Genomic and functional diversity of the human-derived isolates of Faecalibacterium.

Introduction: Faecalibacterium is one of the most abundant bacteria in the gut microbiota of healthy adults, highly regarded as a next-generation probiotic. However, the functions of Faecalibacterium genomes from cultured strains and the distribution of different species in populations may differ among different sources. Methods: We here performed an extensive analysis of pan-genomes, functions, and safety evaluation of 136 Faecalibacterium genomes collected from 10 countries. Results: The genomes are clustered into 11 clusters, with only five of them were characterized and validly nomenclated. Over 80% of the accessory genes and unique genes of Faecalibacterium are found with unknown function, which reflects the importance of expanding the collection of Faecalibacterium strains. All the genomes have the potential to produce acetic acid and butyric acid. Nine clusters of Faecalibacterium are found significantly enriched in the healthy individuals compared with patients with type II diabetes.. Discussion: This study provides a comprehensive view of genomic characteristic and functions and of culturable Faecalibacterium bacterium from human gut, and enables clinical advances in the future.

Epidemiologic features and therapeutic strategies of kerion: A nationwide multicentre study.

BACKGROUND: Kerion is a severe type of tinea capitis that is difficult to treat and remains a public health problem. OBJECTIVES: To evaluate the epidemiologic features and efficacy of different treatment schemes from real-world experience. METHODS: From 2019 to 2021, 316 patients diagnosed with kerion at 32 tertiary Chinese hospitals were enrolled. We analysed the data of each patient, including clinical characteristics, causative pathogens, treatments and outcomes. RESULTS: Preschool children were predominantly affected and were more likely to have zoophilic infection. The most common pathogen in China was Microsporum canis. Atopic dermatitis (AD), animal contact, endothrix infection and geophilic pathogens were linked with kerion occurrence. In terms of treatment, itraconazole was the most applied antifungal agent and reduced the time to mycological cure. A total of 22.5% of patients received systemic glucocorticoids simultaneously, which reduced the time to complete symptom relief. Furthermore, glucocorticoids combined with itraconazole had better treatment efficacy, with a higher rate and shorter time to achieving mycological cure. CONCLUSIONS: Kerion often affects preschoolers and leads to serious sequelae, with AD, animal contact, and endothrix infection as potential risk factors. Glucocorticoids, especially those combined with itraconazole, had better treatment efficacy.

Heterologous SARS-CoV-2 booster vaccine for individuals with hematological malignancies after a primary SARS-CoV-2 mRNA vaccine series.

Heterologous COVID-19 vaccine boosters have not been evaluated for patients with hematological malignancies. A Novavax booster was administered for 56 individuals with hematological malignancies who had received a primary COVID-19 series and prior boosters with mRNA vaccines only. Blood specimens were obtained at baseline (pre-vaccine), 28 days, and 168 days after vaccination with the Novavax booster. The median fold change of anti-Spike IgG was 1.02 (IQR 0.79, 1.3) between baseline and Day 28. Circulating Spike protein-specific B cells increased 1.4-fold at Day 28 (p < 0.05). Increases in antibody and T cell responses were modest without significance, with a waning of humoral and cellular responses at 168 days after vaccination.

Iterative Design of Near-Infrared Fluorescent Probes for Early Diagnosis of Alzheimer's Disease by Targeting Aß Oligomers.

Amyloid-ß oligomers (AßOs), crucial toxic proteins in early Alzheimer's disease (AD), precede the formation of Aß plaques and cognitive impairment. In this context, we present our iterative process for developing novel near-infrared fluorescent (NIRF) probes specifically targeting AßOs, aimed at early AD diagnosis. An initial screening identified compound 18 as being highly selective for AßOs. Subsequent analysis revealed that compound 20 improved serum stability while retaining affinity for AßOs. The most promising iteration, compound 37, demonstrated exceptional qualities: a high affinity for AßOs, emission in the near-infrared region, and good biocompatibility. Significantly, ex vivo double staining indicated that compound 37 detected AßOs in AD mouse brain and in vivo imaging experiments showed that compound 37 could differentiate between 4-month-old AD mice and age-matched wild-type mice. Therefore, compound 37 has emerged as a valuable NIRF probe for early detection of AD and a useful tool in exploring AD's pathological mechanisms.

Puerarin-containing rhein-crosslinked tyramine-modified hyaluronic acid hydrogel for antibacterial and anti-inflammatory wound dressings.

Wound infections, posing a grave risk of severe physical consequences and even mortality, exact a substantial financial toll on society, rendering them among the most formidable challenges confronting our world today. A critical imperative is the development of hydrogel dressings endowed with immune-regulating and antibacterial properties. This study is founded upon the symbiotic physical and efficacious attributes of two small natural molecules. An injectable hydrogel is meticulously crafted by encapsulating puerarin (PUE) into tyramine-modified hyaluronic acid, subsequently introducing rhein (RHE), and catalyzing the formation of inter-phenol crosslinks with H2O2/horseradish peroxidase (HA-Tyr-R@P). Exhibiting a favorable microenvironmental impact the developed hydrogel attains an antibacterial efficacy exceeding 95 %, coupled with a wound closure rate twice that of the control group. HA-Tyr-R@P hydrogels not only inhibit bacterial growth but also mitigate inflammation, fostering wound healing, owing to their harmonized physicochemical characteristics and synergistic therapeutic effects. This work underscores the creation of a singular, versatile hydrogel platform, negating the complexities and side effects associated with pharmaceutical preparations. Furthermore, it offers new ideas for the formulation of RHE-based hydrogels for wound healing, emphasizing the pivotal role of natural small molecules in advancing biological materials.

A review on decoding the roles of YAP/TAZ signaling pathway in cardiovascular diseases: Bridging molecular mechanisms to therapeutic insights.

Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) serve as transcriptional co-activators that dynamically shuttle between the cytoplasm and nucleus, resulting in either the suppression or enhancement of their downstream gene expression. Recent emerging evidence demonstrates that YAP/TAZ is strongly implicated in the pathophysiological processes that contribute to cardiovascular diseases (CVDs). In the cardiovascular system, YAP/TAZ is involved in the orchestration of a range of biological processes such as oxidative stress, inflammation, proliferation, and autophagy. Furthermore, YAP/TAZ has been revealed to be closely associated with the initiation and development of various cardiovascular diseases, including atherosclerosis, pulmonary hypertension, myocardial fibrosis, cardiac hypertrophy, and cardiomyopathy. In this review, we delve into recent studies surrounding YAP and TAZ, along with delineating their roles in contributing to the pathogenesis of CVDs with a link to various physiological processes in the cardiovascular system. Additionally, we highlight the current potential drugs targeting YAP/TAZ for CVDs therapy and discuss their challenges for translational application. Overall, this review may offer novel insights for understanding and treating cardiovascular disorders.

Oridonin, a small molecule inhibitor of cancer stem cell with potent cytotoxicity and differentiation potential.

Cancer stem cells (CSCs) drive malignant tumor progression, recurrence, and metastasis with unique characteristics, including self-renewal and resistance to conventional treatments. Conventional differentiation inducers, although promising, have limited cytotoxicity and may inadvertently enhance CSC stemness. To address these challenges, ongoing efforts are dedicated to developing strategies that can effectively combine both cytotoxicity and differentiation-inducing effects. In this study, we introduce oridonin (Ori), a small molecule with dual differentiation-inducing and cytotoxicity properties capable of eliminating tumor CSCs. We isolated CSCs in B16F10 cells using the Hoechst side population method and assessed the differentiation effect of Ori. Ori's differentiation-inducing effect was further evaluated using human acute promyelocytic leukemia. The cytotoxic potential of Ori against MCF-7 and B16F10 cell lines was assessed through various methods. In vivo anti-tumor and anti-CSC efficacy of Ori was investigated using mouse melanoma and CSCs melanoma models. Safety evaluation included zebrafish embryotoxicity and mouse acute toxicity experiments. As a result, Ori effectively dismantles tumorspheres, inhibits proliferation, and reduces the expression of CSC-specific markers. It induces significant differentiation, especially in the case of NB4. Additionally, Ori upregulates TP53 expression, mitigates the hypoxic tumor microenvironment, suppresses stemness, and inhibits PD-L1 expression, prompting a robust anti-cancer immune response. Ori demonstrates pronounced cytotoxicity, inducing notable pro-apoptotic effects on B16F10 and MCF-7 cells, with specific triggering of mitochondrial apoptosis. Importantly, Ori maintains a commendable biosafety record. The dual-action prowess of Ori not only induces the differentiation of CSCs but also dispatches differentiated and residual tumor cells, effectively thwarting the relentless march of tumor progression.

Diosmetin as a promising natural therapeutic agent: In vivo, in vitro mechanisms, and clinical studies.

Diosmetin, a natural occurring flavonoid, is primarily found in citrus fruits, beans, and other plants. Diosmetin demonstrates a variety of pharmacological activities, including anticancer, antioxidant, anti-inflammatory, antibacterial, metabolic regulation, cardiovascular function improvement, estrogenic effects, and others. The process of literature search was done using PubMed, Web of Science and ClinicalTrials databases with search terms containing Diosmetin, content, anticancer, anti-inflammatory, antioxidant, pharmacological activity, pharmacokinetics, in vivo, and in vitro. The aim of this review is to summarize the in vivo, in vitro and clinical studies of Diosmetin over the last decade, focusing on studies related to its anticancer, anti-inflammatory, and antioxidant activities. It is found that DIO has significant therapeutic effects on skin and cardiovascular system diseases, and its research in pharmacokinetics and toxicology is summarized. It provides the latest information for researchers and points out the limitations of current research and areas that should be strengthened in future research, so as to facilitate the relevant scientific research and clinical application of DIO.

Layer-dependent ultrafast carrier dynamics of PdSe2 investigated by photoemission electron microscopy.

For atomically thin two-dimensional materials, variations in layer thickness can result in significant changes in the electronic energy band structure and physicochemical properties, thereby influencing the carrier dynamics and device performance. In this work, we employ time- and energy-resolved photoemission electron microscopy to reveal the ultrafast carrier dynamics of PdSe2 with different layer thicknesses. We find that for few-layer PdSe2 with a semiconductor phase, an ultrafast hot carrier cooling on a timescale of approximately 0.3 ps and an ultrafast defect trapping on a timescale of approximately 1.3 ps are unveiled, followed by a slower decay of approximately tens of picoseconds. However, for bulk PdSe2 with a semimetal phase, only an ultrafast hot carrier cooling and a slower decay of approximately tens of picoseconds are observed, while the contribution of defect trapping is suppressed with the increase of layer number. Theoretical calculations of the electronic energy band structure further confirm the transition from a semiconductor to a semimetal. Our work demonstrates that TR- and ER-PEEM with ultrahigh spatiotemporal resolution and wide-field imaging capability has great advantages in revealing the intricate details of ultrafast carrier dynamics of nanomaterials.

Theoretical Insights into the Photophysical Properties of 4CzIPN Doped in Different Hosts: A Multiscale Study.

As a typical thermally activated delayed fluorescence (TADF) emitter with green emission, 4CzIPN has attracted much attention recently. Most studies indicated that 4CzIPN doped in different hosts presented different performances; thus, the hosts should have an obvious influence on its photophysical properties. Herein, the influence of four kinds of hosts, including m-CzPym, m-CzTrz, p-CzPym, and p-CzTrz, on the photophysical properties of 4CzIPN is investigated. Molecular dynamics simulations were performed to simulate the host-guest conformations, and the photophysical properties were studied using the combined quantum mechanics/molecular mechanics method coupled with the thermal-vibration correlation function method. It is found that 4CzIPN in doped films has larger transition dipole moments and spin-orbital coupling constants compared to that in nondoped films. Faster radiative decay, intersystem crossing rates, and higher fluorescence efficiency could be obtained in doped films. Our work helps to better understand the photophysical properties of 4CzIPN in doped films and may favor the design of new hosts.

Plant-derived flavonoids are a potential source of drugs for the treatment of liver fibrosis.

Liver fibrosis is a dynamic pathological process that can be triggered by any chronic liver injury. If left unaddressed, it will inevitably progress to the severe outcomes of liver cirrhosis or even hepatocellular carcinoma. In the past few years, the prevalence and fatality of hepatic fibrosis have been steadily rising on a global scale. As a result of its intricate pathogenesis, the quest for pharmacological interventions targeting liver fibrosis has remained a formidable challenge. Currently, no pharmaceuticals are exhibiting substantial clinical efficacy in the management of hepatic fibrosis. Hence, it is of utmost importance to expedite the development of novel therapeutics for the treatment of this condition. Various research studies have revealed the ability of different natural flavonoid compounds to alleviate or reverse hepatic fibrosis through a range of mechanisms, which are related to the regulation of liver inflammation, oxidative stress, synthesis and secretion of fibrosis-related factors, hepatic stellate cells activation, and proliferation, and extracellular matrix synthesis and degradation by these compounds. This review summarizes the progress of research on different sources of natural flavonoids with inhibitory effects on liver fibrosis over the last decades. The anti-fibrotic effects of natural flavonoids have been increasingly studied, making them a potential source of drugs for the treatment of liver fibrosis due to their good efficacy and biosafety.

Evaluating the effectiveness of echocardiographic guidance in diminishing postoperative wound complications for left atrial appendage closure: A clinical retrospective study.

Echocardiographic guidance in left atrial appendage (LAA) closure procedures is increasingly recognized for its potential to enhance patient outcomes in atrial fibrillation (AF). This retrospective study assesses its impact on hospital stay duration, readmission rates and surgical site wound complications in 200 AF patients. Divided equally into an echocardiographically guided group (Group E) and a non-guided group (Group N), the analysis focused on detailed patient data encompassing hospital stay, 30-day readmission and wound complications. Findings revealed that Group E experienced a significantly shorter average hospital stay of 3.5 days, compared with 6.5 days in Group N, along with a lower 30-day readmission rate (5% vs. 18% in Group N). Furthermore, Group E showed a considerable reduction in surgical site wound complications, such as infections and hematomas. The study concludes that echocardiographic guidance in LAA closure procedures markedly improves postoperative wound outcomes, underscoring its potential as a standard practice in cardiac surgeries for AF patients. This approach not only optimizes patient safety and postoperative recovery but also enhances healthcare resource utilization.

Triglyceride to high-density lipoprotein cholesterol ratio associated with long-term adverse clinical outcomes in patients deferred revascularization following fractional flow reserve.

BACKGROUND: Guidelines on coronary intermediate lesions strongly recommend deferred revascularization after detecting a normal fractional flow reserve (FFR). Researches about triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) on cardiovascular diseases has also been well conducted. However, the association of TG/HDL-C and long-term adverse clinical outcomes remains unknown for patients deferred revascularization following FFR. METHODS: This study retrospectively included 374 coronary artery disease (CAD) patients with non-significant coronary lesions diagnosed by coronary angiography (CAG) and FFR. The main outcome measure was the combination of major adverse cardiovascular and cerebrovascular events (MACCEs). All patients were categorized into three subgroups in terms of TG/HDL-C tertiles (T1 < 0.96, 0.96 ≤ T2 < 1.58, T3 ≥ 1.58). Three different Cox regression models were utilized to reveal the association between TG/HDL-C and prevalence of MACCEs. RESULTS: 47 MACCEs were recorded throughout a median monitoring period of 6.6 years. The Kaplan-Meier survival curves showed a higher MACCEs rate occurred in the higher TG/HDL-C group (5.6% vs. 12.9% vs. 19.4%, log-rank P < 0.01). After adjustment, patients in T3 suffered a 2.6-fold risk compared to the T1 group (T3 vs. T1: HR 2.55, 95% CI 1.05-6.21, P = 0.038; T2 vs. T1: HR 1.71, 95% CI 0.65-4.49, P = 0.075; P for trend = 0.001). The restricted cubic spline (RCS) analysis demonstrated that the HR for MACCEs rose as TG/HDL-C increased. Both the receiver operating characteristic (ROC) and time-dependent ROC proved the excellent predictive ability of TG/HDL-C. CONCLUSION: The study illustrates that TG/HDL-C correlates with the risk of MACCEs in CAD patients deferred revascularization following FFR. TG/HDL-C could serve as a dependable predictor of cardiovascular events over the long term in this population.

Hierarchically Ordered Pore Engineering of Metal-Organic Framework-Based Materials for Electrocatalysis.

Ordered pore engineering that embeds uniform pores with periodic alignment in electrocatalysts opens up a new avenue for achieving further performance promotion. Hierarchically ordered porous metal-organic frameworks (HOP-MOFs) possessing multilevel pores with ordered distribution are the promising precursors for the exploration of ordered porous electrocatalysts, while the scalable acquisition of HOP-MOFs with editable components and adjustable pore size regimes is critical. This review presents recent progress on hierarchically ordered pore engineering of MOF-based materials for enhanced electrocatalysis. The synthetic strategies of HOP-MOFs with different pore size regimes, including the self-assembly guided by reticular chemistry, surfactant, nanoemulsion, and nanocasting, are first introduced. Then the applications of HOP-MOFs as the precursors for exploring hierarchically ordered porous electrocatalysts are summarized, selecting representatives to highlight the boosted performance. Especially, the intensification of molecule and ion transport integrated with optimized electron transfer and site exposure over the hierarchically ordered porous derivatives are emphasized to clarify the directional transfer and integration effect endowed by ordered pore engineering. Finally, the remaining scientific challenges and an outlook of this field are proposed. It is hoped that this review will guide the hierarchically ordered pore engineering of nanocatalysts for boosting the catalytic performance and promoting the practical applications.

Chronic Mucocutaneous Candidiasis Due to STAT1 Gene Variant.

This case report describes a man in his 40s who presented with a 5-month history of recurrent pruritic papular erythema with mild scaling on the face, left forearm, and groin.

Association of altitude and frailty in Chinese older adults: using a cumulative frailty index model.

Objective: The population is aging exponentially and the resulting frailty is becoming increasingly evident. We aimed to explore the association between altitude and frailty, and to identify associated factors for frailty. Methods: This is a community-based cross-sectional survey. 1,298 participants aged ≥60 years from three different altitudes were included in the study. To quantify frailty, we constructed a frailty index (FI) and a frailty score (FS). The FI was divided into non-frailty, prefrailty, and frailty. The Odds Ratios and confidence intervals (ORs, 95%CIs) were used to evaluate the association between altitude and FI and FS in multivariate ordinal logistic regression and linear regression. Results: There were 560 (53.1%) participants in the prefrailty and 488 (37.6%) in the frailty group. The FS increased with higher altitude (P for trend <0.001). Multivariate ordinal logistic regression analysis revealed an association between altitude and frailty, OR = 1.91 (95% CI: 1.38-2.64) in mid-high altitude and 2.49 (95% CI:1.40-4.45) in high altitude. The same trend of association was found in the univariate analysis. The FS increased by 1.69 (95% CI: 0.78-2.60) at mid-high altitude and 3.24 (95%CI:1.66-4.81) at high altitude compared to medium altitude. Conclusion: The study indicates that high altitude exposure is an associated factor for frailty in older adults. This association become stronger with higher altitudes. As a result, it is essential to conduct early frailty screening for residents living at high altitudes.