Endowing 1T'-ReS2 Nanosheets with Sonopiezoelectric Property by Theoretical-Guided Vacancy-Manipulated Peierls Distortion for Tumor Ferroptosis Therapy.

Sonopiezoelectric therapy harnesses piezoelectric materials to efficiently generate destructive reactive oxygen species when exposed to ultrasound. This innovative approach shows promise for tumor treatment by combining precise targeting of tumor sites through noninvasive ultrasound control with high reactive oxygen species generation capabilities via the piezoelectric effect. This study utilizes a theoretical-guided method to manipulate atomic vacancy defects and regulate the Peierls distortion in 1T'-ReS2 nanosheets, thereby imparting them with sonopiezoelectric properties not inherent to the original material. Furthermore, the plentiful unsaturated sites of ReS2 nanosheets endow them with excellent catalase- and peroxidase-mimicking activities. The reactive oxygen species generation by the engineered ReS2 nanosheets also leads to the depletion of glutathione. These capabilities are leveraged for tumor ferroptosis therapy via the classical pathway involving the 7-member 11-glutathione-GPX4 signaling axis, alongside the downregulation of dihydroorotate dehydrogenase and ferritin levels and the upregulation of fatty acid CoA ligase 4 expression. This showcases the innovative approach and potential applications of employing 1T'-ReS2 nanosheets in cancer treatment through theoretical design and materials engineering.

Spatiotemporally Controlled Photolabeling of Genetically Unmodified Proteins in Live Cells.

Selective labeling of the protein of interest (POI) in genetically unmodified live cells is crucial for understanding protein functions and kinetics in their natural habitat. In particular, spatiotemporally controlled installation of the labels on a POI under light control without affecting their original activity is in high demand but is a tremendous challenge. Here, we describe a novel ligand-directed photoclick strategy for spatiotemporally controlled labeling of endogenous proteins in live cells. It was realized with a designer labeling reagent skillfully integrating the photochemistries of 2-nitrophenylpropyloxycarbonyl and 3-hydroxymethyl-2-naphthol with an affinity ligand. Highly electrophilic ortho-naphthoquinone methide was photochemically released and underwent a proximity coupling reaction with nucleophilic amino acid residues on the POI in live cells. With fluorescein as a marker, this photoclick strategy enables time-resolved labeling of carbonic anhydrase subtypes localized either on the cell membrane or in the cytoplasm and a discriminable visualization of their metabolic kinetics. Given the versatility underlined by facilely tethering other functional entities (e.g., biotin, a peptide short chain) via acylation or (in cell) Huisgen cycloaddition, this affinity-driven photoclick chemistry opens up enormous opportunities for discovering dynamic functions and mechanistic interrogation of endogenous proteins in live cells.

Topical application of phenformin ameliorates the psoriasis-like inflammatory response via the inhibition of c-Myc expression in keratinocytes.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease characterized by a complex pathogenesis involving various types of cells and cytokines. Among those, the pro-inflammatory cytokine IL-23/IL-17A axis plays a crucial role in the development and rapid progression of psoriasis. Phenformin, a derivative of metformin and a member of the biguanide class of drugs, exhibits superior anti-inflammatory and anti-tumor efficacy compared to metformin. However, the potential role of phenformin in anti-psoriatic skin inflammation has not been explored. METHODS: In this study, we utilized a mouse model of psoriasis and an in vitro model using human keratinocytes to investigate whether phenformin can suppress psoriasis-like inflammatory responses. RESULTS: Our results demonstrate that the topical application of phenformin significantly inhibited acute skin inflammatory responses in the psoriasis mouse model induced by imiquimod (IMQ). Additionally, phenformin suppressed the expression of psoriasis-related cytokines IL-17, IL-23, IL-8, and S100A8/S100A9 in an in vitro psoriatic keratinocyte model induced by IMQ. Furthermore, we found that IMQ-induced psoriatic skin and IMQ-treated keratinocytes exhibited high expression of the c-Myc gene, which was downregulated by phenformin. The c-Myc inhibitor JQ1 similarly inhibited the psoriatic inflammatory response and the expression of psoriasis-related cytokines in both in vitro and in vivo models. CONCLUSION: phenformin ameliorates the psoriasis-like inflammatory response by inhibiting c-Myc expression in keratinocytes, suggesting its potential as a topical drug for the treatment of psoriasis.

Landscape of New Nuclease-Containing Antiphage Systems in Escherichia coli and the Counterdefense Roles of Bacteriophage T4 Genome Modifications.

Many phages, such as T4, protect their genomes against the nucleases of bacterial restriction-modification (R-M) and CRISPR-Cas systems through covalent modification of their genomes. Recent studies have revealed many novel nuclease-containing antiphage systems, raising the question of the role of phage genome modifications in countering these systems. Here, by focusing on phage T4 and its host Escherichia coli, we depicted the landscape of the new nuclease-containing systems in E. coli and demonstrated the roles of T4 genome modifications in countering these systems. Our analysis identified at least 17 nuclease-containing defense systems in E. coli, with type III Druantia being the most abundant system, followed by Zorya, Septu, Gabija, AVAST type 4, and qatABCD. Of these, 8 nuclease-containing systems were found to be active against phage T4 infection. During T4 replication in E. coli, 5-hydroxymethyl dCTP is incorporated into the newly synthesized DNA instead of dCTP. The 5-hydroxymethylcytosines (hmCs) are further modified by glycosylation to form glucosyl-5-hydroxymethylcytosine (ghmC). Our data showed that the ghmC modification of the T4 genome abolished the defense activities of Gabija, Shedu, Restriction-like, type III Druantia, and qatABCD systems. The anti-phage T4 activities of the last two systems can also be counteracted by hmC modification. Interestingly, the Restriction-like system specifically restricts phage T4 containing an hmC-modified genome. The ghmC modification cannot abolish the anti-phage T4 activities of Septu, SspBCDE, and mzaABCDE, although it reduces their efficiency. Our study reveals the multidimensional defense strategies of E. coli nuclease-containing systems and the complex roles of T4 genomic modification in countering these defense systems. IMPORTANCE Cleavage of foreign DNA is a well-known mechanism used by bacteria to protect themselves from phage infections. Two well-known bacterial defense systems, R-M and CRISPR-Cas, both contain nucleases that cleave the phage genomes through specific mechanisms. However, phages have evolved different strategies to modify their genomes to prevent cleavage. Recent studies have revealed many novel nuclease-containing antiphage systems from various bacteria and archaea. However, no studies have systematically investigated the nuclease-containing antiphage systems of a specific bacterial species. In addition, the role of phage genome modifications in countering these systems remains unknown. Here, by focusing on phage T4 and its host Escherichia coli, we depicted the landscape of the new nuclease-containing systems in E. coli using all 2,289 genomes available in NCBI. Our studies reveal the multidimensional defense strategies of E. coli nuclease-containing systems and the complex roles of genomic modification of phage T4 in countering these defense systems.

A Mycorrhiza-Induced UDP-Glucosyl Transferase Negatively Regulates the Arbuscular Mycorrhizal Symbiosis.

Most terrestrial plants can establish a reciprocal symbiosis with arbuscular mycorrhizal (AM) fungi to cope with adverse environmental stresses. The development of AM symbiosis is energetically costly and needs to be dynamically controlled by plants to maintain the association at mutual beneficial levels. Multiple components involved in the autoregulation of mycorrhiza (AOM) have been recently identified from several plant species; however, the mechanisms underlying the feedback regulation of AM symbiosis remain largely unknown. Here, we report that AM colonization promotes the flavonol biosynthesis pathway in tomato (Solanum lycopersicum), and an AM-specific UDP-glucosyltransferase SlUGT132, which probably has the flavonol glycosylation activity, negatively regulates AM development. SlUGT132 was predominantly expressed in the arbuscule-containing cells, and its knockout or knockdown mutants showed increased soluble sugar content, root colonization level and arbuscule formation. Conversely, overexpression of SlUGT132 resulted in declined soluble sugar content and mycorrhization degree. Metabolomic assay revealed decreased contents of astragalin, tiliroside and cynaroside in slugt132 mycorrhizal roots, but increased accumulation of these flavonoid glycosides in SlUGT132-overexpressing plant roots. Our results highlight the presence of a novel, SlUGT132-mediated AOM mechanism, which enable plants to flexibly control the accumulation of soluble sugars and flavonoid glycosides in mycorrhizal roots and modulate colonization levels.

Strip loaded waveguide amplifiers based on erbium-doped nanocomposites with 17†dB internal net gain.

We propose a strip loaded amplifier employing SU-8 as the loaded waveguide and nanoparticles (NPs)-polymethyl methacrylate (PMMA) as the cladding layer. By leveraging the undoped SU-8 loaded waveguide, the polymer waveguide amplifier accomplished remarkably low transmission losses, reaching as low as 1.8 dB/cm at 1530 nm. We prepared NPs-PMMA nanocomposite by utilizing NaLu0.1Y0.7F4: Er3+, Yb3+ @NaLuF4 core-shell nanoparticles, which exhibited a significantly enhanced lifetime of 6.15 ms. An internal net gain of up to 17.7 dB was achieved on a strip loaded waveguide with a length as short as 0.5 cm when the on-chip pump power was 77 mW. Signal enhancement (SE) was measured at different wavelengths, revealing that the strip loaded waveguide exhibited broadband SE ranging from 1510 nm to 1570 nm, covering the C-band. To the best of our knowledge, this work has achieved the highest gain results reported thus far on a polymer matrix and provides an efficient method for optical amplification in passive devices on silicon and Si3N4 platforms, leveraging the ease of integration of polymer materials with diverse photonic platforms.

IAIH-PG consensus for histological criteria of AIH: Multicentre validation with focus on chronic liver diseases in China.

BACKGROUND AND AIMS: The International AIH Pathology Group (IAIH-PG) put forward the new histological criteria of autoimmune hepatitis (AIH) in 2022, which have not undergone adequate verification. In this study, we verified the applicability of the new histological criteria in the population of Chinese patients with chronic liver disease, comparing it with the simplified criteria. METHODS: The gold standard for diagnosis in all patients was based on histological findings, combined with clinical manifestations and laboratory tests and determined after a follow-up period of at least 3 years. A total of 640 patients with various chronic liver diseases from multiple centres underwent scoring using the new histological criteria and the simplified criteria, comparing their diagnostic performance. RESULTS: In this study, the new histological criteria showed a sensitivity of 73.6% and 100% for likely and possible AIH, with specificities of 100% and 69.0% respectively. The coincidence rates of possible AIH for the new histological criteria, simplified histological criteria and simplified score were 81.7%, 72.8% and 69.7% respectively. For likely AIH, the rates were 89.2%, 75.9% and 65.6% respectively. Based on the new histological criteria, all patients with AIH were correctly diagnosed. Specifically, 73.6% were diagnosed with likely AIH and 26.4% were possible AIH. Additionally, the simplified histological criteria achieved a diagnosis rate of 98.6% for AIH, while the simplified score could only diagnose 53.8% of AIH. CONCLUSIONS: Compared with the simplified score and simplified histological criteria, the sensitivity and specificity of the new histological criteria for AIH were significantly improved. The results indicate that the new histological criteria exhibit high sensitivity and specificity for diagnosing AIH in China.

Toward Bicalutamide Analogues with High Structural Diversity Using Catalytic Asymmetric Oxohydroxylation.

A catalytic enantioselective synthesis of bicalutamide derivatives with promising potentials in prostate cancer treatment has been disclosed. The key intermediates, α-hydroxy-ß-keto esters, were efficiently constructed through cinchoninium-mediated asymmetric oxohydroxylation of easily accessible alkenes with potassium permanganate. Good yields and high levels of asymmetric induction are achieved. This method provides a new synthetic route to bicalutamide analogues with high structural diversity, which will beneficially support subsequent structure-activity relationship studies and boost prostate cancer drug development.

Explore variation of salivary bacteria across time and geolocations.

Saliva is an informative body fluid that can be found at various crime scenes, and the salivary bacterial community has been revealed it is a potential auxiliary target for forensic identification. However, the variation of salivary bacterial community composition across time and geolocation needs to be explored. The study was designed to be carried out during the winter vacation that was across about 50 days and eight geographic locations. The high throughput sequencing was performed with the V3-V4 region of the16S rRNA gene to explore salivary bacterial community composition. An overall slight fluctuation of the salivary bacteria was observed, which primarily occurred in the relative abundance of the salivary bacterial taxa. The results of principal coordinate analysis and hierarchical clustering showed samples were clustered by the individuals. All individuals could be correctly identified with the random forest model. In summation, although the relative abundance of salivary bacteria varied across the changes of time and geolocation, the individualized characteristic of salivary bacteria remained steady, which is beneficial for the salivary bacterial application in personal identification.

Development and evaluation of a panel of newly screened Y chromosome InDels for inferring paternal ancestry information in Southwest China.

Y-InDels (insertions/deletions) are genetic markers which are extremely understudied. It is unknown whether this type of markers can be utilized for genetic ancestry inference. We have developed an innovative Y chromosome ancestry inference system tailored for forensic applications. This panel amplifies 21 Y chromosome loci, encompassing Y-InDels and Y-SNPs (Single Nucleotide Polymorphism), utilizing the capillary electrophoresis (CE) platform. The system performed well at DNA concentrations greater than 0.125 ng/ul and produced accurate results at a 1:100 mixing ratio of male and female DNA. The Cumulative probability of matching (CPM) was between 0.95 and 0.97 in the experimental population. The system's efficacy in inferring ancestral origins was demonstrated through intercontinental population discrimination, revealing high discrimination power between African and East Asian populations. Population genetic analyses conducted on Han, Qiang and Hui populations in Southwest China, where the smallest FST value was 0.0002 between Han Chinese in Beijing (from 1000 Genomes Project) and Qiang Chinese from Sichuan (CQSC). Phylogenetic tree construction further illuminated distinct haplotypes among populations, with ethnically unique haplotypes observed in 34.6% of Hui and 7.1% of Qiang populations. K-fold cross-validation show the system's inference abilities at the intercontinental level. In addition, our investigations identified potential associations between the Y-InDel locus Y: 15,385,547 (GRCh37) and haplogroup R1a1a1b2a2- Z2124, as well as locus Y: 13,990,180 (GRCh37) and haplogroup F-M89. In conclusion, we have established a Y-chromosome inference system tailored for grassroots-level application, underscoring the value of incorporating Y-InDel markers in forensic analyses.

Development and validation of a noninvasive prediction model of autoimmune hepatitis in patients with liver diseases.

BACKGROUND AND AIMS: There is no golden standard for the diagnosis of autoimmune hepatitis which still dependent on liver biopsy currently. So, we developed a noninvasive prediction model to help optimize the diagnosis of autoimmune hepatitis. METHODS: From January 2017 to December 2019, 1739 patients who had undergone liver biopsy were seen in the second hospital of Nanjing, of which 128 were here for consultation. Clinical, laboratory, and histologic data were obtained retrospectively. Multivariable logistic regression analysis was employed to create a nomogram model that predicting the risk of autoimmune hepatitis. Internal and external validation was both performed to evaluate the model. RESULTS: A total of 1288 patients with liver biopsy were enrolled (1184 from the second hospital of Nanjing, the remaining 104 from other centers). After the univariate and multivariate logistic regression analysis, nine variables including ALT, IgG, ALP/AST, ALB, ANA, AMA, HBsAg, age, and gender were selected to establish the noninvasive prediction model. The nomogram model exhibits good prediction in diagnosing autoimmune hepatitis with AUROC of 0.967 (95% CI: 0.776-0.891) in internal validation and 0.835 (95% CI: 0.752-0.919) in external validation. CONCLUSIONS: ALT, IgG, ALP/AST, ALB, ANA, AMA, HBsAg, age, and gender are predictive factors for the diagnosis of autoimmune hepatitis in patients with unexplained liver diseases. The predictive nomogram model built by the nine predictors achieved good prediction for diagnosing autoimmune hepatitis.

Fluorescent Molybdenum Disulfide Quantum Dots for Sensitive Detecting Curcumin in Food Samples through FRET Mechanism.

A selective and sensitive fluorometric assay was developed for specific determination of curcumin (Cur) based on fluorescence resonance energy transfer (FRET) between molybdenum disulfide quantum dots (MoS2 QDs) and Cur. The MoS2 QDs were prepared via a one-step hydrothermal protocol using sodium molybdate dihydrate, L-cysteine (Cys) as precursors, and sodium cholate (SC) as a modification agent. The as-prepared MoS2 QDs possessed maximum fluorescence emission at 460 nm with a 20% of fluorescence quantum yield (FQY). It was found that the fluorescence of MoS2 QDs could be quantitatively quenched by Cur through FRET mechanism. Therefore, Cur could be detected in the range of 0.1-20 µg mL- 1 with a detection limit of 5 ng mL- 1. Additionally, the developed MoS2 QDs based fluorescent assay has been successfully applied for real food sample analysis with satisfactory results.

Occurrence and distribution of antibiotic resistance genes in urban rivers with black-odor water of Harbin, China.

Antibiotic resistance gene contamination in polluted rivers remains a widely acknowledged environmental issue. This study focused on investigating the contamination conditions of antibiotic resistance genes (ARGs) in Harbin's urban black-odor rivers, specifically Dongfeng Ditch and Hejia Ditch. The research employed a SmartChip Real-Time PCR System to explore the types, abundance, and distribution of ARGs in diverse habitats, such as surface water and sediment. Additionally, the study examined the correlation of ARGs with mobile genetic elements (MGEs) and various environmental factors. It was found that antibiotic resistance genes were prevalent in both water and sediment within the black-odor ditches. The dominant types of ARGs identified included aminoglycoside, sulfonamide, multidrug-resistant, and ß-lactam ARGs. Notably, the top four ARGs, in terms of relative abundance, were sul1, fox5, qacEdelta1-01 and aadA1. Most categories of ARGs have significant positive connections with MGEs, indicating that the enrichment and spreading of ARGs in rivers are closely related to MGEs. Based on the correlation analysis, it is found that environmental factors such as dissolved oxygen (DO), ammonia nitrogen (NH4-N), and phosphate (PO4-P) played a substantial role in influencing the variations observed in ARGs. By employing a risk assessment framework based on the human association, host pathogenicity, and mobility of ARGs, the identification of seven high-risk ARGs was achieved. In addition, it is important to assess the environmental risk of ARGs from multiple perspectives (abundance,detection rateand mobility). This study provides a significant reference regarding the presence of ARGs contamination in urban inland black-odor rivers, essential for assessing the health risks associated with ARGs and devising strategies to mitigate the threat of antibiotic resistance.

Gallic Acid Alleviates Psoriasis Keratinization and Inflammation by Regulating BRD4 Expression.

Psoriasis is a chronic non-contagious autoimmune disease. Gallic acid is a natural compound with potential health benefits, including antioxidant, anticancer, antiviral and antibacterial properties. Nevertheless, the influence of gallic acid on psoriasis has not been fully determined. This investigation aimed to discover the effect of gallic acid on psoriasis. Thirty-one pairs of psoriatic skin tissues and healthy adult human skin tissues were collected. Human keratinocytes (HaCaT cells) were transfected with interleukin 17A (IL-17A) to create the psoriatic keratinocyte model. The content of bromodomain-containing protein 4 (BRD4) microRNA was assessed using qRT-PCR testing. The content of BRD4 was detected by Western blotting. Cell migration was evaluated by conducting a wound healing assay. Cell proliferation was determined using an EdU assay. Apoptosis was detected by the TUNEL assay. The contents of interferon gamma (IFN-γ), IL-6, IL-8 and IL-17 were detected by ELISA. BRD4 was up-regulated in psoriatic skin tissues and in the IL-17A group compared to the healthy adult human skin tissues and the control group. Silencing BRD4 inhibited cell migration, proliferation and inflammatory response but induced apoptosis in IL-17A-treated HaCaT cells. Conversely, BRD4 over-expression promoted cell migration, proliferation and inflammatory response but suppressed apoptosis in IL-17A-treated HaCaT cells. Gallic acid repressed cell migration, proliferation and inflammatory response but indu-ced apoptosis in HaCaT cells transfected with IL-17A by down-regulating BRD4. Gallic acid represses cell migration, proliferation and inflammatory response but induces apoptosis in IL-17A-transfected HaCaT cells by down-regulating BRD4.

Early detection of gray blight in tea leaves and rapid screening of resistance varieties by hyperspectral imaging technology.

BACKGROUND: Gray blight (GB) is a significant disease of tea leaves, posing a severe threat to both the yield and quality. In this study, the process of leaf infection by a pathogenic isolate of the GB disease (DDZ-6) was simulated. Hyperspectral images of normal leaves, infected leaves without symptoms, and infected leaves with mild and moderate symptoms were collected. Combining convolution neural network (CNN), long short-term memory (LSTM), and support vector machine (SVM) algorithms, the early detection model of GB disease, and the rapid screening model of resistant varieties were established. The generality of this method was verified by collecting datasets under field conditions. RESULTS: The visible red-light band demonstrated a pronounced responsiveness to GB disease, with three sensitive bands identified through rigorous screening processes utilizing uninformative variable elimination (UVE), competitive adaptive reweighted sampling (CARS), and the successive projections algorithm (SPA). The 693, 727, and 766 nm bands emerged as highly sensitive indicators of GB. Under ideal conditions, the CARS-LSTM model excelled in early detection of GB, achieving an accuracy of 92.6%. However, under field conditions, the combination of 693 and 727 nm bands integrated with a CNN provided the most effective early detection model, attaining an accuracy of 87.8%. For screening tea varieties resistant to GB, the SPA-LSTM model excelled, achieving an accuracy of 82.9%. CONCLUSION: This study provides a core algorithm for a GB disease instrument with detection capabilities, which is of great importance for the early prevention of GB disease in tea plantations. © 2024 Society of Chemical Industry.

Care stressors and perceived stress among family caregivers of Chinese older adults with disabilities: The mediation effect of resilience.

OBJECTIVES: Guided by the Stress Process Model, this study examined the mediating effect of resilience on the relationship between care stressors and perceived caregiving stress. METHODS: Data were based on 234 older adults with disabilities and their caregivers from 6 urban districts and 6 rural counties from Jinan, China. Descriptive analysis, analysis of variance, ordinary least squares regression, and mediation analysis were performed. RESULTS: Perceived stress among family caregivers of Chinese older adults with disabilities was affected by the physical and mental health of both themselves and the care recipients, as well as care intensity and financial difficulties. Resilience played a partial mediating role in the associations among three stressors (i.e. older adults' disability levels, number of chronic diseases, and caregivers' self-reported mental) and perceived caregiving stress. CONCLUSIONS: Enhanced resilience aids caregivers' adaptation to their roles, suggesting the need for societal, spiritual, emotional, and behavioral resilience training.

Meta-analysis on the impact of immune senescence: Unravelling the interplay in cutaneous wound healing and lung cancer progression.

The primary objective of this meta-analysis was to provide the comprehensive understanding of the intricate correlation that existed between immune senescence and its effects on the advancement of lung cancer as well as recovery of cutaneous wounds. By conducting this systematic review of six rigorous studies utilizing databases such as PubMed and Web of Science, this research examined the multitude of facets pertaining to immune aging and consequences it bear on the health outcomes. The incorporated studies encompassed wide range of geographical and methodological viewpoints, with the specific emphasis on non-small-cell lung cancer and diverse scenarios related to wound recovery. This analysis synthesized discoveries regarding therapeutic responses, cellular and molecular mechanisms and impact of lifestyle factors on immune senescence. The findings suggested that immune senescence has substantial impact on the effectiveness of treatments for lung cancer and cutaneous wounds healing process; therefore, targeted therapies and holistic approaches may be able to mitigate these effects. By following the revised PRISMA guidelines, this meta-analysis guarantee thorough and ethically sound methodology for amalgamating pre-existing literature. The study concluded by emphasizing the critical nature of comprehending immune senescence in the context of clinical practice and proposed avenues for further investigation to enhance health results among the elderly.

Therapeutic potential of coumestan Pks13 inhibitors for tuberculosis.

Polyketide synthase 13 (Pks13) is an important enzyme found in Mycobacterium tuberculosis (M. tuberculosis) that condenses two fatty acyl chains to produce α-alkyl ß-ketoesters, which in turn serve as the precursors for the synthesis of mycolic acids that are essential building blocks for maintaining the cell wall integrity of M. tuberculosis Coumestan derivatives have recently been identified in our group as a new chemotype that exert their antitubercular effects via targeting of Pks13. These compounds were active on both drug-susceptible and drug-resistant strains of M. tuberculosis as well as showing low cytotoxicity to healthy cells and a promising selectivity profile. No cross-resistance was found between the coumestan derivatives and first-line TB drugs. Here we report that treatment of M. tuberculosis bacilli with 15 times the MIC of compound 1, an optimized lead coumestan compound, resulted in a colony forming unit (CFU) reduction from 6.0 log10 units to below the limit of detection (1.0 log10 units) per mL culture, demonstrating a bactericidal mechanism of action. Single dose (10 mg/kg) pharmacokinetic studies revealed favorable parameters with a relative bioavailability of 19.4%. In a mouse infection and chemotherapy model, treatment with 1 showed dose-dependent mono-therapeutic activity, whereas treatment with 1 in combination with rifampin showed clear synergistic effects. Together these data suggest that coumestan derivatives are promising agents for further TB drug development.

Fluorescent Turn-On Probes for Visualizing GPx4 Levels in Live Cells and Predicting Drug Sensitivity.

Glutathione peroxidase 4 (GPx4) is the membrane peroxidase in mammals that is essential for protecting cells against oxidative damage and critical for ferroptosis. However, no live cell probe is currently available to specifically label GPx4. Herein, we report both inhibitory and noninhibitory fluorescent turn-on probes for specific labeling of GPx4 in live cells. With these probes, the GPx4 expression levels and degradation kinetics in live cells could be visualized, and their real-time responses to the cellular selenium availability were revealed. These probes could also potentially serve as staining reagents to predict the sensitivity of GPx4-related ferroptosis drugs. In view of these features, these GPx4-selective probes will offer opportunities for a deeper understanding of GPx4 function in natural habitats and hold great promise for biomedical applications.

Improved phyllosphere microbiome composition of tea plant with the application of small peptides in combination with rhamnolipid.

BACKGROUND: Small peptides play a crucial role in plant growth and adaptation to the environment. Exogenous small peptides are often applied together with surfactants as foliar fertilizers, but the impact of small peptides and surfactants on the tea phyllosphere microbiome remains unknown. RESULTS: In this study, we investigated the effects of small peptides and different surfactants on the tea phyllosphere microbiome using 16S and ITS sequencing. Our results showed that the use of small peptides reduced the bacterial diversity of the tea phyllosphere microbiome and increased the fungal diversity, while the use of surfactants influenced the diversity of bacteria and fungi. Furthermore, the addition of rhamnolipid to small peptides significantly improved the tea phyllosphere microbiome community structure, making beneficial microorganisms such as Pseudomonas, Chryseobacterium, Meyerozyma, and Vishniacozyma dominant populations. CONCLUSION: Our study suggests that the combined use of small peptides and surfactants can significantly modify the tea phyllosphere microbiome community structure, particularly for beneficial microorganisms closely related to tea plant health. Thus, this preliminary study offers initial insights that could guide the application of small peptides and surfactants in agricultural production, particularly with respect to their potential for modulating the phyllosphere microbiome community in tea plant management.