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Background: Reportedly, the stress–hyperglycemia ratio (SHR) is closely associated with poor prognosis in patients with severe acute disease. However, the community‐dwelling may also be in a state of stress due to environmental exposure. Our study aimed to explore the association between SHR and all‐cause mortality in the community‐dwelling population. Methods: A total of 18 480 participants were included out of 82 091 from the NHANES 1999–2014 survey. The Kaplan–Meier survival analyses were used to assess the disparities in survival rates based on SHR, and the log‐rank test was employed to investigate the distinctions between groups. The multivariate Cox regression analysis and restricted cubic spline (RCS) analysis were performed to assess the association of SHR with all‐cause mortality. A subgroup analysis was also conducted. Results: A total of 3188 deaths occurred during a median follow‐up period of 11.0 (7.7; 15.4) years. The highest risk for all‐cause mortality was observed when SHR≤ 0.843 or SHR ≥0.986 (log‐rank p <.001). After adjusting for the confounding factors, compared with subjects in the second SHR quartile (Q2), participants in the highest (Q4, adjusted hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.28–1.73) and lowest quartiles (Q1, adjusted HR 1.37, 95% CI 1.16–1.60) have a higher probability of all‐cause death. The RCS observed a dose‐response U‐shaped association between SHR and all‐cause mortality. The U‐shaped association between SHR and all‐cause mortality was similar across subgroup analysis. Conclusions: The SHR was significantly associated with all‐cause mortality in the community‐dwelling population, and the relationship was U‐shaped. [ABSTRACT FROM AUTHOR]

Mid- to high-latitude Asia (MHA) is one of the regions with the strongest warming trend and it is also a region where ecosystems are most sensitive to climate variability. However, how the vegetation in the region will change in the future remains uncertain. Using observation-based Leaf Area Index (LAI) and meteorological data and the multiple regression method, this study analyzes the response of vegetation in the MHA to climate elements during 1982–2020. Then, machine learning prediction models based on the Random Forest (RF) and Extreme Random Tree (ERT) algorithms are built and validated. Based on the calibrated meteorological fields from 17 Coupled Model Intercomparison Project Phase 6 (CMIP6) models under intermediate (SSP2-4.5) and high (SSP5-8.5) emission scenarios and the machine learning models, the LAI over the MHA in 2021–2100 is projected. The historical long-term increasing trends of LAI in the MHA since 1982 are found to be mainly caused by the increasing near-surface air temperature, while the interannual variations of LAI are also greatly affected by precipitation and surface downward solar radiation, especially in summer. The LAI over most of the MHA shows a significant increasing trend in the future, except over some dry areas, and the increasing trends are stronger under the SSP5-8.5 scenario than under the SSP2-4.5 scenario. [ABSTRACT FROM AUTHOR]

Background: Serum sodium level is associated with cardiovascular and endocrine health. Though decreased serum sodium is considered to be associated with reduced hypertension risk, some studies also found that it may increase the risk of diabetes. This study aimed to investigate the association of serum sodium with new‐onset diabetes in hypertensive patients. Methods: Based on the annual health examinations from 2011 to 2016 in Dongguan City, Guangdong, China, hypertensive patients without diabetes at baseline were selected. Logistic regression and restricted cubic spline were used to evaluate the association between serum sodium level and new‐onset diabetes. Subgroup analysis was also conducted. Results: A total of 4438 hypertensive patients with a mean age of 58.65 years were included, of whom 48.9% were male. During a median follow‐up of 35.1 months, 617 (13.9%) of the subjects developed new‐onset diabetes. Per 1‐SD (3.39 mmol/L) increment of serum sodium was associated with a 14% lower risk of new‐onset diabetes (odds ratio = 0.86; 95% CI: 0.78, 0.97; p = 0.01). The lowest quartile of serum sodium was associated with the lowest diabetes risk. The restricted cubic spline showed a linear inverse relationship (nonlinear p = 0.72). Across all the subgroups, the inverse association was consistent (p for interaction >0.05). Conclusion: An inverse association of serum sodium with new‐onset diabetes in hypertensive patients was observed. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to investigate the association between body roundness index (BRI) and all-cause mortality and cardiovascular mortality in general population.Design: A retrospective cohort study.Setting: The status of cardiovascular mortality and all-cause mortality of participants were followed through 31 December 2015. Multivariate adjusted Cox restricted cubic spline regression models and Kaplan-Meier survival curves were used to evaluate the relationship between BRI and cardiovascular mortality and all-cause mortality.Participants: A sample of 47 356 participants from the National Health and Nutrition Examination Surveys 1999-2014 with aged ≥18 years.Results: Mean age was 47 years and female were 49·9 %. During a median follow-up of 92 months, 4715 participants died from any cause, with 985 died of CVD. In multivariate adjusted Cox regression, compared with the lowest quartile of Body roundness index (BRI), the hazard ratios (HR) for all-cause mortality from other quartiles were 0·83, 95 % CI (0·75, 0·92), 0·73, 95 % CI (0·65, 0·81) and 0·80, 95 % CI (0·72, 0·89), respectively (Pfor trend < 0·05) and the HR for cardiovascular mortality from other quartiles were 0·79, 95 % CI (0·62, 1·00), 0·78, 95 % CI (0·62, 0·99) and 0·79, 95 % CI (0·62, 1·01), respectively (P for trend > 0·05). In the restricted cubic spline regression models, the relationship was showed U-shaped between BRI and all-cause mortality and cardiovascular mortality. In Kaplan-Meier survival curves, the lowest cumulative survival rate of cardiovascular mortality and all-cause mortality was recorded in the highest BRI quartile.Conclusions: The U-shaped association between BRI and all-cause mortality and cardiovascular mortality in a large population-based cohort was observed. [ABSTRACT FROM AUTHOR]

Background: Patients with comorbidity of hypertension and diabetes are associated with higher morbidity and mortality of cardiovascular disease than those with hypertension or diabetes alone. The present study aimed to identify anthropometric risk factors for diabetes among hypertensive patients who were included in a retrospective cohort study. Methods: Hypertensive adults without diabetes were recruited in China. Demographic, clinical, biochemical, and anthropometric indices were collected at baseline and during the follow-up. Anthropometric measures included BMI, waist circumference, waist-to-height ratio (WHtR), and waist-to-hip ratio, and several novel indices. To estimate the effect of baseline and dynamic changes of each anthropometric index on risk of new-onset diabetes (defined as self-reported physician-diagnosed diabetes and/or use of hypoglycemic medication, or new-onset FPG≥7.0 mmol/L during follow-up), Cox regression models were used. Results: A total of 3852 hypertensive patients were studied, of whom 1167 developed diabetes during follow-up. Multivariate Cox regression analyses showed that there was a graded increased risk of incident diabetes with successively increasing anthropometric indices mentioned above (all P <0.05). Regardless of the baseline general obesity status, elevated WHtR was both related to higher risk of diabetes; the HRs (95%CI) of baseline BMI<24 kg/m2 & WHtR≥0.5 group and BMI≥24 kg/m2 & WHtR≥0.5 group were 1.34 (1.05, 1.72), 1.85 (1.48, 2.31), respectively. Moreover, the dynamic changes of WHtR could sensitively reflect diabetes risk. Diabetes risk significantly increased when patients with baseline WHtR<0.5 progressed to WHtR≥0.5 during the follow-up (HR=1.63; 95%CI, 1.11, 2.40). There was also a decreasing trend towards the risk of incident diabetes when baseline abnormal WHtR reversed to normal at follow-up (HR=1.93; 95%CI, 1.36, 2.72) compared with those whose WHtR remained abnormal at follow-up (HR=2.04; 95%CI, 1.54, 2.71). Conclusions: Central obesity is an independent and modifiable risk factor for the development of diabetes among hypertensive patients. Measuring indices of central obesity in addition to BMI in clinics could provide incremental benefits in the discrimination of diabetes among Chinese hypertensive patients. Dynamic changes of WHtR could sensitively reflect changes in the risk of diabetes. Therefore, long-term monitoring of hypertensive patients using non-invasive anthropometric measures and timely lifestyle intervention could effectively reduce the development of diabetes. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (H. pylori) is one of the gram-negative bacteria that mainly colonize the stomach mucosa and cause many gastrointestinal diseases, such as gastritis, peptic ulcer, and gastric cancer. Macrophages play a key role in eradicating H. pylori. Recent data have shown that Notch signaling could modulate the activation and bactericidal activities of macrophages. However, the role of Notch signaling in macrophages against H. pylori remains unclear. In the present study, in the co-culture model of macrophages with H. pylori , the inhibition of Notch signaling using γ-secretase decreased the expression of inducible nitric oxide synthase (iNOS) and its product, nitric oxide (NO), and downregulated the secretion of pro-inflammatory cytokine and attenuated phagocytosis and bactericidal activities of macrophages to H. pylori. Furthermore, we identified that Jagged1, one of Notch signaling ligands, was both upregulated in mRNA and protein level in activated macrophages induced by H. pylori. Clinical specimens showed that the number of Jagged1+ macrophages in the stomach mucosa from H. pylori -infected patients was significantly higher than that in healthy control. The overexpression of Jagged1 promoted bactericidal activities of macrophages against H. pylori and siRNA-Jagged1 presented the opposite effect. Besides, the addition of exogenous rJagged1 facilitated the pro-inflammatory mediators of macrophages against H. pylori , but the treatment of anti-Jagged1 neutralizing antibody attenuated it. Taken together, these results suggest that Jagged1 is a promoting molecule for macrophages against H. pylori , which will provide insight for exploring Jagged1 as a novel therapeutic target for the control of H. pylori infection. [ABSTRACT FROM AUTHOR]

Background and Aim: Mitochondrial damage is commonly involved in liver injury. We have previously shown that normal mitochondria can be coated with a carrier protein to form complexes that are specifically taken up by liver cells in culture. The aim of the current study was to determine whether mitochondrial complexes could be specifically delivered to the livers of living rats by intravenous injection. Methods: Mitochondria were harvested from fresh mouse liver, mixed with an asialoglycoprotein‐based carrier, asialoorosomucoid‐polylysine (AsOR‐PL), and purified to form complexes. To facilitate the release of internalized mitochondria from endosomes, an endosomolytic peptide, listeriolysin O (LLO), was coupled to AsOR to form AsOR‐LLO. Mitochondria alone, mitochondrial complexes with AsOR‐PL, and mitochondrial complexes plus AsOR‐LLO conjugate all containing the same number of mitochondria were injected intravenously. Animals were killed, and organs were removed and analyzed by quantitative polymerase chain reaction of mouse mitochondrial DNA, electron microscopy (EM), and in situ polymerase chain reaction and hybridization followed by immunohistochemical analyses. Results: Calculations revealed that approximately 27% of the total injected mitochondria was detected in the liver, while less than 2% was found in spleen, and < 1% in lungs. Immunohistochemistry showed that mouse mitochondrial DNA staining was minimal with mitochondrial complexes alone, strong periportal with mitochondrial complexes co‐injected with AsOR‐LLO, and absent with mitochondria alone. Conclusions: Targetable mitochondrial complexes can be delivered to rat liver, and the efficiency of that process is greatly enhanced by co‐injection of a targetable endosomal release agent, AsOR‐LLO. [ABSTRACT FROM AUTHOR]

Graphene (GR), as a 2D carbon nanomaterial with high specific surface area, is one of the primary candidates for energy‐storage applications. In this work, the adsorption properties of graphene and Mn‐modified graphene (Mn‐GR) systems for CH4 molecules are investigated, based on first‐principles density functional theory. It is found that intrinsic graphene adsorbs CH4 molecules weakly. The single side can adsorb up to 4 CH4 molecules, and the average adsorption energy is −0.220 eV per CH4. Mn atom modification can significantly improve the adsorption performance of GR system on CH4. The structure with the largest methane storage capacity is that the GR modified by two Mn atoms that are located in the spacer holes on the opposite sides. The system can adsorb 10 CH4 molecules on both sides, the CH4 adsorption amount can reach 32.93 wt%, and the average adsorption energy is −0.402 eV per CH4. The interaction between the Mn atom and graphene is mainly between the d orbital of the Mn atom and the p orbital of the C atom. After the CH4 molecule is adsorbed, charge transfer occurs between Mn atoms and CH4, which results in a Coulomb attraction and enhances the adsorption performance of CH4 molecules. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) patients have a better ovarian reserve and age-related improvement in endocrine disturbances than non-PCOS patients. The effects of age on in vitro fertilization (IVF) treatment outcomes associated with cumulative live birth rate (CLBR) remain unclear. Objectives: To study the effect of age on CLBR after the first ovarian stimulation in IVF in PCOS patients. Method: This retrospective cohort study included 3,502 PCOS patients and 18,596 patients with tubal factor infertility, who underwent their first IVF cycles and subsequent frozen embryo transfer (ET) attempts. The primary outcome was CLBR associated with a single stimulation cycle and secondary outcomes included the implantation rate, clinical pregnancy rate, live birth rate (LBR), large for gestational age (LGA) rate, small for gestational age (SGA) rate, and preterm birth (PTB) rate of fresh ET cycles. Results: PCOS patients over 40 years had a higher implantation rate (27.8 vs. 15.7%, P < 0.05), clinical pregnancy rate (51.4 vs. 26.1%, P < 0.05), LBR (42.3 vs. 18.2%, P < 0.05), and CLBR (50.0 vs. 21.5%, P < 0.05) than non-PCOS patients over 40 years. These rates were comparable between PCOS patients aged 35 to 40 years and those aged over 40 years (P = 0.263, 0.385, and 0.112, respectively). The changes in the implantation rate, clinical pregnancy rate, and CLBR by age were slower for PCOS patients than for non-PCOS patients (all P < 0.05). Among PCOS patients less than 35 years, BMI was negatively associated with CLBR [aOR: 0.961 (0.939–0.985); P < 0.05]; however, among PCOS patients over 35 years, instead of BMI (P = 0.353), age [aOR: 0.891 (0.803–0.990); P < 0.05] and the number of oocytes retrieved [aOR: 1.093 (1.002–1.078); P < 0.05] were significantly associated with CLBR. No significant differences in LGA, LGA, or PTB were detected between PCOS and non-PCOS patients over 35 years (all P > 0.05). Conclusions: The declines in treatment outcomes with age are slower for PCOS patients than for non-PCOS patients. For patients over 40 years, PCOS patients have reproductive advantages over non-PCOS patients. In contrast to younger PCOS patients (<35 years), older PCOS patients (≥35 years) may benefit less from taking time to lose weight before IVF treatment, and the immediate initiation of assisted reproductive treatment is essential. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by aberrant T cell immune response. Diffuse proliferative lupus nephritis (LN-IV) is the most common, severe, and active form of lupus nephritis. In this study, we investigated the production of Th1, Th2, and Th17 cytokines in prediction of active form of LN-IV. ProcartaPlex multiplex immunoassays panels were used for detection of serum Th1, Th2, and Th17 cytokines profiling. Th1 and Th17 cytokines (IL-18, IFN-γ, IL-12p70, IL-6, and IL-17A) were considerably expressed in the serum of lupus nephritis IV patients in comparison to the healthy control. However, only IL18 and IL6 were higher in class IV versus class III lupus nephritis. Importantly, the ratios of Th1/Th2 (IL-18/IL-4) and Th17/Th2 (IL-17A/IL-4) were significantly elevated in LN-IV when compared with LN-III, LN-V, and healthy controls. Consistently, the serum cytokines IL-18, IL-17A, and IFN-γ were markedly expressed in LN-IV patient glomeruli and interstitial tissue compared to other classes of LN by IHC. ROC further suggests that IL-18 was a potential marker for LN-IV. The data from our study suggests that the early detection and quantification of these cytokines may help in prediction of active form of LN-IV. [ABSTRACT FROM AUTHOR]

Water resources carrying capacity (WRCC) analysis is critically important in providing guidance to the sustainable development strategies of the YarLung Tsangpo River Basin (YTRB) due to the conflicts among the ample water resources, low development level of society, and the fragile ecological environment. This study evaluated the scheduled developing mode of YTRB in the planning years from 2016 to 2030 with a WRCC system containing three components: a hydrological informatics modeling system (HIMS), water resources carrying capacity (WRCC) model, and an index evaluation system. The averaged WRCC index is 4.29, 1.19, and 0.06 for the planning years, and 2.61, 0.98, 0.05 for the baseline years for the three sub-basins. The water deficiency problem becomes more severe in the upper sub-basin and appears in the middle sub-basin with the WRCC index greater than 1, while the water resources are not fully utilized in the lower sub-basin in the planning years, with the WRCC index far less than 1. The GDP of the three sub-basins is greater in the planning years, with 2.25 × 108, 54.60 × 108, and 3.94 × 108 dollars year−1 than those in the baseline years with 1.97 × 108, 47.71 × 108, 3.43 × 108 dollars year−1. However, GDP per capita/cubic meter keeps decreasing due to the great population growth rate and non-enhanced water use efficiency. The sustainability index is 0.04, 0.23, and 0.47 in the planning years, which is lower than the 0.04, 0.31, and 0.50 in the baseline years. Therefore, the scheduled growth rates of the population, urbanization, and GDP are a developing mode with low sustainability and are not appropriate to be continued in the planning years. Further work is needed to identify a sustainable developing mode with a decreased population growth rate, enhanced water use efficiency in the economic system, and the optimized allocation of water resources distribution in the three sub-basins with hydraulic facilities. [ABSTRACT FROM AUTHOR]

It is important to simulate streamflow with hydrological models suitable for the particular study areas, as the hydrological characteristics of water cycling processes are distinctively different due to spatial heterogeneity at the watershed scale. However, most existing hydrological models cannot be customized to simulate water cycling processes of different areas due to their fixed structures and modes. This study developed a HydroInformatic Modeling System (HIMS) model with a flexible structure which had multiple equations available to describe each of the key hydrological processes. The performance of the HIMS model was evaluated with the recommended structure for semi-arid areas by comparisons with two datasets of observed streamflow: the first one of 53 Australian watersheds, the second one of the Lhasa River basin in China. Based on the first dataset, the most appropriate watersheds were identified for the HIMS model utilization with areas of 400–600 km2 and annual precipitation of 800–1200 mm. Based on the second dataset, the model performance was statistically satisfied with Nash-Sutcliffe Efficient (NSE) greater than 0.87 and Water Error (WE) within ±20% on the streamflow simulation at hourly, daily, and monthly time steps. In addition, the water balance was mostly closed with respect to precipitation, streamflow, actual evapotranspiration (ET), and soil moisture change at the annual time steps in both the periods of calibration and validation. Therefore, the HIMS model was reliable in estimating streamflow and simulating the water cycling processes for the structure of semi-arid areas. The simulated streamflow of HIMS was compared with those of the Variable Infiltration Capacity model (VIC) and Soil and Water Assessment Tool (SWAT) models and we found that the HIMS model performed better than the SWAT model, and had similar results to the VIC model with combined runoff generation mechanisms. [ABSTRACT FROM AUTHOR]

Predictions in ungauged basins (PUB) has been always a focus of hydrological research. The problem presented by ungauged basins is how to reasonably estimate water resource availability. To solve the issues of data scale, this study combines field experiments and hydrological models to estimate freshwater availability in a typical ungauged sea island located in southeastern China. The free parameters in the hydrological model were derived from the point-scale rainfall-runoff experiments rather than calibration using river discharge observations. The rainfall-runoff experiments were performed on six sites covering 11 land cover types. Model validation at a sub-catchment showed that the combined method could successfully reproduce monthly streamflow, with a Nash–Sutcliffe Efficiency of 0.82, correlation coefficient of 0.85, and flow volume error of 6.5%. The simulation results indicate high heterogeneity and distinct seasonal dynamics in freshwater availability across the entire island. This pioneering PUB study for Chinese islands could provide reference for planning and management of freshwater in a water shortage area. [ABSTRACT FROM AUTHOR]

[Display omitted] • Al F at channel intersection of HZSM-5 was identified by toluene adsorption. • The affinity of toluene/Al F was enhanced by the ion exchange of H+ by Na+. • Stepwise TPD (STPD) method was designed to quantitate the toluene desorbed from Na+. • The toluene-STPD method is not affected by the coexistence of Al pair and single Al. Precise analysis of the framework Al (Al F) at channel intersections of HZSM-5 zeolite is the basis of fine tuning of the spatial distribution of active sites within different pores which is critical to promote the catalytic performance in various applications. However, existing technologies cannot provide reliable quantitative results either in theory or practice due to the co-existence of Al pair and single Al. Here we report a new method based on toluene adsorption–desorption. As a promising probe, toluene can be preferentially adsorbed on Al F at channel intersection under low loading (≤4 molecules/unit cell) due to spatial matching and energetic heterogeneity. After strengthening the toluene/Al F affinity through replacing H+ by Na+ and designing a new stepwise TPD technique (toluene-STPD), the contents of Al F atoms at channel intersections of HZSM-5 samples were successfully calculated by counting the desorbed toluene molecules based on the 1:1 stoichiometric relationship between adsorbed toluene and Al F. [ABSTRACT FROM AUTHOR]

• The adsorption of the gas molecules on both HsGDY and B-HsGDY is selective. • The doping with B improves the adsorption energies of the gas molecules. • The adsorption of the gas molecules on HsGDY and B-HsGDY is physical adsorption. • After HsGDY and B-HsGDY adsorps NO and NO 2 , the conductivity of systems improves. Hydrogen-substituted graphdiyne (HsGDY) is a novel alkynyl carbon material with a structure similar to that of graphene. In this paper, the adsorption of four gas molecules (NO, NO 2 , NH 3 , and N 2) on HsGDY and B-doped HsGDY (B-HsGDY) was studied using density functional theory. The results show that the adsorption of NO and NO 2 on HsGDY and B-HsGDY is characterized by a larger charge transfer, stronger interaction, and higher adsorption energy compared with that of NH 3 and N 2. Based on the doping with B atoms, the adsorption energies of the gas molecules on HsGDY significantly improve, especially that of NO and NO 2. The gas molecule adsorption on both HsGDY and B-HsGDY is physical adsorption and the adsorption selectivity is good and thus may be applied for gas-sensitive NO and NO 2 materials. [ABSTRACT FROM AUTHOR]

Background: Benefiting from rich knowledge and the exceptional ability to understand text, large language models like ChatGPT have shown great potential in English clinical environments. However, the performance of ChatGPT in non-English clinical settings, as well as its reasoning, have not been explored in depth., Objective: This study aimed to evaluate ChatGPT's diagnostic performance and inference abilities for retinal vascular diseases in a non-English clinical environment., Methods: In this cross-sectional study, we collected 1226 fundus fluorescein angiography reports and corresponding diagnoses written in Chinese and tested ChatGPT with 4 prompting strategies (direct diagnosis or diagnosis with a step-by-step reasoning process and in Chinese or English)., Results: Compared with ChatGPT using Chinese prompts for direct diagnosis that achieved an F 1 -score of 70.47%, ChatGPT using English prompts for direct diagnosis achieved the best diagnostic performance (80.05%), which was inferior to ophthalmologists (89.35%) but close to ophthalmologist interns (82.69%). As for its inference abilities, although ChatGPT can derive a reasoning process with a low error rate (0.4 per report) for both Chinese and English prompts, ophthalmologists identified that the latter brought more reasoning steps with less incompleteness (44.31%), misinformation (1.96%), and hallucinations (0.59%) (all P<.001). Also, analysis of the robustness of ChatGPT with different language prompts indicated significant differences in the recall (P=.03) and F 1 -score (P=.04) between Chinese and English prompts. In short, when prompted in English, ChatGPT exhibited enhanced diagnostic and inference capabilities for retinal vascular disease classification based on Chinese fundus fluorescein angiography reports., Conclusions: ChatGPT can serve as a helpful medical assistant to provide diagnosis in non-English clinical environments, but there are still performance gaps, language disparities, and errors compared to professionals, which demonstrate the potential limitations and the need to continually explore more robust large language models in ophthalmology practice., (©Xiaocong Liu, Jiageng Wu, An Shao, Wenyue Shen, Panpan Ye, Yao Wang, Juan Ye, Kai Jin, Jie Yang. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 22.01.2024.)

Sepsis is a leading cause of fatality in invasive candidiasis. The magnitude of the inflammatory response is a determinant of sepsis outcomes, and inflammatory cytokine imbalances are central to the pathophysiological processes. We previously demonstrated that a Candida albicans F 1 F o -ATP synthase α subunit deletion mutant was nonlethal to mice. Here, the potential effects of the F 1 F o -ATP synthase α subunit on host inflammatory responses and the mechanism were studied. Compared with wild-type strain, the F 1 F o -ATP synthase α subunit deletion mutant failed to induce inflammatory responses in Galleria mellonella and murine systemic candidiasis models and significantly decreased the mRNA levels of the proinflammatory cytokines IL-1β, IL-6 and increased those of the anti-inflammatory cytokine IL-4 in the kidney. During C. albicans -macrophage co-culture, the F 1 F o -ATP synthase α subunit deletion mutant was trapped inside macrophages in yeast form, and its filamentation, a key factor in inducing inflammatory responses, was inhibited. In the macrophage-mimicking microenvironment, the F 1 F o -ATP synthase α subunit deletion mutant blocked the cAMP/PKA pathway, the core filamentation-regulating pathway, because it failed to alkalinize environment by catabolizing amino acids, an important alternative carbon source inside macrophages. The mutant downregulated Put1 and Put2, two essential amino acid catabolic enzymes, possibly due to severely impaired oxidative phosphorylation. Our findings reveal that the C. albicans F 1 F o -ATP synthase α subunit induces host inflammatory responses by controlling its own amino acid catabolism and it is significant to find drugs that inhibit F 1 F o -ATP synthase α subunit activity to control the induction of host inflammatory responses.

Objective: To investigate the prognostic value of early serum lactate, albumin, and lactate/albumin ratio (L/A) on the 28-day prognosis of adult patients with sepsis., Methods: A retrospective cohort study was conducted among adult patients with sepsis admitted to the First Affiliated Hospital of Xinjiang Medical University from January to December in 2020. Gender, age, comorbidities, lactate within 24 hours of admission, albumin, L/A, interleukin-6 (IL-6), procalcitonin (PCT), C-reactive protein (CRP) and 28-day prognosis were recorded. The receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of lactate, albumin and L/A for 28-day mortality in patients with sepsis. Subgroup analysis of patients was performed according to the best cut-off value, Kaplan-Meier survival curves were drawn, and the 28-day cumulative survival of patients with sepsis was analyzed., Results: A total of 274 patients with sepsis were included, and 122 patients died at 28 days, with a 28-day mortality of 44.53%. Compared with the survival group, the age, the proportion of pulmonary infection, the proportion of shock, lactate, L/A and IL-6 in the death group were significantly increased, and albumin was significantly decreased [age (years): 65 (51, 79) vs. 57 (48, 73), pulmonary infection: 75.4% vs. 53.3%, shock: 37.7% vs. 15.1%, lactate (mmol/L): 4.76 (2.95, 9.23) vs. 2.21 (1.44, 3.19), L/A: 0.18 (0.10, 0.35) vs. 0.08 (0.05, 0.11), IL-6 (ng/L): 337.00 (97.73, 2 318.50) vs. 55.88 (25.26, 150.65), albumin (g/L): 27.68 (21.02, 33.03) vs. 29.62 (25.25, 34.23), all P < 0.05]. The area under the ROC curve (AUC) and 95% confidence interval (95%CI) of lactate, albumin, and L/A were 0.794 (95%CI was 0.741-0.840), 0.589 (95%CI was 0.528-0.647), 0.807 (95%CI was 0.755-0.852) for predicting 28-day mortality in sepsis patients. The optimal diagnostic cut-off value of lactate was 4.07 mmol/L, the sensitivity was 57.38%, the specificity was 92.76%. The optimal diagnostic cut-off value of albumin was 22.28 g/L, the sensitivity was 31.15%, the specificity was 92.76%. The optimal diagnostic cut-off of L/A was 0.16, the sensitivity was 54.92%, and the specificity was 95.39%. Subgroup analysis showed that the 28-day mortality of sepsis patients in the L/A > 0.16 group was significantly higher than that in the L/A ≤ 0.16 group [90.5% (67/74) vs. 27.5% (55/200), P < 0.001]. The 28-day mortality of sepsis patients in the albumin ≤ 22.28 g/L group was significantly higher than that in the albumin > 22.28 g/L group [77.6% (38/49) vs. 37.3% (84/225), P < 0.001]. The 28-day mortality in the group with lactate > 4.07 mmol/L was significantly higher than that in the group with lactate ≤ 4.07 mmol/L [86.4% (70/81) vs. 26.9% (52/193), P < 0.001]. The three were consistent with the analysis results of Kaplan-Meier survival curve., Conclusions: The early serum lactate, albumin, and L/A were all valuable in predicting the 28-day prognosis of patients with sepsis, and L/A was better than lactate and albumin.

Background: The relationship between the total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) ratio and all-cause and cardiovascular mortality has not been elucidated. Herein, we intend to probe the effect of the TC/HDL-C ratio on all-cause and cardiovascular mortality in the general population., Methods: From the 1999-2014 National Health and Nutrition Examination Surveys (NHANES), a total of 32,405 health participants aged ≥18 years were included. The TC/HDL-C levels were divided into five groups: Q1: <2.86, Q2: 2.86-3.46, Q3: 3.46-4.12, Q4: 4.12-5.07, Q5: >5.07. Multivariate Cox regression models were used to explore the relationship between the TC/HDL-C ratio and cardiovascular and all-cause mortality. Two-piecewise linear regression models and restricted cubic spline regression were used to explore nonlinear and irregularly shaped relationships. Kaplan-Meier survival curve and subgroup analyses were conducted., Results: The population comprised 15,675 men and 16,730 women with a mean age of 43 years. During a median follow-up of 98 months (8.1 years), 2,859 mortality cases were recorded. The TC/HDL-C ratio and all-cause mortality showed a nonlinear association after adjusting for confounding variables in the restricted cubic spline analysis. Hazard ratios (HRs) of all-cause mortality were particularly positively related to the level of TC/HDL-C ratio in the higher range >5.07 and in the lower range <2.86 (HR 1.26; 95% CI 1.10, 1.45; HR 1.18; 95% CI 1.00, 1.38, respectively), although the HRs of cardiovascular disease mortality showed no difference among the five groups. In the two-piecewise linear regression model, a TC/HDL-C ratio range of ≥4.22 was positively correlated with cardiovascular mortality (HR 1.13; 95% CI 1.02, 1.25). In the subgroup analysis, a nonlinear association between TC/HDL-C and all-cause mortality was found in those aged <65 years, men, and the no lipid drug treatment population., Conclusion: A nonlinear association between the TC/HDL-C ratio and all-cause mortality was found, indicating that a too-low or too-high TC/HDL-C ratio might increase all-cause mortality. However, for cardiovascular mortality, it does not seem so. The cutoff value was 4.22. The individuals had higher cardiovascular mortality with a TC/HDL-C ratio >4.22., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Liu, Lo, Huang and Feng.)

Purpose: The association between the preoperative Geriatric Nutritional Risk Index (GNRI) and postoperative short-term and long-term clinical outcomes remains unclear. The aim of this meta-analysis was to identify the predictive role of the preoperative GNRI for postoperative clinical outcomes of gastric cancer patients based on current evidence., Methods: Several databases were searched up to July 28, 2022. The primary and secondary outcomes were long-term survival, including overall survival (OS), cancer-specific survival (CSS) and postoperative complications. Meanwhile, the hazard ratios (HRs) and relative risks (RRs) with 95% confidence intervals (CIs) were combined to assess the association of preoperative GNRI with postoperative survival and complications separately. The results Eight studies involving 4,189 patients were included, and they were all from Japan. The pooled results demonstrated that a lower preoperative GNRI was significantly related to worse OS (HR = 1.72, 95% CI: 1.18-2.53, P  = 0.005) and CSS (HR = 1.67, 95% CI: 1.20-2.32, P  = 0.002). Meanwhile, a lower preoperative GNRI was significantly associated with postoperative complications (RR = 1.97, 95% CI: 1.51-2.58, P  < 0.001). Further analysis focusing on elderly patients showed similar results., Conclusion: Preoperative GNRI is related to postoperative short-term and long-term clinical outcomes of Japanese gastric cancer patients, and a lower GNRI predicts poorer prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Lu, Shen, Zou, Li, Liu and Jian.)

Defects in mitochondria are responsible for various genetic and acquired diseases. Mitochondrial transplantation, a method that involves introduction of healthy donor mitochondria into cells with dysfunctional mitochondria, could offer a novel approach to treat such diseases. Some studies have demonstrated the therapeutic benefit of mitochondrial transplantation and targeted delivery in vivo and in vitro within hepatocytes and the liver. This review discusses the issues regarding isolation and delivery of mitochondria to hepatocytes and the liver, and examines the existing literature in order to elucidate the utility and practicality of mitochondrial transplantation in the treatment of liver disease. Studies reviewed demonstrate that mitochondrial uptake could specifically target hepatocytes, address the challenge of non-specific localization of donor mitochondria, and provide evidence of changes in liver function following injection of mitochondria into mouse and rat disease models. While potential benefits and advantages of mitochondrial transplantation are evident, more research is needed to determine the practicality of mitochondrial transplantation for the treatment of genetic and acquired liver diseases., Competing Interests: GYW has been the editor-in-chief of Journal of Clinical and Translational Hepatology since 2012. The other authors have no conflict of interests related to this publication., (© 2022 Authors.)

Human dihydroorotate dehydrogenase ( h DHODH), as the fourth and rate-limiting enzyme of the de novo pyrimidine synthesis pathway, is regarded as an attractive target for malignancy therapy. In the present study, a novel series of teriflunomide derivatives were designed, synthesized, and evaluated as h DHODH inhibitors. 13t was the optimal compound with promising enzymatic activity (IC 50 = 16.0 nM), potent antiproliferative activity against human lymphoma Raji cells (IC 50 = 7.7 nM), and excellent aqueous solubility (20.1 mg/mL). Mechanistically, 13t directly inhibited h DHODH and induced cell cycle S-phase arrest in Raji cells. The acute toxicity assay indicated a favorable safety profile of 13t . Notably, 13t displayed significant tumor growth inhibition activity with a tumor growth inhibition (TGI) rate of 81.4% at 30 mg/kg in a Raji xenograft model. Together, 13t is a promising inhibitor of h DHODH and a preclinical candidate for antitumor therapy, especially for lymphoma.

Objective: Individuals with both hypertension and diabetes have been confirmed to significantly increase the risk of cardiovascular disease morbidity and mortality compared with those with only hypertension or diabetes. This study aimed to evaluate the potential of different anthropometric indices for predicting diabetes risk among hypertensive patients. Methods: The study group consisted of 6,990 hypertensive adults without diabetes who were recruited in China. Demographic and clinical assessment, physical examinations, laboratory tests, and anthropometric measurements, including body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), and novel indices (ABSI, AVI, BAI, BRI, CI, WWI, and WHHR), were performed at baseline and during the (median) 3-year follow-up. Cox regression analyses were conducted to estimate effects from these indices for the onset of diabetes. Receiver operator characteristic (ROC) analyses were conducted to assess the predictive capacities of the anthropometric indices and determine the optimal cut-points. Results: A total of 816 (11.7%) developed diabetes during our prospective study. Multivariate Cox regression analyses revealed weight, WC, WHR, WHtR, BAI, BRI, and WWI as the independent risk factor for diabetes among hypertensive patients, regardless of whether it was treated as a continuous or categorical variable ( P < 0.05). Further Cox analyses combining BMI and different central obesity indices showed that elevated WC, WHR, WHtR, AVI, BRI, CI, regardless of the general obesity status, were found to be each independently associated with increased diabetes risk ( P < 0.05). Dynamic increases of BRI < 5.24 to BRI ≥ 5.24 were associated with increased risk (HR = 1.29; 95% CI, 1.02, 1.64), and its reversal was associated with reduced risk (HR = 1.56; 95% CI, 1.23, 1.98) compared with the others (HR = 1.95; 95% CI, 1.63, 2.32). ROC analysis indicated that the areas under the ROC curves (AUC) of the anthropometric indices ranged from 0.531 to 0.63, with BRI (cut-off value = 4.62) and WHtR having the largest area. Conclusions: Based on this novel study, BRI was the most superior predictor and independent determinant for diabetes onset among the hypertensive population. Hypertensive patients with BRI > 4.62, regardless of general obesity status, were at high risk of diabetes. Thus, the prompt screening and diagnosis of diabetes should be carried out among these patients for timely integrated intervention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Liu, Guan, Zhang, Zhu, Fu, Chen, Tang, Feng and Kuang.)