Forecasting influenza epidemics in China using transmission dynamic model with absolute humidity.

Background: An influenza forecasting system is critical to influenza epidemic preparedness. Low temperature has long been recognized as a condition favoring influenza epidemic, yet it fails to justify the summer influenza peak in tropics/subtropics. Recent studies have suggested that absolute humidity (AH) had a U-shape relationship with influenza survival and transmission across climate zones, indicating that a unified influenza forecasting system could be established for China with various climate conditions. Methods: Our study has generated weekly influenza forecasts by season and type/subtype in northern and southern China from 2011 to 2021, using a forecasting system combining an AH-driven susceptible-infected-recovered-susceptible (SIRS) model and the ensemble adjustment Kalman filter (EAKF). Model performance was assessed by sensitivity and specificity in predicting epidemics, and by accuracies in predicting peak timing and magnitude. Results: Our forecast system can generally well predict seasonal influenza epidemics (mean sensitivity>87.5%; mean specificity >80%). The average forecast accuracies were 82% and 60% for peak timing and magnitude at 3-6 weeks ahead for northern China, higher than those of 42% and 20% for southern China. The accuracy was generally better when the forecast was made closer to the actual peak time. Discussion: The established AH-driven forecasting system can generally well predict the occurrence of seasonal influenza epidemics in China.

PPAR gamma and PGC-1alpha activators protect against diabetic nephropathy by suppressing the inflammation and NF-kappaB activation.

AIM: Inflammation plays a critical role in the progression of diabetic nephropathy. Peroxisome proliferator-activated receptor gamma (PPARγ) and its coactivator PPARγ coactivator-1 alpha (PGC-1α) enhance mitochondrial biogenesis and cellular energy metabolism but inhibit inflammation. However, the molecular mechanism through which these two proteins cooperate in the kidney remains unclear. The aim of the present study was to investigate this mechanism. METHODS: HK-2 human proximal tubular cells were stimulated by inflammatory factors, the expression of PPARγ and PGC-1α were determined via reverse transcription-quantitative polymerase chain reaction (PCR) and western blotting (WB), and DNA binding capacity was measured by an EMSA. Furthermore, db/db mice were used to establish a diabetic nephropathy model and were administered PPARγ and PGC-1α activators. Kidney injury was evaluated microscopically, and the inflammatory response was assessed via WB, immunohistochemistry and immunofluorescence staining. Besides, HK-2 cells were stimulated by high glucose and inflammatory factors with and without ZLN005 treatment, the expression of PPARγ, PGC-1α, p-p65 and p65 were determined via qPCR and WB. RESULTS: Our results revealed that both TNF-α and IL-1ß significantly decreased PPARγ and PGC-1 expression in vitro. Cytokines obviously decreased PPARγ DNA binding capacity. Moreover, we detected rapid activation of the NF-κB pathway in the presence of TNF-α or IL-1ß. PPARγ and PGC-1α activators effectively protected against diabetic nephropathy and suppressed NF-κB expression both in db/db mice and HK-2 cells. CONCLUSION: PPARγ and its coactivator PGC-1α actively participate in protecting against renal inflammation by regulating the NF-κB pathway, which highlights their potential as therapeutic targets for renal diseases.

Fe─S Bond-Mediated Efficient Electron Transfer in Quantum Dots/Metal-Organic Frameworks for Boosting Photoelectrocatalytic Nitrogen Fixation.

Effective electron supply to produce ammonia in photoelectrochemical nitrogen reduction reaction (PEC NRR) remains challenging due to the sluggish multiple proton-coupled electron transfer and unfavorable carrier recombination. Herein, InP quantum dots decorated with sulfur ligands (InP QDs-S2-) bound to MIL-100(Fe) as a benchmark catalyst for PEC NRR is reported. It is found that MIL-100(Fe) can combined with InP QDs-S2- via Fe─S bonds as bridge to facilitate the electron transfer by experimental results. The formation of Fe─S bonds can facilitate electron transfer from inorganic S2- ligands of InP QDs to the Fe metal sites of MIL-100(Fe) within 52 ps, ensuring a more efficient electron transfer and electron-hole separation confirmed by the time-resolved spectroscopy. More importantly, the process of photo-induced carrier transfer can be traced by in situ attenuated total reflection surface-enhanced infrared tests, certifying that the effective electron transfer can promote N≡N dissociation and N2 hydrogenation. As a result, InP QDs-S2-/MIL-100(Fe) exhibits prominent performance with an outstanding NH3 yield of 0.58 µmol cm-2 h-1 (3.09 times higher than that of MIL-100(Fe)). This work reveals an important ultrafast dynamic mechanism for PEC NRR in QDs modified metal-organic frameworks, providing a new guideline for the rational design of efficient MOFs photocathodes.

Overexpression of SlALC Increases Drought and Salt Tolerance and Affects Fruit Dehiscence in Tomatoes.

The bHLH transcription factors are important plant regulators against abiotic stress and involved in plant growth and development. In this study, SlALC, a gene coding for a prototypical DNA-binding protein in the bHLH family, was isolated, and SlALC-overexpression tomato (SlALC-OE) plants were generated by Agrobacterium-mediated genetic transformation. SlALC transgenic lines manifested higher osmotic stress tolerance than the wild-type plants, estimated by higher relative water content and lower water loss rate, higher chlorophyll, reducing sugar, starch, proline, soluble protein contents, antioxidant enzyme activities, and lower MDA and reactive oxygen species contents in the leaves. In SlALC-OE lines, there were more significant alterations in the expression of genes associated with stress. Furthermore, SlALC-OE fruits were more vulnerable to dehiscence, with higher water content, reduced lignin content, SOD/POD/PAL enzyme activity, and lower phenolic compound concentrations, all of which corresponded to decreased expression of lignin biosynthetic genes. Moreover, the dual luciferase reporter test revealed that SlTAGL1 inhibits SlALC expression. This study revealed that SlALC may play a role in controlling plant tolerance to drought and salt stress, as well as fruit lignification, which influences fruit dehiscence. The findings of this study have established a foundation for tomato tolerance breeding and fruit quality improvement.

Evaluation of Saffron Quality Using Rapid Quantitative Inspection Technology with Near-Infrared Spectroscopy.

A predictive model utilizing near-infrared spectroscopy was developed to estimate the loss on drying, total contents of crocin I and crocin II, and picrocrocin content of saffron. Initially, the LD values were determined using a moisture-ash analyzer, while HPLC was employed for measuring the total contents of crocin I, crocin II, and picrocrocin. The near-infrared spectra of 928 saffron samples were collected and preprocessed using first derivative, standard normal variable transformation, detrended correction, multivariate scattering correction, Savitzky-Golay smoothing, and mean centering methods. Leveraging the partial least squares method, regression models were constructed, with parameters optimized through a selective combination of the above six preprocessing methods. Subsequently, prediction models for loss on drying, total contents of crocin I and crocin II, and picrocrocin content were established, and the prediction accuracy of the models was verified. The correlation coefficients and root mean square error of loss on drying, total contents of crocin I and crocin II, and picrocrocin content demonstrated high accuracy, with R2 values of 0.8627, 0.8851, and 0.8592 and root mean square error values of 0.0260, 0.0682, and 0.0465. This near-infrared prediction model established in the present study offers a precise and efficient means of assessing loss on drying, total contents of crocin I and crocin II, and picrocrocin content in saffron and is useful for the development of a rapid quality evaluation system.

SlFSR positively regulates ethylene biosynthesis and lycopene accumulation during fruit ripening in tomato.

Transcription factors (TFs) are crucial for regulating fruit ripening in tomato (Solanum lycopersicum). The GRAS (GAI, RGA, and SCR) TFs are involved in various physiological processes, but their role in fruit ripening has seldom been reported. We have previously identified a gene encoding GRAS protein named SlFSR (Fruit Shelf-life Regulator), which is implicated in fruit ripening by regulating cell wall metabolism; however, the underlying mechanism remains unclear. Here, we demonstrate that SlFSR proteins are localized to the nucleus, where they could bind to specific DNA sequences. SlFSR acts downstream of the master ripening regulator RIN and could collaborate with RIN to control the ripening process by regulating expression of ethylene biosynthesis genes. In SlFSR-CR (CRISPR/Cas9) mutants, the initiation of fruit ripening was not affected but the reduced ethylene production and a delayed coloring process occurred. RNA-sequencing (RNA-seq) and promoter analysis reveal that SlFSR directly binds to the promoters of two key ethylene biosynthesis genes (SlACO1 and SlACO3) and activates their expression. However, SlFSR-CR fruits displayed a significant down-regulation of key rate-limiting genes (SlDXS1 and SlGGPPS2) in the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway, which may account for the impaired lycopene synthesis. Altogether, we propose that SlFSR positively regulates ethylene biosynthesis and lycopene accumulation, providing valuable insights into the molecular mechanisms underlying fruit ripening.

Pyrolysis-induced migration and transformation of heavy metals in sewage sludge containing microplastics.

Stabilizing heavy metals (HMs) in sewage sludge is urgently needed to facilitate its recycling and reuse. Pyrolysis stands out as a promising method for not only stabilizing these metals but also producing biochar. Our research delves into the migration and transformation of specific HMs (Cr, Mn, Ni, Cu, Zn, As, and Pb) during co-pyrolysis under various conditions, including the presence and absence of microplastics (PVC and PET). We examined different concentrations of these plastics (1 %, 5 %, 10 %, and 15 %) and temperatures (300 °C, 500 °C, and 700 °C). Findings reveal that microplastics, particularly PVC, enhance the migration of Zn and Mn, leading to significant volatilization of Zn and Pb at higher temperatures, peaking at 700 °C. The increase in temperature also markedly influences HM migration, with As showcasing notable loss rates that climbed by 18.0 % and 16.3 % in systems with PET and PVC, respectively, as temperatures soared from 300 °C to 700 °C. Moreover, our speciation analysis indicates that microplastics aid in transforming certain HMs from unstable to more stable forms, suggesting their beneficial role in HM stabilization during pyrolysis. This study significantly enriches our understanding of microplastics' impact on HM behavior in sewage sludge pyrolysis, offering new avenues for pollution control and environmental management strategies.

Lower regional urbanicity and socioeconomic status attenuate associations of green spaces with hypertension and diabetes mellitus: a national representative cross-sectional study in China.

BACKGROUND: High blood pressure (HBP) and diabetes mellitus (DM) are two of the most prevalent cardiometabolic disorders globally, especially among individuals with lower socio-economic status (SES). Studies have linked residential greenness to decreased risks of HBP and DM. However, there has been limited evidence on whether SES may modify the associations of residential greenness with HBP and DM. METHODS: Based on a national representative cross-sectional study among 44,876 adults, we generated the normalized difference vegetation index (NDVI) at 1 km spatial resolution to characterize individuals' residential greenness level. Administrative classification (urban/rural), nighttime light index (NLI), individual income, and educational levels were used to characterize regional urbanicity and individual SES levels. RESULTS: We observed weaker inverse associations of NDVI with HBP and DM in rural regions compared to urban regions. For instance, along with per interquartile range (IQR, 0.26) increment in residential NDVI at 0∼5 year moving averages, the ORs of HBP were 1.04 (95%CI: 0.94, 1.15) in rural regions and 0.85 (95%CI: 0.79, 0.93) in urban regions (P = 0.003). Along with the decrease in NLI levels, there were continuously decreasing inverse associations of NDVI with DM prevalence (P for interaction <0.001). In addition, weaker inverse associations of residential NDVI with HBP and DM prevalence were found among individuals with lower income and lower education levels compared to their counterparts. CONCLUSIONS: Lower regional urbanicity and individual SES could attenuate the associations of residential greenness with odds of HBP and DM prevalence.

Acupuncture and moxibustion intervention in functional dyspepsia: Gastric and duodenal regulation.

Functional dyspepsia (FD) is a brain-gut interaction disorder located in the stomach and duodenum, which has complex pathophysiological mechanisms, and there is no effective treatment for FD. Acupuncture and moxibustion have been proven to have definite and significant efficacy on FD. Focusing on the affected area and combined with the potential pathophysiology of FD, here we discuss the possible mechanisms of acupuncture and moxibustion in treating FD to guide future clinical and experimental research. We argue that the pathological causes of FD can be roughly divided into gastrointestinal dysfunction, duodenal low-grade inflammation, visceral hypersensitivity, and duodenal intestinal barrier and microbial imbalance. Correspondingly, the possible mechanisms of acupuncture and moxibustion in treating FD are elucidated from the perspective of how they improve gastric accommodation, regulate gastrointestinal motility, reduce gastric visceral sensitivity, regulate eosinophil-mast cell axis, inhibit low-grade inflammatory responses, and possibly regulate intestinal microbial homeostasis and duodenal barrier function through the microbiota-gut-brain axis. Although some evidence is still lacking, acupuncture remains a promising treatment for FD. In the future, it is necessary to conduct additional clinical and experimental research on acupuncture and moxibustion in treating FD to further explore their effects and mechanisms.

Health resource allocation within the close-knit medical consortium after the Luohu healthcare reform in China: efficiency, productivity, and influencing factors.

Objective: This study aims to assess the efficiency and productivity of the Luohu Hospital Group after the reform and to identify factors influencing the efficiency to support the future development of medical consortia. Methods: Data on health resources from Shenzhen and the Luohu Hospital Group for the years 2015 to 2021 were analyzed using the super-efficiency slack-based measure data envelopment analysis (SE-SBM-DEA) model, Malmquist productivity index (MPI), and Tobit regression to evaluate changes in efficiency and productivity and to identify determinants of efficiency post-reform. Results: After the reform, the efficiency of health resource allocation within the Luohu Hospital Group improved by 33.87%. Community health centers (CHCs) within the group had an average efficiency score of 1.046. Moreover, the Luohu Hospital Group's average total factor productivity change (TFPCH) increased by 2.5%, primarily due to gains in technical efficiency change (EFFCH), which offset declines in technical progress change (TECHCH). The efficiency scores of CHCs were notably affected by the ratio of general practitioners (GPs) to health technicians and the availability of home hospital beds. Conclusion: The reform in the Luohu healthcare system has shown preliminary success, but continuous monitoring is necessary. Future strategies should focus on strengthening technological innovation, training GPs, and implementing the home hospital bed policy. These efforts will optimize the efficiency of health resource allocation and support the integration and development of resources within the medical consortium.

Comprehensive Identification and Expression Analysis of the Multidrug and Toxic Compound Extrusion (MATE) Gene Family in Brachypodium distachyon.

The Multidrug and Toxic Compound Extrusion (MATE) proteins serve as pivotal transporters responsible for the extrusion of metabolites, thereby playing a significant role in both plant development and the detoxification of toxins. The MATE gene family within the Brachypodium distachyon, which is an important model organism of the Poaceae family, remains largely unexplored. Here, a comprehensive identification and analysis of MATE genes that complement B. distachyon were conducted. The BdMATE genes were systematically categorized into five distinct groups, predicated on an assessment of their phylogenetic affinities and protein structure. Furthermore, our investigation revealed that dispersed duplication has significantly contributed to the expansion of the BdMATE genes, with tandem and segmental duplications showing important roles, suggesting that the MATE genes in Poaceae species have embarked on divergent evolutionary trajectories. Examination of ω values demonstrated that BdMATE genes underwent purifying selection throughout the evolutionary process. Furthermore, collinearity analysis has confirmed a high conservation of MATE genes between B. distachyon and rice. The cis-regulatory elements analysis within BdMATEs promoters, coupled with expression patterns, suggests that BdMATEs play important roles during plant development and in response to phytohormones. Collectively, the findings presented establish a foundational basis for the subsequent detailed characterization of the MATE gene family members in B. distachyon.

Ganoderma lucidum polysaccharide promotes broiler health by regulating lipid metabolism, antioxidants, and intestinal microflora.

Ganoderma lucidum polysaccharides (GLP) are the primary bioactive macromolecular compounds of Ganoderma lucidum, possessing antioxidant and immunomodulatory effects. Hot water extract of Juncao-substrate Ganoderma Lucidum residue (HWE-JGLR) is abundant in GLP. There are few research reports on the application of HWE-JGLR in animal husbandry. Therefore, this study aims to investigate the effects of HWE-JGLR supplementation on growth performance, serum biochemistry, the antioxidant function of serum and liver, and the intestinal microbiota of yellow-feathered broilers. The control group was fed a corn-soybean meal basal diet, while the HJ I, II, and III groups received diets supplemented with 0.25 %, 0.5 %, and 1 % of HWE-JGLR, respectively. Results showed that HWE-JGLR increased the serum HDL-C content and decreased the TG content in broilers. Moreover, HWE-JGLR enhanced the antioxidant function by the Keap1-Nrf2/ARE signaling pathway and the antioxidative enzyme in broilers. In addition, the cecum of the metagenomic analysis of 16S rRNA showed that the relative abundance of no-rank Ruminococcacea was increased in the HJ I group. Our findings indicate that HWE-JGLR has strong potential for development as a green feed additive based on its functions of lipid-lowering, antioxidation, and the modulation of gut microbiota composition.

Empowering probiotics with high xanthine transport for effective hyperuricemia management.

Hyperuricemia, a prevalent metabolic disorder, poses a susceptibility to various complications. The conventional pharmacotherapeutic approaches for hyperuricemia often entail notable adverse effects, posing substantial clinical challenges. Hence, the imperative lies in the development of novel, safe and effective strategies for preventing and treating hyperuricemia. Here, we developed a probiotic Escherichia coli Nissle 1917 strain, designated as YES301, which contains a rationally designed xanthine importer XanQ, enabling efficient uptake of xanthine and hypoxanthine, consequently leading to reduced serum uric acid concentrations and amelioration of renal impairments in a murine model of hyperuricemia. Importantly, YES301 exhibited a therapeutic efficacy comparable to allopurinol, a conventional uric acid-lowering agent, and manifesting fewer adverse effects and enhanced biosafety. These findings highlight the promising potential of engineered probiotics in the management of hyperuricemia through reducing intestinal purine levels.

Effect of sarcopenia on liver cirrhosis with complicating oesophageal and gastric varices after endoscopic therapy.

Several investigators have reported that sarcopenia is common in patients with liver cirrhosis. However, few studies have probed the association between sarcopenia and liver cirrhosis complicated with oesophageal and gastric variceal bleeding (LC-EGVB). We aimed to investigate the impact of sarcopenia on rebleeding after endoscopic therapy in patients with LC-EGVB. Computed tomography (CT) radiographs from the third lumbar vertebra were selected to analyse body composition, including skeletal muscle tissue, visceral and subcutaneous adipose tissue using SliceOmatic software. Sarcopenia was defined using validated cutoff values for patients with liver cirrhosis: 44.77 cm2/m2 for men and 32.50 cm2/m2 for women. A total of 187 patients with LC-EGVB and 309 controls were included in this study. The rate of sarcopenia in controls (17.4 %) was significantly lower than that in patients with LC-EGVB (41.2 %). Patients with LC-EGVB exhibiting sarcopenia showed a high prevalence of portal vein thrombosis and rebleeding rate at 1 year. The rate of sarcopenia in the rebleeding group was significantly higher than that in the non-rebleeding group. Univariate and multivariate analyses showed that sarcopenia was an independent risk factor for rebleeding within 1 year in patients with LC-EGVB. Patients with LC-EGVB displayed a high prevalence of sarcopenia. Sarcopenia was observed to be an independent risk factor for rebleeding within 1 year.

GPR97 depletion aggravates imiquimod-induced psoriasis pathogenesis via amplifying IL-23/IL-17 axis signal pathway.

Skin psoriasis is defined as receiving external stimulation to activate skin dendritic cells (DCs) which can release interleukin 23 (IL-23) to interlink the innate and adaptive immunity as well as induce T helper 17 (Th17) cell differentiation leading to elevated production of interleukin 17 (IL-17) for keratinocytes over production. This autoimmune loop in psoriasis pathogenesis is influenced by G protein-coupled receptor (GPCR) signalling transduction, and in particular, function of adhesion molecule GPR97 in psoriasis endures to be utterly addressed. In this research, our team allocated GPR97 depletion (GPR97-/-), GPR97 conditional depletion on dendritic cell (DC-cKO), and keratin 14-conditional knockout (K14-cKO) mice models to explore the function of GPR97 which influences keratinocytes and skin immunity. It was found that significantly aggravated psoriasis-like lesion in GPR97-/- mice. In addition, hyperproliferative keratinocytes as well as accumulation of DCs and Th17 cells were detected in imiquimod (IMQ)-induced GPR97-/- mice, which was consistent with the results in DC-cKO and K14-cKO psoriasis model. Additional investigations indicated that beclomethasone dipropionate (BDP), an agonist of GPR97, attenuated the psoriasis-like skin disease and restricted HaCaT cells abnormal proliferation as well as Th17 cells differentiation. Particularly, we found that level of NF-κB p65 was increased in GPR97-/- DCs and BDP could inhibit p65 activation in DCs. Role of GPR97 is indispensable and this adhesion receptor may affect immune cell enrichment and function in skin and alter keratinocytes proliferation as well as differentiation in psoriasis.

Discussion on the evaluation of the therapeutic efficacy of uterine artery blood flow parameters and serum PLGF and sFlt-1 in patients with recurrent spontaneous abortion.

OBJECTIVE: To investigate the effects of different drug treatments on uterine artery blood flow parameters, serum placental growth factor (PLGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and sFlt-1/PLGF in patients with recurrent spontaneous abortion and to explore the predictive value of uterine artery blood flow parameters, serum PLGF, sFlt-1, and sFlt-1/PLGF for pregnancy outcomes. METHODS: This retrospective cohort study included 173 patients who experienced recurrent spontaneous abortion and 100 control patients. Patients with recurrent spontaneous abortion were divided into an aspirin group (75 patients), aspirin combined with low molecular weight heparin (LMWH) group (68 patients), and non-drug group (30 patients) based on different drug treatments. Uterine artery blood flow parameters at gestational weeks 30-31+6 were monitored for the four groups, and serum samples were collected at gestational weeks 30-31+6 to measure the levels of serum PLGF and sFlt-1 and calculate the sFlt-1/PLGF ratio. RESULTS: 1. Uterine artery blood flow parameters at gestational weeks 30-31+6 were significantly greater in the non-drug group than in the aspirin group, combined drug group, and control group (p<0.05). 2. Serum PLGF levels and the sFlt-1/PLGF ratio at gestational weeks 30-31+6 were significantly lower in the non-drug group than in the aspirin group, combined drug group, and control group, while serum sFlt-1 levels were significantly greater in the non-drug group than in the aspirin group, combined drug group, and control group (p<0.05). 3. Serum PLGF, sFlt-1, and sFlt-1/PLGF had lower diagnostic efficiency for predicting hypertensive disorders during pregnancy than the combined diagnostic efficiency of serum PLGF, sFlt-1, and sFlt-1/PLGF with uterine artery blood flow parameters at gestational weeks 30-31+6. CONCLUSION: Aspirin and aspirin combined with LMWH can upregulate serum PLGF and decrease serum sFlt-1 levels in patients with recurrent spontaneous abortion, reduce the miscarriage rate, and significantly improve pregnancy outcomes. The combination of serum PLGF, sFlt-1, sFlt-1/PLGF, and uterine artery blood flow parameters can effectively predict hypertensive disorders during pregnancy.

Upregulated PrPC by HBx enhances NF-κB signal via liquid-liquid phase separation to advance liver cancer.

Cellular prion protein (PrPC) has been implicated in carcinogenic through the activation of various signal pathways, however, the precise mechanisms remain elusive. In vitro studies have shown that PrPC is prone to undergo liquid-liquid phase separation (LLPS). However, it remains unknown whether PrPC contributes to LLPS-inducing cancer development. Herein, we observed an upregulation of PrPC expression in hepatitis B virus-positive hepatocellular carcinoma (HCC). Subsequent investigation revealed that HBx of HBV enhances PrPC expression in a dose-dependent manner by binding to CREB1. Furthermore, we demonstrated that PrPC undergoes LLPS and recruits TRAF2/6, TAB2/3, and TAK1 protein, thereby activating the NF-κB signaling pathway and promoting tumor progression. Notably, although unable to undergo LLPS itself, the α3 helix of PrPC is essential for its activation of the NF-κB signaling pathway during the LLPS process. Further analysis unveiled that disulfide bond formation within the C-terminal domain of PrPC is necessary for its LLPS and subsequent activation of the NF-κB signaling pathway. Additionally, our findings indicate that NF-κB activation by PrPC condensates leads to increased IL-8 expression which further promotes tumor development.

Association of antihypertensive drugs with periodontitis: a comprehensive drug-target Mendelian randomization study.

AIMS: The aim of this study was to elucidates the nuanced interactions between antihypertensive medications and the risk of periodontitis using Mendelian randomization (MR) analysis method. METHODS: Our study adopted a drug-target Mendelian randomization method to assess the long-term effects of nine antihypertensive drug categories on the risk of periodontitis in both acute and chronic cases. We selected genetic variants located in or near genes relevant to the targets of these drugs and associated with systolic blood pressure (SBP) to simulate the influence of antihypertensive treatments. Genetic information on SBP and periodontitis susceptibility was extracted from extensive genome wide association studies for both acute and chronic conditions. Additionally, we conducted a secondary analysis using expression quantitative trait loci for the genes of interest as alternative proxies.Colocalizaion analysis was performed to explore shared variants between antihypertensive drugs and periodontitis. RESULTS: Our analysis revealed that the use of angiotensin converting enzyme inhibitors with an increased risk of acute periodontitis (odds ratio [OR] [95% confidence interval]: 1.43 [1.11, 1.85] per 1 mmHg reduction in SBP; p = 5.93×10-3) and loop diuretics with a decreased risk of chronic periodontitis (OR: 0.94 [0.90, 0.98]; p = 2.94×10-3). Moreover, genetically mimicking the use of a suggestive protective effect of thiazides and related diuretics on acute periodontitis was observed in both acute (OR: 0.95 [0.90, 0.99]; p = 0.021) and chronic (OR: 0.98 [097, 1.00]; p = 0.045) periodontitis. Colocalizaion analysis revealed antihypertensive drugs and periodontitis shared causal variants in ACE and SLC12A2 locus. CONCLUSION: The research indicates that loop diuretics might decrease the risk of 31 periodontitis, while angiotensin-converting enzyme inhibitors could heighten the risk. Further investigations are required to evaluate the potential of reusing antihypertensive drugs for periodontitis prevention.

The GaCl3-Catalyzed Knoevenagel Condensation To Achieve Acceptor-Donor-Acceptor Small-Molecule Acceptors: A DFT Mechanistic Study.

Herein, the reaction mechanism for the GaCl3-catalyzed Knoevenagel condensation of 2-formylindacenodithieno[3,2-b]thiophene (ITIC-CHO) and active methylene compound 1,1-dicyanomethylene-3-indanone (IC) to synthesize ITIC in the presence of acetic anhydride was investigated using the density functional theory (DFT) method. The calculated results indicate that this reaction follows a bimolecular GaCl3 catalytic mechanism. The free energy span for the monomolecular GaCl3 catalytic mechanism is the highest (31.8 kcal/mol), followed by the trimolecular GaCl3 catalytic mechanism (26.4 kcal/mol) and the bimolecular GaCl3 catalytic mechanism (26.3 kcal/mol). The trimolecular GaCl3 path and bimolecular GaCl3 path are competitive, but the former path is limited by the concentration of GaCl3. The inclusion of GaCl3 could stabilize the transition states of C-H activation. Compared to the GaCl3-catalyzed Knoevenagel condensation, that catalyzed by pyridine is not advantageous, owning a high energy span of 31.7 kcal/mol. These agree well with experimental results. This work could provide a novel theoretical understanding of the Knoevenagel condensation, which could inspire the development of a synthesis strategy for electron acceptor materials.

Antioxidant and anti-inflammatory peptides in dry-fermented sausages fermented with Staphylococcus simulans QB7.

This study focused on investigating the impacts of Staphylococcus simulans QB7 (S. simulans QB7) on the generation of antioxidant and anti-inflammatory peptides in dry-fermented sausages and the associated mechanisms by in silico. S. simulans QB7 remarkably increased (P < 0.05) the peptide concentration, antioxidant, and anti-inflammatory capacity of peptide extracts. There were 29 peptide sequences with potential activities of antioxidation and anti-inflammation according to BIOPEP-UWM prediction. Molecular docking results indicated that peptide GPGPWG can bind to Kelch-like ECH-associated protein 1 (Keap1) with highest interaction energy, while peptide ANPILEAFG showed highest interaction energy towards p65, I kappa B kinase 2 (IKK-ß), c-Jun N-terminal kinases (JNK), and p38 kinases (p38) due to form salt bridge, h-bond, and pi-alkyl. These results suggested that S. simulans QB7 promoted antioxidant and anti-inflammatory peptide generation within dry-fermented sausages.