Untargeted metabonomics and TLR4/ NF-κB signaling pathway analysis reveals potential mechanism of action of Dendrobium huoshanense polysaccharide in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is marked by hepatic steatosis accompanied by an inflammatory response. At present, there are no approved therapeutic agents for NAFLD. Dendrobium Huoshanense polysaccharide (DHP), an active ingredient extracted from the stems of Dendrobium Huoshanense, and exerts a protective effect against liver injury. However, the therapeutic effects and mechanisms of action DHP against NAFLD remain unclear. DHP was extracted, characterized, and administered to mice in which NAFLD had been induced with a high-fat and high-fructose drinking (HFHF) diet. Our results showed that DHP used in this research exhibits the characteristic polysaccharide peak with a molecular weight of 179.935 kDa and is composed primarily of Man and Glc in a molar ratio of 68.97:31.03. DHP treatment greatly ameliorated NAFLD by significantly reducing lipid accumulation and the levels of liver function markers in HFHF-induced NAFLD mice, as evidenced by decreased serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC) and total triglyceride (TG). Furthermore, DHP administration reduced hepatic steatosis, as shown by H&E and Oil red O staining. DHP also inhibited the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway expression, thereby reducing levels of hepatic proinflammatory cytokines. Besides, untargeted metabolomics further indicated that 49 metabolites were affected by DHP. These metabolites are strongly associated the metabolism of glycine, serine, threonine, nicotinate and nicotinamide, and arachidonic acid. In conclusion, DHP has a therapeutic effect against NAFLD, whose underlying mechanism may involve the modulation of TLR4/NF-κB, reduction of inflammation, and regulation of the metabolism of glycine, serine, threonine, nicotinate and nicotinamide metabolism, and arachidonic acid metabolism.

Incidence and prognosis of olfactory and gustatory dysfunctions related to SARS-CoV-2 Omicron strain infection in China: A national multicenter survey of 35,566 individuals.

Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

Diachronic evolvement from tetra-icosahedral to quasi-hexagonal close-packed bimetal clusters.

Here we report a diachronic evolvement from tetra-icosahedral Au30Ag12(C[triple bond, length as m-dash]CR)24 to quasi-hcp (hexagonal close-packed) Au47Ag19(C[triple bond, length as m-dash]CR)32 via a one-step reduction, in which the size/structure conversion of the two clusters is not a typical Oswald growth process, but involves interface shrinking followed by core rearrangement and surface polymerization. Au30Ag12(C[triple bond, length as m-dash]CR)24 has an aesthetic Au18Ag8 kernel that is composed of four interpenetrating Au10Ag3 icosahedra, while Au47Ag19(C[triple bond, length as m-dash]CR)32 has a twisted Au19 core capped by a Au12Ag19 shell that are stacked in a layer-by-layer manner with a quasi-hcp pattern. The discovery of the two clusters not only provides further evidence for icosahedral clusters with longer excited-state lifetime compared to hcp-like clusters, but also discloses a double increase in catalytic reactivity for electrocatalytic oxidation of ethanol over quasi-hcp clusters in comparison with icosahedral clusters. This work provides the rationale for reversing the bottom-up growth process to remake bimetal clusters.

Analysis of medical images super-resolution via a wavelet pyramid recursive neural network constrained by wavelet energy entropy.

Recently, multi-resolution pyramid-based techniques have emerged as the prevailing research approach for image super-resolution. However, these methods typically rely on a single mode of information transmission between levels. In our approach, a wavelet pyramid recursive neural network (WPRNN) based on wavelet energy entropy (WEE) constraint is proposed. This network transmits previous-level wavelet coefficients and additional shallow coefficient features to capture local details. Besides, the parameter of low- and high-frequency wavelet coefficients within each pyramid level and across pyramid levels is shared. A multi-resolution wavelet pyramid fusion (WPF) module is devised to facilitate information transfer across network pyramid levels. Additionally, a wavelet energy entropy loss is proposed to constrain the reconstruction of wavelet coefficients from the perspective of signal energy distribution. Finally, our method achieves the competitive reconstruction performance with the minimal parameters through an extensive series of experiments conducted on publicly available datasets, which demonstrates its practical utility.

Peripheral Neuropathy Associated with Higher Mortality in Population with Chronic Kidney Disease: National Health and Nutrition Examination Surveys.

Introduction: Peripheral neuropathy (PN), one of the commonest neurological complications of chronic kidney disease (CKD), was associated with physical limitation. Studies showed that a decrease in physical capability in patients with CKD is related with an increased risk of mortality. The objective of our research was to directly explore the relationship between PN and risk of mortality in patients with CKD. Method: 1,836 participants with CKD and 6,036 participants without CKD, which were classified by PN based on monofilament examination in National Health and Nutrition Examination Survey (NHANES), were collected from the 1999 to 2004 National Health and Nutrition Examination Surveys. Multivariable Cox proportional hazard models were conducted to assess the relationships of PN and deaths in patients with CKD and non-CKD. Results: During 14 years of a median follow-up from 1999 to 2015 and 2004 to 2015, 1,072 (58.4%) and 1,389 (23.0%) deaths were recorded in participants with CKD and without CKD, respectively. PN was related with increased all-cause mortality even after adjusting possible confounding factors in population with CKD (hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.17-1.53) and without CKD (HR 1.27, 95% CI 1.12-1.43). And the adjusted HRs (95% CI) for cardiovascular mortality of the people with CKD and without CKD who suffered from PN were 1.42 (1.07, 1.90) and 1.23 (0.91, 1.67), respectively, versus those without PN. Conclusion: PN was related with a higher risk of all-cause and cardiovascular death in people with CKD, which clinically suggests that the adverse prognostic impact of PN in the CKD population deserves attention and is an important target for intervention.

An aldehyde dehydrogenase gene, GhALDH7B4_A06, positively regulates fiber strength in upland cotton (Gossypium hirsutum L.).

High fiber strength (FS) premium cotton has significant market demand. Consequently, enhancing FS is a major objective in breeding quality cotton. However, there is a notable lack of known functionally applicable genes that can be targeted for breeding. To address this issue, our study used specific length-amplified fragment sequencing combined with bulk segregant analysis to study FS trait in an F2 population. Subsequently, we integrated these results with previous quantitative trait locus mapping results regarding fiber quality, which used simple sequence repeat markers in F2, F2:3, and recombinant inbred line populations. We identified a stable quantitative trait locus qFSA06 associated with FS located on chromosome A06 (90.74-90.83 Mb). Within this interval, we cloned a gene, GhALDH7B4_A06, which harbored a critical mutation site in coding sequences that is distinct in the two parents of the tested cotton line. In the paternal parent Ji228, the gene is normal and referred to as GhALDH7B4_A06O; however, there is a nonsense mutation in the maternal parent Ji567 that results in premature termination of protein translation, and this gene is designated as truncated GhALDH7B4_A06S. Validation using recombinant inbred lines and gene expression analysis revealed that this mutation site is correlated with cotton FS. Virus-induced gene silencing of GhALDH7B4 in cotton caused significant decreases in FS and fiber micronaire. Conversely, GhALDH7B4_A06O overexpression in Arabidopsis boosted cell wall component contents in the stem. The findings of our study provide a candidate gene for improving cotton fiber quality through molecular breeding.

The Role of the Tissue Perfusion Index in Predicting Disease Severity and Prognosis in Patients with Severe and Critical COVID-19.

OBJECTIVES: The study investigated whether percutaneous partial pressure of oxygen (PtcO2), percutaneous partial pressure of carbon dioxide (PtcCO2), and the derived tissue perfusion index (TPI) can predict the severity and short-term outcomes of severe and critical COVID-19. DESIGN: Prospective observational study conducted from January 1, 2023 to February 10, 2023. SETTING: A teaching hospital specializing in tertiary care in Nanjing City, Jiangsu Province, China. PARTICIPANTS: Adults (≥18 years) with severe and critical COVID-19. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The general information and vital signs of the patients were collected. The PtcO2 and PtcCO2 were monitored in the left dorsal volar. The ratio of TPI was defined as the ratio of PtcO2/fraction of inspired oxygen (FiO2) to PtcCO2. Mortality at 28 was recorded. The ability of the TPI to assess disease severity and predict prognosis was determined. ENDPOINT: Severity of the disease on the enrollment and mortality at 28. RESULTS: A total of 71 patients with severe and critical COVID-19, including 40 severe and 31 critical cases, according to the COVID-19 treatment guidelines published by WHO, were recruited. Their median age was 70 years, with 56 (79%) males. The median SpO2/FiO2, PtcO2, PtcCO2, PtcO2/ FiO2, and TPI values were 237, 61, 42, 143, and 3.6 mm Hg, respectively. Compared with those for severe COVID-19, the TPI, PtcO2/ FiO2, SpO2/FiO2, and PtcO2 were significantly lower in critical COVID-19, while the PtcCO2 was significantly higher. After 28 days, 26 (37%) patients had died. TPI values < 3.5 were correlated with more severe disease status (AUC 0.914; 95% CI: 0.847-0.981, P < 0.001), and TPI < 3.3 was associated with poor outcomes (AUC 0.937; 95% CI 0.880-0.994, P < 0.001). CONCLUSIONS: The tissue perfusion index (TPI), PtcCO2, and PtcO2/ FiO2 can predict the severity and outcome of severe and critical COVID-19.

Structural characterization and improves cognitive disorder in ageing mice of a glucomannan from Dendrobium huoshanense.

In the present work, a neutral polysaccharide (DHP-2W) with attenuating cognitive disorder was identified from Dendrobium huoshanense and its structure was clarified. The polysaccharide was successfully purified from D. huoshanense by column chromatography and its activity was evaluated. With a molecular weight of 508.934kDa, this polysaccharide is composed of mannose and glucose at a molar ratio of 75.81: 24.19. Structural characterization revealed that DHP-2W has a backbone consisting of 4)-ß-D-Manp-(1 and 4)-ß-D-Glcp-(1. In vivo experiments revealed that DHP-2W improved cognitive disorder in D-galactose treated mice and relieved oxidative stress and inflammation. DHP-2W attenuates D-galactose-induced cognitive disorder by inhibiting the BCL2/BAX/CASP3 pathway and activating the AMPK/SIRT pathway, thereby inhibiting apoptosis. Furthermore, DHP-2W had a significant effect on regulating the serum levels of Flavin adenine dinucleotide, Shikimic acid, and Kynurenic acid in aged mice. These, in turn, had a positive impact on AMPK/SIRT1 and BCL2/BAX/CASP3, resulting in protective effects against cognitive disorder.

Age-adjusted Charlson comorbidity index is associated with the risk of osteoporosis in older fall-prone men: a retrospective cohort study.

BACKGROUND: There is growing evidence linking the age-adjusted Charlson comorbidity index (aCCI), an assessment tool for multimorbidity, to fragility fracture and fracture-related postoperative complications. However, the role of multimorbidity in osteoporosis has not yet been thoroughly evaluated. We aimed to investigate the association between aCCI and the risk of osteoporosis in older adults at moderate to high risk of falling. METHODS: A total of 947 men were included from January 2015 to August 2022 in a hospital in Beijing, China. The aCCI was calculated by counting age and each comorbidity according to their weighted scores, and the participants were stratified into two groups by aCCI: low (aCCI < 5), and high (aCCI ≥5). The Kaplan Meier method was used to assess the cumulative incidence of osteoporosis by different levels of aCCI. The Cox proportional hazards regression model was used to estimate the association of aCCI with the risk of osteoporosis. Receiver operating characteristic (ROC) curve was adapted to assess the performance for aCCI in osteoporosis screening. RESULTS: At baseline, the mean age of all patients was 75.7 years, the mean BMI was 24.8 kg/m2, and 531 (56.1%) patients had high aCCI while 416 (43.9%) were having low aCCI. During a median follow-up of 6.6 years, 296 participants developed osteoporosis. Kaplan-Meier survival curves showed that participants with high aCCI had significantly higher cumulative incidence of osteoporosis compared with those had low aCCI (log-rank test: P < 0.001). When aCCI was examined as a continuous variable, the multivariable-adjusted model showed that the osteoporosis risk increased by 12.1% (HR = 1.121, 95% CI 1.041-1.206, P = 0.002) as aCCI increased by one unit. When aCCI was changed to a categorical variable, the multivariable-adjusted hazard ratios associated with different levels of aCCI [low (reference group) and high] were 1.00 and 1.557 (95% CI 1.223-1.983) for osteoporosis (P <  0.001), respectively. The aCCI (cutoff ≥5) revealed an area under ROC curve (AUC) of 0.566 (95%CI 0.527-0.605, P = 0.001) in identifying osteoporosis in older fall-prone men, with sensitivity of 64.9% and specificity of 47.9%. CONCLUSIONS: The current study indicated an association of higher aCCI with an increased risk of osteoporosis among older fall-prone men, supporting the possibility of aCCI as a marker of long-term skeletal-related adverse clinical outcomes.

Catalase-templated nanozyme-loaded microneedles integrated with polymyxin B for immunoregulation and antibacterial activity in diabetic wounds.

Diabetic wounds are characterized by chronic trauma, with long-term non-healing attributed to persistent inflammation and recurrent bacterial infections. Exacerbation of the inflammatory response is largely due to increased levels of reactive oxygen species (ROS). In this study, catalase (CAT) was used as a biological template to synthesize nanozyme-supported natural enzymes (CAT-Mn(SH)x) using a biomimetic mineralization method. Subsequently, polymyxin B (CAT-Mn(SH)x@PMB) was immobilized on its surface through electrostatic assembly. CAT-Mn(SH)x@PMB demonstrates the ability for slow and sustained release of hydrogen sulfide (H2S). Finally, CAT-Mn(SH)x@PMB loaded microneedles (MNs) substrate were synthesized using polyvinyl alcohol (PVA) and hydroxyethyl methacrylate (HEMA), and named CAT-(MnSH)x@PMB-MNs. It exhibited enhanced enzyme and antioxidant activities, along with effective antibacterial properties. Validation findings indicate that it can up-regulate the level of M2 macrophages and reduce the level of pro-inflammatory cytokine tumor necrosis factor-α (TNF-α). Additionally, it promotes angiogenesis and rapid nerve regeneration, thereby facilitating wound healing through its dual anti-inflammatory and antibacterial effects. Hence,this study introduces a time-space tissue-penetrating and soluble microneedle patch with dual anti-inflammatory and antibacterial effects for the treatment of diabetic wounds.

CRISPR/Cas9-mediated ebony knockout causes melanin pigmentation and prevents moth Eclosion in Ectropis grisescens.

Ectropis grisescens (Lepidoptera: Geometridae) is a destructive tea pest in China. Mimesis, characterized by changing body color, is an important trait of E. grisescens larvae. Hence, identifying melanin pathway-related genes may contribute to developing new pest control strategies. In the present study, we cloned Egebony, a gene potentially involved in melanin pigmentation in E. grisescens, and subsequently conducted CRISPR/Cas9-mediated targeted mutagenesis of Egebony to analyze its role in pigmentation and development. At the larvae, prepupae, and pupae stages, Egebony-knockout individuals exhibited darker pigmentation than the wild-type. However, Egebony knockout did not impact the colors of sclerotized appendants, including ocelli, setae, and claws. While mutant pupae could successfully develop into moths, they were unable to emerge from the puparium. Notably, embryo hatchability and larval survival of mutants remained normal. Further investigation indicated that mutant pupae exhibited significantly stronger shearing force than the wild-type, with the pigmented layer of mutant pupae appearing darker and thicker. Collectively, these results suggest that the loss of Egebony might increase the rigidity of the puparium and prevent moth eclosion. This study provides new insights into understanding the function and diversification of ebony in insect development and identifies a lethal gene that can be manipulated for developing effective pest control strategies.

Changes in bacterial community composition in the uterus of Holstein cow with endometritis before and after treatment with oxytetracycline.

It is important to study the bacteria that cause endometritis to identify effective therapeutic drugs for dairy cows. In this study, 20% oxytetracycline was used to treat Holstein cows (n = 6) with severe endometritis. Additional 10 Holstein cows (5 for healthy cows, 5 for cows with mild endometritis) were also selected. At the same time, changes in bacterial communities were monitored by high-throughput sequencing. The results show that Escherichia coli, Staphylococcus aureus and other common pathogenic bacteria could be detected by traditional methods in cows both with and without endometritis. However, 16S sequencing results show that changes in the abundance of these bacteria were not significant. Endometritis is often caused by mixed infections in the uterus. Oxytetracycline did not completely remove existing bacteria. However, oxytetracycline could effectively inhibit endometritis and had a significant inhibitory effect on the genera Bacteroides, Trueperella, Peptoniphilus, Parvimonas, Porphyromonas, and Fusobacterium but had no significant inhibitory effect on the bacterial genera Marinospirillum, Erysipelothrix, and Enteractinococcus. During oxytetracycline treatment, the cell motility, endocrine system, exogenous system, glycan biosynthesis and metabolism, lipid metabolism, metabolism of terpenoids, polyketides, cofactors and vitamins, signal transduction, and transport and catabolism pathways were affected.

Prevalence and risk factors of anxiety and depression in patients with multi-drug/rifampicin-resistant tuberculosis.

Background: Mental health disorders in patients with multi-drug or rifampicin-resistant tuberculosis (MDR/RR-TB) receive consistent attention. Anxiety and depression can manifest and may impact disease progression in patients with MDR/RR-TB. Given the heightened stressors resulting from the COVID-19 pandemic, this scenario is even more concerning. Objective: To evaluate the prevalence of and risk factors associated with anxiety and depression among patients with MDR/RR-TB in southern China. Methods: A facility-based cross-sectional study was undertaken at Guangzhou Chest Hospital in southern China, encompassing a cohort of 219 patients undergoing outpatient and inpatient treatment for MDR/RR-TB. Anxiety and depressive symptoms were assessed using the 7-Item Generalized Anxiety Disorder (GAD-7) scale and Patient Health Questionnaire-9 (PHQ-9). The ramifications of anxiety and depression were examined using univariate and multivariate logistic regression analyses, with odds ratios (ORs) and age- and sex-adjusted ORs (AORs) employed to quantify their influence. All data underwent statistical analysis using SPSS 25.0, with statistical significance established at P < 0.05. Results: Two hundred and nineteen individuals with MDR/RR-TB were included in the study. The prevalence of anxiety and depression was 57.53% (n = 126) and 65.75% (n = 144), respectively, with 33.3% (n = 73) of the participants experiencing both conditions simultaneously. Multivariate logistic regression analysis revealed that an age of 20-40 years [anxiety AOR = 3.021, 95% confidence interval (CI): 1.240-7.360; depression AOR = 3.538, 95% CI: 1.219-10.268], disease stigma (anxiety AOR = 10.613, 95% CI: 2.966-37.975; depression AOR = 4.514, 95% CI: 2.051-10.108) and poor physical health (anxiety AOR = 7.636, 95% CI: 2.938-19.844; depression AOR = 6.190, 95% CI: 2.468-15.529) were significant risk factors for moderate levels of anxiety and depression. Conclusions: We found that individuals with MDR/RR-TB had an elevated risk of anxiety and depression. To decrease the likelihood of unfavorable treatment outcomes, it is imperative to carefully monitor the psychological wellbeing of patients with MDR/RR-TB and promptly address any detrimental psychiatric conditions.

Exploring the Risk Factors for Deep Vein Thrombosis after Percutaneous Nephrolithotomy.

BACKGROUND: Deep vein thrombosis (DVT), a frequent complication following percutaneous nephrolithotomy (PCNL), may lead to severe conditions like pulmonary embolism. Current knowledge on postoperative DVT risk factors is, however, limited. The aim of our study was to investigate the risk of DVT after PCNL. METHODS: A retrospective study was conducted on patients who underwent PCNL from March 2020 to March 2023 at our institution. Patient demographics and clinical data, including, DVT-specific information, preoperative labs, and surgical details, was evaluated. RESULTS: One hundred patients were included. Thirty-two (20 males, 12 females, mean age 52.5 ± 7.4 years) developed lower limb DVT post-surgery, while the remaining 68 (48 males, 20 females, mean age 51.1 ± 5.5 years) had no DVT symptoms. Analysis revealed significant correlations between hyperlipidemia, operating time, postoperative bed rest duration, D-dimer level on the first day after surgery, Caprini risk assessment model (RAM) score, and DVT risk. D-dimer on the first day after percutaneous nephrolithotomy, postoperative bed rest time and Caprini RAM scores were independent risk factors for DVT after PCNL. Sex, age, hypertension status, diabetes status and smoking and drinking habits were not significantly associated with DVT risk. CONCLUSIONS: D-dimer on the first day after PCNL, postoperative bed rest time and Caprini RAM scores were independent risk factors for DVT after PCNL.

Schiff base functionalized dialdehyde starch for enhanced removal of Cu (II): Preparation, performances, DFT calculations.

Dialdehyde starch modified by 2-hydrazinopyridine (HYD-DAS) based on the reaction of dialdehyde starch (DAS) and 2-hydrazinopyridine was synthesized and characterized by FT-IR spectra, element analysis and SEM. HYD-DAS can efficiently adsorb Cu (II) ion to demonstrate visual color changes from yellow to dark brown in aqueous solutions. The influence on HYD-DAS to Cu (II) adsorption including pH value of solution, isotherm, kinetics, thermodynamics and possible mechanism had also been examined. Batch experiments indicate that HYD-DAS's to Cu (II) adsorption reaches equilibrium within 250 min, and its adsorption capacity and rate are 195.75 mg/g and 98.63 %, respectively. Moreover, HYD-DAS to Cu (II) adsorption remains robust and underscoring after five cycles to exhibit good selectivity and reusability. Kinetics studies suggest the absorption process follows a quasi-second-order with isotherms aligning to the Langmuir monolayer model, and thermodynamics reveals that it is a spontaneous endothermic nature of adsorption. Based on the analyses of XPS and DFT calculations, a possible mechanism for HYD-DAS to Cu (II) adsorption is that Cu (II) combined with nitrogen atoms from Schiff base and hydrazine pyridine ring in HYD-DAS.

Endoscopic ultrasound for the diagnosis and treatment of primary hepatocellular carcinoma.

Chronic liver disease has emerged as a significant global concern, with primary hepatocellular carcinoma (HCC) representing a critical consequence of this disease. However, early detection of HCC remains challenging in clinical practice. Recently, there has been a growing interest in applying endoscopic ultrasound (EUS) as a diagnostic tool for gastrointestinal diseases. Nevertheless, using EUS to diagnose and treat HCC is uncommon. In this review we described the diagnostic and therapeutic applications of EUS in primary HCC and evaluated its clinical significance. The diagnostic procedures primarily involve EUS-guided fine-needle biopsy or aspiration, assessment of metastatic lymph nodes and portal vein thrombosis, portal pressure monitoring, and portal vein blood collection. Treatment mainly includes EUS-guided tumor ablation, brachytherapy, injectable chemotherapy, and managing variceal hemorrhage related to portal hypertension.

Novel Isoalantolactone-Based Derivatives as Potent NLRP3 Inflammasome Inhibitors: Design, Synthesis, and Biological Characterization.

The NLRP3 inflammasome has been recognized as a promising therapeutic target in drug discovery for inflammatory diseases. Our initial research identified a natural sesquiterpene isoalantolactone (IAL) as the active scaffold targeting NLRP3 inflammasome. To improve its activity and metabolic stability, a total of 64 IAL derivatives were designed and synthesized. Among them, compound 49 emerged as the optimal lead, displaying the most potent inhibitory efficacy on nigericin-induced IL-1ß release in THP-1 cells, with an IC50 value of 0.29 µM, approximately 27-fold more potent than that of IAL (IC50: 7.86 µM), and exhibiting higher metabolic stability. Importantly, 49 remarkably improved DSS-induced ulcerative colitis in vivo. Mechanistically, we demonstrated that 49 covalently bound to cysteine 279 in the NACHT domain of NLRP3, thereby inhibiting the assembly and activation of NLRP3 inflammasome. These results provided compelling evidence to further advance the development of more potent NLRP3 inhibitors based on this scaffold.

The association between circulating fatty acids and stroke in hypertensive patients.

BACKGROUND: Stroke is prevalent in hypertensive population. It has been suggested that unsaturated fatty acids (USFA) have protective effect on stroke. The effect of saturated fatty acids (SFAs) on stroke is still unclear. Therefore, we studied the relationship between circulating fatty acids and acute ischemic stroke (AIS) in hypertensive patients. METHODS: Eighty-nine pairs including 100 men and 78 women matched by sex and age were recruited. Each pair included a hypertensive patient within 48h of AIS onset and a hypertensive patient without stroke. Six circulating fatty acids were methylated before concentration determination which was repeated twice with percent recovery estimated. RESULTS: There were differences in educational level (P = 0.002) and occupation (P < 0.001) between stroke and non-stroke participants. All the 6 fatty acid levels were higher in non-stroke participants (P = 0.017 for palmitoleic acid, 0.001 for palmitic acid, <0.001 for linoleic acid, <0.001 for behenic acid, <0.001 for nervonic acid and 0.002 for lignoceric acid). In logistic regression analysis, AIS was inversely associated with fatty acid levels except for lignoceric acid. After adjustment for education and occupation, the palmitoleic acid and palmitic acid levels were no longer inversely associated with AIS. After further adjustment for systolic blood pressure, smoking, drinking, total cholesterol and triglyceride, the inverse associations of linoleic acid (OR = 0.965, 95%CI = 0.942-0.990, P = 0.005), behenic acid (OR = 0.778, 95%CI = 0.664-0.939, P = 0.009), nervonic acid (OR = 0.323, 95%CI = 0.121-0.860, P = 0.024) with AIS remained significant. CONCLUSIONS: Circulating fatty acids except lignoceric acid were inversely associated with AIS. Both USFAs and SFAs may have beneficial effect on stroke prevention in hypertensive population.

JUNO high purity nitrogen plant.

The Jiangmen Underground Neutrino Observatory (JUNO) is a 20 kt low level radioactivity liquid scintillator detector in a laboratory 650 m underground. An excellent energy resolution and a large volume offer exciting opportunities for addressing many important topics in neutrino physics. High purity nitrogen is an important factor to ensure the low background of the JUNO detector. High Purity Nitrogen (HPN) is used for detector purging, pipe cleaning, and scintillator purification, among other things in JUNO. According to JUNO's requirements, the radon concentration in HPN should be less than 10 µBq/m3. To meet this requirement, A high-purity nitrogen plant with 100 Nm3/h maximum rate was designed and constructed. Low-temperature adsorption technology is used to remove radioactive impurities in nitrogen. High purification efficiency was ensured by using an activated carbon column with high column height-to-diameter ratio. Electrostatic collection and low-temperature enrichment methods are combined to measure radon in nitrogen. After ten days of continuous operation at 50 Nm3/h flux rate, the plant can to reduce the radon concentration in nitrogen from 37.4±1.8µBq/m3 to less than 1.33 µBq/m3. After HPN with flow rate of 50 Nm3/h passing through low-background pipeline (About 1.3 km), the radon concentration of HPN is 5.6±0.6µBq/m3.