Identification of 3-ketocapnine reductase activity within the human microbiota.

The microbial synthesis of sulfonolipids within the human body is likely involved in maintaining human health or causing diseases. However, the enzymes responsible for their biosynthesis remain largely unknown. In this study, we identified and verified the role of 3-ketocapnine reductase, the third-step enzyme, in the four-step conversion of l-phosphoserine into sulfobacin B both in vivo and in vitro. This finding builds upon our previous research into sulfonolipid biosynthesis, which focused on the vaginal bacterium Chryseobacterium gleum DSM 16776 and the gut bacterium Alistipes finegoldii DSM 17242. Through comprehensive gene mapping, we demonstrate the widespread presence of potential sulfonolipid biosynthetic genes across diverse bacterial species inhabiting various regions of the human body. These findings shed light on the prevalence of sulfonolipid-like metabolites within the human microbiota, suggesting a potential role for these lipid molecules in influencing the intricate biointeractions within the complex microbial ecosystem of the human body.

A quenched fluorescence sensor array based on bis-lanthanide metal-organic framework for acetaldehyde detection and Baijiu discrimination.

Discrimination of segmented Baijiu contributes to stabilizing the quality of products, improving revenue-generating effects. A fluorescence sensor array is constructed based on four fluorescence characteristic peaks of terbium@lanthanum metal-organic framework (Tb@La-MOF). Its fluorescence signal is specifically quenched, when Tb@La-MOF encounters acetaldehyde. Acetaldehyde may inhibit the absorption of energy by the organic ligands in MOF, or/and hydrogen bonding with -COOH on the organic ligand, resulting in energy transfer to Tb(Ⅲ). According to this, the quantitative detection of acetaldehyde is completed with a range of 10-300 µM and the detection limit of 5.5 µM. At the same time, it has been successfully applied to the discrimination of segmented Baijiu. Fifteen segmented from three wine cellars are 100 % discriminated with the combined processing of sensor arrays and analytical methods. Accuracy, simplicity, and low-cost are highlights of this fluorescence sensor array, which has considerable potential for application in detection, production, and food field.

A photoluminescent hydrogen-bonded biomass aerogel for sustainable radiative cooling.

Passive radiant cooling is a potentially sustainable thermal management strategy amid escalating global climate change. However, petrochemical-derived cooling materials often face efficiency challenges owing to the absorption of sunlight. We present an intrinsic photoluminescent biomass aerogel, which has a visible light reflectance exceeding 100%, that yields a large cooling effect. We discovered that DNA and gelatin aggregation into an ordered layered aerogel achieves a solar-weighted reflectance of 104.0% in visible light regions through fluorescence and phosphorescence. The cooling effect can reduce ambient temperatures by 16.0°C under high solar irradiance. In addition, the aerogel, efficiently produced at scale through water-welding, displays high reparability, recyclability, and biodegradability, completing an environmentally conscious life cycle. This biomass photoluminescence material is another tool for designing next-generation sustainable cooling materials.

Do rheumatic diseases, long-term glucocorticoids, and immunosuppressant treatment, and vaccination impact the COVID-19 severity? Insight from a retrospective cohort study.

OBJECTIVES: The impact of rheumatic diseases, long-term medication, and vaccination on COVID-19 severity remain insufficiently understood, hindering effective patient management. This study aims to investigate factors influencing COVID-19 severity in Chinese rheumatic patients and to provide real-world evidence for patient care. METHODS: We conducted a retrospective observational study consisting of two cohorts, followed by a nested case-control analysis. The outpatient cohort included non-severe COVID-19 patients, while the inpatient cohort included consecutive severe COVID-19 inpatients. Additionally, rheumatic patients from both cohorts were included for the nested case-control study. Clinical information was obtained from electronic medical records and surveys. RESULTS: A total of 749 outpatients and 167 inpatients were enrolled. In the outpatient cohort, rheumatic diseases were identified as a risk factor for the severity of dyspnea (No rheumatic disease: OR = 0.577, 95% CI = 0.396-0.841, p = .004), but not for mortality, length of hospitalization, or hospitalization costs in the inpatient cohort. Long-term glucocorticoids use was identified as an independent risk factor for severity of dyspnea in rheumatic patients (OR = 1.814, 95% CI = 1.235-2.663, p = .002), while vaccination and immunosuppressant treatment showed no association. Vaccination was identified as a protective factor against hospitalization due to COVID-19 in patients with rheumatic diseases (OR = 0.031, 95% CI = 0.007-0.136, p < .001), whereas long-term glucocorticoids and immunosuppressant treatment showed no association. CONCLUSIONS: Rheumatic diseases and long-term glucocorticoids use are significant risk factors for COVID-19 severity in the Chinese population, whereas emphasizing the protective effects of vaccines against COVID-19 severity is crucial. Additionally, the investigation provides preliminary support for the concept that long-term immunosuppressant therapy does not necessarily require additional prescription adjustments.

Ubiquitin-induced RNF168 condensation promotes DNA double-strand break repair.

Rapid accumulation of repair factors at DNA double-strand breaks (DSBs) is essential for DSB repair. Several factors involved in DSB repair have been found undergoing liquid-liquid phase separation (LLPS) at DSB sites to facilitate DNA repair. RNF168, a RING-type E3 ubiquitin ligase, catalyzes H2A.X ubiquitination for recruiting DNA repair factors. Yet, whether RNF168 undergoes LLPS at DSB sites remains unclear. Here, we identified K63-linked polyubiquitin-triggered RNF168 condensation which further promoted RNF168-mediated DSB repair. RNF168 formed liquid-like condensates upon irradiation in the nucleus while purified RNF168 protein also condensed in vitro. An intrinsically disordered region containing amino acids 460-550 was identified as the essential domain for RNF168 condensation. Interestingly, LLPS of RNF168 was significantly enhanced by K63-linked polyubiquitin chains, and LLPS largely enhanced the RNF168-mediated H2A.X ubiquitination, suggesting a positive feedback loop to facilitate RNF168 rapid accumulation and its catalytic activity. Functionally, LLPS deficiency of RNF168 resulted in delayed recruitment of 53BP1 and BRCA1 and subsequent impairment in DSB repair. Taken together, our finding demonstrates the pivotal effect of LLPS in RNF168-mediated DSB repair.

Silencing LINC00987 ameliorates adriamycin resistance of acute myeloid leukemia via miR-4458/HMGA2 axis.

BACKGROUND: Most patients with acute myeloid leukemia (AML) eventually develop drug resistance, leading to a poor prognosis. Dysregulated long gene non coding RNAs (lincRNAs) have been implicated in chemoresistance in AML. Unfortunately, the effects of lincRNAs which participate in regulating the Adriamycin (ADR) resistance in AML cells remain unclear. Thus, the purpose of this study is to determine LINC00987 function in ADR-resistant AML. METHODS: In this study, ADR-resistant cells were constructed. LINC00987, miRNAs, and HMGA2 mRNA expression were measured by qRT-PCR. P-GP, BCRP, and HMGA2 protein were measured by Western blot. The proliferation was analyzed by MTS and calculated IC50. Soft agar colony formation assay and TUNEL staining were used to analyze cell colony formation and apoptosis. Xenograft tumor experiment was used to analyze the xenograft tumor growth of ADR-resistant AML. RESULTS: We found that higher expression of LINC00987 was observed in AML patients and associated with poor overall survival in AML patients. LINC00987 expression was increased in ADR-resistant AML cells, including ADR/MOLM13 and ADR/HL-60 cells. LINC00987 downregulation reduces ADR resistance in ADR/MOLM13 and ADR/HL-60 cells in vitro and in vivo, while LINC00987 overexpression enhanced ADR resistance in MOLM13 and HL-60 cells. Additionally, LINC00987 functions as a competing endogenous RNA for miR-4458 to affect ADR resistance in ADR/MOLM13 and ADR/HL-60 cells. HMGA2 is a target of miR-4458. LINC00987 knockdown and miR-4458 overexpression reduced HMGA2 expression. HMGA2 overexpression enhanced ADR resistance, which reversed the function of LINC00987 silencing in suppressing ADR resistance of ADR/MOLM13 and ADR/HL-60 cells. CONCLUSIONS: Downregulation of LINC00987 weakens ADR resistance by releasing miR-4458 to deplete HMGA2 in ADR/MOLM13 and ADR/HL-60. Therefore, LINC00987 may act as the therapeutic target for treating chemoresistant AML.

Histidine modified Fe3O4 nanoparticles improving the ethanol yield and tolerance of Saccharomyces cerevisiae.

Saccharomyces cerevisiae, the primary microorganism involved in ethanol production, is hindered by the accumulation of ethanol, leading to reduced ethanol production. In this study, we employed histidine-modified Fe3O4 nanoparticles (His-Fe3O4) for the first time, to the best of our knowledge, as a method to enhance ethanol yield during the S. cerevisiae fermentation process. The results demonstrated that exposing S. cerevisiae cells to Fe3O4 nanoparticles (Fe3O4 NPs) led to increased cell proliferation and glucose consumption. Moreover, the introduction of His-Fe3O4 significantly boosted ethanol content by 17.3% (p < 0.05) during fermentation. Subsequent findings indicated that the increase in ethanol content was associated with enhanced ethanol tolerance and improved electron transport efficiency. This study provided evidence for the positive effects of His-Fe3O4 on S. cerevisiae cells and proposed a straightforward approach to enhance ethanol production in S. cerevisiae fermentation. The mediation of improved ethanol tolerance offers significant potential in the fermentation and bioenergy sectors.

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The radial growth of trees in alpine timberline is particularly sensitive to climate change. We sampled and disposed tree-ring cores of three coniferous tree species including Juniperus saltuaria, Abies forrestii, and Larix potaninii at alpine timberline in Yading Nature Reserve. The standard tree-ring chronology was used to explore the response of radial growth of different timberline species to climate change. The results showed that radial growth of L. potaninii increased after 2000, while that of A. forrestii declined after 2002, and J. saltuaria showed a significant decreasing growth trend in the past 10 years. Such results indicated divergent growth responses to climate factors among the three tree species at alpine timberline. The radial growth of J. saltuaria was sensitive to temperature, and was positively correlated with the minimum temperature from previous October to current August, the mean tempera-ture from previous November to current April and from current July to October, but was negatively associated with the relative humidity from current July to October. The radial growth of A. forrestii showed negative correlation with mean temperature and the maximum temperature from May to June in the current year, while it exhibited positive association with the relative humidity and the Palmer drought severity index from May to June in the current year. L. potaninii radial growth was positively associated with mean temperature and the maximum temperature of November-December in the previous year, the maximum temperature of current March and mean temperature of current August. The temporal stability of climate-growth relationship varied among different timberline species. The positive correlation between radial growth of A. forrestii and J. saltuaria and temperature gradually decreased, while the posi-tive relationship of L. potaninii radial growth and temperature gradually increased. Under the background of climate warming, rapid rise in surface air temperatures may promote the radial growth of L. potaninii, while inhibit that of J. saltuaria and A. forrestii, which may change the position of regional timberline.

HDAC inhibitors support long-term expansion of porcine hepatocytes in vitro.

Hepatocyte transplantation is an effective treatment for end-stage liver disease. However, due to the limited supply of human hepatocytes, porcine hepatocytes have garnered attention as a potential alternative source. Nonetheless, traditional primary porcine hepatocytes exhibit certain limitations in function maintenance and in vitro proliferation. This study has discovered that by using histone deacetylase inhibitors (HDACi), primary porcine hepatocytes can be successfully reprogrammed into liver progenitor cells with high proliferative potential. This method enables porcine hepatocytes to proliferate over an extended period in vitro and exhibit increased susceptibility in lentivirus-mediated gene modification. These liver progenitor cells can readily differentiate into mature hepatocytes and, upon microencapsulation transplantation into mice with acute liver failure, significantly improve the survival rate. This research provides new possibilities for the application of porcine hepatocytes in the treatment of end-stage liver disease.

Amelioration activity of the high bioaccessible chrysanthemum (Gongju) phenolics on alcohol-induced oxidative injury in AML-12 cells.

The main bioavailable phenolics from of Gongju (GJ) and their mechanism for hepato-protection remain unclear. To select the GJ phenolics with high bioavailability, chrysanthemum digestion and Caco-2 cells were used and their hepato-protective potential were examined by using AML-12 cells. The digestive recovery and small intestinal transit rate of the main phenolic compounds ranged from 28.52 to 69.53% and 6.57% âˆ¼ 15.50%, respectively. Among them, chlorogenic acid, 3,5-dicaffeoylquinic acid, and 1,5-dicaffeoylquinic acid, showed higher small intestinal transit rates and digestive recoveries. Furthermore, we found that by increasing intracellular Catalase (CAT) and Superoxide dismutase (SOD) viability and lowering Malondialdehyde (MDA) level (P < 0.05), 3,5-dicaffeoylquinic acid significantly mitigated the oxidative damage of AML-12 liver cells more than the other two phenolics. Our results demonstrated that 3,5-dicaffeoylquninic acid was the primary phenolic compounds in GJ that effectively reduced liver damage, providing a theoretical basis for the development of GJ as a potentially useful resource for hepatoprotective diet.

The impacts of biodegradable and non-biodegradable microplastic on the performance and microbial community characterization of aerobic granular sludge.

Introduction: Microplastics (MPs), identified as emerging contaminants, have been detected across diverse environmental media. Their enduring presence and small size facilitate the adsorption of organic pollutants and heavy metals, leading to combined pollution effects. MPs also accumulate in the food chain thus pose risks to animals, plants, and human health, garnering significant scholarly attention in recent years. Aerobic granular sludge (AGS) technology emerges as an innovative approach to wastewater treatment. However, the impacts of MPs on the operational efficiency and microbial characteristics of AGS systems has been insufficiently explored. Methods: This study investigated the effects of varying concentration (10, 50, and 100 mg/L) of biodegradable MPs (Polylactic Acid, PLA) and non-biodegradable MPs (Polyethylene Terephthalate, PET) on the properties of AGS and explored the underlying mechanisms. Results and discussions: It was discovered that low and medium concentration of MPs (10 and 50 mg/L) showed no significant effects on COD removal by AGS, but high concentration (100 mg/L) of MPs markedly diminished the ability to remove COD of AGS, by blocking most of the nutrient transport channels of AGS. However, both PLA and PE promoted the nitrogen and phosphorus removal ability of AGS, and significantly increased the removal efficiency of total inorganic nitrogen (TIN) and total phosphorus (TP) at stages II and III (P < 0.05). High concentration of MPs inhibited the growth of sludge. PET noticeably deteriorate the sedimentation performance of AGS, while 50 mg/L PLA proved to be beneficial to sludge sedimentation at stage II. The addition of MPs promoted the abundance of Candidatus_Competibacter and Acinetobacter in AGS, thereby promoting the phosphorus removal capacity of AGS. Both 50 mg/L PET and 100 mg/L PLA caused large amount of white Thiothrix filamentous bacteria forming on the surface of AGS, leading to deterioration of the sludge settling performance and affecting the normal operation of the reactor. Comparing with PET, AGS proved to be more resistant to PLA, so more attention should be paid to the effect of non-biodegradable MPs on AGS in the future.

Bacillus licheniformis-based intensive fermentation of Tibetan tea improved its bioactive compounds and reinforced the intestinal barrier in mice.

Tibetan tea changes during microorganism fermentation. Research on microorganisms in Tibetan tea has focused on their identification, while studies on the influence of specific microorganisms on the components and health functions of Tibetan tea are lacking. Bacillus licheniformis was inoculated into Tibetan tea for intensive fermentation, and the components of B. licheniformis-fermented tea (BLT) were detected by liquid chromatography with tandem mass spectrometry (UHPLC-TOF-MS), and then the effects of BLT on intestinal probiotic functions were investigated by experiments on mice. The results revealed the metabolites of BLT include polyphenols, alkaloids, terpenoids, amino acids, and lipids. Intensified fermentation also improved the antioxidant capacity in vivo and the protective effect on the intestinal barrier of Tibetan tea. In addition, the enhanced fermentation of Tibetan tea exerted intestinal probiotic effects by modulating the relative abundance of short-chain fatty acid-producing bacteria in the intestinal flora. Therefore, intensive fermentation with B. licheniformis can improve the health benefits of Tibetan tea.

New wheat straw fermentation feed: recombinant Schizosaccharomyces pombe efficient degradation of lignocellulose and increase feed protein.

Wheat straw contains a high amount of lignin, hindering the action of cellulase and hemicellulase enzymes, leading to difficulties in nutrient absorption by animals from straw feed. However, currently, the biological treatment of straw relies primarily on fungal degradation and cannot be directly utilized for the preparation of livestock feed. This study focuses on enzymatic co-fermentation of wheat straw to produce high-protein, low-cellulose biological feed, integrating lignin degradation with feed manufacturing, thereby simplifying the feed production process. After the optimization using Box-Behnken Design for the feed formulation, with a glucose oxidase addition of 2.46%, laccase addition of 3.4%, and malonic acid addition of 0.6%, the wheat straw feed prepared in this experiment exhibited a true protein content of 9.35%. This represented a fourfold increase compared to the non-fermented state, and the lignocellulose degradation rate of wheat straw reached 45.42%. These results not only highlight the substantial enhancement in protein content but also underscore the significant advancement in lignocellulose breakdown. This formulation significantly enhanced the palatability and nutritional value of the straw feed, contributing to the industrial development of straw feed.

Discovery of Novel p53-MDM2 Inhibitor (RG7388)-Conjugated PlatinumIV Complexes as Potent Antitumor Agents.

While a number of p53-MDM2 inhibitors have progressed into clinical trials for the treatment of cancer, their progression has been hampered by a variety of problems, including acquired drug resistance, dose-dependent toxicity, and limited clinical efficiency. To make more progress, we integrated the advantages of MDM2 inhibitors and platinum drugs to construct novel PtIV-RG7388 (a selective MDM2 inhibitor) complexes. Most complexes, especially 5a and 5b, displayed greatly improved antiproliferative activity against both wild-type and mutated p53 cancer cells. Remarkably, 5a exhibited potent in vivo tumor growth inhibition in the A549 xenograft model (66.5%) without apparent toxicity. It arrested the cell cycle at both the S phase and the G2/M phase and efficiently induced apoptosis via the synergistic effects of RG7388 and cisplatin. Altogether, PtIV-RG7388 complex 5a exhibited excellent in vitro and in vivo antitumor activities, highlighting the therapeutic potential of PtIV-RG7388 complexes as antitumor agents.

Phage tailspike protein coated gold nanoparticles combined with smartphone for rapid bacterial detection and photothermal sterilization.

The integration of recognition and therapeutic functions in multifunctional biosensors is of great importance in guaranteeing food security and reducing the occurrence of foodborne illness caused by foodborne pathogens. In this study, a biosensor utilizing a "sense-and-treat" approach was developed by integrating phage tailspike protein (TSP) with gold nanoparticles (AuNPs@TSP). The synthesized AuNPs@TSP showed strong binding affinity towards Salmonella typhimurium causing color changes and exhibited effective bactericidal activity when exposed to near-infrared (NIR) irradiation. This biosensor facilitated rapid colorimetric detection of S. typhimurium in 50 min, with a LOD (limit of detection) of 2.53 × 103 CFU/mL output on a smartphone APP after analyzing the red-green-blue (RGB) values from color rendering results. Furthermore, the biosensor displayed high selectivity, rapid response time, and broad applicability when tested with real samples. Moreover, the biosensor exhibited a remarkably efficient antibacterial efficacy of 100 % against S. typhimurium under 808 nm light irradiation for 6 min. This study provides a comprehensive investigation into the potential utilization of biosensors for rapid detection and eradication of foodborne pathogens in food industry.

Blueberry anthocyanin based active intelligent wheat gluten protein films: Preparation, characterization, and applications for shrimp freshness monitoring.

The aim of this study was to prepare active intelligent gluten protein films using wheat gluten protein (WG) and apple pectin (AP) as film-forming matrices, and blueberry anthocyanin extract (BAE) as a natural indicator. SEM and FT-IR analyses demonstrated the successful immobilization of BAE in the film matrix by hydrogen bonding interactions and its compatibility with WG and AP. The resultant WG-AP/BAE indicator films demonstrated notable antioxidant activity, color stability, barrier qualities, pH and ammonia response sensitivity, and mechanical properties. Among them, WG-AP/BAE5 exhibited the best mechanical properties (TS: 0.83 MPa and EB: 242.23%) as well as the lowest WVP (3.92 × 10-8 g.m/m2.Pa.s), and displayed high sensitivity to volatile ammonia. In addition, WG-AP/BAE5 showed a color shift from purplish red to green to yellowish green, demonstrating the monitoring of shrimp freshness in real time. Consequently, this study offers a firm scientific foundation for the development of active intelligent gluten protein films and their use in food freshness assessments.

Impact of Duration of Diabetes Mellitus on Long-Term Outcome in Type 2 Diabetic Patients with Primary Percutaneous Coronary Intervention after the First Myocardial Infarction.

BACKGROUND: Diabetes mellitus (DM) increases the risk of mortality in patients with acute myocardial infarction (AMI). The impact of the diabetes duration on the long-term outcome of those with percutaneous coronary intervention (PCI) after the first AMI is unclear. In this study, we evaluated the predictive value of diabetes duration in the occurrence of major adverse cardiovascular and cerebrovascular events (MACCEs). METHODS: A total of 394 type 2 DM patients with PCI after the first AMI were enrolled and were divided into two groups by the diabetes duration: a short-DM group with diabetes duration of <5 years and a long-DM group with a duration of ≥5 years. The clinical endpoint was MACCEs. RESULTS: Multivariate Cox regression analysis found that the diabetes duration was independently associated with increased occurrence of MACCEs (HR: 1.512, 95% CI: 1.033, 2.215, p = 0.034), along with hypertension, Killip class III or IV, creatinine, multivessel disease, and continuous hypoglycemic therapy. After adjusting for the confounding variables, a nested Cox model showed that diabetes duration was still an independent risk factor of MACCEs (HR: 1.963, 95% CI: 1.376, 2.801, p < 0.001). The Kaplan-Meier survival curve illustrated a significantly high risk of MACCEs (HR: 2.045, p < 0.0001) in long-duration DM patients. After propensity score matching, a longer diabetes duration was associated with an increased risk of MACCE occurrence. CONCLUSION: Long-duration diabetes was independently associated with poor clinical outcomes after PCI in patients with their first myocardial infarction. Despite the diabetes duration, continuous hypoglycemic therapy significantly improved long-term clinical outcomes.

FARPA-based tube array coupled with quick DNA extraction enables ultra-fast bedside detection of antibiotic-resistant pathogens.

Rapid and accurate detection of pathogens and antimicrobial-resistant (AMR) genes of the pathogens are crucial for the clinical diagnosis and effective treatment of infectious diseases. However, the time-consuming steps of conventional culture-based methods inhibit the precise and early application of anti-infection therapy. For the prompt treatment of pathogen-infected patients, we have proposed a novel tube array strategy based on our previously reported FARPA (FEN1-aided recombinase polymerase amplification) principle for the ultra-fast detection of antibiotic-resistant pathogens on site. The entire process from "sample to result" can be completed in 25 min by combining quick DNA extraction from a urine sample with FARPA to avoid the usually complicated DNA extraction step. Furthermore, a 36-tube array made from commercial 384-well titre plates was efficiently introduced to perform FARPA in a portable analyser, achieving an increase in the loading sample throughput (from several to several tens), which is quite suitable for the point-of-care testing (POCT) of multiple pathogens and multiple samples. Finally, we tested 92 urine samples to verify the performance of our proposed method. The sensitivities for the detection of E. coli, K. pneumoniae, E. faecium, and E. faecalis were 92.7%, 93.8%, 100% and 88.9%, respectively. The specificities for the detection of the four pathogens were 100%. Consequently, our rapid, low-cost and user-friendly POCT method holds great potential for guiding the rational use of antibiotics and reducing bacterial resistance.