehyde (FA) and FA-induced Aß aggregation in the onset course of AD. Document evidence has shown that Aß can bind with alcohol dehydrogenase (ADH) to form the complex of Aß/ADH (ABAD) and result in the generation of reactive oxygen species (ROS) and aldehydes including malondialdehyde, hydroxynonenal and FA; in turn, ROS-derived H2O2 and FA promotes Aß self-aggregation; subsequently, this vicious cycle accelerates neuron death and AD occurrence. Especially, FA can directly induce neuron death by stimulating ROS generation and tau hyper hyperphosphorylation, and impair memory by inhibiting NMDA-receptor. Recently, some new therapeutical methods including inhibition of ABAD activity by small molecules/synthetic polypeptides, degradation of FA by phototherapy or FA scavengers, have been developed and achieved positive effects in AD transgenic models. Thus, breaking the vicious loop may be promising interventions for halting AD progression.

Midbrain FA initiates neuroinflammation and depression onset in both acute and chronic LPS-induced depressive model mice.

Both exogenous gaseous and liquid forms of formaldehyde (FA) can induce depressive-like behaviors in both animals and humans. Stress and neuronal excitation can elicit brain FA generation. However, whether endogenous FA participates in depression occurrence remains largely unknown. In this study, we report that midbrain FA derived from lipopolysaccharide (LPS) is a direct trigger of depression. Using an acute depressive model in mice, we found that one-week intraperitoneal injection (i.p.) of LPS activated semicarbazide-sensitive amine oxidase (SSAO) leading to FA production from the midbrain vascular endothelium. In both in vitro and in vivo experiments, FA stimulated the production of cytokines such as IL-1ß, IL-6, and TNF-α. Strikingly, one-week microinfusion of FA as well as LPS into the midbrain dorsal raphe nucleus (DRN, a 5-HT-nergic nucleus) induced depressive-like behaviors and concurrent neuroinflammation. Conversely, NaHSO3 (a FA scavenger), improved depressive symptoms associated with a reduction in the levels of midbrain FA and cytokines. Moreover, the chronic depressive model of mice injected with four-week i.p. LPS exhibited a marked elevation in the levels of midbrain LPS accompanied by a substantial increase in the levels of FA and cytokines. Notably, four-week i.p. injection of FA as well as LPS elicited cytokine storm in the midbrain and disrupted the blood-brain barrier (BBB) by activating microglia and reducing the expression of claudin 5 (CLDN5, a protein with tight junctions in the BBB). However, the administration of 30 nm nano-packed coenzyme-Q10 (Q10, an endogenous FA scavenger), phototherapy (PT) utilizing 630-nm red light to degrade FA, and the combination of PT and Q10, reduced FA accumulation and neuroinflammation in the midbrain. Moreover, the combined therapy exhibited superior therapeutic efficacy in attenuating depressive symptoms compared to individual treatments. Thus, LPS-derived FA directly initiates depression onset, thereby suggesting that scavenging FA represents a promising strategy for depression treatment.

ω-transaminase-catalyzed synthesis of (R)-2-(1-aminoethyl)-4-fluorophenol, a chiral intermediate of novel anti-tumor drugs.

The chiral amine (R)-2-(1-aminoethyl)-4-fluorophenol has attracted increasing attentions in recent years in the field of pharmaceuticals because of its important use as a building block in the synthesis of novel anti-tumor drugs targeting tropomyosin receptor kinases. In the present study, a ω-transaminase (ωTA) library consisting of 21 (R)-enantioselective enzymes was constructed and screened for the asymmetric biosynthesis of (R)-2-(1-aminoethyl)-4-fluorophenol from its prochiral ketone. Using (R)-α-methylbenzylamine, D-alanine, or isopropylamine as amino donor, 18 ωTAs were identified with target activity and the enzyme AbTA, which was originally identified from Arthrobacter sp. KNK168, was found to be a potent candidate. The E. coli whole cells expressing AbTA could be used as catalysts. The optimal temperature and pH for the activity were 35-40 °C and pH8.0, respectively. Simple alcohols (such as ethanol, isopropanol, and methanol) and dimethyl sulfoxide were shown to be good cosolvents. High activities were detected when using ethanol and dimethyl sulfoxide at the concentrations of 5-20%. In the scaled-up reaction of 1-liter containing 13 mM ketone substrate, about 50% conversion was achieved in 24 h. 6.4 mM (R)-2-(1-aminoethyl)-4-fluorophenol was generated. After a simple and efficient process of product isolation and purification (with 98.8% recovery), 0.986 g yellowish powder of the product (R)-2-(1-aminoethyl)-4-fluorophenol with high (R)-enantiopurity (up to 100% enantiomeric excess) was obtained. This study established an overall process for the biosynthesis of the high value pharmaceutical chiral amine (R)-2-(1-aminoethyl)-4-fluorophenol by ωTA. Its applicable potential was exemplified by gram-scale production.

The Association Between Blood Mercury and Lipid Biomarkers in US Hypertensive Adults.

Mercury (Hg) is detrimental to human health, but its impact on lipid biomarkers remains a subject of controversy. This study sought to delineate a clear link between blood Hg and lipid biomarkers correlated with cardiovascular disease (CVD), including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG), in hypertensive adults in the USA. METHODS: This cross-sectional research gathered data from a total of 4415 participants sourced from the National Health and Nutrition Examination Survey (NHANES). The Holm-Bonferroni stepdown procedure was utilized to control the type I error rate in multiple comparisons. We employed multivariable linear regression models to assess the correlation between blood Hg and lipid biomarkers. Subsequently, subgroup analyses were conducted, categorized by both gender and race. Additionally, we used smooth curve fittings and generalized additive models to confirm the presence of non-linear relationships. When non-linearity was detected, we applied a recursive algorithm to calculate the inflection points. Finally, we established a weighted two-piecewise linear regression model to illustrate the associations on either side of the inflection point. RESULTS: In our multivariable linear regression models, clear associations emerged. Specifically, positive correlations were observed between blood mercury and TC (ß = 0.025; 95% CI 0.009 to 0.041; corrected P = 0.011), LDL-C (ß = 0.022; 95% CI 0.007 to 0.036; corrected P = 0.012), and HDL-C (ß = 0.007; 95% CI 0.001 to 0.013; corrected P = 0.058). However, there was no significant correlation with TG (ß = - 0.007; 95% CI - 0.018 to 0.004; corrected P = 0.526). Notably, it has been demonstrated that distinct inverted U-shaped and U-shaped curves exist when stratified by gender in our analysis. CONCLUSIONS: Blood Hg exhibited a positive correlation with TC, LDL-C, and HDL-C in hypertensive adults in the USA. Nonetheless, no significant association was observed with TG.