Protection against experimental cryptococcosis elicited by Cationic Adjuvant Formulation 01-adjuvanted subunit vaccines.

The fungal infection, cryptococcosis, is responsible for >100,000 deaths annually. No licensed vaccines are available. We explored the efficacy and immune responses of subunit cryptococcal vaccines adjuvanted with Cationic Adjuvant Formulation 01 (CAF01). CAF01 promotes humoral and T helper (Th) 1 and Th17 immune responses and has been safely used in human vaccine trials. Four subcutaneous vaccines, each containing single recombinant Cryptococcus neoformans protein antigens, partially protected mice from experimental cryptococcosis. Protection increased, up to 100%, in mice that received bivalent and quadrivalent vaccine formulations. Vaccinated mice that received a pulmonary challenge with C. neoformans had an influx of leukocytes into the lung including robust numbers of polyfunctional CD4+ T cells which produced Interferon gamma (IFNγ), tumor necrosis factor alpha (TNFα), and interleukin (IL)-17 upon ex vivo antigenic stimulation. Cytokine-producing lung CD8+ T cells were also found, albeit in lesser numbers. A significant, durable IFNγ response was observed in the lungs, spleen, and blood. Moreover, IFNγ secretion following ex vivo stimulation directly correlated with fungal control in the lungs. Thus, we have developed multivalent cryptococcal vaccines which protect mice from experimental cryptococcosis using an adjuvant which has been safely tested in humans. These preclinical studies suggest a path towards human cryptococcal vaccine trials.

Novel serum biomarker of Golgi protein 73 for the diagnosis of clinically significant portal hypertension in patients with compensated cirrhosis.

Hepatic venous pressure gradient (HVPG) is the gold standard for evaluating clinically significant portal hypertension (CSPH). However, reliable noninvasive methods are limited. Our study aims to investigate the diagnostic value of serum Golgi protein 73 (GP73) for CSPH in patients with compensated cirrhosis. The study enrolled 262 consecutive patients with compensated cirrhosis from three centers in China from February 2021 to September 2023, who underwent both serum GP73 tests and HVPG measurements. CSPH was defined as HVPG ≥ 10 mmHg. Diagnostic accuracy was evaluated using the areas under the receiver operating characteristic curve (AUC). The prevalence of CSPH was 56.9% (n = 149). There were significant differences between the CSPH and non-CSPH groups in the median serum GP73 level (126.8 vs. 73.1 ng/mL, p < 0.001). GP73 level showed a significant positive linear correlation with HVPG (r = 0.459, p < 0.001). The AUC for the diagnosis of CSPH using serum GP73 alone was 0.75 (95% confidence interval [CI] 0.68-0.81). Multivariate logistic regression analysis determined that the levels of GP73, platelets and international normalized ratio were independently associated with CSPH. The combination of these three markers was termed "IP73" score with an AUC value of 0.85 (95% CI 0.80-0.89) for CSPH. Using 0 as a cut-off value, the specificity and sensitivity of IP73 score were 77.9% and 81.9%, respectively. The IP73 score offers a novel, simple and noninvasive method of assessing CSPH in patients with compensated cirrhosis. A cut-off value of the IP73 score at 0 can distinguish patients with or without CSPH.

Retinopathy as a predictive indicator for significant hepatic fibrosis according to T2DM status: A cross-sectional study based on the national health and nutrition examination survey data.

INTRODUCTION AND OBJECTIVES: Type 2 Diabetes Mellitus (T2DM), a prevalent metabolic disorder, often coexists with a range of complications, with retinopathy being particularly common. Recent studies have shed light on a potential connection between diabetic retinopathy (DR) and hepatic fibrosis, indicating a possible shared pathophysiological foundation in T2DM. This study investigates the correlation between retinopathy and hepatic fibrosis among individuals with T2DM, as well as evaluates the diagnostic value of DR for significant hepatic fibrosis. MATERIALS AND METHODS: Our cross-sectional analysis incorporated 5413 participants from the National Health and Nutrition Examination Survey (NHANES) 2005-2008. The Fibrosis-4 score (FIB-4) classified hepatic fibrosis into different grades (F0-F4), with significant hepatic fibrosis marked as F2 or higher. Retinopathy severity was determined using retinal imaging and categorized into four levels. The analysis of variance or Chi-square tests facilitated group comparisons. Additionally, the receiver operating characteristic (ROC) analysis appraised the predictive accuracy of retinopathy for significant hepatic fibrosis in the T2DM population. RESULTS: Among 5413 participants, the mean age was 59.56 ± 12.41, with 50.2% male. And 20.6% were diagnosed with T2DM. Hepatic fibrosis grading was positively associated with retinopathy severity (OR [odds ratio]: 1.521, 95%CI [confidence interval]: 1.152-2.008, P = 0.003) across the entire population. The association was amplified in the T2DM population according to Pearson's analysis results. The ROC curve demonstrated retinopathy's diagnostic capacity for significant hepatic fibrosis in the T2DM population (AUC [area under curve] = 0.72, 95%CI: 0.651-0.793, P < 0.001). CONCLUSIONS: Retinopathy could serve as an independent predictor of significant hepatic fibrosis in T2DM population. Ophthalmologists are advised to closely monitor T2DM patients with retinopathy.

Cross-country health inequalities of four common nutritional deficiencies among children, 1990 to 2019: data from the Global Burden of Disease Study 2019.

BACKGROUND: Nutritional deficiencies remain serious medical and public health issues worldwide, especially in children. This study aims to analyze cross-country inequality in four common nutritional deficiencies (protein-energy malnutrition, dietary iron deficiency, vitamin A deficiency and iodine deficiency) among children from 1990 to 2019 based on Global Burden of Disease (GBD) 2019 data. METHODS: Prevalence and disability-adjusted life years (DALYs) data as measures of four nutritional deficiency burdens in people aged 0 to 14 years were extracted from the GBD Results Tool. We analyzed temporal trends in prevalence by calculating the average annual percent change (AAPC) and quantified cross-country inequalities in disease burden using the slope index. RESULTS: Globally, the age-standardized prevalence rates of dietary iron deficiency, vitamin A deficiency and iodine deficiency decreased, with AAPCs of -0.14 (-0.15 to -0.12), -2.77 (-2.96 to -2.58), and -2.17 (-2.3 to -2.03) from 1999 to 2019, respectively. Significant reductions in socio-demographic index (SDI)-related inequality occurred in protein-energy malnutrition and vitamin A deficiency, while the health inequality for dietary iron deficiency and iodine deficiency remained basically unchanged. The age-standardized prevalence and DALY rates of the four nutritional deficiencies decreased as the SDI and healthcare access and quality index increased. CONCLUSIONS: The global burden of nutritional deficiency has decreased since 1990, but cross-country health inequalities still exist. More efficient public health measures are needed to reduce disease burdens, particularly in low-SDI countries/territories.

Single-cell transcriptome analysis reveals endometrial immune microenvironment in minimal/mild endometriosis.

Endometriosis is a common inflammatory disorder in women of reproductive age due to an abnormal endometrial immune environment and is associated with infertility. This study aimed to systematically understand the endometrial leukocyte types, inflammatory environment, and impaired receptivity at single-cell resolution. We profiled single-cell RNA transcriptomes of 138 057 endometrial cells from endometriosis patients (n = 6) and control (n = 7), respectively, using 10x Genomics platform. We found that one cluster of epithelial cells that expressed PAEP and CXCL14 was mostly from the control during the window of implantation (WOI). This epithelial cell type is absent in the eutopic endometrium during the secretory phase. The proportion of endometrial immune cells decreased in the secretory phase in the control group, whereas the cycle variation of total immune cells, NK cells, and T cells was absent in endometriosis. Endometrial immune cells secreted more IL-10 in the secretory phase than in the proliferative phase in the control group; the opposite trend was observed in endometriosis. Proinflammatory cytokines levels in the endometrial immune cells were higher in endometriosis than in the control group. Trajectory analysis revealed that the secretory phase epithelial cells decreased in endometriosis. Ligand-receptor analysis revealed that 11 ligand-receptor pairs were upregulated between endometrial immune and epithelial cells during WOI. These results provide new insights into the endometrial immune microenvironment and impaired endometrial receptivity in infertile women with minimal/mild endometriosis.

Individualized Choice of Simultaneous Cholecystectomy in Patients with Gastric Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: Patients undergoing gastrectomy for gastric cancer are more likely to develop gallstones than the general population. Prophylactic cholecystectomy remains controversial. METHODS: Studies from 2000-2022 were systematically searched in the PubMed, EMBASE, and Cochrane Library databases. The search included simultaneous cholecystectomy or risk factors for gallstone formation with gastrectomy alone. Major prognostic factors included complications and mortality, and risk factor analyses included age, sex, TNM stage, gastrectomy type, lymph node dissection, diabetes, and duodenal exclusion. Random effects regression models were used to analyze risk estimates and data were presented as odds ratios (ORs) with corresponding 95% confidence intervals (CIs). RESULTS: There were no significant differences in postoperative morbidity (OR 1.12, 95% CI 0.90-1.39; p = 0.33, I2 = 11%) and mortality (OR 1.23, 95% CI 0.62-2.43; p = 0.56, I2 = 0%) between gastrectomy alone and simultaneous cholecystectomy. Older age (OR 1.48, 95% CI 1.36-1.59; p < 0.001, I2 = 59%), male sex (OR 1.38, 95% CI 1.10-1.71; p = 0.004, I2 = 77%), total gastrectomy (OR 1.50, 95% CI 1.25-1.81; p < 0.001, I2 = 72%), diabetes mellitus (OR 1.38, 95% CI 1.17-1.63; p < 0.001, I2 = 8%), and duodenal exclusion (OR 1.77, 95% CI 1.47-2.15; p < 0.001, I2 = 30%) were risk factors for cholecystolithiasis. CONCLUSIONS: Simultaneous cholecystectomy did not increase the incidence of postoperative complications or mortality. Older age, male sex, total gastrectomy, duodenal exclusion, and diabetes were risk factors for gallstone development after gastrectomy.

Ambient fine particulate matter and allergic symptoms in the middle-aged and elderly population: results from the PIFCOPD study.

BACKGROUND: The associations between short- and long-term exposure to ambient fine particulate matter with an aerodynamic diameter ≤ 2.5 µm (PM2.5) and allergic symptoms in middle-aged and elderly populations remain unclear, particularly in China, where most cities have severe air pollution. METHODS: Participants (n = 10,142; age = 40-75 years) were recruited from ten regions in China from 2018 to 2021 for the Predictive Value of Inflammatory Biomarkers and Forced Expiratory Volume in 1 s (FEV1) for Chronic Obstructive Pulmonary Disease (PIFCOPD) study. Short-term (lag0 and lag0-7 day) and long-term (1-, 3- and 5-year) PM2.5 concentrations at residences were extracted from the air pollutant database known as Tracking Air Pollution (TAP) in China. Multivariate logistic regression models were used to estimate associations for short- and long-term PM2.5 exposure concentrations and long-term exposure models were additionally adjusted for short-term deviations. RESULTS: A 10 µg/m3 increase in PM2.5 on the day the allergic symptoms questionnaire was administered (lag0 day) was associated with higher odds of allergic nasal (1.09, 95% CI 1.05, 1.12) and eye symptoms (1.08, 95% CI 1.05, 1.11), worsening dyspnea caused by allergens (1.06, 95% CI 1.02, 1.10), and ≥ 2 allergic symptoms (1.07, 95% CI 1.03, 1.11), which was similar in the lag0-7 day concentrations. A 10 µg/m3 increase in the 1-year average PM2.5 concentration was associated with an increase of 23% for allergic nasal symptoms, 22% for eye symptoms, 20% for worsening dyspnea caused by allergens, and 21% for ≥ 2 allergic symptoms, similar to the 3- and 5-year average PM2.5 concentrations. These associations between long-term PM2.5 concentration and allergic symptoms were generally unchanged after adjustment for short-term deviations. CONCLUSIONS: Short- and long-term exposure to ambient PM2.5 was associated with an increased risk of allergic nasal and eye symptoms, worsening dyspnea caused by allergens, and ≥ 2 allergic symptoms. TRIAL REGISTRATION: Clinical trial ID: NCT03532893 (29 Mar 2018).

A theoretical study on the ORR electrocatalytic activity of axial ligand modified cobalt polyphthalocyanine.

In this work, the catalytic activity in the oxygen reduction reaction (ORR) of cobalt polyphthalocyanine whose central Co atom is coordinated at the axial position by ligands (L = -F, -OH, -OCH3, -N3, -Cl, -Br, -I, -SCN, and -CN) (CoPPc-L) was investigated using theoretical calculations in alkaline medium. Among all CoPPc-L, CoPPc-N3 exhibited the lowest ORR overpotential of 0.23 V vs. a standard hydrogen electrode, which is significantly lower than those of CoPPc (0.48 V) and Pt(111) (0.43 V). There is a good linear relationship between ΔG*OOH and the electronegativity of ligating atoms in axial ligands of CoPPc-L. The greater the electronegativity, the stronger the adsorption of the catalyst to the intermediate. Additionally, the adsorption strength of CoPPc to the intermediate is modified by the axial ligands, which adjust the distribution of anti-bonding electronic states of dz2, dxz, and dyz orbitals near the Fermi level, Ef. A larger Mayer bond order of the Co-L bond resulted in a smaller bond order of the Co-O bond. CoPPc-N3 exhibited a moderate Co-O bond order of 0.737, corresponding to moderate adsorption energy to the OOH intermediate. This study demonstrates that the interaction strength between CoPPc and ORR intermediates can be adjusted by selecting appropriate axial ligands, which can modulate the ORR catalytic activity.

Long-Term Ozone Exposure and Small Airway Dysfunction: The China Pulmonary Health (CPH) Study.

Rationale: It remains unknown whether long-term ozone exposure can impair lung function. Objectives: To investigate the associations between long-term ozone exposure and adult lung function in China. Methods: Lung function results and diagnosis of small airway dysfunction (SAD) were collected from a cross-sectional study, the China Pulmonary Health Study (N = 50,991). We used multivariable linear and logistic regression models to examine the associations of long-term ozone exposure with lung function parameters and SAD, respectively, adjusting for demographic characteristics, individual risk factors, and longitudinal trends. We then performed a stratification analysis by chronic obstructive pulmonary disease (COPD). Measurements and Main Results: We observed that each 1 SD (4.9 ppb) increase in warm-season ozone concentrations was associated with a 14.2 ml/s (95% confidence interval [CI], 8.8-19.6 ml/s] decrease in forced expiratory flow at the 75th percentile of vital capacity and a 29.5 ml/s (95% CI, 19.6-39.5 ml/s) decrease in mean forced expiratory flow between the 25th and 75th percentile of vital capacity. The odds ratio of SAD was 1.09 (95% CI, 1.06-1.11) for a 1 SD increase in warm-season ozone concentrations. Meanwhile, we observed a significant association with decreased FEV1/FVC but not with FEV1 or FVC. The association estimates were greater in the COPD group than in the non-COPD group. Conclusions: We found independent associations of long-term ozone exposure with impaired small airway function and higher SAD risks, while the associations with airflow obstruction were weak. Patients with COPD appear to be more vulnerable.

Effect of fracture risk in inhaled corticosteroids in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.

BACKGROUND: The fracture risk of patients with chronic obstructive pulmonary disease (COPD) treated with inhaled corticosteroids is controversial. And some large-scale randomized controlled trials have not solved this problem. The purpose of our systematic review and meta-analysis including 44 RCTs is to reveal the effect of inhaled corticosteroids on the fracture risk of COPD patients. METHODS: Two reviewers independently retrieved randomized controlled trials of inhaled corticosteroids or combinations of inhaled corticosteroids in the treatment of COPD from PubMed, Embase, Medline, Cochrane Library, and Web of Science. The primary outcome was a fracture event. This study was registered at PROSPERO (CRD42022366778). RESULTS: Forty-four RCTs were performed in 87,594 patients. Inhaled therapy containing ICSs (RR, 1.19; 95%CI, 1.04-1.37; P = 0.010), especially ICS/LABA (RR, 1.30; 95%CI, 1.10-1.53; P = 0.002) and triple therapy (RR, 1.49; 95%CI, 1.03-2.17; P = 0.04) were significantly associated with the increased risk of fracture in COPD patients when compared with inhaled therapy without ICSs. Subgroup analyses showed that treatment duration ≥ 12 months (RR, 1.19; 95%CI, 1.04-1.38; P = 0.01), budesonide therapy (RR, 1.64; 95%CI., 1.07-2.51; P = 0.02), fluticasone furoate therapy (RR, 1.37; 95%CI, 1.05-1.78; P = 0.02), mean age of study participants ≥ 65 (RR, 1.27; 95%CI, 1.01-1.61; P = 0.04), and GOLD stage III(RR, 1.18; 95%CI, 1.00-1.38; P = 0.04) were significantly associated with an increased risk of fracture. In addition, budesonide ≥ 320 ug bid via MDI (RR, 1.75; 95%CI, 1.07-2.87; P = 0.03) was significantly associated with the increased risk of fracture. CONCLUSION: Inhalation therapy with ICSs, especially ICS/LABA or triple therapy, increased the risk of fracture in patients with COPD compared with inhaled therapy without ICS. Treatment duration, mean age of participants, GOLD stage, drug dosage form, and drug dose participated in this association. Moreover, different inhalation devices of the same drug also had differences in risk of fracture.

Tuning the Site-to-Site Interaction of Heteronuclear Diatom Catalysts MoTM/C2N (TM = 3d Transition Metal) for Electrochemical Ammonia Synthesis.

Ammonia (NH3) synthesis is one of the most important catalytic reactions in energy and chemical fertilizer production, which is of great significance to the sustainable development of society and the economy. The electrochemical nitrogen reduction reaction (eNRR), especially when driven by renewable energy, is generally regarded as an energy-efficient and sustainable process to synthesize NH3 in ambient conditions. However, the performance of the electrocatalyst is far below expectations, with the lack of a high-efficiency catalyst being the main obstacle. Herein, by means of comprehensive spin-polarized density functional theory (DFT) computations, the catalytic performance of MoTM/C2N (TM = 3d transition metal) for use in eNRR was systematically evaluated. Among the results, MoFe/C2N can be considered the most promising catalyst due to its having the lowest limiting potential (-0.26 V) and high selectivity in the context of eNRR. Compared with its homonuclear counterparts, MoMo/C2N and FeFe/C2N, MoFe/C2N can balance the first protonation step and the sixth protonation step synergistically, showing outstanding activity regarding eNRR. Our work not only opens a new door to advancing sustainable NH3 production by tailoring the active sites of heteronuclear diatom catalysts but also promotes the design and production of novel low-cost and efficient nanocatalysts.

Construction of Ni2P-MoC/Coal-Based Carbon Fiber Self-Supporting Catalysts for Enhanced Hydrogen Evolution.

Efficient and inexpensive electrocatalysts play an important role in the hydrogen evolution reaction (HER) of electrolytic water splitting. Herein, Ni2P-MoC/coal-based carbon fiber (Ni2P-MoC/C-CF) self-supporting catalysts were obtained by low-temperature phosphorization and high-temperature carbonization. The Mo source and oxidized coal were uniformly dispersed in the carbon support by electrospinning technology. A precursor of Ni was introduced by the impregnation method. The synergistic effect of MoC and Ni2P may reduce the strong hydrogen adsorption capacity of pure MoC and provide a fast hydrogen release process. In addition, the C-CFs prepared by electrospinning can not only prevent the agglomeration of MoC and Ni2P particles at a high temperature but also provide a self-supporting support for the catalyst. As a result, the catalytic performance of the HER was improved greatly, and a low overpotential of 112 mV at 10 mA cm-2 was exhibited stably by the Ni2P-MoC/C-CFs. This work not only converts coal into coal-based carbon materials but also provides a feasible pathway for the rational design of large-scale molded hydrogen electrocatalysts.

[Research and application of model fruit fly in prevention and treatment of neuropsychiatric disorders by traditional Chinese medicine and natural compounds: a review].

As an important model animal, fruit fly is characterized by outstanding genetic characteristics, relatively perfect nervous system, rapid reproduction, and low cost. Thus, it has been applied in the research on neuropsychiatric disorders in recent years, showing great potential in life science. The incidence of neuropsychiatric disorders has been on the rise, and the disorders have high disability rate and low case fatality rate. The global drug demand for such diseases is second only to cardiovascular and cerebrovascular diseases. At the moment, the demand of the drugs for the diseases have been rising, and it is an urgent task to develop related drugs. However, the research and development of the drugs are time-intensive and have a high failure rate. A suitable animal model can help shorten the time for drug screening and development, thereby reducing the cost and failure rate. This study reviews the application of fruit flies in several common neuropsychiatric disorders, which is expected to provide new ideas for the research and application of the model animals in traditional Chinese medicine.

Associations of residential greenness with lung function and chronic obstructive pulmonary disease in China.

BACKGROUND: Studies on the association of greenness with respiratory health are scarce in developing countries, and previous studies in China have focused on only one or two indicators of lung function. OBJECTIVE: The study aims to evaluate the associations of residential greenness with full-spectrum lung function indicators and prevalence of chronic obstructive pulmonary disease (COPD). METHODS: This nationwide cross-sectional survey included 50,991 participants from the China Pulmonary Health study. Lung function indicators included four categories: indicators of obstructive ventilatory dysfunction (FEV1, FVC and FEV1/FVC); an indicator of large-airway dysfunction (PEF); indicators of small-airway dysfunction (FEF25-75% and FEV3/FEV6); and other indicators. Residential greenness was assessed by the Normalized Difference Vegetation Index (NDVI). Multivariable linear regression models and logistic regression models were used to analyze associations of greenness with lung function and COPD prevalence. RESULTS: Within the 500 m buffer, an interquartile range (IQR) increase in NDVI was associated with higher FEV1 (24.76 mL), FVC (16.52 mL), FEV1/FVC (0.38), FEF50% (56.34 mL/s), FEF75% (33.43 mL/s), FEF25-75% (60.73 mL/s), FEV3 (18.59 mL), and FEV6 (21.85 mL). However, NDVI was associated with lower PEF. In addition, NDVI was significantly associated with 10% lower odds of COPD. The stratified analyses found that the associations were only significant in middle-young people, females, and nonsmokers. The associations were influenced by geographic regions. CONCLUSIONS: Residential greenness was associated with better lung function and lower odds of COPD in China. These findings provide a scientific basis for healthy community planning.

Deciphering variation of 239 elite japonica rice genomes for whole genome sequences-enabled breeding.

Revealing genomic variation of representative and diverse germplasm is the cornerstone of deploying genomics information into genetic improvement programs of species of agricultural importance. Here we report the re-sequencing of 239 japonica rice elites representing the genetic diversity of japonica germplasm in China, Japan and Korea. A total of 4.8 million SNPs and PAV of 35,634 genes were identified. The elites from Japan and Korea are closely related and relatively less diverse than those from China. A japonica rice pan-genome was constructed, and 35 Mb non-redundant novel sequences were identified, from which 1131 novel genes were predicted. Strong selection signals of genomic regions were detected on most of the chromosomes. The heading date genes Hd1 and Hd3a have been artificially selected during the breeding process. The results from this study lay the foundation for future whole genome sequences-enabled breeding in rice and provide a paradigm for other species.

Development and Validation of a Screening Questionnaire of COPD from a Large Epidemiological Study in China.

OBJECTIVE: We aimed to establish an easy-to-use screening questionnaire with risk factors and suspected symptoms of COPD for primary health care settings. METHODS: Based on a nationwide epidemiological study of pulmonary health among adults in mainland China (China Pulmonary Health, CPH study) between 2012 and 2015, participants ≥40 years who completed the questionnaire and spirometry tests were recruited and randomly divided into development set and validation set by the ratio of 2:1. Parameters including sex, age, BMI, residence, education, smoking status, smoking pack-years, biomass exposure, parental history of respiratory diseases and daily respiratory symptoms were initially selected for the development of scoring system. Receiver operating characteristic (ROC) curve, area under curve (AUC), positive and negative predictive values were calculated in development set and validation set. RESULTS: After random split by 2:1 ratio, 22443 individuals were assigned to development set and 11221 to validation set. Ten variables were significantly associated with COPD independently in development set after a stepwise selection by multivariable logistic model and used to develop scoring system. The scoring system yielded good discrimination, as measured by AUC of 0.7737, and in the validation set, the AUC was 0.7711. When applying a cutoff point of ≥16, the sensitivity in development set was 0.69 (0.67 - 0.71); specificity 0.72 (0.71 - 0.73), PPV 0.25 (0.24 - 0.26) and NPV 0.94 (0.94 - 0.95). CONCLUSION: We developed and validated a comprehensive screening questionnaire, COPD-CPHS, with good discrimination. The score system still needs to be validated by large cohort in the future.Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2022.2042504 .

Synthesis and Structure Elucidation of Two Essential Metal Complexes: In-Vitro Studies of Their BSA/HSA-Binding Properties, Docking Simulations, and Anticancer Activities.

Imidazole and tetrazole derivatives are widely used as clinical drugs since they possess a variety of pharmaceutical function. Zinc and iron are essential trace elements of the human body, with less toxicity and good biocompatibility. In this paper, two new essential metal mononuclear complexes [M(H2tmidc)2(H2O)2]·2H2O (M = Zn (1), Fe (2)) were synthesized through the reaction of 2-((1H-tetrazol-1-yl)methylene)-1H-imidazole-4,5-dicarboxylic acid (H3tmidc) and ZnSO4·7H2O or FeSO4·7H2O. The crystal structures were determined by means of the X-ray single crystal diffraction technique. Results from fluorescence investigations show that both complexes could interact with BSA as well as HSA through the static quenching mechanism. van der Waals forces and hydrogen bonds play important roles in the interaction of complexes and BSA/HSA since both ΔH and ΔS values are negative. The results of molecular docking are consistent with those in experimental studies. Furthermore, the anticancer activity of H3tmidc and both complexes against Eca-109 were preliminarily evaluated and the results show that both complexes have better anticancer activity than the corresponding ligand H3tmidc.

Stepwise selection of natural variations at CTB2 and CTB4a improves cold adaptation during domestication of japonica rice.

The improvement of cold adaptation has contributed to the increased growing area of rice. Standing variation and de novo mutation are distinct natural sources of beneficial alleles in plant adaptation. However, the genetic mechanisms and evolutionary patterns underlying these sources in a single population during crop domestication remain elusive. Here we cloned the CTB2 gene, encoding a UDP-glucose sterol glucosyltransferase, for cold tolerance in rice at the booting stage. A single standing variation (I408V) in the conserved UDPGT domain of CTB2 originated from Chinese Oryza rufipogon and contributed to the cold adaptation of Oryza sativa ssp. japonica. CTB2 is located in a 56.8 kb region, including the previously reported gene CTB4a in which de novo mutation arose c. 3200 yr BP in Yunnan province, China, conferring cold tolerance. Standing variation of CTB2 and de novo mutation of CTB4a underwent stepwise selection to facilitate cold adaptation to expand rice cultivation from high-altitude to high-latitude regions. These results provide an example of stepwise selection on two kinds of variation and describe a new molecular mechanism of cold adaptation in japonica rice.

Dicyanamide Anion-Based Ionic Liquid-Functionalized Graphene-Supported Pt Catalysts for Boosting Methanol Electrooxidation.

As an environmentally friendly energy technology, direct methanol fuel cells (DMFCs) meet the needs of sustainable development. Herein, novel dicyanamide anion-based (N(CN)2-) ionic liquid (IL)-functionalized reduced graphene oxide (rGO)-supported Pt catalysts are synthesized via a facile one-pot room temperature reduction method, which show a boost in methanol oxidation performance compared with Pt/rGO. The mass activities of the as-prepared Pt/emimN(CN)2/rGO (863.6 mA mg-1Pt) and Pt/epyN(CN)2/rGO (524.9 mA mg-1Pt) are about five and three times higher than that of Pt/rGO (178.6 mA mg-1Pt), and about six and four times higher than that of Pt/C (140.2 mA mg-1Pt), respectively. The participation of ILs significantly improves the CO poisoning resistance, stability, and activity for methanol oxidation of catalysts. The relationship between the structures and conductivities of diverse ILs and the performance of Pt catalysts are studied systematically. These findings may offer a promising prospect of ILs in DMFCs.

Adiponectin antagonises LPS-regulated secretion of inflammatory factors in airway epithelial cells, and its expression is regulated by many factors.

Many studies have shown that adiponectin is closely related to chronic obstructive pulmonary disease (COPD), but the specific role of adiponectin in COPD is still not well understood. Adiponectin and IL-6 expression in patients with acute exacerbation of COPD (AECOPD) was detected by ELISA. Human bronchial epithelial cells (HBECs) were stimulated with TNF-α, IL-6, apoptotic cells or LPS. Then, the expression of adiponectin was detected by qRT-PCR and western blotting, and pro- and anti-inflammatory factors were detected by ELISA. Adiponectin expression in AECOPD patients increased after treatment. TNF-α and apoptotic cells promoted adiponectin expression in HBECs in a dose-dependent manner, and apoptotic cells significantly promoted adiponectin secretion. IL-6 also promoted adiponectin expression, but it inhibited adiponectin expression at high doses and with long treatment times. LPS inhibited adiponectin expression, but when HBECs were pretreated with anti-TNF-α and then treated with LPS, the expression and secretion of adiponectin increased significantly with increasing anti-TNF-α concentrations. Adiponectin stimulated the secretion of pro-inflammatory factors in HBECs, but this effect was not concentration dependent. Adiponectin promoted the secretion of anti-inflammatory factors in a dose-dependent manner. Although LPS also stimulated HBECs to secrete pro-inflammatory and anti-inflammatory factors, adiponectin inhibited LPS-induced pro-inflammatory factor secretion and enhanced anti-inflammatory factor secretion. Many factors regulate the expression and secretion of adiponectin, and adiponectin regulates the balance of the inflammatory response and inhibits further expansion of inflammation. SIGNIFICANCE OF THE STUDY: Many studies have shown that adiponectin is closely related to chronic obstructive pulmonary disease (COPD), but the specific role of adiponectin in COPD is still not well understood. Adiponectin expression in AECOPD patients increased after treatment. TNF-α, IL-6 and apoptotic cells promoted adiponectin expression in HBECs. Adiponectin stimulated the secretion of pro-inflammatory factors in HBECs, but this effect was not concentration dependent. Adiponectin promoted the secretion of anti-inflammatory factors in a dose-dependent manner. Adiponectin inhibited LPS-induced pro-inflammatory factor secretion and enhanced anti-inflammatory factor secretion. Therefore, many factors regulate the expression and secretion of adiponectin, and adiponectin regulates the balance of the inflammatory response and inhibits further expansion of inflammation.