Development of Oxadiazolone Activity-Based Probes Targeting FphE for Specific Detection of Staphylococcus aureus Infections.

Staphylococcus aureus (S. aureus) is a major human pathogen that is responsible for a wide range of systemic infections. Since its propensity to form biofilms in vivo poses formidable challenges for both detection and treatment, tools that can be used to specifically image S. aureus biofilms are highly valuable for clinical management. Here, we describe the development of oxadiazolone-based activity-based probes to target the S. aureus-specific serine hydrolase FphE. Because this enzyme lacks homologues in other bacteria, it is an ideal target for selective imaging of S. aureus infections. Using X-ray crystallography, direct cell labeling, and mouse models of infection, we demonstrate that oxadiazolone-based probes enable specific labeling of S. aureus bacteria through the direct covalent modification of the FphE active site serine. These results demonstrate the utility of the oxadizolone electrophile for activity-based probes and validate FphE as a target for the development of imaging contrast agents for the rapid detection of S. aureus infections.

Discovery of Thioether-Cyclized Macrocyclic Covalent Inhibitors by mRNA Display.

Macrocyclic peptides are promising scaffolds for the covalent ligand discovery. However, platforms enabling the direct identification of covalent macrocyclic ligands in a high-throughput manner are limited. In this study, we present an mRNA display platform allowing selection of covalent macrocyclic inhibitors using 1,3-dibromoacetone-vinyl sulfone (DBA-VS). Testcase selections on TEV protease resulted in potent covalent inhibitors with diverse cyclic structures, among which cTEV6-2, a macrocyclic peptide with a unique C-terminal cyclization, emerged as the most potent covalent inhibitor of TEV protease described to-date. This study outlines the workflow for integrating chemical functionalization─installation of a covalent warhead─with mRNA display and showcases its application in targeted covalent ligand discovery.

Overexpression of dehydroascorbate reductase gene IbDHAR1 improves the tolerance to abiotic stress in sweet potato.

Dehydroascorbate reductase (DHAR), an indispensable enzyme in the production of ascorbic acid (AsA) in plants, is vital for plant tolerance to various stresses. However, there is limited research on the stress tolerance functions of DHAR genes in sweet potato (Ipomoea batatas [L.] Lam). In this study, the full-length IbDHAR1 gene was cloned from the leaves of sweet potato cultivar Xu 18. The IbDHAR1 protein is speculated to be located in both the cytoplasm and the nucleus. As revealed by qRT-PCR, the relative expression level of IbDHAR1 in the proximal storage roots was much greater than in the other tissues, and could be upregulated by high-temperature, salinity, drought, and abscisic acid (ABA) stress. The results of pot experiments indicated that under high salinity and drought stress conditions, transgenic Arabidopsis and sweet potato plants exhibited decreases in H2O2 and MDA levels. Conversely, the levels of antioxidant enzymes APX, SOD, POD, and ACT, and the content of DHAR increased. Additionally, the ratio of AsA/DHA was greater in transgenic lines than in the wild type. The results showed that overexpression of IbDHAR1 intensified the ascorbic acid-glutathione cycle (AsA-GSH) and promoted the activity of the related antioxidant enzyme systems to improve plant stress tolerance and productivity.

First detection and biological characterization of an avian metaavulavirus 8 isolated from a migratory swan goose in Qinghai Lake, Northwest China.

Avian metaavulavirus 8 (AMAV-8), formerly known as avian paramyxovirus 8 (APMV-8), has been detected sporadically in wild birds worldwide since it was first identified in a Canadian goose in 1976. However, the presence of AMAV-8 in birds has never been reported in China. To understand the epidemiological situation of AMAV-8 and its ability to infect chickens, we conducted a surveillance study and in vivo analysis of the AMAV-8 isolate identified in total of 14,909 clinical samples collected from wild and domestic birds from 2014 to 2022 in China. However, in 2017, only one AMAV-8 virus (Y7) was successful isolated from the fresh droppings of a migratory swan goose in Qinghai Lake in Northwest China. Thereafter, we report the complete genome sequence of the Y7 strain with a genome length of 15,342 nucleotides and the Y7 isolate was genetically closely-related to wild bird-origin AMAV-8 viruses previously circulated in the United States, Japan, and Kazakhstan. Furthermore, AMAV-8 infections of one-day-old specific pathogen-free (SPF) chicks did not induce any clinical signs over the entire observation period but was associated with viral shedding for up to 8 days. Interestingly, although all birds infected with the Y7 strain seroconverted within the first week of infection, virus replication was only detected in the trachea but not in other tissues such as the brain, lung, or heart. Here, we report the complete genome, genetic and biological characterization, replication and pathogenicity analysis in vivo and first detection of AMAV-8 in China.

Synthesis and biological evaluation of novel isobenzofuran-1(3H)-one derivatives as antidepressant agents.

A series of novel isobenzofuran-1(3H)-one derivatives were designed and synthesized as antidepressants. Firstly, the serotonin reuptake inhibition of these compounds was tested in vitro, and most of them exhibited activity. Particularly, compounds 9d, 10a, and 10c demonstrated superior inhibitory effects and possibly avoided addiction via the µ-opioid receptor and CCK-B receptor. Secondly, the antidepressant effect of compound 10a was evaluated using chronic restraint stress (CRS)-induced mice. The results showed that compound 10a significantly improved CRS-induced depression-like behavior by increasing the neurotransmitters 5-HT in the cortex and THP2 expression in the hippocampus. Thirdly, compound 10a was further investigated and found to enhance CRS-induced hippocampal neuron damage recovery and elevate the expression of synaptic-associated proteins such as BDNF, TrkB, PSD95, and Spinophilin in CRS-induced mice. These findings suggested that novel isobenzofuran-1(3H)-one derivative showed efficacy in treating depression, with compound 10a emerging as a potential lead compound warranting further investigation.

The first report and biological characterization of Avian Orthoavulavirus 16 in wild migratory waterfowl and domestic poultry in China reveal a potential threat to birds.

RESEARCH HIGHLIGHTS: First confirmation of AOAV-16 in domestic and wild birds in China.AOAV-16 are low virulent viruses for chickens.Co-circulation/co-infection of AOAV-16 and H9N2 subtype AIV enhanced pathogenicity.Different intergenic sequences and recombination events exist within AOAV-16.

Similarity of Chinese and Pakistani oral microbiome.

Oral microbiota is vital for human health and can be affected by various factors (i.e. diets, ethnicity). However, few studies have compared oral microbiota of individuals from different nationalities in the same environment. Here, we explored the assembly and interaction of oral microbial communities of Chinese and Pakistanis in one university. Firmicutes and Proteobacteria were the predominant microorganisms in the oral cavity of Chinese and Pakistanis. Streptococcus and Neisseria were the dominant genera of China, while Streptococcus and Haemophilus were the dominant genera of Pakistanis. In addition, the oral community membership and structure were not influenced by season, Chinese/Pakistani student and gender, reflecting the stability of the human oral microbiome. The beta diversity of oral microbiomes between Chinese and Pakistanis significantly differed in winter, but not in spring. The alpha diversity of Chinese students and Pakistani students was similar. Moreover, oral microbial community of both Chinese and Pakistani students was mainly driven by stochastic processes. The microbial network of Chinese was more complexity and stability than that of Pakistanis. Our study uncovers the characteristics of human oral microbiota, which is of great significance for oral and human health.

Overexpression of sweetpotato glutamylcysteine synthetase (IbGCS) in Arabidopsis confers tolerance to drought and salt stresses.

Various environmental stresses induce the production of reactive oxygen species (ROS), which have deleterious effects on plant cells. Glutathione (GSH) is an antioxidant used to counteract reactive oxygen species. Glutathione is produced by glutamylcysteine synthetase (GCS) and glutathione synthetase (GS). However, evidence for the GCS gene in sweetpotato remains scarce. In this study, the full-length cDNA sequence of IbGCS isolated from sweetpotato cultivar Xu18 was 1566 bp in length, which encodes 521 amino acids. The qRT-PCR analysis revealed a significantly higher expression of the IbGCS in sweetpotato flowers, and the gene was induced by salinity, abscisic acid (ABA), drought, extreme temperature and heavy metal stresses. The seed germination rate, root elongation and fresh weight were promoted in T3 Arabidopsis IbGCS-overexpressing lines (OEs) in contrast to wild type (WT) plants under mannitol and salt stresses. In addition, the soil drought and salt stress experiment results indicated that IbGCS overexpression in Arabidopsis reduced the malondialdehyde (MDA) content, enhanced the levels of GCS activity, GSH and AsA content, and antioxidant enzyme activity. In summary, overexpressing IbGCS in Arabidopsis showed improved salt and drought tolerance.

Nonspecific immune, histology and accumulation of marine worm, Urechis unicinctus in response to bisphenol A (BPA).

Bisphenol A (BPA) is one of the environmental endocrine disruptors, due to its chemical stability it exists in abundant concentrations in water and soil consequently accumulating in the food chain and causing many endocrine-related health problems. So far, studies on the effects of BPA on marine invertebrates have focused on acute toxicity, endocrine regulation, reproduction, and development. However, fewer studies have been conducted on marine benthos. The current study aimed to detect the accumulation of BPA and its impact on tissue structure, antioxidant capacity, and immune indexes in marine worm, Urechis unicinctus. U. unicinctus, as a common marine benthic animal, were exposed to different concentrations of BPA. Blood cells and intestinal tract were taken for tissue structure inspection, and supernatant of the coelomic fluid was collected for oxidative and antioxidant biomarkers. Results showed that the accumulation of BPA in muscles of U. unicinctus tended to increase with exposure time. BPA induced a rise in H2O2 and MDA content, and altered the activities of CAT, T-SOD, GST, LSZ and ACP, weaken the immune system functions. Moreover, pathological observation showed that BPA caused severe histopathology in the respiratory intestine, stomach, and midgut. These results will be helpful to understand the response mechanism of U. unicinctus under BPA exposure and provide a reference for controlling the aquaculture conditions and marine water quality of U. unicinctus.

Expanding the horizons of levan: from microbial biosynthesis to applications and advanced detection methods.

Levan, a ß-(2,6)-linked fructose polymer, exhibits diverse properties that impart versatility, rendering it a highly sought-after biopolymer with various industrial applications. Levan can be produced by various microorganisms using sucrose, food industry byproducts and agricultural wastes. Microbial levan represents the most potent cost-effective process for commercial-scale levan production. This study reviews the optimization of levan production by understanding its biosynthesis, physicochemical properties and the fermentation process. In addition, genetic and protein engineering for its increased production and emerging methods for its detection are introduced and discussed. All of these comprehensive studies could serve as powerful tools to optimize levan production and broaden its applications across various industries.

Cadaverine and putrescine exposure influence carbon and nitrogen cycling genes in water and sediment of the Yellow River.

The response patterns of microbial functional genes involved in biogeochemical cycles to cadaver decay is a central topic of recent environmental sciences. However, the response mechanisms and pathways of the functional genes associated with the carbon (C) and nitrogen (N) cycling to cadaveric substances such as cadaverine and putrescine remain unclear. This study explored the variation of functional genes associated with C fixation, C degradation and N cycling and their influencing factors under cadaverine, putrescine and mixed treatments. Our results showed only putrescine significantly increased the alpha diversity of C fixation genes, while reducing the alpha diversity of N cycling genes in sediment. For the C cycling, the mixed treatment significantly decreased the total abundance of reductive acetyl-CoA pathway genes (i.e., acsB and acsE) and lig gene linked to lignin degradation in water, while only significantly increasing the hydroxypropionate-hydroxybutylate cycle (i.e., accA) gene abundance in sediment. For the N cycling, mixed treatment significantly decreased the abundance of the nitrification (i.e., amoB), denitrification (i.e., nirS3) genes in water and the assimilation pathway gene (i.e., gdhA) in sediment. Environmental factors (i.e., total carbon and total nitrogen) were all negatively associated with the genes of C and N cycling. Therefore, cadaverine and putrescine exposure may inhibit the pathway in C fixation and N cycling, while promoting C degradation. These findings can offer some new insight for the management of amine pollution caused by animal cadavers.

Research progress on labial protuberances of anterior teeth in orthodontic treatment. / æ­£ç•¸æ²»ç–—ä¸­å‰ç‰™ç‰™æ§½éª¨å”‡ä¾§éª¨æ€§å‡¸èµ·ç ”ç©¶è¿›å±•.

Orthodontic treatment is a commonly utilized method for improving both facial aesthetics and occlusal function. During orthodontic treatment irregular, nodular labial protuberances on the labial side of the anterior teeth may occasionally occur, varying in number and size, which is closely connected to the differential bone remodeling patterns on the internal and external surfaces of the labial alveolar bone. Labial protuberances can not only affect the aesthetic results of orthodontic treatment, but also pose potential risks to periodontal health. Currently, it is believed that the influencing factors of the formation of the labial protuberances may be related to the patient's gender and age, tooth movement speed, and extent of anterior teeth retraction. Labial protuberances typically resolve spontaneously, however, if it is persistent, alveoloplasty may be necessary for treatment. This review provides a summary on the occurrence hypothesis, influencing factors of formation, potential biological mechanisms, and corresponding treatment methods of labial protuberances during orthodontic treatment.

Deep Neutral Network Enhanced Mesoscopic Thermodynamic Model for Unlocking the Electrode/Electrolyte Interface.

Structure and properties of the electrode/electrolyte interface significantly influence the electrochemical processes of energy storage and conversion, yet the challenge lies in accurate description of both molecular characteristics and external field effects. Here, we develop a mesoscopic thermodynamic model that calculates the thermodynamic properties of electrolytes based on chemical potential, and its efficiency is enhanced by a deep neutral network. The deep neutral network enhanced mesoscopic thermodynamic (DeepMT) model effectively bridges the gap between micro-level characteristics of ions and macro-level effects of external field, enabling precise presentation of ion density distributions over complex conditions. Our result indicates that the DeepMT model not only demonstrates a computational efficiency improvement of approximately four orders of magnitude over direct theoretical calculations, but also accurately predicts interface properties including ion adsorption, surface charge, and differential capacitance through the statistical analysis of density distributions.

Study on DNA Storage Encoding Based IAOA under Innovation Constraints.

With the informationization of social processes, the amount of related data has greatly increased, making traditional storage media unable to meet the current requirements for data storage. Due to its advantages of a high storage capacity and persistence, deoxyribonucleic acid (DNA) has been considered the most prospective storage media to solve the data storage problem. Synthesis is an important process for DNA storage, and low-quality DNA coding can increase errors during sequencing, which can affect the storage efficiency. To reduce errors caused by the poor stability of DNA sequences during storage, this paper proposes a method that uses the double-matching and error-pairing constraints to improve the quality of the DNA coding set. First, the double-matching and error-pairing constraints are defined to solve problems of sequences with self-complementary reactions in the solution that are prone to mismatch at the 3' end. In addition, two strategies are introduced in the arithmetic optimization algorithm, including a random perturbation of the elementary function and a double adaptive weighting strategy. An improved arithmetic optimization algorithm (IAOA) is proposed to construct DNA coding sets. The experimental results of the IAOA on 13 benchmark functions show a significant improvement in its exploration and development capabilities over the existing algorithms. Moreover, the IAOA is used in the DNA encoding design under both traditional and new constraints. The DNA coding sets are tested to estimate their quality regarding the number of hairpins and melting temperature. The DNA storage coding sets constructed in this study are improved by 77.7% at the lower boundary compared to existing algorithms. The DNA sequences in the storage sets show a reduction of 9.7-84.1% in the melting temperature variance, and the hairpin structure ratio is reduced by 2.1-80%. The results indicate that the stability of the DNA coding sets is improved under the two proposed constraints compared to traditional constraints.

The Application of Nanoparticle-Based Imaging and Phototherapy for Female Reproductive Organs Diseases.

Various female reproductive disorders affect millions of women worldwide and bring many troubles to women's daily life. Let alone, gynecological cancer (such as ovarian cancer and cervical cancer) is a severe threat to most women's lives. Endometriosis, pelvic inflammatory disease, and other chronic diseases-induced pain have significantly harmed women's physical and mental health. Despite recent advances in the female reproductive field, the existing challenges are still enormous such as personalization of disease, difficulty in diagnosing early cancers, antibiotic resistance in infectious diseases, etc. To confront such challenges, nanoparticle-based imaging tools and phototherapies that offer minimally invasive detection and treatment of reproductive tract-associated pathologies are indispensable and innovative. Of late, several clinical trials have also been conducted using nanoparticles for the early detection of female reproductive tract infections and cancers, targeted drug delivery, and cellular therapeutics. However, these nanoparticle trials are still nascent due to the body's delicate and complex female reproductive system. The present review comprehensively focuses on emerging nanoparticle-based imaging and phototherapies applications, which hold enormous promise for improved early diagnosis and effective treatments of various female reproductive organ diseases.

Molecular epidemiology analysis of symptomatic and asymptomatic norovirus infections in Chinese infants.

BACKGROUND: Norovirus is a leading cause of acute gastroenteritis among children. Previous studies based on symptomatic infections indicated that mutations, rather than recombination drove the evolution of the norovirus ORF2. These characteristics were found in hospital-based symptomatic infections, whereas, asymptomatic infections are frequent and contribute significantly to transmission. METHODS: We conducted the first norovirus molecular epidemiology analysis covering both symptomatic and asymptomatic infections derived from a birth cohort study in the northern China. RESULTS: During the study, 14 symptomatic and 20 asymptomatic norovirus infections were detected in 32 infants. Out of the 14 strains that caused symptomatic infections, 12 strains were identified as GII.3[P12], and others were GII.4[P31]. Conversely, 17 asymptomatic infections were caused by GII.4[P31], two by GII.2[P16], and one by GII.4[P16]. Regardless of symptomatic and asymptomatic infections, the mutations were detected frequently in the ORF2 region, and almost all recombination were identified in the RdRp-ORF2 region. The majority of the mutations were located around the predefined epitope regions of P2 subdomain indicating a potential for immune evasion. CONCLUSION: The role of symptomatic as well as asymptomatic infections in the evolution of norovirus needs to be evaluated continuously.

Extreme environments and human health: From the immune microenvironments to immune cells.

Exposure to extreme environments causes specific acute and chronic physiological responses in humans. The adaptation and the physiological processes under extreme environments predominantly affect multiple functional systems of the organism, in particular, the immune system. Dysfunction of the immune system affected by several extreme environments (including hyperbaric environment, hypoxia, blast shock, microgravity, hypergravity, radiation exposure, and magnetic environment) has been observed from clinical macroscopic symptoms to intracorporal immune microenvironments. Therefore, simulated extreme conditions are engineered for verifying the main influenced characteristics and factors in the immune microenvironments. This review summarizes the responses of immune microenvironments to these extreme environments during in vivo or in vitro exposure, and the approaches of engineering simulated extreme environments in recent decades. The related microenvironment engineering, signaling pathways, molecular mechanisms, clinical therapy, and prevention strategies are also discussed.

Mammalian carcass decay increases carbon storage and temporal turnover of carbon-fixing microbes in alpine meadow soil.

Corpse decomposition is of great significance to the carbon cycle of natural ecosystem. Carbon fixation is a carbon conversion process that converts carbon dioxide into organic carbon, which greatly contributes to carbon emission reduction. However, the effects of wild animal carcass decay on carbon-fixing microbes in grassland soil environment are still unknown. In this research, thirty wild mammal (Ochotona curzoniae) corpses were placed on alpine meadow soil to study the carbon storage and carbon-fixing microbiota succession for a 94-day decomposition using next-generation sequencing. Our results revealed that 1) the concentration of total carbon increased approximately 2.24-11.22% in the corpse group. 2) Several carbon-fixing bacterial species (Calothrix parietina, Ancylobacter rudongensis, Rhodopseudomonas palustris) may predict the concentration of total carbon. 3) Animal cadaver degradation caused the differentiation of carbon-fixing microbiota structures during succession and made the medium-stage networks of carbon-fixing microbes more complicated. 4) The temporal turnover rate in the experimental groups was higher than that in the control groups, indicating a quick change of gravesoil carbon-fixing microbiota. 5) The deterministic process dominates the assembly mechanism of experimental groups (ranging from 53.42% to 94.94%), which reflects that the carbon-fixing microbial community in gravesoil can be regulated. Under global climate change, this study provides a new perspective for understanding the effects of wild animal carcass decay on soil carbon storage and carbon-fixing microbes.

Implications of occlusal plane in diagnosis and treatment of malocclusion. / 平面对错 畸形诊断和治疗的意义.

Occlusal plane (OP) is one of the essential factors affecting craniofacial morphology and function. The OP not only assists in diagnosing malocclusion but also serves as an important reference for making treatment plans. Patients with different types of malocclusions have different forms of OP. Compared with patients with standard skeletal facial type, the occlusal plane of patients with skeletal class Ⅱ and high angle is steeper, while that of patients with skeletal class Ⅲ and low angle is more even. In orthodontic treatment, adjusting and controlling the OP can promote the normal growth and development of the mandible in most patients with malocclusion during the early stage of growth, while causing favorable rotation of the mandible in some adults with mild-to-moderate malocclusion. For moderate-to-severe malocclusion, the OP rotation by orthodontic-orthognathic treatment can achieve better long-term stability. This article reviews the evolution of the definition of OP and its implications for diagnosing and the guiding treatment of malocclusion.

Genetic characterization of two G8P[8] rotavirus strains isolated in Guangzhou, China, in 2020/21: evidence of genome reassortment.

BACKGROUND: The G8 rotavirus genotype has been detected frequently in children in many countries and even became the predominant strain in sub-Saharan African countries, while there are currently no reports from China. In this study we described the genetic characteristics and evolutionary relationship between rotavirus strains from Guangzhou in China and the epidemic rotavirus strains derived from GenBank, 2020-2021. METHODS: Virus isolation and subsequent next-generation sequencing were performed for confirmed G8P[8] specimens. The genetic characteristics and evolutionary relationship were analyzed in comparison with epidemic rotavirus sequences obtained from GenBank. RESULTS: The two Guangzhou G8 strains were DS-1-like with the closest genetic distance to strains circulating in Southeast Asia. The VP7 genes of the two strains were derived from a human, not an animal G8 rotavirus. Large genetic distances in several genes suggested that the Guangzhou strains may not have been transmitted directly from Southeast Asian countries, but have emerged following reassortment events. CONCLUSIONS: We report the whole genome sequence information of G8P[8] rotaviruses recently detected in China; their clinical and epidemiological significance remains to be explored further.