Differences of Typical Wuyi Rock Tea in Taste and Nonvolatiles Profile Revealed by Multisensory Analysis and LC-MS-Based Metabolomics.

Wuyi Rock tea, specifically Shuixian and Rougui, exhibits distinct sensory characteristics. In this study, we investigated the sensory and metabolite differences between Shuixian and Rougui. Quantitative description analysis revealed that Rougui exhibited higher intensity in bitter, thick, harsh, and numb tastes, while Shuixian had stronger salty and umami tastes. Nontargeted metabolomics identified 151 compounds with 66 compounds identified as key differential metabolites responsible for metabolic discrimination. Most of the catechins and flavonoids were enriched in Rougui tea, while epigallocatechin-3,3'-di-O-gallate, epigallocatechin-3,5-di-O-gallate, gallocatechin-3,5-di-O-gallate, isovitexin, and theaflavanoside I were enriched in Shuixian tea. Catechins, kaempferol, quercetin, and myricetin derivatives were positively correlated with bitter taste and numb sensation. Sour taste was positively correlated to organic acids. Amino acids potentially contributed to salty and umami tastes. These results provide further insights into the taste characteristics and the relationship between taste attributes and specific metabolites in Wuyi Rock tea.

Lumbar lordosis and sacral slope do not differ in two types of postoperative lumbar disc re-herniation: a cross-sectional observational study.

BACKGROUND: To identify the differences of lumbar lordosis (LL) and sacral slope (SS) angles between two types of postoperative lumbar disc re-herniation, including the recurrence of same level and adjacent segment herniation (ASH). METHODS: We searched the medical records of lumbar disc herniation (LDH) patients with re-herniation with complete imaging data (n = 58) from January 1, 2013 to December 30, 2020 in our hospital. After matching for age and sex, 58 patients with LDH without re-herniation from the same period operated by the same treatment group in our hospital were served as a control group. Re-herniation patients were divided into two groups, same-level recurrent lumbar disc herniation group (rLDHG) and adjacent segment herniation group with or without recurrence (ASHG). The preoperative, postoperative and one month after operation LL and SS were measured on standing radiographs and compared with the control group by using t-test, ANOVA, and rank-sum test. Next, we calculated the odds ratios (ORs) by unconditional logistic regression, progressively adjusted for other confounding factors. RESULTS: Compared with the control group, the postoperative LL and SS were significantly lower in LDH patients with re-herniation. However, there were no differences in LL and SS between ASHG and rLDHG at any stage. After progressive adjustment for confounding factors, no matter what stage is, LL and SS remained unassociated with the two types of re-herniation. CONCLUSIONS: Low postoperative LL and SS angles are associated with degeneration of the remaining disc. Low LL and SS may be independent risk factors for re-herniation but cannot determine type of recurrence (same or adjacent disc level).

Application of pectin hydrolyzing bacteria in tobacco to improve flue-cured tobacco quality.

To study the relationship between the diversity of the surface microbial community and tobacco flavor, and to improve tobacco quality using microorganisms. The microbial community composition and diversity of 14 samples of flue-cured tobacco from tobacco-producing areas in Yunnan with varying grades were analyzed by high-throughput sequencing. PICRUSt was used for predicting microbial functions. A strain of Bacillus amyloliquefaciens W6-2 with the ability to degrade pectin was screened from the surface of flued-cured tobacco leaves from Yunnan reroasted tobacco leave. The enzyme preparation was prepared through fermentation and then applied for treating flue-cured tobacco. The improvement effect was evaluated by measuring the content of macromolecule and the changes in volatile components, combined with sensory evaluations. The bacterial communities on the surface of flue-cured tobacco exhibited functional diversity, consisting primarily of Variovorax, Pseudomonas, Sphingomonas, Burkholderia, and Bacillus. These bacterial strains played a role in the aging process of flue-cured tobacco leaves by participating in amino acid metabolism and carbohydrate metabolism. These metabolic activity converted complex macromolecules into smaller molecular compounds, ultimately influence the smoking quality and burning characteristics of flue-cured tobacco. The pectinase preparation produced through fermentation using W6-2 has been found to enhance the aroma and sweetness of flue-cured tobacco, leading to improved aroma, reduced impurities, and enhanced smoothness. Additionally, the levels of pectin, cellulose, and hemicellulose decreased, while the levels of water-soluble sugar and reducing sugar increased, and the contents of esters, ketones, and aldehydes increased, and the contents of benzoic acid decreased. The study revealed the correlation between surface microorganisms and volatile components of Yunnan tobacco leaves, and the enzyme produced by the pectin-degrading bacteria W6-2 effectively improved the quality of flue-cured tobacco.

NT-proBNP ratio is a potential predictor for COVID-19 outcomes in adult Chinese patients: a retrospective study.

Despite the progressive decline in the virulence of the novel coronavirus, there has been no corresponding reduction in its associated hospital mortality. Our aim was to redefine an accurate predictor of mortality risk in COVID-19 patients, enabling effective management and resource allocation. We conducted a retrospective analysis of 2917 adult Chinese patients diagnosed with COVID-19 who were admitted to our hospital during two waves of epidemics, involving the Beta and Omicron variants. Upon admission, NT-proBNP levels were measured, and we collected demographic, clinical, and laboratory data. We introduced a new concept called the NT-proBNP ratio, which measures the NT-proBNP level relative to age-specific maximum normal values. The primary outcome was all-cause in-hospital mortality. Our analysis revealed a higher in-hospital mortality rate in 2022, as shown by the Kaplan-Meier Survival Curve. To assess the predictive value of the NT-proBNP ratio, we employed the time-dependent receiver operating characteristic (ROC) curve. Notably, the NT-proBNP ratio emerged as the strongest predictor of mortality in adult Chinese hospitalized COVID-19 patients (area under the curve, AUC = 0.826; adjusted hazard ratio [HR], 3.959; 95% confidence interval [CI] 3.001-5.221; P < 0.001). This finding consistently held true for both the 2020 and 2022 subgroups. The NT-proBNP ratio demonstrates potential predictive capability compared to several established risk factors, including NT-proBNP, hsCRP, and neutrophil-to-lymphocyte ratio, when it comes to forecasting in-hospital mortality among adult Chinese patients with COVID-19.Trial registration Clinical Trial Registration: www.clinicaltrials.gov NCT05615792.

New Insights into the Umami and Sweet Taste of Oolong Tea: Formation of Enhancer N-(1-carboxyethyl)-6-(hydroxymethyl) pyridinium-3-ol (Alapyridaine) in Roasting Via Maillard Reaction.

Roasting is pivotal for enhancing the flavor of Wuyi rock tea (WRT). A study investigated a novel compound that enhances the umami taste of WRT. Metabolomics of Shuixian tea (SXT) and Rougui tea (RGT) under light roasting (LR), medium roasting (MR), and heavy roasting (HR) revealed significant differences in nonvolatiles compounds. Compared LR reducing sugars and amino acids notably decreased in MR and HR, with l-alanine declining by 69%. Taste-guided fractionation identified fraction II-B as having high umami and sweet intensities. A surprising taste enhancer, N-(1-carboxyethyl)-6-(hydroxymethyl) pyridinium-3-ol (alapyridaine), was discovered and identified. It formed via the Maillard reaction, positively correlated with roasting in SXT and RGT. Alapyridaine levels were highest in SXT among the five oolong teas. Roasting tea with glucose increased alapyridaine levels, while EGCG inhibited its formation. HR-WRT exhibited enhanced umami and sweet taste, highlighting alapyridaine's impact on WRT's flavor profile. The formation of alapyridaine during the roasting process provides new insights into the umami and sweet perception of oolong tea.

Long-term effects of compound passivator coupled with silicon fertilizer on the reduction of cadmium and arsenic accumulation in rice and health risk evaluation.

Cadmium (Cd) and arsenic (As) are precedence-controlled contaminants in paddy soils, that can easily accumulate in rice grains. Limestone and sepiolite (LS) compound passivator can obviously reduce Cd uptake in rice, whereas Si fertilizer can effectively decrease rice As uptake. Here, the synergistic effects of the LS compound passivator coupled with Si fertilizer (LSCS) on the soil pH and availability of Si, Cd, and As, as well as rice grain Cd and As accumulation and its health risk were studied based on a 3-year consecutive field experiment. The results showed that the LSCS performed the best in terms of synchronously decreasing soil Cd and As availability and rice Cd and As uptake. In the LSCS treatments, soil pH gradually decreased with the rice-planting season, while soil available Cd and As contents gradually increased, suggesting that the influence of LSCS on Cd and As availability gradually weakened with rice cultivation. Nonetheless, the contents of Cd and inorganic As (i-As) in rice grains treated with LSCS were slightly affected by cultivation but were significantly lower than the single treatments of LS compound passivator or Si fertilizer. According to the Cd and As limit standards in food (GB2762-2022), the Cd and i-As content in rice grains can be lowered below the standard by using the 4500 kg/hm2 LS compound passivator coupled with 90 kg/hm2 Si fertilizer in soil and spraying 0.4 g/L Si fertilizer on rice leaves for at least three years. Furthermore, health risk evaluation revealed that LSCS treatments significantly reduced the estimated daily intake, annual excess lifetime cancer risk, and hazard quotient of Cd and i-As in rice grains. These findings suggest that LSCS could be a viable approach for reducing Cd and As accumulation in rice grains and lowering the potential health risks associated with rice.

Development of a novel hybrid antimicrobial peptide for enhancing antimicrobial spectrum and potency against food-borne pathogens.

AIMS: To address the increasingly serious challenge of the transmission of foodbrone pathogens in the food chain. METHODS AND RESULTS: In this study, we employed rational design strategies, including truncation, amino acid substitution, and heterozygosity, to generate seven engineered peptides with α-helical structure, cationic property, and amphipathic characteristics based on the original Abhisin template. Among them, as the hybird antimicrobial peptide (AMP), AM exhibits exceptional stability, minimal toxicity, as well as broad-spectrum and potent antimicrobial activity against foodborne pathogens. Besides, it was observed that the electrostatic incorporation demonstrates by AM results in its primary targeting and disruption of the cell wall and membrane of Escherichia coli O157: H7 (EHEC) and methicillin-resistant Staphylococcus aureus (MRSA), resulting in membrane perforation and enhanced permeability. Additionally, AM effectively counteracts the deleterious effects of lipopolysaccharide, eradicating biofilms and ultimately inducing the demise of both food spoilage and pathogenic microorganisms. CONCLUSIONS: The findings highlight the significant potential of AM as a highly promising candidate for a novel food preservative and its great importance in the design and optimization of AMP-related agents.

Cypin Inhibition as a Therapeutic Approach to Treat Spinal Cord Injury-Induced Mechanical Pain.

Cypin (cytosolic postsynaptic density protein 95 interactor) is the primary guanine deaminase in the central nervous system (CNS), promoting the metabolism of guanine to xanthine, an important reaction in the purine salvage pathway. Activation of the purine salvage pathway leads to the production of uric acid (UA). UA has paradoxical effects, specifically in the context of CNS injury as it confers neuroprotection, but it also promotes pain. Since neuropathic pain is a comorbidity associated with spinal cord injury (SCI), we postulated that small molecule cypin inhibitor B9 treatment could attenuate SCI-induced neuropathic pain, potentially by interfering with UA production. However, we also considered that this treatment could hinder the neuroprotective effects of UA and, in doing so, exacerbate SCI outcomes. To address our hypothesis, we induced a moderate midthoracic contusion SCI in female mice and assessed whether transient intrathecal administration of B9, starting at 1 d postinjury (dpi) until 7 dpi, attenuates mechanical pain in hindlimbs at 3 weeks pi. We also evaluated the effects of B9 on the spontaneous recovery of locomotor function. We found that B9 alleviates mechanical pain but does not affect locomotor function. Importantly, B9 does not exacerbate lesion volume at the epicenter. In accordance with these findings, B9 does not aggravate glutamate-induced excitotoxic death of SC neurons in vitro. Moreover, SCI-induced increased astrocyte reactivity at the glial scar is not altered by B9 treatment. Our data suggest that B9 treatment reduces mechanical pain without exerting major detrimental effects following SCI.

A Comprehensive Prognostic and Immune Infiltration Analysis of RBM4 in Pan-Cancer.

BACKGROUND: Aberrant splicing has been closely associated with human cancer, though the precise underlying mechanisms linking the two remain not fully understood. Investigating the role of splicing factors in cancer progression may aid in the development of targeted therapies for dysregulated splicing, thereby opening up new avenues for cancer treatment. RNA-binding motif 4 (RBM4) has been identified as a critical participant in the condensin II complex, which is involved in chromosome condensation and stabilization during mitosis. Its significance in tumors is currently gaining attention. The genetic characteristics of RBM4 suggest its potential to elucidate the malignant progression of tumors in a broader context, encompassing various types of cancer, known as pan-cancer. METHODS: This study aims to comprehensively explore the potential function of RBM4 in pan-cancer by leveraging existing databases such as The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). RESULTS: RBM4 is found to be overexpressed in almost all tumors and exhibits significant prognostic and diagnostic efficacy. The correlation between RBM4 and immune signatures, including immune cell infiltration and immune checkpoint genes, indicates that RBM4 could serve as a guiding factor for immunotherapy. CONCLUSIONS: As a member of the pan-oncogene, RBM4 has the potential to become a biomarker and therapeutic target for various malignant tumors, offering novel possibilities for precision medicine.

The inhibitory action of lactocin 63 on deterioration of seabass (Lateolabrax japonicus) during chilled storage.

BACKGROUND: The bacteriocins, particularly derived from lactic acid bacteria, currently exhibit potential as a promising food preservative owing to their low toxicity and potent antimicrobial activity. This study aimed to evaluate the efficacy of lactocin 63, produced by Lactobacillus coryniformis, in inhibiting the deterioration of Lateolabrax japonicas during chilled storage, while also investigating its underlying inhibitory mechanism. The measurement of total viable count, biogenic amines, and volatile organic compounds were conducted, along with high-throughput sequencing and sensory evaluation. RESULTS: The findings demonstrated that treatment with lactocin 63 resulted in a notable retardation of bacterial growth in L. japonicas fish fillet during refrigerated storage compared with the water-treated and nisin-treated groups. Moreover, lactocin 63 effectively maintained the microbial flora balance in the fish fillet and inhibited the proliferation and metabolic activity of specific spoilage microorganisms, particularly Shewanella, Pseudomonas, and Acinetobacter. Furthermore, the production of unacceptable volatile organic compounds (e.g. 1-octen-3-ol, hexanal, nonanal), as well as the biogenic amines derived from the bacterial metabolism, could be hindered, thus preventing the degradation in the quality of fish fillets and sustaining relatively high sensory quality. CONCLUSION: The results of this study provide valuable theoretical support for the development and application of lactocin 63, or other bacteriocins derived from lactic acid bacteria, as potential bio-preservatives in aquatic food. © 2024 Society of Chemical Industry.

Spermidine protects cartilage from IL-1ß-mediated ferroptosis.

Rheumatoid arthritis is characterized by a burst of inflammation, the destruction of cartilage and the abundant release of inflammatory factors such as IL-1ß. Thus, the effect of IL-1ß on cartilage was examined in this study. IL-1ß could cause lipid peroxidation and disturbances in iron metabolism by increasing the expression of NCOA4 and decreasing the expression of FTH, which also induced ferritinophagy. In addition, the expression of the key antioxidant proteins SLC7A11 and GPX4 was inhibited by IL-1ß, resulting in ferroptosis in chondrocytes. Spermidine (SPD), a low-molecular-weight aliphatic nitrogen-containing compound that widely exists in animals, has been reported to be an antioxidant. In our study, we found that SPD could inhibit ferritinophagy and reverse the decrease in the expression of SLC7A11 and GPX4. Therefore, we uncovered one of the molecular mechanisms of cartilage destruction and inflammation and provide a potential polyamine for the treatment of RA.

TIL-Derived CAR T Cells Improve Immune Cell Infiltration and Survival in the Treatment of CD19-Humanized Mouse Colorectal Cancer.

Chimeric antigen receptor-engineered T cells (CAR Ts) targeting CD19 have shown unprecedented prognosis in treating hematological cancers. However, the lack of a tumor-specific antigen as the target and an inhospitable tumor environment limit the clinical application of CAR T in solid tumors. Tumor-infiltrating T lymphocytes (TIL) exhibit diverse T cell receptor clonality and superior tumor-homing abilities. Therefore, in our study, human CD19-target TIL CAR-Ts armed with CD3ζ and 4-1BB signaling domains were constructed. Mouse colorectal cancer CT26 cells expressing human CD19 (hCD19+-CT26) were developed to assess the anti-tumor activity of TIL CAR-T cells, both in vitro and in vivo. Compared with splenic CAR T adoptive transfer, TIL CAR-T administration showed superior tumor suppression ability in hCD19+-CT26 tumor-bearing mice. Furthermore, more T cells were found at the tumor site and had lower exhaustion-related inhibitory receptor (T cell immunoglobulin and mucin domain-containing protein 3, Tim3) expression and higher immune memory molecule (CD62L) expression. Overall, we provided an artificial tumor-specific antigen in solid tumors and demonstrated that combined CAR-expressing TIL-Ts (TIL CAR-Ts) exhibited strong anti-tumor activity, with improved T cell infiltration and immune memory. Our humanized tumor antigen presented platform of mice suggests that TIL CAR-T-based adoptive therapy could be a promising strategy for solid cancer treatment.

Lonicerin promotes wound healing in diabetic rats by enhancing blood vessel regeneration through Sirt1-mediated autophagy.

Among the numerous complications of diabetes mellitus, diabetic wounds seriously affect patients' quality of life and result in considerable psychological distress. Promoting blood vessel regeneration in wounds is a crucial step in wound healing. Lonicerin (LCR), a bioactive compound found in plants of the Lonicera japonica species and other honeysuckle plants, exhibits anti-inflammatory and antioxidant activities, and it recently has been found to alleviate ulcerative colitis by enhancing autophagy. In this study we investigated the efficacy of LCR in treatment of diabetic wounds and the underlying mechanisms. By comparing the single-cell transcriptomic data from healing and non-healing states in diabetic foot ulcers (DFU) of 5 patients, we found that autophagy and SIRT signaling activation played a crucial role in mitigating inflammation and oxidative stress, and promoting cell survival in wound healing processes. In TBHP-treated human umbilical vein endothelial cells (HUVECs), we showed that LCR alleviated cell apoptosis, and enhanced the cell viability, migration and angiogenesis. Furthermore, we demonstrated that LCR treatment dose-dependently promoted autophagy in TBHP-treated HUVECs by upregulating Sirt1 expression, and exerted its anti-apoptotic effect through the Sirt1-autophagy axis. Knockdown of Sirt1 significantly decreased the level of autophagy, and mitigated the anti-apoptotic effect of LCR. In a STZ-induced diabetic rat model, administration of LCR significantly promoted wound healing, which was significantly attenuated by Sirt1 knockdown. This study highlights the potential of LCR as a therapeutic agent for the treatment of diabetic wounds and provides insights into the molecular mechanisms underlying its effects.

Plasma Aß42:Aß40 ratio as a biomarker for cognitive impairment in haemodialysis patients: a multicentre study.

Background: Mild cognitive impairment (MCI) and dementia are more prevalent in patients undergoing haemodialysis (HD). Although the cerebrospinal fluid amyloid beta (Aß) and tau (τ) have proven to be valid biomarkers for the diagnosis of Alzheimer's disease (AD) in the general population, the roles of plasma Aß and τ for the diagnosis of cognitive impairment in HD patients remain unknown. Methods: We conducted a cross-sectional study including patients receiving HD in three hospitals in Shanghai. All patients completed the Montreal Cognitive Assessment-Basic (MoCA-B). To validate the effectiveness of the MoCA-B score for screening MCI, a subset group underwent neuropsychological batteries. Serum proteomes were compared in HD patients with normal cognitive function and dementia. Plasma Aß42, Aß40 and total τ were measured using a single molecule array. Results: A total of 311 HD patients were enrolled (mean age 63 years, 55% male). The best cut-off score of MoCA-B for differentiating MCI and normal cognition was 24, with an area under the curve of 0.94. Serum proteomics revealed that neurodegenerative pathways related to AD were enriched in HD patients with dementia. The plasma Aß42:Aß40 ratio was significantly reduced in patients with MCI and dementia and was independently associated with cognitive function after adjusting for age, sex and education levels. Conclusions: We validated the MoCA-B as an optimal cognitive function screening instrument for MCI in HD patients. The plasma Aß42:Aß40 ratio was a potential biomarker in distinguishing normal cognition, MCI and dementia in HD populations.

Loss of SETD2 aggravates colorectal cancer progression caused by SMAD4 deletion through the RAS/ERK signalling pathway.

BACKGOUND: Colorectal cancer (CRC) is a complex, multistep disease that arises from the interplay genetic mutations and epigenetic alterations. The histone H3K36 trimethyltransferase SET domain-containing 2 (SETD2), as an epigenetic signalling molecule, has a 5% mutation rate in CRC. SETD2 expression is decreased in the development of human CRC and mice treated with Azoxymethane /Dextran sodium sulfate (AOM/DSS). Loss of SETD2 promoted CRC development. SMAD Family member 4 (SMAD4) has a 14% mutation rate in CRC, and SMAD4 ablation leads to CRC. The co-mutation of SETD2 and SMAD4 predicted advanced CRC. However, little is known on the potential synergistic effect of SETD2 and SMAD4. METHODS: CRC tissues from mice and SW620 cells were used as research subjects. Clinical databases of CRC patients were analyzed to investigate the association between SETD2 and SMAD4. SETD2 and SMAD4 double-knockout mice were established to further investigate the role of SETD2 in SMAD4-deficient CRC. The intestinal epithelial cells (IECs) were isolated for RNA sequencing and chromatin immunoprecipitation sequencing (ChIP-seq) to explore the mechanism and the key molecules resulting in CRC. Molecular and cellular experiments were conducted to analyze the role of SETD2 in SMAD4-deficient CRC. Finally, rescue experiments were performed to confirm the molecular mechanism of SETD2 in the development of SMAD4-dificient CRC. RESULTS: The deletion of SETD2 promotes the malignant progression of SMAD4-deficient CRC. Smad4Vil-KO ; Setd2Vil-KO mice developed a more severe CRC phenotype after AOM/DSS induction, with a larger tumour size and a more vigorous epithelial proliferation rate. Further mechanistic findings revealed that the loss of SETD2 resulted in the down-regulation of DUSP7, which is involved in the inhibition of the RAS/ERK signalling pathway. Finally, the ERK1/2 inhibitor SCH772984 significantly attenuated the progression of CRC in Smad4Vil-KO ;Setd2Vil-KO mice, and overexpression of DUSP7 significantly inhibited the proliferation rates of SETD2KO ; SMAD4KO SW620 cells. CONCLUSIONS: Our results demonstrated that SETD2 inhibits the RAS/ERK signaling pathway by facilitating the transcription of DUSP7 in SMAD4-deficient CRC, which could provide a potential therapeutic target for the treatment of advanced CRC.

SETD2 deficiency promotes renal fibrosis through the TGF-ß/Smad signalling pathway in the absence of VHL.

BACKGROUND: Renal fibrosis is the final development pathway and the most common pathological manifestation of chronic kidney disease. Epigenetic alteration is a significant intrinsic factor contributing to the development of renal fibrosis. SET domain-containing 2 (SETD2) is the sole histone H3K36 trimethyltransferase, catalysing H3K36 trimethylation. There is evidence that SETD2-mediated epigenetic alterations are implicated in many diseases. However, it is unclear what role SETD2 plays in the development of renal fibrosis. METHODS: Kidney tissues from mice as well as HK2 cells were used as research subjects. Clinical databases of patients with renal fibrosis were analysed to investigate whether SETD2 expression is reduced in the occurrence of renal fibrosis. SETD2 and Von Hippel-Lindau (VHL) double-knockout mice were used to further investigate the role of SETD2 in renal fibrosis. Renal tubular epithelial cells isolated from mice were used for RNA sequencing and chromatin immunoprecipitation sequencing to search for molecular signalling pathways and key molecules leading to renal fibrosis in mice. Molecular and cell biology experiments were conducted to analyse and validate the role of SETD2 in the development of renal fibrosis. Finally, rescue experiments were performed to determine the molecular mechanism of SETD2 deficiency in the development of renal fibrosis. RESULTS: SETD2 deficiency leads to severe renal fibrosis in VHL-deficient mice. Mechanically, SETD2 maintains the transcriptional level of Smad7, a negative feedback factor of the transforming growth factor-ß (TGF-ß)/Smad signalling pathway, thereby preventing the activation of the TGF-ß/Smad signalling pathway. Deletion of SETD2 leads to reduced Smad7 expression, which results in activation of the TGF-ß/Smad signalling pathway and ultimately renal fibrosis in the absence of VHL. CONCLUSIONS: Our findings reveal the role of SETD2-mediated H3K36me3 of Smad7 in regulating the TGF-ß/Smad signalling pathway in renal fibrogenesis and provide an innovative insight into SETD2 as a potential therapeutic target for the treatment of renal fibrosis.

Rational Design and Antimicrobial Potency Assessment of Abaecin Analogues.

The widespread and escalating emergence of multidrug resistance is now recognized as one of the most severe global threats to human health. To address the urgent issue of drug-resistant bacteria and the limitation of effective clinical treatments, antimicrobial peptides (AMPs) have been developed as promising substituents of conventional antibiotics. In this study, rational design strategies were employed to acquire seven cationic and α-helical engineered peptides based on the original template of Abaecin. After investigation, we found that AC7 (LLRRWKKLFKKIIRWPRPLPNPGH) demonstrated potent and broad-spectrum antimicrobial activity. Additionally, it demonstrated low cytotoxicity and hemolysis while maintaining good stability. Notably, AC7 displays the antibacterial mechanism with superior abilities in cell membrane disruption and potential DNA binding in vitro, as well as effectively disrupting biofilms. Moreover, the murine skin wound model infected with drug-resistant Pseudomonas aeruginosa was employed to evaluate the anti-infective efficacy and therapeutic potential of AC7. It was observed that AC7 displays a remarkable capacity to inhibit wound colonization, reduce levels of inflammatory cytokines (TNF-α) and inflammatory cells (white blood cells (WBC), monocytes (MONO), lymphocytes (LYMPH), neutrophils (GRAN)), promote the levels of IL-10 and VEGF, and enhance wound healing. Overall, these findings demonstrate the potential of AC7 as a viable alternative to traditional antibiotics.

Comparative analysis of microbial communities and volatile flavor components in the brewing of Hongqu rice wines fermented with different starters.

As one of the quintessential representatives of Chinese rice wine, Hongqu rice wine is brewed with glutinous rice as the main raw material and Hongqu (Gutian Qu or Wuyi Qu) as the fermentation starter. The present study aimed to investigate the impact of Hongqu on the volatile compositions and the microbial communities in the traditional production of Gutian Hongqu rice wine (GT) and Wuyi Hongqu rice wine (WY). Through the OPLS-DA analysis, 3-methylbutan-1-ol, isobutanol, ethyl lactate, ethyl acetate, octanoic acid, diethyl succinate, phenylethyl alcohol, hexanoic acid and n-decanoic acid were identified as the characteristic volatile flavor components between GT and WY. Microbiome analysis revealed significant enrichments of Lactobacillus, Pediococcus, Aspergillus and Hyphopichia in WY brewing, whereas Monascus, Saccharomyces, Pantoea, and Burkholderia-Caballeronia-Paraburkholderia were significantly enriched in GT brewing. Additionally, correlation analysis showed that Saccharomyces, Lactobacillus, Weissella and Pediococcus were significantly positively correlated wih most characteristic volatile components. Conversely, Picha, Monascus, Franconibacter and Kosakonia showed significant negative correlations with most of the characteristic volatile components. Furthermore, bioinformatical analysis indicated that the gene abundances for enzymes including glucan 1,4-alpha-glucosidase, carboxylesterase, alcohol dehydrogenase, dihydroxy-acid dehydratase and branched-chain-amino-acid transaminase were significantly higher in WY compared to GT. This finding explains the higher content of higher alcohols and characteristic esters in WY relative to GT. Collectively, this study provides a theoretical basis for improving the flavor profile of Hongqu rice wine and establishing a solid scientific foundation for the sustainable development of Hongqu rice wine industry.

Insights into microbial communities and metabolic profiles in the traditional production of the two representative Hongqu rice wines fermented with Gutian Qu and Wuyi Qu based on single-molecule real-time sequencing.

Hongqu rice wine, a famous traditional fermented alcoholic beverage, is brewed with traditional Hongqu (mainly including Gutian Qu and Wuyi Qu). This study aimed to compare the microbial communities and metabolic profiles in the traditional brewing of Hongqu rice wines fermented with Gutian Qu and Wuyi Qu. Compared with Hongqu rice wine fermented with Wuyi Qu (WY), Hongqu rice wine fermented with Gutian Qu (GT) exhibited higher levels of biogenic amines. The composition of volatile flavor components of Hongqu rice wine brewed by different fermentation starters (Gutian Qu and Wuyi Qu) was obviously different. Among them, ethyl acetate, isobutanol, 3-methylbutan-1-ol, ethyl decanoate, ethyl palmitate, ethyl oleate, nonanoic acid, 4-ethylguaiacol, 5-pentyldihydro-2(3H)-furanone, ethyl acetate, n-decanoic acid etc. were identified as the characteristic aroma-active compounds between GT and WY. Microbiome analysis based on high-throughput sequencing of full-length 16S rDNA/ITS-5.8S rDNA amplicons revealed that Lactococcus, Leuconostoc, Pseudomonas, Serratia, Enterobacter, Weissella, Saccharomyces, Monascus and Candida were the predominant microbial genera during the traditional production of GT, while Lactococcus, Lactobacillus, Leuconostoc, Enterobacter, Kozakia, Weissella, Klebsiella, Cronobacter, Saccharomyces, Millerozyma, Monascus, Talaromyces and Meyerozyma were the predominant microbial genera in the traditional fermentation of WY. Correlation analysis revealed that Lactobacillus showed significant positive correlations with most of the characteristic volatile flavor components and biogenic amines. Furthermore, bioinformatical analysis based on PICRUSt revealed that microbial enzymes related to biogenic amines synthesis were more abundant in GT than those in WY, and the enzymes responsible for the degradation of biogenic amines were less abundant in GT than those in WY. Collectively, this study provides important scientific data for enhancing the flavor quality of Hongqu rice wine, and lays a solid foundation for the healthy and sustainable development of Hongqu rice wine industry.

Myocardial injury and related mortality in hospitalized patients with COVID-19 during the Omicron pandemic: new perspectives and insights.

Myocardial injury is one of the most common comorbidity in SARS-CoV-2 infected patients, and has poor prognosis. However, the incidence of myocardial injury in patients with SARS-CoV-2 infection has not been sufficiently investigated during the Omicron wave. We conducted a retrospective study of 2690 patients with confirmed SARS-CoV-2 Omicron infection from Tongji Hospital. The results indicated that the myocardial injury accounted for 30.8% of the total patients with SARS-CoV-2 infection and was associated with higher in-hospital mortality than those without injury before and after propensity score matching (PSM) [adjusted hazard ratio (HR), 10.61; 95% confidence interval (CI), 7.76-14.51; P â€‹< â€‹0.001; adjusted HR, 2.70; 95% CI, 1.86-3.93; P â€‹< â€‹0.001; respectively]. Further, the levels of cytokines (IL-1ß, IL-6, IL-10, and TNF-α) in patients with myocardial injury were higher than those without injury, and the higher levels of cytokines in the myocardial injury group were associated with increased mortality. Administration of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB) could significantly reduce the mortality in patients with myocardial injury (adjusted HR, 0.52; 95% CI, 0.38-0.71; P â€‹< â€‹0.001). Additionally, the level of angiotensin II increased in patients with SARS-CoV-2 infection was even higher in myocardial injury group compared to those without injury. Collectively, the study summarized the clinical characteristic and outcome of SARS-CoV-2 infected patients with myocardial injury during the Omicron wave in China, and validated the protective role of ACEI/ARB in improving the survival of those with myocardial injury.