Refining biome labeling for large-scale microbial community samples: Leveraging neural networks and transfer learning.

Microbiome research has generated an extensive amount of data, resulting in a wealth of publicly accessible samples. Accurate annotation of these samples is crucial for effectively utilizing microbiome data across scientific disciplines. However, a notable challenge arises from the lack of essential annotations, particularly regarding collection location and sample biome information, which significantly hinders environmental microbiome research. In this study, we introduce Meta-Sorter, a novel approach utilizing neural networks and transfer learning, to enhance biome labeling for thousands of microbiome samples in the MGnify database that have incomplete information. Our findings demonstrate that Meta-Sorter achieved a remarkable accuracy rate of 96.7% in classifying samples among the 16,507 lacking detailed biome annotations. Notably, Meta-Sorter provides precise classifications for representative environmental samples that were previously ambiguously labeled as "Marine" in MGnify, thereby elucidating their specific origins in benthic and water column environments. Moreover, Meta-Sorter effectively distinguishes samples derived from human-environment interactions, enabling clear differentiation between environmental and human-related studies. By improving the completeness of biome label information for numerous microbial community samples, our research facilitates more accurate knowledge discovery across diverse disciplines, with particular implications for environmental research.

Rapid identification of micro and nanoplastics by line scan Raman micro-spectroscopy.

Microplastic pollution has become an environmental problem that cannot be ignored in our society. Raman spectroscopy technology has been widely used in the field of microplastics detection due to its non-contact, non-destructive chemical specificity. Traditional point confocal Raman micro-spectroscopy technology uses single-point detection, resulting in long measurement times to scan the large areas of interest of typical samples. In this paper, we present a line scan confocal Raman micro-spectroscopy tool for fast detection and identification of microplastic particles. We show size and composition identification of particles and imaging over large areas. Compared with point confocal Raman imaging, the line scan confocal Raman technology increases the imaging speed by 1-2 orders of magnitude.

High performance boron doped peroxidase-like nanozyme Cu/B-NC for detection of epinephrine and catalase.

Herein, a novel peroxidase-like (POD-like) nanozyme Cu/B-NC was synthesized. The Cu and B co-doped nanozyme Cu/B-NC has competitive POD-like activity but negligible oxidase-like (OXD-like) activity, which is proved to partly benefit from the doping of boron atom. The catalytic activity of Cu/B-NC is high with great affinity for TMB and H2O2 and high reaction velocity. Cu/B-NC was utilized to catalyze the condensation of phenolic substance epinephrine (EP) and 4-aminoantipyrine (4-AAP) to form colored quinone imine in the presence of H2O2. UV-vis absorbance of quinone imine at 492 nm was used for EP determination. Catalase (CAT) could decompose H2O2, so CAT could also be quantified through absorbance variation. The linear ranges of colorimetric detection for EP and CAT were 2-100 µM and 1-30 U mL-1, respectively. The limits of detection (LODs) for EP and CAT were 0.97 µM and 0.57 U mL-1, respectively. The practicability of this sensing platform was further validated by successful application in actual samples.

A dual-mode sensing system based on carbon quantum dots and Fe nanozymes for the detection of α-glucosidase and its inhibitors.

In this research, a sensitive fluorometric and colorimetric dual-mode sensing platform based on nitrogen-doped carbon quantum dots (NCDs) and magnetic Fe nanoparticles with peroxidase-like activity (Fe nanozymes, Fe NZs) was established, and was further applied for the detection of α-glucosidase (α-glu) and its inhibitors. The ⋅OH that produced by H2O2 catalyzed by Fe NZs can oxidize the colorless diammonium 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) to green oxABTS, and a noticeable absorption peak at 417 nm appeared. Simultaneously, oxABTS can quench the fluorescence of NCDs at 402 nm via fluorescence resonance energy transfer (FRET). 2-O-α-D-glucopyranosyl-L-ascorbic acid (AAG) can be decomposed by α-glu to glucose and ascorbic acid (AA), AA can prevent the oxidation of ABTS, resulting in the absorption at 417 nm decreased. Moreover, the quenching effect of oxABTS on NCDs is weakened, and the fluorescence at 402 nm is restored. Therefore, based on the change of absorption at 417 nm and fluorescence at 402 nm, the fluorometric and colorimetric dual-mode sensing method can be used for the determination of acarbose and voglibose that are the inhibitors of α-glu.

Association of oral contraceptive pill use and depression among US women.

BACKGROUND: The link between oral contraceptive pill (OCP) and depression is still unclear. This work analyses the prevalence and correlates of major depression in US women using OCP. METHODS: This study used the National Health and Nutrition Examination Survey (NHANES) 2005-2012 data to provide the prevalence and correlates of major depression in women using OCP. Major depression was defined as a score of ≥10 using the Patient Health Questionnaire-9 (PHQ-9). RESULTS: A total of 6239 women aged 18-55 years were included in the present analysis. Current OCP users had a lower prevalence of major depression (4.6 %; 95 % CI, 3.2 to 6.6) compared to former users of OCP (11.4 %; 95 % CI, 10.1 to 12.9) and never users of OCP (10 %; 95 % CI, 8.3 to 12.1). Current users of OCP were significantly less likely to report major depression compared to former users of OCP (OR 0.59; 95CI%, 0.39 to 0.90) after adjusting for potential confounders. The prevalence of major depression was higher in women who were: black or Hispanic, widowed/divorced/separated, those with a low and middle income, current smokers, current users of antidepressants, and with history of cancer and thyroid problems. LIMITATIONS: This is a cross-sectional study. CONCLUSION: The prevalence of major depression among women using OCP may be lower than in former users of OCP, however, the burden of depression remains high. Further research with longitudinal follow-up for depression in women using OCP is needed to understand real world effect of the OCP on depression.

Microfluidic-assisted integrated nucleic acid test strips for POCT.

Numerous diseases have posed significant threats to public health, notably the global pandemic of COVID-19, resulting in widespread devastation due to its high infectivity and severity. The nucleic acid lateral flow assay (NALFA) addresses challenges of complexity, cost, and time associated with traditional assays, offering a reliable platform for rapid and precise nucleic acid target detection. NALFA is gaining prominence as a point-of-care testing (POCT) technique, thanks to its user-friendly operation and rapid results. Nevertheless, conventional NALFA relies on specialized technicians and involves labor-intensive steps like DNA extraction and PCR processes, impeding its efficiency. To overcome these limitations, integrating NALFA with microfluidic technology, widely employed in rapid field detection, holds promise. This review comprehensively outlines prevailing strategies for integrating NALFA, encompassing both research initiatives and commercial applications. Addressing the bottleneck of nucleic acid amplification as a rate-limiting step, the review delves into progress in amplification-free NALFA and highlights prevalent signal amplification techniques. Ultimately, the review outlines the future prospect of integrated NALFA development, capturing the technology's evolution and providing valuable insights for academic and commercial endeavors.

Disposable and instrument-free nucleic acid lateral flow cassette for rapid and on-site identification of adulterated goat milk.

Species identification has become a significant concern due to the growing use of food alternatives that may cause allergies and reduce nutritional value. To address the issue of fraudulent adulteration of goat milk products with cow milk, we have developed an affordable, portable, and user-friendly platform called microfluidic-integrated nucleic acid lateral flow strips (LFS). This platform enables simultaneous detection of components derived from both goats and cows in goat milk. In this study, we have introduced an innovative nucleic acid labeling method. The loop primers of loop-mediated isothermal amplification (LAMP) have been modified with amplification terminator spacer C3 and an oligonucleotide sequence, thus eliminating the requirement for costly antibodies in traditional nucleic acid LFS. This modification not only lowers costs but also enables multiple detections. Additionally, we have integrated the LAMP and LFS assay steps into a microfluidic chip, allowing convenient on-site detection while effectively preventing aerosol contamination of LAMP products. The testing process includes rapid DNA extraction, followed by a short nucleic acid addition and incubation for visualized results in about 50 min. This platform is user-friendly, requiring no specialized equipment or extensive training, making it suitable for rapid on-site detection of dairy products by personnel in diverse fields.

Single-Cell Transcriptional Analysis of Lamina Propria Lymphocytes in the Jejunum Reveals Innate Lymphoid Cell-like Cells in Pigs.

Pigs are the most suitable model to study various therapeutic strategies and drugs for human beings, although knowledge about cell type-specific transcriptomes and heterogeneity is poorly available. Through single-cell RNA sequencing and flow cytometry analysis of the types in the jejunum of pigs, we found that innate lymphoid cells (ILCs) existed in the lamina propria lymphocytes (LPLs) of the jejunum. Then, through flow sorting of live/dead-lineage (Lin)-CD45+ cells and single-cell RNA sequencing, we found that ILCs in the porcine jejunum were mainly ILC3s, with a small number of NK cells, ILC1s, and ILC2s. ILCs coexpressed IL-7Rα, ID2, and other genes and differentially expressed RORC, GATA3, and other genes but did not express the CD3 gene. ILC3s can be divided into four subgroups, and genes such as CXCL8, CXCL2, IL-22, IL-17, and NCR2 are differentially expressed. To further detect and identify ILC3s, we verified the classification of ILCs in the porcine jejunum subgroup and the expression of related hallmark genes at the protein level by flow cytometry. For systematically characterizing ILCs in the porcine intestines, we combined our pig ILC dataset with publicly available human and mice ILC data and identified that the human and pig ILCs shared more common features than did those mouse ILCs in gene signatures and cell states. Our results showed in detail for the first time (to our knowledge) the gene expression of porcine jejunal ILCs, the subtype classification of ILCs, and the markers of various ILCs, which provide a basis for an in-depth exploration of porcine intestinal mucosal immunity.

The bioavailability enhancement and insight into the action mechanism of poorly soluble natural compounds from co-crystals preparation: Oridonin as an example.

BACKGROUND: Natural bioactive molecules are important sources for the development of new drugs. However, most of them were limited in clinical applications due to their low aqueous solubility and bioavailability. Oridonin (ORI) is a powerful anticancer compound with above characteristics. OBJECTIVE: This study aimed to find an effective method to improve the bioavailability of poorly soluble natural compounds, and explore the action mechanisms of them to promote their application. RESULTS: In this study, ORI-nicotinamide (NCT) cocrystal was successfully prepared for the first time to overcome the defects of ORI. The solubility and oral bioavailability of cocrystal (COC) increased 1.34 and 1.18 times compared with ORI. Moreover, MTT assay was applied to compare the cytotoxicity of positive control drug sorafenib with ORI and COC. The IC50 values of sorafenib, ORI and COC on HepG2 cells were 7.61, 8.79 and 7.36 nmol·mL-1, which indicated that the cytotoxicity of ORI could be enhanced by cocrystal preparation. The cellular metabolomics was innovatively introduced to gain insight into the difference of cytotoxicity mechanism between ORI and COC. The results showed that there were 78 metabolites with significant differences in content between the two groups, while these differential metabolites were related to 11 metabolic pathways. Among these, glycerophospholipid metabolism and cysteine and methionine metabolism were the significant differential pathways, and the downregulation of PC(14:0/16:1(9z)) and upregulation of homocysteine were the likely main reasons for higher cytotoxicity of COC. CONCLUSIONS: This study has presented novel approaches for enhancing the bioavailability and drug efficacy of natural compounds, while also offering fresh insights into the underlying action mechanisms of pharmaceutical cocrystals.

Argonaute-DNAzyme tandem biosensing for highly sensitive and simultaneous dual-gene detection of methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA), a common zoonotic multidrug-resistant bacterium, puts a great threat to public health and food safety. Rapid and reliable detection of MRSA is crucial to guide effective patient treatment at early stages of infection and control the spread of MRSA infections. Herein, we developed a Simultaneous dual-gene and ulTra-sensitive detection for methicillin-resistant Staphylococcus aureus using Argonaute-DNAzyme tandem Detection (STAND). Simply, loop-mediated isothermal amplification (LAMP) was used for the amplification of the species-specific mecA and nuc gene, followed by STAND enabled by the site-specific cleavage of programable Argonaute. The Argonaute-DNAzyme tandem reaction rendered a conceptually novel signal amplification and transduction module that was more sensitive (1 or 2 order of magnitude higher) than the original Argonaute-based biosensing. With the strategy, the target nucleic acid signals gene were dexterously converted into fluorescent signals. STAND could detect the nuc gene and mecA gene simultaneously in a single reaction with 1 CFU/mL MRSA and a dynamic range from 1 to 108 CFU/mL. This method was confirmed by clinical samples and challenged by identifying contaminated foods and MRSA-infected animals. This work enriches the arsenal of Argonaute-mediated biosensing and presents a novel biosensing strategy to detect pathogenic bacteria with ultra-sensitivity, specificity and on-site capability.

Racial and ethnic disparities in prevalence and correlates of depressive symptoms and suicidal ideation among adults in the United States, 2017-2020 pre-pandemic.

BACKGROUND: This study aims to estimate the pre-COVID-19 pandemic prevalence of mild, major depressive symptoms, and suicide ideation among U.S. adults and evaluate their correlates and racial/ethnic disparities. METHODS: This is a cross-sectional analysis of a nationally representative sample of adults ≥20 years from the National Health and Nutrition Examination Survey study 2017-2020 Pre-Pandemic. Overall and racial/ethnic-specific weighted prevalence and 95%CI of mild and major depressive symptoms and suicidal ideation assessed by the Patient Health Questionnaire-9 were calculated. Multivariable logistic regression modelings were used to examine overall and racial/ethnic-specific correlates. RESULTS: Data on 7917 US adults (Weighted N = 210,200,829; 51.8 % females) were analyzed. The prevalence of mild, major depressive symptoms, and suicidal ideation was 8.5 %, 16.5 %, and 3.2 %, respectively. Overall, consistent correlates for all three conditions included smoking, short/long sleep duration, and obesity. Females, non-Hispanic Blacks, low family-poverty-income ratio, prolonged sitting time, and a history of cardiovascular disease were consistent correlates for mild and major depressive symptoms. Younger age, never married/living without a partner, physical inactivity, drinking alcohol, and a history of diabetes were related to major depressive symptoms. Never married/living without a partner and having a low family-poverty-income ratio correlate with suicide ideation. Having cancer diagnosis was only negatively associated with major depressive symptoms in non-Hispanic Blacks. Females, current smoking, short/long sleep duration, and having cardiovascular disease were correlated with suicidal ideation among Hispanics. CONCLUSIONS: The prevalence of mild, major depressive symptoms, and suicidal ideation were high among U.S. adults. Unique correlates were identified among different racial and ethnic groups.

Transposable elements cause the loss of self-incompatibility in citrus.

Self-incompatibility (SI) is a widespread prezygotic mechanism for flowering plants to avoid inbreeding depression and promote genetic diversity. Citrus has an S-RNase-based SI system, which was frequently lost during evolution. We previously identified a single nucleotide mutation in Sm -RNase, which is responsible for the loss of SI in mandarin and its hybrids. However, little is known about other mechanisms responsible for conversion of SI to self-compatibility (SC) and we identify a completely different mechanism widely utilized by citrus. Here, we found a 786-bp miniature inverted-repeat transposable element (MITE) insertion in the promoter region of the FhiS2 -RNase in Fortunella hindsii Swingle (a model plant for citrus gene function), which does not contain the Sm -RNase allele but are still SC. We demonstrate that this MITE plays a pivotal role in the loss of SI in citrus, providing evidence that this MITE insertion prevents expression of the S-RNase; moreover, transgenic experiments show that deletion of this 786-bp MITE insertion recovers the expression of FhiS2 -RNase and restores SI. This study identifies the first evidence for a role for MITEs at the S-locus affecting the SI phenotype. A family-wide survey of the S-locus revealed that MITE insertions occur frequently adjacent to S-RNase alleles in different citrus genera, but only certain MITEs appear to be responsible for the loss of SI. Our study provides evidence that insertion of MITEs into a promoter region can alter a breeding strategy and suggests that this phenomenon may be broadly responsible for SC in species with the S-RNase system.

Function and regulation of ubiquitin-like SUMO system in heart.

The small ubiquitin-related modifier (SUMOylation) system is a conserved, reversible, post-translational protein modification pathway covalently attached to the lysine residues of proteins in eukaryotic cells, and SUMOylation is catalyzed by SUMO-specific activating enzyme (E1), binding enzyme (E2) and ligase (E3). Sentrin-specific proteases (SENPs) can cleave the isopeptide bond of a SUMO conjugate and catalyze the deSUMOylation reaction. SUMOylation can regulate the activity of proteins in many important cellular processes, including transcriptional regulation, cell cycle progression, signal transduction, DNA damage repair and protein stability. Biological experiments in vivo and in vitro have confirmed the key role of the SUMO conjugation/deconjugation system in energy metabolism, Ca2+ cycle homeostasis and protein quality control in cardiomyocytes. In this review, we summarized the research progress of the SUMO conjugation/deconjugation system and SUMOylation-mediated cardiac actions based on related studies published in recent years, and highlighted the further research areas to clarify the role of the SUMO system in the heart by using emerging technologies.

ß-hydroxybutyrate administration improves liver injury and metabolic abnormality in postnatal growth retardation piglets.

Abnormal hepatic energy metabolism limits the growth and development of piglets. We hypothesized that ß-hydroxybutyrate (BHB) might improve the growth performance of piglets by maintaining hepatic caloric homeostasis. A total of 30 litters of newborn piglets were tracked, and 30 postnatal growth retardation (PGR) piglets and 40 healthy piglets were selected to treat with normal saline with or without BHB (25 mg/kg/days) at 7-d-old. At the age of 42 days, 8 piglets in each group were sacrificed, and serum and liver were collected. Compared with the healthy-control group piglets, PGR piglets showed lower body weight (BW) and liver weight (p < 0.05), and exhibited liver injury and higher inflammatory response. The contents of serum and hepatic BHB were lower (p < 0.05), and gene expression related to hepatic ketone body production were down-regulated in PGR piglets (p < 0.05). While BHB treatment increased BW and serum BHB levels, but decreased hepatic BHB levels in PGR piglets (p < 0.05). BHB alleviated the liver injury by inhibiting the apoptosis and inflammation in liver of PGR piglets (p < 0.05). Compared with the healthy-control group piglets, liver glycogen content and serum triglyceride level of PGR piglets were increased (p < 0.05), liver gluconeogenesis gene and lipogenesis gene expression were increased (p < 0.05), and liver NAD+ level was decreased (p < 0.05). BHB supplementation increased the ATP levels in serum and liver (p < 0.05), whereas decreased the serum glucose, cholesterol, triglyceride and high-density lipoprotein cholesterol levels and glucose and lipid metabolism in liver of PGR piglets (p < 0.05). Therefore, BHB treatment might alleviate the liver injury and inflammation, and improve hepatic energy metabolism by regulating glucose and lipid metabolism, thereby improving the growth performance of PGR piglets.

The therapeutic effect of wine-processed Corni Fructus on chronic renal failure in rats through the interference with the LPS/IL-1-mediated inhibition of RXR function.

ETHNOPHARMACOLOGICAL RELEVANCE: Corni Fructus, derived from the fruit of Cornus officinalis Sieb. et Zucc, is a widely utilized traditional Chinese medicine (TCM) with established efficacy in the treatment of diverse chronic kidney diseases. Crude Corni Fructus (CCF) and wine-processed Corni Fructus (WCF) are the main processed forms of Corni Fructus. Generally, TCM is often used after processing (paozhi). Despite the extensive use of processed TCM, the underlying mechanisms of processing for most TCMs have been unclear so far. AIM OF THE STUDY: In this study, an integrated strategy combined renal metabolomics with proteomics was established and investigated the potential processing mechanisms of CCF or WCF on chronic renal failure (CRF) models. MATERIALS AND METHODS: Firstly, the differences in biochemical parameters and pathological histology were compared to evaluate the effects of CCF and WCF on CRF model rats. Then, the tissue differential metabolites and proteins between CCF and WCF on CRF model rats were screened based on metabolomics and proteomics technology. Concurrently, a combined approach of metabolomics and proteomics was employed to investigate the underlying mechanisms associated with these marker metabolic products and proteins. RESULTS: Compared to the MG group, there were 27 distinct metabolites and 143 different proteins observed in the CCF-treatment group, while the WCF-treatment group exhibited 24 distinct metabolites and 379 different proteins. Further, the integration interactions analysis of the protein and lipid metabolite revealed that both WCF and CCF improved tryptophan degradation and LPS/IL-1-mediated inhibition of RXR function. WCF inhibited RXR function more than CCF via the modulation of LPS/IL-1 in the CRF model. Experimental results were validated by qRT-PCR and western blotting. Notably, the gene expression amount and protein levels of FMO3 and CYP2E1 among 8 genes influenced by WCF were higher compared to CCF. CONCLUSION: The results of this study provide a theoretical basis for further study of Corni Fructus with different processing techniques in CRF. The findings also offer guidance for investigating the mechanism of action of herbal medicines in diseases employing diverse processing techniques.

Characterizations of the multi-kingdom gut microbiota in Chinese patients with gouty arthritis.

OBJECTIVE: The gut microbial composition has been linked to metabolic and autoimmune diseases, including arthritis. However, there is a dearth of knowledge on the gut bacteriome, mycobiome, and virome in patients with gouty arthritis (GA). METHODS: We conducted a comprehensive analysis of the multi-kingdom gut microbiome of 26 GA patients and 28 healthy controls, using whole-metagenome shotgun sequencing of their stool samples. RESULTS: Profound alterations were observed in the gut bacteriome, mycobiome, and virome of GA patients. We identified 1,117 differentially abundant bacterial species, 23 fungal species, and 4,115 viral operational taxonomic units (vOTUs). GA-enriched bacteria included Escherichia coli_D GENOME144544, Bifidobacterium infantis GENOME095938, Blautia_A wexlerae GENOME096067, and Klebsiella pneumoniae GENOME147598, while control-enriched bacteria comprised Faecalibacterium prausnitzii_G GENOME147678, Agathobacter rectalis GENOME143712, and Bacteroides_A plebeius_A GENOME239725. GA-enriched fungi included opportunistic pathogens like Cryptococcus neoformans GCA_011057565, Candida parapsilosis GCA_000182765, and Malassezia spp., while control-enriched fungi featured several Hortaea werneckii subclades and Aspergillus fumigatus GCA_000002655. GA-enriched vOTUs mainly attributed to Siphoviridae, Myoviridae, Podoviridae, and Microviridae, whereas control-enriched vOTUs spanned 13 families, including Siphoviridae, Myoviridae, Podoviridae, Quimbyviridae, Phycodnaviridae, and crAss-like. A co-abundance network revealed intricate interactions among these multi-kingdom signatures, signifying their collective influence on the disease. Furthermore, these microbial signatures demonstrated the potential to effectively discriminate between patients and controls, highlighting their diagnostic utility. CONCLUSIONS: This study yields crucial insights into the characteristics of the GA microbiota that may inform future mechanistic and therapeutic investigations.

A preparation technology of volatile components in Linggui Zhugan decoction based on the transfer of cinnamaldehyde and its anti-gastric ulcer effect.

Purpose: This study aims to preserve the volatile components of Linggui Zhugan (LGZG) decoction, offering an experimental foundation for subsequent preparations efforts. Methods: Two modern sample preparation processes were compared with the traditional method approach using HPLC fingerprints. After identifying the main volatile components in LGZG aqueous decoction, the inclusion method of inclusion compounds (IC-LGZG) was established and optimized at laboratory, pilot and production scales. Characterization, stability testing of IC-LGZG, and experiments on gastric ulcer rats were conducted to validate the transferability of chemical composition and pharmaceutical efficacy. Results: The study focused on preserving the volatile components in LGZG modern preparations. HPLC analysis revealed cinnamaldehyde (CA) as the main volatile component in LGZG decoction. The optimized IC-LGZG preparation involved heating aromatic water to 40 °C, adding 20 g/L of ß-Cyclodextrin (ß-CD), keeping warm and stirring at 300 r for 30 min. This process exhibited good repeatability across different verification tests at varying scales. IC-LGZG obtained effectively transferred CA molecules into the ß-CD molecules via encapsulation, remaining stable when stored in sealed and dark conditions. Finally, CA, IC-LGZG and M-LGZG (a mixture of IC-LGZG and water-soluble extract powder) effectively prevented the formation of gastric ulcer by mitigating reductions in IL-10, SOD and the increase of TNF-α, NO, MDA in serum. Conclusion: The IC-LGZG prepared using this process successfully transfers volatile components, both chemically and pharmacologically, making it suitable for modern preparations of LGZG.

Identification of hypervirulent Klebsiella pneumoniae based on biomarkers and Galleria mellonella infection model.

BACKGROUND: Currently, clinical laboratories lack an effective method to differentiate between classical Klebsiella pneumoniae (cKP) and hypervirulent Klebsiella pneumoniae (hvKP) strains, leading to delays in diagnosing and treating hvKP infections. Previous studies have identified peg-344, iroB, iucA, prmpA, prmpA2, and siderophores (SP) yields greater than 30 µg/ml as reliable markers for distinguishing hvKP from cKp strains. However, these diagnostic tests were conducted on a relatively small study population and lacked sufficient clinical data support. In this study, hvKP strains were identified by biomarker analysis and the Galleria mellonella model. Combined with in vitro and in vivo experiments, the reliability of clinical identification method of hvKP was verified, which provided an experimental basis for timely diagnosis of hvKP infection. RESULTS: According to the clinical data, a total of 108 strains of hvKP were preliminary screened. Among them, 94 strains were further identified using PCR analysis of biomarkers and quantitative determination of SP. The high virulence of hvKP was subsequently confirmed through infection experiments on Galleria mellonella. Additionally, susceptibility testing revealed the identification of 58 carbapenem-resistant hvKP (CR-hvKP) strains and 36 carbapenem-sensitive hvKP (CS-hvKP) strains. By comparing molecular diagnostic indexes, molecular characteristics such as high SP production of CR-hvKP were found. CONCLUSION: The combination of clinical data and molecular diagnostic index analysis effectively enables the identification of hvKP, particularly CR-hvKP. This study provides a scientific basis for accurate clinical identification and timely treatment of hvKP.

Fe Cluster Modified Co9 S8 Heterojunction: Highly Efficient Photoelectrocatalyst for Overall Water Splitting and Flexible Zinc-Air Batteries.

Designing bifunctional low-cost photo-assisted electrocatalysts for converting solar and electric energy into hydrogen energy remains a huge challenge. Herein, a heterojunction (Fe cluster modified Co9 S8 loaded on carbon nanotubes, Co9 S8 -Fe@CNT) for both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is demonstrated. Benefiting from the good electronic conductivity and spatial confinement of the carbon skeleton, as well as the electronic structure regulation of the Fe cluster, Co9 S8 -Fe@CNT exhibits excellent catalytic performance with a low overpotential of 150 mV for OER and 135 mV for HER at 10 mA cm-2 . Upon light irradiation, holes and electrons are generated in the valence band and conduction band of the Co9 S8 , respectively. Part of the charges are transferred to the interface to facilitate the catalytic reaction, while the remaining are transferred by the electrode. When working as a bifunctional catalyst for overall water splitting, the performance can reach 1.33 V at under light conditions, which is significantly better than 1.52 V in a dark environment. Theoretical calculations revealed lowered Gibbs free energy (∆GH *) of the heterojunction with the effect of Fe modification of Co9 S8 . This work sheds a new light in designing novel photoelectrochemical materials to convert solar and electric energy into chemical energy.

A new function of thymol nanoemulsion for reversing colistin resistance in Salmonella enterica serovar Typhimurium infection.

BACKGROUND: Adjuvant addition of approved drugs or foodborne additives to colistin might be a cost-effective strategy to overcome the challenge of plasmid-mediated mobile colistin resistance gene emergence, which poses a threat in the clinic and in livestock caused by infections with Gram-negative bacteria, especially carbapenem-resistant Enterobacteriaceae. METHODS: Chequerboard assay was applied to screen the colistin adjuvants from natural compounds. The killing-time curve, combined disc test and membrane permeation assay were conducted to identify the synergy efficacy of thymol and colistin in vitro. Thin-layer chromatography (TLC), LC-MS and fluorescence spectra were used to indicate the interaction of thymol and MCR-1. The potential binding sites were then investigated by molecular simulation dynamics. Finally, a thymol nanoemulsion was prepared with high-pressure homogenization as the clinical dosage form. RESULTS: Thymol presented an excellent synergistic effect in vitro with colistin against Salmonella enterica serovar Typhimurium and Escherichia coli bacteria. Thymol addition, forming a complex with MCR-1, might interfere with the efficacy of MCR-1. Moreover, thymol strengthened colistin activity associated with potentiating membrane damage, destroying the biofilm and enhancing reactive oxygen species-mediated oxidative damage. Thymol nanoemulsion combined with colistin remarkably prevented the intestinal damage caused by S. Typhimurium infection, resulting in a survival rate higher than 60%. CONCLUSIONS: This study achieved a promising thymol oral formulation as colistin adjuvant to combat S. Typhimurium infection, which could be used to extend the lifespan of colistin in clinical veterinary medicine.