Caffeic acid combined with arabinoxylan or ß-glucan attenuates diet-induced obesity in mice via modulation of gut microbiota and metabolites.

Polyphenols and dietary fibers in whole grains are important bioactive compounds to reduce risks for obesity. However, whether the combination of the two components exhibits a stronger anti-obesity effect remains unclear. Caffeic acid is a major phenolic acid in cereals, and arabinoxylan and ß-glucan are biological macromolecules with numerous health benefits. Here, we investigated the effect of caffeic acid combined with arabinoxylan or ß-glucan on glucose and lipid metabolism, gut microbiota, and metabolites in mice fed a high-fat diet (HFD). Caffeic acid combined with arabinoxylan or ß-glucan significantly reduced the body weight, blood glucose, and serum free fatty acid concentrations. Caffeic acid combined with ß-glucan effectively decreased serum total cholesterol levels and hepatic lipid accumulation, modulated oxidative and inflammatory stress, and improved gut barrier function. Compared with arabinoxylan, ß-glucan, and caffeic acid alone, caffeic acid combined with arabinoxylan or ß-glucan exhibited a better capacity to modulate gut microbiota, including increased microbial diversity, reduced Firmicutes/Bacteroidetes ratio, and increased abundance of beneficial bacteria such as Bifidobacterium. Furthermore, caffeic acid combined with ß-glucan reversed HFD-induced changes in microbiota-derived metabolites involving tryptophan, purine, and bile acid metabolism. Thus, caffeic acid and ß-glucan had a synergistic anti-obesity effect by regulating specific gut microbiota and metabolites.

Characteristics of Klebsiella pneumoniae pyogenic liver abscess from 2010-2021 in a tertiary teaching hospital of South China.

OBJECTIVES: Pyogenic liver abscess (PLA) is a severe and potentially fatal infectious disease. Klebsiella pneumoniae (K. pneumoniae) is the predominant pathogen responsible for PLA. This study aims to investigate the clinical characteristics and prognostic factors of K. pneumoniae-induced pyogenic liver abscess (KP-PLA), particularly those caused by carbapenem-resistant K. pneumoniae (CRKP). METHODS: Analyses were performed on PLA patients from January 2010 to December 2021, to investigate the differences of K. pneumoniae from other etiologically infected PLA patients. Univariate and multivariate logistic regression analyses were used to compare prognostic factors between patients with carbapenem-resistant K. pneumoniae PLA (CRKP-PLA) and patients with carbapenem-sensitive K. pneumoniae PLA. RESULTS: Univariate analysis demonstrated a significant association between KP-PLA and factors including diabetes mellitus (P < 0.001), cholecystitis and cholelithiasis (P = 0.032), single abscess (P = 0.016), and abscesses with a diameter over 50 mm (P = 0.004). The CRKP group exhibited a higher prevalence of therapeutic interventions before K. pneumoniae infection, including abdominal surgery, mechanical ventilation, sputum suction, tracheal cannula, routine drainage of the abdominal cavity, and peripherally inserted central venous catheters (P < 0.05). Multivariate logistic regression analysis revealed that admission to the intensive care unit was an independent risk factor associated with CRKP-PLA (odds ratio 36; 95% confidence interval 1.77-731.56; P = 0.020). CONCLUSION: The KP-PLA patients were significantly associated with diabetes and were more likely to have single abscesses larger than 50 mm. PLA patients with a history of admission to intensive care unit or invasive therapeutic procedures should be given special consideration if combined with CRKP infection.

Demographics moderated the association of symptom burden with falls and fall-related outcomes.

OBJECTIVES: To examine whether (1) prior-year symptom burden predicted later-year falls and fall-related outcomes and (2) demographics moderated the longitudinal effects of symptom burden on falls and fall-related outcomes among community-dwelling older adults. METHODS: We used 2011-2018 National Health and Aging Trends Study data that included 9,060 community-dwelling older adults (contributed 34,327 observations). Falls and fall-related outcomes included self-reported falls, multiple falls, fear of falling (FOF), and FOF limiting activity. Symptom burden was defined as the presence of pain, insomnia, breathing difficulty, depressive symptoms, anxiety, and fatigue, and calculated the number of symptoms (range from 0 to 6). Binomial logistic regression was used to examine the associations between symptom burden and falls and fall-related outcomes and the moderation effects of demographic factors. RESULTS: The majority of the sample were aged between 65 and 79 years old (57.7%), non-Hispanic White (70.5%), and female (58.4%). Each additional symptom was associated with an increased risk of falls (Adjusted Odds Ratio [AOR]: 1.13, 95% CI: 1.10-1.15), multiple falls (AOR: 1.15, 95% CI: 1.12-1.18), FOF (AOR: 1.20, 95% CI: 1.18-1.23), and FOF limiting activity (AOR: 1.24, 95% CI: 1.20-1.28). Age, race/ethnicity, education, and living arrangement statistically significantly moderated the relationships between symptom burden and falls and fall-related outcomes. CONCLUSIONS: Symptom burden predicted falls, multiple falls, FOF and FOF limiting activity, and demographics may differentially modify this risk. Individually tailored symptom assessment and management plans should be incorporated into fall risk assessment and interventions for community-dwelling older adults living.

Tenofovir amibufenamide vs tenofovir alafenamide for treating chronic hepatitis B: A real-world study.

BACKGROUND: The efficacy and safety profile of tenofovir amibufenamide (TMF) in chronic hepatitis B (CHB) patients is not well-established. AIM: To compare the efficacy and safety of TMF and tenofovir alafenamide (TAF) over a 48-wk period in patients with CHB. METHODS: A total of 215 subjects meeting the inclusion criteria were enrolled and divided into two groups: TMF group (n = 106) and the TAF group (n = 109). The study included a comparison of virological response (VR): Undetectable hepatitis B virus DNA levels, alanine transaminase (ALT) normalization rates, renal function parameters, and blood lipid profiles. RESULTS: At 24 and 48 wk, VR rates for the TMF group were 53.57% and 78.57%, respectively, compared with 48.31% and 78.65% for the TAF group (P > 0.05). The VR rates were also similar in both groups among patients with low-level viremia, both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative subgroups. The TMF cohort showed ALT normalization and renal safety profiles similar to the TAF group. There was a notable increase in total cholesterol levels in the TAF group (P = 0.045), which was not observed in the TMF group (P > 0.05). In patients with liver cirrhosis, both groups exhibited comparable VR and ALT normalization rates and renal safety profiles. However, the fibrosis 4 score at 48 wk showed a significant reduction in the TAF group as compared to the TMF group within the liver cirrhosis subgroup. CONCLUSION: Our study found TMF is as effective as TAF in treating CHB and has a comparable safety profile. However, TAF may be associated with worsening lipid profiles.

Electrospun Fe3O4-chitosan/polyvinyl alcohol nanofibrous film for improved capture and elimination of foodborne pathogens.

This study developed a new "capture and killing" antibacterial approach for efficient elimination of foodborne pathogens. Fe3O4-Chitosan (CS)/polyvinyl alcohol (PVA) nanofibrous films with improved antibacterial and mechanical properties were fabricated by a simple, environmentally friendly, and cost-effective electrospinning technique. The relationship between the physical properties (viscosity, surface tension, and conductivity) and spinnability of CS/PVA as fiber forming matrix was explored. Electrospun Fe3O4-CS/PVA films (0.03-0.12 mm) with smooth and bead-free nanofibrous structures (145-169 nm) were successfully obtained. Compared with the film electrospun from neat CS/PVA, incorporating Fe3O4 nanoparticles (NPs) (1.25-5 wt%) in CS/PVA nanofibrous film promoted bacterial attachment and increased the final inactivated efficiency, showing a difference with Fe3O4 loading and bacterial strain, which had the highest value against Escherichia coli (E. coli) and Staphyloccus aureus (S. aureus) being 90 % and 66.30 %, respectively. The tensile strength and elongation at break of Fe3O4-CS/PVA films enhanced by 46-192 % and 92-141 %, respectively. Results of the cytotoxicity test indicated that the resulting films had high biocompatibility. These promising findings provide a novel strategy for effective foodborne pathogens elimination, which could apply to sterilizing and food packaging to extend the shelf life of liquid food.

Clinicopathologic characteristics of liver inflammation and fibrosis in 310 patients with chronic hepatitis B. / 310ä¾‹æ ¢æ€§ä¹™åž‹è‚ç‚Žæ‚£è€ è‚è„ç‚Žç—‡åŠçº¤ç»´åŒ–çš„ä¸´åºŠç— ç†ç‰¹å¾.

OBJECTIVES: Long-term hepatitis B virus (HBV) infection can cause recurrent inflammation in the liver, and then develop into liver fibrosis, cirrhosis, and liver cancer. The hepatic pathological change is one of the important criteria for guiding antiviral therapy in patients with chronic hepatitis B (CHB). Due to the limitations of liver biopsy, it is necessary to find valuable non-invasive indicators to evaluate the hepatic pathological changes in CHB patients and guide the antiviral therapy. This study aims to analyze the clinical characteristics of different pathological changes in CHB patients, and to explore the factors influnencing the degree of liver inflammation and fibrosis in CHB patients with normal alanine aminotransferase (ALT). METHODS: This retrospective study was conducted on 310 CHB patients. Liver biopsy was performed in all these patients. The clinical data of the patients were collected. The liver biopsy pathological results were used as the gold standard to analyze the relationship between clinical indicators and liver pathological changes. Then CHB patients with normal ALT were screened, and the independent factors influencing the degree of liver inflammation and fibrosis were explored. RESULTS: Among the 310 patients with CHB, there were 249 (80.3%) patients with significant liver inflammation [liver inflammation grade (G) ≥2] and 119 (38.4%) patients with significant liver fibrosis [liver fibrosis stage (S) ≥2]. The results of univariate analysis of total samples showed that the ALT, γ-glutamyl transferase, alkaline phosphatase, and HBV DNA were related to the significant liver pathological changes. Among the 132 CHB patients with normal ALT, the patients with liver pathology G/S≥2, G≥2, and S≥2 were 80.3% (106/132), 68.2% (90/132), and 43.2% (57/132), respectively. The results showed that the independent influencing factor of significant liver inflammation was HBV DNA>2 000 U/mL (OR=3.592, 95% CI 1.534 to 8.409), and the independent influencing factors of significant liver fibrosis were elevated alkaline phosphatase level (OR=1.022, 95% CI 1.002 to 1.043), decreased platelet count (OR=0.990, 95% CI 0.982 to 0.998), and positive in hepatitis B e antigen (HBeAg) (OR=14.845, 95% CI 4.898 to 44.995). According to the multivariate analysis, a diagnostic model for significant liver fibrosis in CHB patients with normal ALT was established, and the area under the receiver operating characteristic curve was 0.844 (95% CI 0.779 to 0.910). CONCLUSIONS: The liver pathological changes should be evaluated in combination with different clinical indicators. A considerable number of CHB patients with normal ALT still have significant liver pathological changes, which need to be identified and treated with antiviral therapy in time. Among them, HBV DNA>2 000 U/mL suggests the significant liver inflammation, and the diagnostic model for significant liver fibrosis based on alkaline phosphatase, platelet count, and HBeAg can help to evaluate the degree of liver fibrosis.

Tenofovir alafenamide versus entecavir for treating hepatitis B virus-related acute-on-chronic liver failure: real-world study.

Background and aims: Real-world data regarding hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients receiving tenofovir alafenamide (TAF) as an antiviral drug are limited. Hence, we evaluated the efficacy and kidney safety of TAF among this population. Methods: A total of 272 HBV-related ACLF patients hospitalized at Xiangya Hospital of Central South University were enrolled in this retrospective research. All patients received antiviral therapy with TAF (n = 100) or ETV (n = 172) and comprehensive medical treatments. Results: Through 1:1 propensity score matching, 100 patients were finally included in each group. At week 48, the survival rates without transplantation of the TAF group and ETV group were 76.00 and 58.00%, separately (P = 0.007). After 4 weeks of treatment, the TAF treatment group exhibited a significantly decline in HBV DNA viral load (P = 0.029). The mean estimated glomerular filtration rate was apparently improved in the TAF group compared with the ETV group (TAF 5.98 ± 14.46 vs. ETV 1.18 ± 18.07 ml/min/1.73 m2) (P < 0.05). There were 6 patients in TAF group and 21 patients in ETV group with chronic kidney disease (CKD) stage progression ≥ 1. By contrast, the ETV treatment group has a greater risk of renal function progression in CKD 1 stage patients (P < 0.05). Conclusion: This real-world clinical study showed that TAF is more effective than ETV in reducing viral load and improving survival rate in HBV-ACLF patients and the risk of renal function decline is lower. Clinical trial registration: https://ClinicalTrials.gov, identifier NCT05453448.

Inhibition of ACAA1 Restrains Proliferation and Potentiates the Response to CDK4/6 Inhibitors in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with unfavorable outcomes. Developing therapeutic targets for TNBC remains a challenge. Here, we identified that acetyl-CoA acyltransferase 1 (ACAA1) is highly expressed in the luminal androgen receptor (LAR) subtype of TNBC compared with adjacent normal tissues in our TNBC proteomics dataset. Inhibition of ACAA1 restrained TNBC proliferation and potentiated the response to the cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor abemaciclib. Mechanistically, ACAA1 interacted with CDK4, and the inhibition of ACAA1 blocked RB transcriptional corepressor 1 (RB1) phosphorylation, resulting in G1-S cell-cycle arrest. Importantly, trimetazidine, a traditional drug for ischemic heart disease, caused a decrease in ACAA1 protein levels and enhanced the efficacy of abemaciclib in preclinical TNBC models. In conclusion, this study identifies that ACAA1 is a therapeutic target in TNBC and suggests the combination of trimetazidine and abemaciclib could be beneficial for ACAA1-high TNBCs. SIGNIFICANCE: ACAA1 is highly expressed in TNBC, serving as a potential therapeutic target in ACAA1-high tumors and a predictive biomarker of resistance to CDK4/6 inhibitors for RB1-proficient patients.

Longitudinal associations of concurrent falls and fear of falling with functional limitations differ by living alone or not.

Background: Falls and fear of falling (FOF) are independent risk factors for functional limitations in older adults. However, the combined effect of falls and FOF on functional limitations and the moderating role of living alone or not is unclear. We aimed to examine (1) the independent and combined effect of falls and FOF on functional limitations in older adults and (2) whether living alone moderates these associations. Methods: We used data from the National Health and Aging Trends Study (NHATS) and included 5,950 U.S. community-dwelling older adults aged 65 and older from Round 1 (Year 2011) and Round 2 (Year 2012). Falls and FOF were ascertained by asking participants whether they had any falls in the last year and whether they had worried about falling in the previous month at R1. Assessed functional limitations included any difficulties with mobility, self-care, or household activities at R2. Poisson regression models were used to examine the longitudinal associations of falls and FOF with functional limitations and the moderation effects of baseline living alone. Results: Of the 5,950 participants, 16.3% had falls only; 14.3% had FOF only; 14.3% had both, and 55.1% had neither at baseline. In the adjusted model, those who experienced concurrent falls and FOF in R1 had a higher risk of functional limitations at R2 than those with neither (Mobility: Incidence risk ratio [IRR] = 1.34, 95% CI: 1.24-1.45; Self-care: IRR = 1.18, 95% CI: 1.11-1.26; Household: IRR = 1.20, 95% CI: 1.11-1.30). Moreover, living alone significantly moderated the longitudinal associations of concurrent falls and FOF with mobility activity limitations. Conclusion: The findings suggest that strategies to improve falls and FOF together could potentially help prevent functional limitations. Older adults who live with others and have falls or FOF should receive interventions to promote their mobility activities.

Bidirectional relationship between fear of falling and frailty among community-dwelling older adults: A longitudinal study.

This study aims to examine the bidirectional association between fear of falling (FOF) and frailty among community-dwelling older adults. Longitudinal analyses were conducted over a representative sample of 5,829 community-dwelling individuals ≥65 years from the National Health and Aging Trends Study. FOF was ascertained by asking participants whether they worried about falling and if this worry ever limited their activities. Frailty status was assessed based on frailty phenotype. At baseline, 71.4% of participants reported no FOF, 16.7% reported FOF without fear-related activity restriction (FAR), and 11.9% reported FOF with FAR. The proportion of robust, pre-frail and frail respondents at baseline was 36.1%, 48.7% and 15.2%, respectively. Multinomial logistic regression models indicated FOF with and without FAR predicted pre-frailty and frailty. Pre-frailty predicted FOF with and without FAR, while frailty only predicted FOF with FAR. Tailored intervention strategies are needed for preventing adverse outcomes of FOF and frailty among the older population.

Efficacy and Economic Evaluation of Nonbiological Artificial Liver Therapy in Acute-on-chronic Hepatitis B Liver Failure.

Background and Aims: Nonbiological artificial liver (NBAL) is frequently used as a first-line treatment for hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF). This study aimed to compare the therapeutic efficacy and cost-effectiveness ratio (CER) of comprehensive medical treatment, plasma exchange (PE), and double plasma molecular adsorption system (DPMAS) plus half-dose PE (DPMAS+PE) in patients with HBV-ACLF. Methods: A total of 186 patients with HBV-ACLF randomly received comprehensive medical treatment, PE, or DPMAS+PE and were prospectively evaluated. Patients were divided into four subgroups based on the pretreatment prothrombin activity (PTA): Group I (PTA>40%), group II (PTA 30-40%), group III (PTA 20-30%), and group IV (PTA<20%). The main outcome measures were 28 day effectiveness; 90 day liver transplantation-free survival; change of biochemical parameters; and CER. Results: DPMAS+PE treatment was associated with significantly higher 28 day effectiveness and 90 day liver transplantation-free survival compared with PE treatment in patients with group I liver failure. Clearance of serum total bilirubin (TBIL), AST, and creatinine (Cr) were significantly higher in the DPMAS+PE group than in the PE group. For subjects with group I liver failure, DPMAS+PE treatment had advantages of lower CER values and better cost-effectiveness. Conclusions: Compared with comprehensive medical treatment and PE alone, DPMAS with half-dose sequential PE treatment more effectively improved TBIL, AST, and Cr in HBV-ACLF patients, improved 28 day effectiveness and 90 day survival rates in patients with group I liver failure, and was more cost effective. DPMAS+PE is a viable NBAL approach for treatment of HBV-ACLF.

The bidirectional relationship between homebound status and falls among older adults: a longitudinal study.

BACKGROUND: Previous research has shown an association between homebound status and falls among older adults. However, this association was primarily drawn from cross-sectional studies. This study aimed to determine the bidirectional relationship between homebound status and falls among older adults in the community. METHODS: We used data of the community-dwelling older adults from 2011 to 2015 of the National Health and Aging Trends Study, a nationally representative survey of Medicare Beneficiaries in the United States (Sample 1 [No falls at baseline]: N = 2,512; Sample 2 [Non-homebound at baseline]: N = 2,916). Homebound status was determined by the frequency, difficulty, and needing help for outdoor mobility. Falls were ascertained by asking participants whether they had a fall in the last year. Generalized estimation equation models were used to examine the bidirectional association between homebound status and falls longitudinally. RESULTS: Participants with no falls at baseline (n = 2,512) were on average, 76.8 years old, non-Hispanic whites (70.1%), and female (57.1%). After adjusting for demographics and health-related variables, prior year homebound status significantly contributed to falls in the following year (Odds ratio [OR], 1.28, 95% CI: 1.09-1.51). Participants who were non-homebound at baseline (n = 2,916) were on average, 75.7 years old, non-Hispanic white (74.8%), and female (55.8%). Previous falls significantly predicted later homebound status (OR, 1.26, 95% CI: 1.10-1.45) in the full adjusted model. CONCLUSION: This is the first longitudinal study to determine the bidirectional association between homebound status and falls. Homebound status and falls form a vicious circle and mutually reinforce each other over time. Our findings suggest the importance of developing programs and community activities that reduce falls and improve homebound status among older adults.

Mediating role of homebound status between depressive symptoms and cognitive impairment among community-dwelling older adults in the USA: a cross-sectional analysis of a cohort study.

OBJECTIVE: Depressive symptoms are known modifiable factors of cognitive impairment in older adults. However, the pathway through which depressive symptoms lead to cognitive impairment is not well understood. This study aimed to investigate whether homebound status (defined as usually unable to leave home unassisted) mediates the association between depressive symptoms and cognitive impairment in community-dwelling older adults in the USA. DESIGN: A secondary analysis of cross-sectional data. SETTINGS: Communities in the USA. PARTICIPANTS: Community-dwelling older adults (N=7537) from the 2011 National Health and Aging Trends Study, a nationally representative survey of Medicare Beneficiaries in the USA. MAIN OUTCOME MEASURES: Participants' cognitive impairment status was classified using a composite measure. Depressive symptoms were assessed using Patient Health Questionnaire-2. Homebound status was determined by the frequency, difficulty and needing help in getting outdoors. We used logistic regression and the Paramed command in STATA to analyse whether homebound mediated the association between depressive symptoms and cognitive impairment. RESULTS: Participants were on average, 77.7 years old, female (58.3%) and non-Hispanic white (68.1%). About 26% of the participants were classified as having cognitive impairment, 16% reported depressive symptoms and 25% were homebound. Depressive symptoms (adjusted OR, 1.60; 95% CI 1.36 to 1.89) and homebound status (adjusted OR, 1.58; 95% CI 1.34 to 1.86) were independently associated with cognitive impairment. Homebound significantly mediated 12.5% of the total effect between depressive symptoms and cognitive impairment, with significant indirect effect (OR, 1.07; 95% CI 1.04 to 1.10), direct effect (OR, 1.61; 95% CI 1.36 to 1.91) and total effect (OR, 1.72; 95% CI 1.46 to 2.03). CONCLUSIONS: This study supports a mediating role of homebound status in the relationship between depressive symptoms and cognitive impairment. Interventions to promote outdoor mobility should be studied for their ability to delay cognitive impairment for older adults with depressive symptoms.

Carbon-nitrogen trading in symbiotic nodules depends on magnesium import.

Symbiotic nitrogen fixation provides large amounts of nitrogen for global agricultural systems with little environmental or economic costs. The basis of symbiosis is the nutrient exchange occurring between legumes and rhizobia, but key regulators controlling nutrient exchange are largely unknown. Here, we reveal that magnesium (Mg), an important nutrient factor that preferentially accumulates in inner cortical cells of soybean nodules, shows the most positive correlation with nodule carbon (C) import and nitrogen (N) export. We further identified a pair of Mg transporter genes, GmMGT4 and GmMGT5, that are specifically expressed in the nodule cortex, modulating both nodule Mg import and C-N transport processes. The GmMGT4&5-dependent Mg import activates the activity of a plasmodesmata-located ß-1,3-glucanase GmBG2 and consequently keeps plasmodesmata permeable for C-N transport in nodule inner cortical cells. Our studies discovered an important regulating pathway for host plants fine-tuning nodule C-N trading to achieve optimal growth, which may be helpful for optimizing nutrient management for soybean production.

A natural uORF variant confers phosphorus acquisition diversity in soybean.

Phosphorus (P) is an essential element for all organisms. Because P fertilizers are a non-renewable resource and high fixation in soils, sustainable agriculture requires researchers to improve crop P acquisition efficiency. Here, we report a strong association signal at a locus of CPU1 (component of phosphorus uptake 1), from a genome-wide association study of P acquisition efficiency in a soybean core collection grown in the field. A SEC12-like gene, GmPHF1, is identified as the causal gene for CPU1. GmPHF1 facilitates the ER (endoplasmic reticulum) exit of the phosphate transporter, GmPT4, to the plasma membrane of root epidermal cells. A common SNP in an upstream open reading frame (uORF) of GmPHF1, which alters the abundance of GmPHF1 in a tissue-specific manner, contributes to P acquisition diversity in soybean. A natural genetic variation conditions diversity in soybean P acquisition, which can be used to develop P-efficient soybean genotypes.

Cyanidin-3-glucoside improves the barrier function of retinal pigment epithelium cells by attenuating endoplasmic reticulum stress-induced apoptosis.

Excessive exposure to blue light from smartphones, computers, and other video equipment causes retinal degeneration. Cyanidin-3-glucoside (C3G) exerts protective effects on retinal cells. However, the mechanism by which C3G enhances the barrier function of retinal pigment epithelial (RPE) cells remains unclear. This study investigated the effects of C3G on blue light-irradiated A2E-containing RPE cells and explored whether or not the endoplasmic reticulum (ER) stress and downstream nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathways are involved in the mechanism. Results showed that C3G (10 and 25 µM) observably increased the viability and inhibited the apoptosis of RPE cells. Furthermore, C3G enhanced the barrier function of RPE cells and upregulated the expression of tight junction proteins. Blue light irradiation triggered ER stress, but C3G significantly suppressed the PERK/eIF2α/ATF4/CHOP pathway and maintained normal ER morphology in RPE cells. C3G also activated the Nrf2 pathway to promote RPE survival, which was independent of ER stress modulating Nrf2 activity. This study suggests that C3G promotes the barrier function of RPE cells by regulating ER stress-induced apoptosis, thereby offering a new approach to preventing retinal diseases. Thus, C3G is a potential functional food ingredient to improve visual health.

Comparison of tenofovir alafenamide and entecavir for hepatitis B virus-related acute-on-chronic liver failure. / å¯Œé©¬é ¸ä¸™é šæ›¿è¯ºç¦éŸ¦ä¸Žæ©æ›¿å¡éŸ¦æ²»ç–—ä¹™åž‹è‚ç‚Žç— æ¯’ç›¸å ³æ ¢åŠ æ€¥æ€§è‚è¡°ç«­çš„æ•ˆæžœå¯¹æ¯”.

OBJECTIVES: Hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) is the most common type of liver failure in China, with a high mortality. Early rapid reduction of HBV-DNA load can improve the survival rate of HBV-ACLF patients. At present, the commonly used drugs are nucleoside (acid) analogues, such as entecavir (ETV), tenofovir, and so on. The newly listed tenofovir alafenamide fumarate (TAF) has attracted great attention of clinicians because of its stronger antiviral effect, higher transaminase normalization rate, better bone and kidney safety, and zero drug resistance. However, there are few clinical research data on the efficacy and safety of TAF in the treatment of Chinese HBV-ACLF patients, and there is a lack of pharmacoeconomic evaluation. This study aims to compare the efficacy, safety, and cost-effectiveness between TAF and ETV in patients with HBV-ACLF. METHODS: The data were collected from 196 HBV-ACLF patients (80 patients in the TAF group and 116 patients in the ETV group) who were hospitalized in Xiangya Hospital, Central South University from May 2020 to March 2021. Biochemistry and virology were detected before and after treatment (at baseline, Week 2, 4, and 12). Clinical features, disease prognosis, and cost-effectiveness were compared between the 2 groups. According to the baseline, HBV-ACLF patients were divided into 4 stages including pre-liver failure stage, early stage, medium stage, and end stage. And the liver transplantation rate and mortality was also compared. Pharmacoeconomic evaluation was taken using cost-effectiveness analysis and cost minimization analysis．. RESULTS: After 4 weeks of treatment, there were no significant differences in the efficacy (liver function, viral load) between the 2 groups (all P>0.05). The TAF group showed lower creatinine [(80.35±18.77) µmol/L vs (105.59±82.32) µmol/L, P<0.05] and higher estimated glomerular filtration rate (eGFR) levels [(95.65±23.21) mL/(min·1.73 m2) vs (82.68±26.32) mL/(min·1.73 m2), P<0.05] than the ETV group. After 12 weeks of treatment, the analysis of overall the liver transplantation rate and mortality between the 2 groups showed similar conclusion. However, the TAF group had a lower the liver transplantation rate and mortality than the ETV group in patients with pre-liver failure (0vs13.89%, P<0.05). No evident distinction was found in the liver transplantation rate and mortality during the early, medium, or end stages of liver failure (13.04% vs 17.65%, 37.50% vs 37.04%, and 54.55% vs 68.42%, respectively). Ratio of cost to effectiveness in the ETV group was higher than that in the TAF group. CONCLUSIONS: TAF is not more efficient than ETV group in improving liver function and reducing viral load for HBV-ACLF patients and they also show similar safety. However, TAF has a greater advantage over ETV not only in preserving renal function, but also in reducing the liver transplantation rate and mortality in patients with pre-liver failure. TAF can provide economic benefit to patients with HBV-ACLF.

Proteome-centric cross-omics characterization and integrated network analyses of triple-negative breast cancer.

We report a comprehensive proteomic study of a 90-case cohort of paired samples of triple-negative breast cancer (TNBC) in quantification, phosphorylation, and DNA-binding capacity. Four integrative subtypes (iP-1-4) are stratified on the basis of global proteome and phosphoproteome, each of which exhibits distinct molecular and pathway features. Scaffold and co-expression network analyses of three proteomic datasets, integrated with those from genome and transcriptome of the same cohort, reveal key pathways and master regulators that, characteristic of TNBC subtypes, play important regulatory roles within and between scaffold sub-structures and co-expression communities. We find that NAE1 is a potential drug target for subtype iP-1, and a series of key molecules in fatty acid metabolism, such as AKT1/FASN, are plausible targets for subtype iP-2. Libraries of proteins, pathways and networks of TNBC provide a valuable molecular infrastructure for further clinical exploration and in-depth studies of the molecular mechanisms of the disease.

A Novel Seven Gene Signature-Based Prognostic Model to Predict Distant Metastasis of Lymph Node-Negative Triple-Negative Breast Cancer.

BACKGROUND: The prognosis of lymph node-negative triple-negative breast cancer (TNBC) is still worse than that of other subtypes despite adjuvant chemotherapy. Reliable prognostic biomarkers are required to identify lymph node-negative TNBC patients at a high risk of distant metastasis and optimize individual treatment. METHODS: We analyzed the RNA sequencing data of primary tumor tissue and the clinicopathological data of 202 lymph node-negative TNBC patients. The cohort was randomly divided into training and validation sets. Least absolute shrinkage and selection operator Cox regression and multivariate Cox regression were used to construct the prognostic model. RESULTS: A clinical prognostic model, seven-gene signature, and combined model were constructed using the training set and validated using the validation set. The seven-gene signature was established based on the genomic variables associated with distant metastasis after shrinkage correction. The difference in the risk of distant metastasis between the low- and high-risk groups was statistically significant using the seven-gene signature (training set: P < 0.001; validation set: P = 0.039). The combined model showed significance in the training set (P < 0.001) and trended toward significance in the validation set (P = 0.071). The seven-gene signature showed improved prognostic accuracy relative to the clinical signature in the training data (AUC value of 4-year ROC, 0.879 vs. 0.699, P = 0.046). Moreover, the composite clinical and gene signature also showed improved prognostic accuracy relative to the clinical signature (AUC value of 4-year ROC: 0.888 vs. 0.699, P = 0.029; AUC value of 5-year ROC: 0.882 vs. 0.693, P = 0.038). A nomogram model was constructed with the seven-gene signature, patient age, and tumor size. CONCLUSIONS: The proposed signature may improve the risk stratification of lymph node-negative TNBC patients. High-risk lymph node-negative TNBC patients may benefit from treatment escalation.

Microcliamte changes caused by black inter-row mulch decrease flavonoids concentrations in grapes and wines under semi-arid climate.

In this study, black geotextile inter-row mulch, a weed control practice, was applied under a semi-arid climate to attenuate solar reflection in 2015-2017, and it concurrently increased soil temperature and fruit-zone high temperature duration and decreased low temperature duration. Inter-row mulch decreased anthocyanins concentrations in grapes in 2015-2016, and consistently inhibited flavonols accumulation in 2015-2017. Correlation analysis between microclimate parameters and flavonoids concentrations reflected the importance of solar reflection, fruit-zone high and low temperature duration, heat accumulation and soil temperature to flavonoids accumulation. Basal leaf removal, a widely applied practice to increase fruit-zone light exposure, was applied to mulch-treated grapevines to investigate if increasing incident light could mitigate the impact of inter-row mulch on flavonoids, and it had limited influence on anthocyanins whereas compensated the loss of flavonols in grapes caused by inter-row mulch. Notably, inter-row mulch wines showed less red and more yellow color than controls because of lower anthocyanins concentrations.