Postoperative body weight change and its influencing factors in patients with gastric cancer.

BACKGROUND: The high incidence and mortality of gastric cancer (GC) pose a significant threat to human life and health, and it has become an important public health challenge in China. Body weight loss is a common complication after surgical treatment in patients with GC and is associated with poor prognosis and GC recurrence. However, current attention to postoperative weight change in GC patients remains insufficient, and the descriptions of postoperative weight change and its influencing factors are also different. AIM: To investigate body weight changes in patients with GC within 6 mo after gastrectomy and identify factors that influence dynamic body weight changes. METHODS: We conducted a prospective longitudinal study of 121 patients with GC and collected data before (T0) and 1 (T1), 3 (T2), and 6 (T3) mo after gastrectomy using a general data questionnaire, psychological distress thermometer, and body weight measurements. The general estimation equation (GEE) was used to analyze the dynamic trends of body weight changes and factors that influence body weight changes in patients with GC within 6 mo of gastrectomy. RESULTS: The median weight loss at T1, T2, and T3 was 7.29% (2.84%, 9.40%), 11.11% (7.64%, 14.91%), and 14.75% (8.80%, 19.84%), respectively. The GEE results showed that preoperative body mass index (BMI), significant psychological distress, religious beliefs, and sex were risk factors for weight loss in patients with GC within 6 mo after gastrectomy (P < 0.05). Compared with preoperative low-weight patients, preoperative obese patients were more likely to have weight loss (ß = 14.685, P < 0.001). Furthermore, patients with significant psychological distress were more likely to lose weight than those without (ß = 2.490, P < 0.001), and religious patients were less likely to lose weight 6 mo after gastrectomy than those without religious beliefs (ß = -6.844, P = 0.001). Compared to female patients, male patients were more likely to experience weight loss 6 mo after gastrectomy (ß = 4.262, P = 0.038). CONCLUSION: Male patients with GC with high preoperative BMI, significant psychological distress, and no religious beliefs are more likely to lose weight after gastrectomy.

Photoinduced Single Electron Reduction of the 4-O-5 Linkage in Lignin Models for C-P Coupling Catalyzed by Bifunctional N-Heterocyclic Carbenes.

Catalytic activation of Caryl-O bonds is considered as a powerful strategy for the production of aromatics from lignin. However, due to the high reduction potentials of diaryl ether 4-O-5 linkage models, their single electron reduction remains a daunting challenge. This study presents the blue light-induced bifunctional N-heterocyclic carbene (NHC)-catalyzed one-electron reduction of diaryl ether 4-O-5 linkage models for the synthesis of trivalent phosphines. The H-bond between the newly devised bifunctional NHC and diaryl ethers is responsible for the success of the single electron transfer. Furthermore, this approach demonstrates selective one-electron reduction of unsymmetric diaryl ethers, oligomeric phenylene oxide, and lignin model.

Characterising polycyclic aromatic hydrocarbons in road dusts and stormwater in urban environments.

The presence of polycyclic aromatic hydrocarbons (PAHs) pollution on urban road surfaces is one of the major environmental concerns. However, knowledge on the distribution variability of PAHs in road dusts (RDS) and stormwater is limited, which would restrict the further risk evaluation and mitigation implementation of PAHs in road stormwater runoff. This study collected RDS samples and stormwater samples on fourteen urban roads in Shenzhen, China. This study investigated the variation of sixteen PAHs species in RDS and stormwater, and further evaluated the intrinsic and extrinsic factors which influence PAHs accumulation on urban road surfaces. The research outcomes showed significant differences on spatial distribution of PAHs in RDS and in stormwater. The land use types, industrial, commercial and port areas and vehicular volume have a positive relationship with PAHs abundance while dust particle size showed a negative correlation with PAHs abundance. For two phases in stormwater, fluctuation of PAHs with the rainfall duration in total dissolved solid (TDS) was more intensive than in dissolved liquid phase (DLP). This indicated when PAHs attached to RDS enter stormwater, most of PAHs still tend to be on solid particles than in liquid. The study outcomes are expected to contribute to efficient designs of PAHs polluted stormwater mitigation.

Ultrasound sensing with optical microcavities.

Ultrasound sensors play an important role in biomedical imaging, industrial nondestructive inspection, etc. Traditional ultrasound sensors that use piezoelectric transducers face limitations in sensitivity and spatial resolution when miniaturized, with typical sizes at the millimeter to centimeter scale. To overcome these challenges, optical ultrasound sensors have emerged as a promising alternative, offering both high sensitivity and spatial resolution. In particular, ultrasound sensors utilizing high-quality factor (Q) optical microcavities have achieved unprecedented performance in terms of sensitivity and bandwidth, while also enabling mass production on silicon chips. In this review, we focus on recent advances in ultrasound sensing applications using three types of optical microcavities: Fabry-Perot cavities, π-phase-shifted Bragg gratings, and whispering gallery mode microcavities. We provide an overview of the ultrasound sensing mechanisms employed by these microcavities and discuss the key parameters for optimizing ultrasound sensors. Furthermore, we survey recent advances in ultrasound sensing using these microcavity-based approaches, highlighting their applications in diverse detection scenarios, such as photoacoustic imaging, ranging, and particle detection. The goal of this review is to provide a comprehensive understanding of the latest advances in ultrasound sensing with optical microcavities and their potential for future development in high-performance ultrasound imaging and sensing technologies.

Progestin-primed ovarian stimulation with letrozole using different doses of medroxyprogesterone acetate per day: a retrospective cohort study.

Background: In the progestin-primed ovarian stimulation protocol, the oral administration of medroxyprogesterone acetate has been observed to effectively inhibit the LH surge during ovarian stimulation in patients experiencing infertility. Nevertheless, the use of utilizing medroxyprogesterone acetate during ovarian stimulation can result in more pronounced pituitary suppression, potentially necessitating increased doses of gonadotropins and extended treatment durations. Therefore, it is necessary to determine the optimal dose of medroxyprogesterone acetate, aiming to use relatively lower concentrations of medroxyprogesterone acetate to effectively and safely suppress early LH surges. Method: This retrospective cohort study included 710 patients who underwent cycles of in vitro fertilization or intracytoplasmic sperm injection and were subjected the progestin-primed ovarian stimulation protocol utilizing letrozole between from 1st January 2021 to 31st December 2021. The study population was divided into low, medium, and high concentration groups based on the daily dosage of medroxyprogesterone acetate.The primary focus of this investigation was on the cumulative live birth rate. Secondary outcomes encompassed the occurrence of a premature surge in luteinizing hormone, the quantity of retrieved oocytes, viable embryos, and high-quality embryos, as well as clinical pregnancy rate, abortion rate, ectopic pregnancy rate, and multiple pregnancy rate. Results: In this study, significant differences were observed among three groups in various parameters including body mass index, baseline levels of Anti-Müllerian hormone and luteinizing hormone, antral follicle count, total dose of gonadotropin, and duration of gonadotropin administration (p<0.05). The number of oocytes and viable embryos were significantly higher in medium group and higher than those in the low dose group. Following adjustments for confounding factors related to medroxyprogesterone acetate for various outcome measures, we conducted multiple regression analysis to investigate the independent effects of daily medroxyprogesterone acetate dosage within the combined progestin-primed ovarian stimulation and letrozole protocol. Following multivariable regression analysis, no disparities were found in embryo characteristics (number of oocytes retrieved, number of available embryos, number of high-quality embryos) or pregnancy outcomes (clinical pregnancy rate, cumulative live birth rate) among the three groups. Conclusion: Progestin-primed ovarian stimulation with letrozole using different dose of medroxyprogesterone acetate per day was comparable in terms of the number of oocytes retrieved, the number of high-quality embryos, clinical pregnancy rate and cumulative live birth rate after frozen embryo transfer.

Centipeda minima and 6-O-angeloylplenolin enhance the efficacy of immune checkpoint inhibitors in non-small cell lung cancer.

BACKGROUND: Chemotherapeutic agents including cisplatin, gemcitabine, and pemetrexed, significantly enhance the efficacy of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) by increasing PD-L1 expression and potentiating T cell cytotoxicity. However, the low response rate and adverse effects limit the application of chemotherapy/ICI combinations in patients. METHODS: We screened for medicinal herbs that could perturb PD-L1 expression and enhance T cell cytotoxicity in the presence of anti-PD-L1 antibody, and investigated the underlying mechanisms. RESULTS: We found that the aqueous extracts of Centipeda minima (CM) significantly enhanced the cancer cell-killing activity and granzyme B expression level of CD8+ T cells, in the presence of anti-PD-L1 antibody. Both CM and its active component 6-O-angeloylplenolin (6-OAP) upregulated PD-L1 expression by suppressing GSK-3ß-ß-TRCP-mediated ubiquitination and degradation. CM and 6-OAP significantly enhanced ICI-induced reduction of tumor burden and prolongation of overall survival of mice bearing NSCLC cells, accompanied by upregulation of PD-L1 and increase of CD8+ T cell infiltration. CM also exhibited anti-NSCLC activity in cells and in a patient-derived xenograft mouse model. CONCLUSIONS: These data demonstrated that the induced expression of PD-L1 and enhancement of CD8+ T cell cytotoxicity underlay the beneficial effects of 6-OAP-rich CM in NSCLCs, providing a clinically available and safe medicinal herb for combined use with ICIs to treat this deadly disease.

The prognostic value of pretreatment 18F-FDG PET-CT parameters with peripheral blood markers in patients with de novo metastatic nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: To develop and validate a prognostic nomogram based on pretreatment 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET-CT)radiomics parameters and peripheral blood markers for risk stratification in patients with de novo metastatic nasopharyngeal carcinoma (dmNPC). MATERIALS AND METHODS: A total of 558 patients with dmNPC were retrospectively enrolled between 2011 and 2019. Eligible patients were randomly divided into training and validation cohorts (7:3 ratio). A Cox regression model was used to identify prognostic factors for overall survival (OS). The predictive accuracy and discriminative ability of the prognostic nomogram were determined using the concordance index (C-index) and calibration curve. RESULTS: Independent factors derived from multivariable analysis of the training cohort to predict death were lactate dehydrogenase levels, pretreatment Epstein-Barr virus DNA, total lesion glycolysis of locoregional lesions, number of metastatic lesions, and age, all of which were assembled into a nomogram with (nomogram B) or without PET-CT parameters (nomogram A). The C-index of nomogram B for predicting death was 0.70, which was significantly higher than the C-index values for nomogram A. Patients were then stratified into low- and high-risk groups based on the scores calculated using nomogram B for OS. The median OS was significantly higher in the low-risk group than in the high-risk group (69.60 months [95 % CI: 58.50-108.66] vs. 21.40 months [95 % CI: 19.20-23.90]; p＜0.01). All the results were confirmed in the validation cohort. CONCLUSION: The proposed nomogram including PET-CT parameters yielded accurate prognostic predictions for patients with dmNPC, enabling effective risk stratification for these patients.

Suppression of excitatory synaptic transmission in the centrolateral amygdala via presynaptic histamine H3 heteroreceptors.

The central histaminergic system has a pivotal role in emotional regulation and psychiatric disorders, including anxiety, depression and schizophrenia. However, the effect of histamine on neuronal activity of the centrolateral amygdala (CeL), an essential node for fear and anxiety processing, remains unknown. Here, using immunostaining and whole-cell patch clamp recording combined with optogenetic manipulation of histaminergic terminals in CeL slices prepared from histidine decarboxylase (HDC)-Cre rats, we show that histamine selectively suppresses excitatory synaptic transmissions, including glutamatergic transmission from the basolateral amygdala, on both PKC-δ- and SOM-positive CeL neurons. The histamine-induced effect is mediated by H3 receptors expressed on VGLUT1-/VGLUT2-positive presynaptic terminals in CeL. Furthermore, optoactivation of histaminergic afferent terminals from the hypothalamic tuberomammillary nucleus (TMN) also significantly suppresses glutamatergic transmissions in CeL via H3 receptors. Histamine neither modulates inhibitory synaptic transmission by presynaptic H3 receptors nor directly excites CeL neurons by postsynaptic H1, H2 or H4 receptors. These results suggest that histaminergic afferent inputs and presynaptic H3 heteroreceptors may hold a critical position in balancing excitatory and inhibitory synaptic transmissions in CeL by selective modulation of glutamatergic drive, which may not only account for the pathophysiology of psychiatric disorders but also provide potential psychotherapeutic targets. KEY POINTS: Histamine selectively suppresses the excitatory, rather than inhibitory, synaptic transmissions on both PKC-δ- and SOM-positive neurons in the centrolateral amygdala (CeL). H3 receptors expressed on VGLUT1- or VGLUT2-positive afferent terminals mediate the suppression of histamine on glutamatergic synaptic transmission in CeL. Optogenetic activation of hypothalamic tuberomammillary nucleus (TMN)-CeL histaminergic projections inhibits glutamatergic transmission in CeL via H3 receptors.

Enantiodivergent Cyclization of Racemic Cyclohexadienones via Parallel Kinetic Asymmetric Transformation.

Strategies that fully convert available racemic substrates into valuable enantioenriched products are urgently needed in organic synthesis. Reported herein is the first parallel kinetic asymmetric transformation of racemic cyclohexadienones. Racemic cyclohexadienones are first diastereoselectively converted into a new pair of racemic transient dienol intermediates, which are then parallel protonated by chiral phosphoric acid to deliver two sets of hydroindole products bearing a quaternary stereocenter with generally excellent enantioselectivity.

The burden of cardiovascular disease attributable to high fasting plasma glucose：Findings from the global burden of disease study 2019.

AIM: High fasting plasma glucose (HFPG) is a key risk factor for cardiovascular disease (CVD). Few studies have evaluated the CVD burden attributable to HFPG globally. It is urgent to investigate the current epidemiological pattern and past trends of CVD attributable to HFPG. METHODS: We used the Global Burden of Disease Study (GBD) 2019 to describe the CVD burden attributable to HFPG in 2019 and evaluate temporal trends between 1990 and 2019. RESULTS: Global Disability-Adjusted Life Years (DALYs) cases and death cases of HFPG-related CVD were approximately 72,591,163 and 3,763,298 in 2019, with an increase of 107.4 % and 114.6 % compared with 1990, respectively. Despite the increases, the age-standardized DALYs rate (ASDAR) and age-standardized death rate (ASDR) of HFPG-related CVD contributed to 895.2 per 100,000 people and 48.4 per 100,000 people in 2019, with an estimated annual percentage change (EAPC) of -0.22 and -0.31, respectively, from 1990. The highest ASDAR and ASDR of HFPG-related CVD were in 2019 observed in the low-middle SDI (Socio-demographic Index) and middle-SDI regions. Low SDI and some low-middle SDI regions showed an increase in ASDAR and ASDR of HFPG-related CVD from 1990 to 2019. Males are more affected by HFPG-related CVD than females across all years. The CVD burden attributable to HFPG in the elderly are higher than those in the young in 2019. The main causes of the global CVD burden attributable to HFPG in 2019 were ischemic heart disease, stroke, and peripheral arterial disease. CONCLUSION: The CVD burden attributable to HFPG remains a serious public health challenge threatening human health worldwide. It is necessary to develop more targeted and specific strategies to reduce CVD burden attributable to HFPG, especially in males, elderly, and lower SDI regions.

MiR-3074-5p suppresses non-small cell lung cancer progression by targeting the YWHAZ/Hsp27 axis.

Non-small cell lung cancer (NSCLC) accounts for more than 80% of lung cancer cases, and the 5-year survival rate of patients remains unsatisfactory. MicroRNAs (miRNAs) are small endogenous noncoding RNAs that are considered essential posttranscriptional regulators of tumorigenesis, including NSCLC. In this study, we aimed to investigate the biological role of miR-3074-5p in NSCLC cells and the underlying molecular mechanisms. We showed that miR-3074-5p expression was decreased in human NSCLC specimens and cell lines. Moreover, miR-3074-5p overexpression inhibited cell proliferation, migration and invasion and induced apoptosis and cell cycle arrest. In addition, miR-3074-5p overexpression not only suppressed tumor growth but also enhanced the antitumor effect of paclitaxel (PTX) on NSCLC cells in vitro and in vivo. A transcriptome sequencing assay revealed genes that were differentially expressed after miR-3074-5p overexpression, and among the genes whose expression levels were most significantly decreased, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) was a target of miR-3074-5p. The regulatory effect of miR-3074-5p on YWHAZ expression was verified by Western blotting and dual-luciferase reporter assays. The inhibition of A549 cell growth, migration and invasion was reversed by YWHAZ overexpression. Furthermore, we showed that PTX stimulated the expression of the YWHAZ and Hsp27 proteins and promoted the phosphorylation of Hsp27 (at S15 and S78). YWHAZ was confirmed to interact with Hsp27 in A549 cells, and downregulating YWHAZ expression promoted the degradation of the Hsp27 protein. Taken together, these results suggest that the miR-3074-5p/YWHAZ/Hsp27 axis may be a novel therapeutic target for NSCLC treatment.

Sesame lignans modulate aroma formation in sesame oil through the Maillard reaction and lipid oxidation in model systems.

The unknown effect of sesame lignans on aroma formation in sesame oil via the Maillard reaction (MR) and lipid oxidation was investigated. Sesamin, sesamolin, or sesamol was added to 3 models: lysine+glucose (MR), cold-pressed sesame oil (SO), and MR + SO, and were heated at 120 °C for 60 min. All three lignans suppressed SO oxidation while increasing DPPH scavenging ability (p < 0.05). Lignans increased depletions of lysine and glucose and MR browning (p < 0.05). Lignans reduced most aroma-active pyrazines, aldehydes, ketones, alcohols, and esters (p < 0.05). Sesamol and sesamolin increased perceptions of the preferable aromas of nutty, roasted sesame, and popcorn while reducing the undesirable green and rancid aromas (p < 0.05). Sesamol demonstrated a stronger effect on lipid oxidation, MR browning, aroma formation, and sensory perception than sesamin and sesamolin. This study suggests that sesame lignans can modulate aroma formation and sensory perception of sesame oil by interacting with the MR and lipid oxidation pathways.

Trends in maternal and child health in China and its urban and rural areas from 1991 to 2020: a joinpoint regression model.

The long-term trends in maternal and child health (MCH) in China and the national-level factors that may be associated with these changes have been poorly explored. This study aimed to assess trends in MCH indicators nationally and separately in urban and rural areas and the impact of public policies over a 30‒year period. An ecological study was conducted using data on neonatal mortality rate (NMR), infant mortality rate (IMR), under-five mortality rate (U5MR), and maternal mortality ratio (MMR) nationally and separately in urban and rural areas in China from 1991 to 2020. Joinpoint regression models were used to estimate the annual percentage changes (APC), average annual percentage changes (AAPC) with 95% confidence intervals (CIs), and mortality differences between urban and rural areas. From 1991 to 2020, maternal and child mortalities in China gradually declined (national AAPC [95% CI]: NMRs - 7.7% [- 8.6%, - 6.8%], IMRs - 7.5% [- 8.4%, - 6.6%], U5MRs - 7.5% [- 8.5%, - 6.5%], MMRs - 5.0% [- 5.7%, - 4.4%]). However, the rate of decline nationally in child mortality slowed after 2005, and in maternal mortality after 2013. For all indicators, the decline in mortality was greater in rural areas than in urban areas. The AAPCs in rate differences between rural and urban areas were - 8.5% for NMRs, - 8.6% for IMRs, - 7.7% for U5MRs, and - 9.6% for MMRs. The AAPCs in rate ratios (rural vs. urban) were - 1.2 for NMRs, - 2.1 for IMRs, - 1.7 for U5MRs, and - 1.9 for MMRs. After 2010, urban‒rural disparity in MMR did not diminish and in NMR, IMR, and U5MR, it gradually narrowed but persisted. MCH indicators have declined at the national level as well as separately in urban and rural areas but may have reached a plateau. Urban‒rural disparities in MCH indicators have narrowed but still exist. Regular analyses of temporal trends in MCH are necessary to assess the effectiveness of measures for timely adjustments.

High-temperature responses of Myzus persicae and its parasitoid Aphidius gifuensis in relation to heat level, duration and developmental stage.

BACKGROUND: Understanding how parasitoids respond to temperature is crucial for improving biological control strategies under the context of global warming. This study examined the suitability of Myzus persicae and its parasitoid Aphidius gifuensis to varying temperature conditions, as well as the stage-specific response of A. gifuensis to high temperatures. RESULTS: High temperatures had a significant impact on the both M. persicae and A. gifuensis. When exposed to 36°C, M. persicae developed more slowly and produced smaller adults compared to control, regardless of the duration of exposure (2, 4 or 6 h); additionally, the survival rate of M. persicae nymphs sharply decreased under these conditions. Exposure to 36°C for 4 h negatively impacted the development of A. gifuensis. Female parasitoids exposed to 32°C developed into smaller adults, whereas males exposed to all three temperature levels were smaller compared to control group. Female parasitoids exposed to high temperatures, regardless of the specific heat level and duration, exhibited reduced longevity and decreased fecundity. None of the parasitoids exposed to 36°C for 6 h daily developed into adults. Heat treated during early developmental stages (2 and 4 days old) had a greater influence on parasitoid development, whereas heat treatment at 4 and 6 days old had a more significant impact on its fecundity. CONCLUSION: High temperatures not only directly affected the performance of A. gifuensis, but also exerted indirect effects by influencing the quality of the host aphids M. persicae. The deleterious effects of high temperature on larvae can persist into the adult stage, affecting the longevity and reproduction of adults. These findings are important for the utilization of A. gifuensis in the control of M. persicae in warming environments. © 2024 Society of Chemical Industry.

[Effects of Biochar Application on the Structure and Function of Fungal Community in Continuous Cropping Watermelon Soil].

This study was conducted to clarify the long-term effects of biochar application on the structure and function of the fungal community in continuous cropping watermelon soil. Taking watermelon root soil as the research object, Illumina NovaSeq high-throughput sequencing and FUNGuild platform were used to analyze the differences in soil fungal community composition, diversity, and function after 3-year biochar additions of 7.5, 15.0, and 30.0 t·hm-2 and to explore the correlation between soil environmental factors and fungal community structure under the control of biochar. The results showed that compared to that in the absence of biochar (control), the soil pH, available phosphorus, available potassium, total nitrogen, organic matter, and cation exchange capacity increased, but available nitrogen decreased with biochar addition. High-throughput sequencing results showed that biochar amendment improved the fungal community structure in continuous cropping watermelon soil and increased the richness and diversity of soil fungi. A total of 922 OTU were obtained from all soil samples, and the species annotation results indicated that the dominant fungal groups were Ascomycota, Basidiomycota, Mortierellomycota, Chytridiomycota, and Glomeromycota, with these phyla accounting for 85.70 %-92.45 % of the total sequences.The relative abundance of Ascomycota and Basidiomycota decreased, whereas the abundance of Mortierellomycota and Glomeromycota increased with biochar addition.At the genus level, the application of biochar increased the relative abundance of Mortierella and Rhizophlyctis but decreased the abundance of Fusarium. The Mantel test showed that soil available potassium, available nitrogen, organic matter, and pH were the main environmental factors leading to the shift in the soil fungal community composition.The functional prediction with FUNGuild showed that the many nutrient types among the different treatments were saprotrophic, pathotrophic, and symbiotrophic. The relative abundance of pathotrophs significantly decreased, but the abundance of symbiotrophs significantly increased with the medium and high doses of biochar treatment. In conclusion, the application of biochar changed the soil physicochemical properties, promoted the development of soil fungal community structure and functional groups in a healthy and beneficial direction, and improved the quality of continuous cropping watermelon soil.

The novel HLA-DPB1*1553:01 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-DPB1*1553:01 differs from HLA-DPB1*09:01:01:01 by one nucleotide in exon 3.

Rule-based omics mining reveals antimicrobial macrocyclic peptides against drug-resistant clinical isolates.

Antimicrobial resistance remains a significant global threat, driving up mortality rates worldwide. Ribosomally synthesized and post-translationally modified peptides have emerged as a promising source of novel peptide antibiotics due to their diverse chemical structures. Here, we report the discovery of new aminovinyl-(methyl)cysteine (Avi(Me)Cys)-containing peptide antibiotics through a synergistic approach combining biosynthetic rule-based omics mining and heterologous expression. We first bioinformatically identify 1172 RiPP biosynthetic gene clusters (BGCs) responsible for Avi(Me)Cys-containing peptides formation from a vast pool of over 50,000 bacterial genomes. Subsequently, we successfully establish the connection between three identified BGCs and the biosynthesis of five peptide antibiotics via biosynthetic rule-guided metabolic analysis. Notably, we discover a class V lanthipeptide, massatide A, which displays excellent activity against gram-positive pathogens, including drug-resistant clinical isolates like linezolid-resistant S. aureus and methicillin-resistant S. aureus, with a minimum inhibitory concentration of 0.25 µg/mL. The remarkable performance of massatide A in an animal infection model, coupled with a relatively low risk of resistance and favorable safety profile, positions it as a promising candidate for antibiotic development. Our study highlights the potential of Avi(Me)Cys-containing peptides in expanding the arsenal of antibiotics against multi-drug-resistant bacteria, offering promising drug leads in the ongoing battle against infectious diseases.