Site 1 protease aggravates acute kidney injury by promoting tubular epithelial cell ferroptosis through SIRT3-SOD2-mtROS signaling.

Ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) is a common clinical syndrome with high morbidity and mortality. Ferroptosis, a newly discovered form of oxidative cell death, is involved in the pathogenesis of renal I/R injury; however, the underlying mechanism remains to be explored. Here, we reported that site 1 protease (S1P) promotes ischemic kidney injury by regulating ferroptotic cell death of tubular epithelial cells. S1P abundance was measured in hypoxia/reoxygenation (H/R)-treated Boston University mouse proximal tubular (BUMPT) cells and I/R-induced murine kidney tissue. S1P expression in BUMPT cells and kidneys was initially activated by hypoxic stimulation, accompanied by the ferroptotic response. Blocking S1P blunted H/R-induced ferroptotic cell death, which also restored sirtuin 3 (SIRT3) expression and superoxide dismutase 2 (SOD2) activity in BUMPT cells. Next, inhibition of S1P expression restored I/R-suppressed SIRT3 abundance, SOD2 activity and reduced the elevated level of mitochondria reactive oxygen species (mtROS), which attenuated tubular cell ferroptosis and renal I/R injury. In conclusion, S1P promoted renal tubular epithelial cell ferroptosis under I/R status by activating SIRT3-SOD2-mtROS signaling, thereby accelerating kidney injury. Thus, targeting S1P signaling may serve as a promising strategy for I/R kidney injury.

Overview of tumor immunotherapy based on approved drugs.

Tumor immunotherapy has become a new hotspot for cancer treatment. Various immunotherapies, such as immune checkpoint inhibitors, oncolytic viruses (OVs), cytokines, and cancer vaccines, have been used to treat tumors. They operate through different mechanisms, along with certain toxicities and side effects. Understanding the mechanisms by which immunotherapy modulates the immune system is essential for improving the efficacy and managing these adverse effects. This article discusses various currently approved cancer immunotherapy mechanisms and related agents approved by the Food and Drug Administration, the European Medicines Agency, and the Medicines and Medical Devices Agency. We also review the latest progress in immune drugs approved by the National Medical Products Administration, including monoclonal antibodies, cytokines, OVs, and chimeric antigen receptor-T cell therapy, to help understand the clinical application of tumor immunotherapy.

ER Stress-Perturbed Intracellular Protein O-GlcNAcylation Aggravates Podocyte Injury in Diabetes Nephropathy.

Diabetes nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) worldwide, and podocyte injury is the central contributor to the progression of DN. Despite the emerging evidence that has established the importance of podocyte endoplasmic reticulum (ER) stress in the pathogenesis of DN, abnormal protein O-GlcNAcylation is also augmented. Currently, the mechanism associating these two hyperglycemia-induced disorders remains poorly understood. This study intended to elucidate whether ER stress drives hyper-protein O-GlcNAcylation to cause podocyte injury in DN. We used both type 1 and type 2 DN models to confirm the occurrence of ER stress and excessive protein O-GlcNAcylation, and then podocyte purification was also conducted for further investigation. Nephroseq V5 data were mined and in vitro studies were applied to reveal the involvement of ER stress and hyper-O-GlcNAcylation in podocyte injury. Our results indicated that ER stress was induced in both type 1 and type 2 DN, and the human RNA-seq data from Nephroseq V5 showed that O-GlcNAcylation-related genes were significantly upregulated in the DN patients. We further demonstrated that ER stress occurred prior to hyper-O-GlcNAc modification and that pharmacologically inhibited protein O-GlcNAcylation can help decrease the podocyte apoptosis induced by hyperglycemia. Together, these discoveries will aid in uncovering the activation of the ER stress-O-GlcNAcylation axis in podocyte injury under DN, which will help open up new therapeutic approaches for preventing DN progression.

Correlation between air pollution and cognitive impairment among older individuals: empirical evidence from China.

BACKGROUND: Little information is available regarding the impact of air pollution on cognitive impairment in older individuals in developing countries. This study empirically tested the impacts of the air quality index (AQI), air pollution intensity (quantified by the number of days of extreme air pollution in a year), and different pollutants on the cognitive abilities of older Chinese individuals. METHODS: A panel of 28,395 participants spanning 122 cities in 2015 and 2018 was used, based on 3-year follow-up survey data from the China Health and Retirement Longitudinal Study (CHARLS) database. Data from the two phases of the CHARLS microsurvey were combined with relevant statistical data on air pollution in each region in the current year. These two surveys were used to investigate changes in basic health and macro-environmental indicators in older individuals in China, and a mean difference test was conducted. We then reduced the sample selection error by controlling for environmental migration and used two-way fixed and instrumental variable methods for endogenous treatment to avoid the estimation error caused by missing variables. RESULTS: Air pollution had a significantly negative effect on the cognitive abilities of older individuals (odds ratio [OR]: 1.4633; 95% confidence interval [95% CI]: 1.20899-1.77116). Different pollution intensities(only AQI value is greater than 200 or more) had apparent effects on cognitive impairment, with an OR of approximately 1.0. Sulfur dioxide had significantly negative effects on cognitive ability, with OR of 1.3802 (95% CI: 1.25779-1.51451). Furthermore, air pollution impact analysis showed heterogeneous results in terms of age, sex, education, and regional economic development level. In addition, social adaptability (calculated using social participation, learning, adaptability, and social support) not only had a significant positive effect on the cognitive abilities of older individuals, but also regulated the cognitive decline caused by air pollution. CONCLUSIONS: Air pollution affects cognitive impairment in older individuals, especially in those with lower education levels, and living in economically underdeveloped areas. This effect is synchronous and has a peak at an AQI of > 200.

Incidence and severity of SARS-CoV-2 reinfection, a multicenter cohort study in Shanghai, China.

During March 2022 to January 2023, two Omicron waves hit Shanghai and caused a massive number of reinfections. To better understand the incidence and clinical characteristics of SARS-CoV-2 reinfection in Shanghai, China, we conducted a multicenter cohort study. COVID-19 patients first infected with BA.2 (March 1, 2022-May 23, 2022) who were quarantined in Huashan Hospital, Renji Hospital, and Shanghai Jing'an Central Hospital were followed up for reinfection from June 1, 2022 to January 31, 2023. Of 897 primary infections, 148 (16.5%) experienced reinfection. Incidence rate of reinfection was 0.66 cases per 1000 person-days. Female gender (adjusted odds ratio [aOR]= 2.19, 95% confidence interval [CI]: 1.29-3.83) was a risk factor for reinfection. The four most common symptoms of reinfections during the circulation of BA.5 sublineages were cough (62.59%), sore throat (54.42%), fatigue (48.98%), and fever (42.57%). Having received a booster vaccination was not associated with reduced severity of reinfection in comparison with not having received booster vaccination. After matched 1:1 by age and sex, we found that reinfections with BA.5 sublineages had significantly lower occurrence and severity of fever, fatigue, sore throat, and cough, as compared to primary infections with BA.5 sublineages. SARS-CoV-2 Omicron reinfections were less severe than Omicron primary infections during the circulation of the same subvariant. Protection offered by both vaccination and previous infection was poor against SARS-CoV-2 reinfection.

Natural deep eutectic solvent-A novel green solvent for protein stabilization.

Natural deep eutectic solvents (NADESs) have been explored to provide a favorable environment for protein stabilization. In this context, NADESs were prepared with the molar ratio of trehalose to betaine ranging from 1:3 to 1:9 (NADES 1-3 to NADES 1-9). There was a strong hydrogen bond interaction between trehalose and betaine, and the interaction weakened with the reduction of trehalose. The NADES 1-7 had good thermal stability (-60-100 °C), low viscosity, and suitable pH (around 7). Trypsin had the highest relative enzyme activity in 50 % (v/v) NADES 1-7 under different temperatures, pH, and storage time. Furthermore, the changes in kinetic parameters indicated that the hydrogen bond environment of 50 % NADES 1-7 increased the contact between the substrate and the trypsin, speeding up the enzymatic reaction rate. This stabilizing effect mainly derived from the virtue of NADES 1-7 itself rather than the superposition of individual components. Additionally, spectral analysis revealed that the NADES 1-7 promoted trypsin conformational folding, effectively protecting the natural structure of trypsin. Importantly, the NADES 1-7 had good biocompatibility, further expanding its application.

Potential predictors for the efficacy of non-steroidal anti-inflammatory drugs in patients with migraine.

Objectives: To explore potential predictors of the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) in patients with migraine. Methods: Consecutive migraine patients were recruited and divided into responders and non-responders to NSAIDs according to follow-up for at least three months. Demographic data, migraine-related disabilities and characteristics, and psychiatric comorbidities were evaluated and used to build multivariable logistic regression models. Subsequently, we generated receiver operating characteristic (ROC) curves to explore the performance of these traits in predicting NSAIDs efficacy. Results: A total of 567 patients with migraine who completed at least three months of follow-up were enrolled. In the multivariate regression analysis, five factors were identified as potential predictors for NSAIDs efficacy in treating migraine. Namely, attack duration (odds ratio (OR) = 0.959; p < 0.001), headache impact (OR = 0.966; p = 0.015), depression (OR = 0.889; p < 0.001), anxiety (OR = 0.748; p < 0.001), and education level (OR = 1.362; p < 0.001) were associated with response to NSAIDs treatment. The area under the curve, sensitivity, and specificity combining these five factors for predicting the efficacy of NSAIDs were 0.834, 0.909 and 0.676. Conclusions: These findings suggest that migraine-related and psychiatric factors are associated with the response to NSAIDs in migraine management. Identifying such key factors may help to optimize individualized migraine management strategy.

The Interactive Effects of Deficit Irrigation and Bacillus pumilus Inoculation on Growth and Physiology of Tomato Plant.

The effects of inoculating plant growth promoting rhizobacteria (PGPR) and soil water deficits on crop growth and physiology remain largely unknown. Here, the responses of leaf gas exchange, growth, and water use efficiency (WUE) of tomato plants to Bacillus pumilus (B.p.) inoculation under four irrigation strategies (I1-I4) were investigated in a greenhouse. Results showed that soil water deficits, especially at I4 (20%, v/v), significantly decreased leaf stomatal conductance (gs), transpiration rate (Tr), and photosynthetic rate (An), and the decrease of gs and Tr were more pronounced than An. Reduced irrigation regimes significantly lowered dry matter and plant water use both in the non-B.p. control and the B.p. plants, while reduced irrigation significantly increased plant WUE, and B.p. inoculation had little effect on this parameter. Synergistic effects of PGPR and deficit irrigation on leaf gas exchange, leaf abscisic acid content, and stomatal density were found in this study, and specifically, B.p. treated plants at I4 possessed the highest WUE at stomatal and leaf scales, suggesting that B.p. inoculation could optimize water use and partly alleviate the negative effects of soil water deficit. These findings provide useful information for effective irrigation management and the application of PGPR in agriculture in the future.

The effect of city size on the disability rate of the older adults: empirical evidence from CHARLS data.

Background: Exploring the value orientation of city development from the perspective of people's well-being is key to clarifying the current debate on city size strategies. Methods: Based on the survey data of the China Health and Retirement Longitudinal Study in two phases, and by using the unbalanced panel-ordered logit model, stepwise analysis method, and KHB method, among others, we discuss the impact of city size on the disability rate of older adults. Results: The study finds that city size significantly and positively affects the activities of daily living (ADL) of older adults, with odd ratios of 1.3286 (95% CI = [1.082243, 1.631089]), and exhibits significant group heterogeneity in terms of age, registered residence, income, and education level. City size has indeed played an mediation role through the health improvement effect, disease mitigation effect, emotional effect, and employment structure optimization effect, with a cumulative contribution rate of the mediation effect of 35.17%. In addition, the urban sprawl index has a significant moderation role. Discussion: Robust urban sprawl is conducive to promoting the improvement of the regional health environment, the improvement of the medical security policy, the optimization of the family support policy, and the employment structure, thus helping to reduce the disability rate of older adults.

Effects of ß2 Integrins on Osteoclasts, Macrophages, Chondrocytes, and Synovial Fibroblasts in Osteoarthritis.

ß2 integrins are transmembrane receptors that exist widely in human immune cells and participate in pathological processes such as chronic inflammation, thrombosis, and malignant tumor formation. They mainly mediate intercellular adhesion, coordinate the ingestion of extracellular matrix components, and regulate cytoskeleton formation, thereby regulating cell signaling. Osteoarthritis (OA) is a chronic joint disease that causes joint pain and increases disease burden; it has a high prevalence among populations worldwide. Previous studies have reported that ß2 integrins are overexpressed in OA and may play an essential role in the occurrence of OA. The important roles of ß2 integrins in the maturation and differentiation of osteoclasts, the regulation of bone homeostasis, and the polarization and migration of macrophages have also been reported. The present review aims to highlight the role of ß2 integrins in OA pathogenesis and outline their potential for serving as therapeutic targets.

Impact of socioeconomic status and health risk on fall inequality among older adults.

Socio-economic status (SES) is one of the important indicators reflecting individual social participation and resource allocation, and it plays an important role in individual health shock. Health shock indicates the body being in a non-healthy state, such as illness, injury and death. This study used data from the China Health and Retirement Longitudinal Study conducted in 2013, 2015 and 2018 and utilised the panel logit model, causal step-by-step analysis and path analysis to empirically test the impact of SES on fall inequality among the elderly and the mediating effect of health shock. The results demonstrated obvious group inequality in the fall risk among older adults, the core of which was the impact of SES on health, causing health inequality and affecting fall inequality. The activities of daily living and pain rate of the high-income group were 61.16% and 28.69%, respectively, that of the low-income group. The evaluation of good sight and hearing were 3.6833 and 3.8572 times, respectively, that of the low-income group. The non-depressive status was 38.4638 times of the low-income group. The path effect confirmed the mediating role of health shock. Therefore, this study concluded that SES had an important impact on the risk of falls among the elderly, and this impact was mainly from health shock. This study proposed that to reduce the incidence of falls among the elderly, differences in health shock risks among the elderly with different SES must be actively monitored and accurate and effective policy interventions should be implemented from the level of group heterogeneity.

Prolonged exposure of azocyclotin induced inter- and transgenerational endocrine disruption on Danio rerio linked to transcriptomic and DNA methylomic alterations.

The transgenerational effect assessment linked to epigenetic analysis of environmental pollutants on eco (toxico)logical relevant species is regarded as a potential future risk-assessment tool. As an organotin acaricide widely used in China, azocyclotin can lead to endocrine disrupting effect on directly exposed environmental organisms, but whether it has transgenerational negative impact remains unknown. In order to illustrate this issue, in the present study, zebrafish, an aquatic model animal, was exposed to azocyclotin at less than µg/L level in a time span of embryonic stage to adult stage. Subsequently, the developmental and reproductive endocrine disrupting effects of azocyclotin on exposed F0 and unexposed offspring (F1 and F2) were evaluated. Result indicated that parentally exposed to 0.36 µg/L azocyclotin induced embryonic toxicity to unexposed offspring, and significantly (p < 0.05) reduced body weight (by 8.5%-13.9%), whole body length (by 4.8%-14.3%), hepatosomatic index (by 15.6%-24.3%), gonadosomatic index (by 5.3%-17.1%), egg production (by 19.5%-25.4%), estradiol content (47.0%-65.0%) and proportion of mature germ cells (by 29.3%-41.0% and 39.2%-47.7% for late oocytes and spermatozoa, respectively) in adults of F0 and offspring. Additionally, azocyclotin decreased the contents of 5-methycytosine in gonads of unexposed offspring (by 9.9%-38.6%, p < 0.05), led to genome-wide gene up-regulated expression bias and genomic DNA hypomethylation tendency in unexposed offspring. Moreover, based on the level of differentially methylated cytosine in promoter regions/gene body regions, it was found totally 5331/11,170 (in F1) and 3808/7507 (in F2) differentially expressed genes were closely related with differentially methylated genes (r > 0.6). The present study provided a primary evidence that prolonged exposure to low dose azocyclotin induced inter- and transgenerational endocrine disrupting effects on zebrafish probably linked to transcriptomic and DNA methylomic alterations.

Prophylactic Effect of Lactobacillus fermentum TKSN02 on Gastric Injury Induced by Hydrochloric Acid/Ethanol in Mice Through Its Antioxidant Capacity.

In this article, the preventive and protective effect of a new Lactobacillus fermentum, (Lactobacillus fermentum TKSN02: LF-N2), which was isolated and identified from Xinjiang naturally fermented yogurt, on hydrochloric acid (HCl)/ethanol induced gastric injury in mice was studied. A total of 40 mice were divided into the following five groups: normal, model, LF-N2, LB (Lactobacillus bulgaricus), and Ranitidine groups. Except for the normal and model groups, mice in the other groups were treated with LF-N2, LB (Lactobacillus bulgaricus), and Ranitidine separately, and the injury of the gastric tissue was observed by taking photos and pathological sections. The levels of oxidation indicators, gastrointestinal hormone and the inflammatory cytokines in serum and gastric tissue in each group were measured. Further more, the gene expression levels of oxidative stress and inflammation related genes in the colon tissue were determined by the Real-Time PCR method. Pathological observation confirmed that LF-N2 could inhibit the gastric injury caused by HCl/ethanol. Observation of the appearance of the gastric indicated that LF-N2 could effectively reduce the area of gastric injury. Biochemical results showed that the serum gastrin (GAS) and gastric motilin (MTL) levels in the LF-N2 group were significantly lower and the serum somatostatin (SS) level was higher than in the model group and there was no significant difference between all treatment groups. The activities of total superoxide dismutase (T-SOD) and glutathione (GSH) were increased while the malondialdehyde (MDA) content was decreased in LF-N2 treatment group mice, which suggested that LF-N2 has a good antioxidant effect. Further RT-PCR experiments also showed that LF-N2 could promote the related mRNA expression of antioxidant enzymes (Cu/Zn-SOD, Mn-SOD, and CAT) and anti-inflammatory cytokines (IL-4, and IL-10), while it inhibited the gene expression of pro-inflammatory cytokine (IL-6) and apoptosis factor (Caspase-3). As observed, LF-N2 exerted a good preventive effect on HCl/ethanol induced gastric injury in mice, and the effect was close to that of LB, which indicated that LF-N2 has potential use as a probiotic due to its gastric injury treatment effects.

Evaluating the long-term care insurance policy from medical expenses and health security equity perspective: evidence from China.

BACKGROUND: Since the national long-term care (LTCI) policy pilot in 2016 of China, the LTCI policy has had significant impact on the residents in the pilot area. METHODS: From the perspective of medical expenses and health security equity, this study selects tracking survey data from the CHARLS database in 2013, 2015, and 2018 and empirically investigates the effect of LTCI policy pilot by using differences-in-differences method (DID). Moreover, this study measures the economic distribution and health equity of the treated and untreated groups using the concentration and Theil indices. RESULTS: The results showed that group heterogeneity of medical expenses and health level of elderly in the treatment group were narrowing. Moreover, the policy results showed that the LTCI policy pilot significantly affects the outpatient, hospital expenses, and length of stay of elders. Residence registration, income level, and basic medical insurance play a significant regulatory role. Additionally, LTCI policy pilot significantly improved the overall health of the elderly. CONCLUSIONS: The measurement results of inequality show that the policy increases the income of low-income people, lowers the inequality level of outpatient and inpatient reimbursement, and reduces the concentration index of ADL disability and serious diseases. However, the inequality of serious diseases is becoming higher. Based on this, this paper provides several suggestions on optimizing the pilot policy of LTCI.

Estrogen receptor: A potential linker of estrogenic and dopaminergic pathways in zebrafish larvae following deltamethrin exposure.

Deltamethrin (DM), a type II pyrethroid insecticide, is widely used to control agricultural pests. However, its excessive use exerts a detrimental effect on the ecological environment and human health, indicating the need to study its potential risks in detail. In the present study, zebrafish embryos were exposed to varying concentrations of DM (0.1, 1, 10, and 25 µg/L) for 96 h to assess the alterations in the transcript levels of proteins of the estrogenic and dopaminergic pathways. In addition, its effect on zebrafish locomotor activity was studied. The mRNA expression of cyp19a1b, erα, erß2, fshr, gnrh2, gnrhr3, vtg3, dat, and dr1 significantly changed after exposing the embryos to DM. Deltamethrin at 10 and 25 µg/L significantly reduced the average swimming speed of zebrafish larvae. In addition, embryos injected with zebrafish estrogen receptor α (erα) and ß (erß) morpholinos and co-exposed to 25 µg/L DM for 96 h showed reduced expression of vtg3 mRNA compared to embryos exposed to 25 µg/L DM only. The locomotor activity of erα and erß knockdown zebrafish following DM exposure was increased significantly when compared with that of larvae exposed to 25 µg/L DM only. Our results demonstrated that DM altered the locomotor activity of zebrafish larvae and the transcript levels of the components of estrogenic and dopaminergic pathways; erα and erß knockdown weakened these effects.

Deficit drip irrigation based on crop evapotranspiration and precipitation forecast improves water- use efficiency and grain yield of summer maize.

BACKGROUND: Limited and erratic precipitation with inefficient irrigation scheduling often leads to an unstable crop yield and low water-use efficiency (WUE) in semi-arid and semi-humid regions. A 2-year field experiment was conducted to evaluate the effect of three irrigation strategies (conventional irrigation (CK), full-drip irrigation (FI), based on crop evapotranspiration and precipitation forecast, and deficit drip irrigation (DI) (75% FI)) on photosynthetic characteristics, leaf-to-air temperature difference (∆T), grain yield, and the WUE of summer maize. RESULTS: The results showed that the daily average net photosynthetic rate (Pn) of DI and FI increased by 25.4% and 25.8% at jointing stage in 2018, and 26.3% and 26.5% at grain-filling stage in 2019 compared with CK, respectively. At jointing stage in 2018 and grain-filling stage in 2019, the transpiration rate (Tr) of DI was significantly lower than that of FI (P < 0.05) but there was insignificant difference in Pn value (P > 0.05). The ∆T between 12:00-14:00 of DI and FI was significantly lower than that of CK at jointing stage in 2018 and grain-filling stage in 2019 (P < 0.05). The 2-year average grain yields of DI and FI were 11.4 and 11.5 t ha-1 , which increased by 32.4% and 32.8% compared with CK, respectively. The WUE of DI was 2.82 kg m-3 , which was 17.9% and 33.8% higher than that of FI and CK, respectively. CONCLUSION: Deficit drip irrigation based on crop evapotranspiration and precipitation forecast improves crop WUE and maintains high grain yields in semi-arid and semi-humid regions. © 2021 Society of Chemical Industry.

Unraveling the central and bridge psychological symptoms of people living with HIV: A network analysis.

Background: People living with HIV (PLWH) experience multiple psychological symptoms. Few studies have provided information on central and bridge psychological symptoms among PLWH. This information has implications for improving the efficiency and efficacy of psychological interventions. Our study aimed to identify the central and bridge psychological symptoms of PLWH and to explore the interconnectedness among symptoms and clusters. Methods: Our study used data from the HIV-related Symptoms Monitoring Survey, a multisite, cross-sectional study conducted during 2017-2021. We used R to visualize the network of 16 symptoms and analyzed the centrality and predictability indices of the network. We further analyzed the bridge symptoms among the three symptom clusters. Results: A total of 3,985 participants were included in the analysis. The results suggested that sadness had the highest strength (r S = 9.69) and predictability (70.7%) compared to other symptoms. Based on the values of bridge strength, feeling unsafe (r bs = 0.94), uncontrollable worry (r bs = 0.82), and self-abasement (r bs = 0.81) were identified as bridge symptoms. We also found a strong correlation between sadness and self-abasement (r = 0.753) and self-loathing and self-blame (r = 0.744). Conclusion: We found that sadness was the central psychological symptom of PLWH, indicating that sadness was the center of the psychological symptom network from a mechanistic perspective and could be a target for intervention. Deactivating bridge symptoms, including "feeling unsafe," "self-abasement," and "uncontrollable worry," could be more effective in preventing symptom activation from spreading (e.g., one symptom activating another).

Prokaryotic expression of human-sourced and zebrafish-sourced protein kinase A alpha catalytic subunits combined with in vitro and in silico assay.

The extensively studied cAMP-dependent protein kinase A (PKA) is involved in the regulation of critical cell processes, including metabolism, gene expression, and cell proliferation. Therefore, PKA has been viewed increasingly as potential target for variety of drugs and environmental endocrine disruptors. Consequentially, the preparation of PKA protein became an important initial step for the subsequent exploration of PKA's character in endocrine disrupting effects of pesticides. To investigate PKA protein, which is potential to be the environmental endocrine toxicity target of triazole fungicides, a strategy to heterologously express protein kinase A catalytic alpha subunit of human (hPKAcα) and zebrafish (zPKAcα) in Escherichia coli (E. coli) BL21(DE3) host cells was demonstrated. After optimizing conditions and protein purification, we successfully obtained enzymatically active hPKAcα and zPKAcα. Western blot analysis indicated that the recombinant hPKAcα and zPKAcα still retained their characteristic antigenicity and binding activity, while in vitro kinase activity assays revealed that the recombinant hPKAcα and zPKAcα maintained enzyme activity. By in silico methods including homology modelling and molecular docking, the affinity of ligands and the models of hPKAcα and zPKAcα were further tested. The present study offered a valuable method to achieve the prokaryotic expression of a eukaryotic protein kinase and laid a foundation to facilitate further investigation of toxicological target of triazole pesticides.

Interventional effect of dietary fiber on blood glucose and pregnancy outcomes in patients with gestational diabetes mellitus.

To investigate the effect of dietary fiber on blood glucose and pregnancy outcomes in patients with gestational diabetes mellitus (GDM). One hundred and twelve patients with GDM in the second trimester of pregnancy were recruited from Women's Hospital, Zhejiang University School of Medicine. Patients were randomized into two groups with 56 in each group: the control group received basic nutrition support; while the dietary fiber group were given additional dietary fiber ( total dietary fiber per day) before meals in addition to basic nutrition support. Intervention for all cases lasted for 8 weeks. Fasting blood glucose and postprandial blood glucose (2 h BG) were measured every week, and oral glucose tolerance test (OGTT) was performed at 42 d postpartum to evaluate the glycemic outcomes. Perinatal outcomes were recorded. The dietary fiber intervention markedly improved 2 h BG in patients with GDM and significantly elevated the glucose compliance rate from the 3rd to 8th week compared to the control group ( <0.05 or <0.01). OGTT 2 h glucose and the incidence of impaired glucose tolerance in the dietary fiber group were significantly lower than those in the control group, while the glucose compliance rate was significantly higher than that in the control group (all <0.01). Moreover, the rates of adverse perinatal outcomes, such as premature rupture of membranes and neonatal hyperbilirubinemia were declined in the dietary fiber group (<0.05 or <0.01). Dietary fiber intervention can ameliorate hyperglycemia in GDM patients, improve perinatal outcomes and reduce the incidence of postpartum impaired glucose tolerance.

Enhanced nutrient removal and facilitating granulation via intermittent aeration in simultaneous partial nitrification endogenous denitrification and phosphorus removal (SPNEDpr) process.

A novel simultaneous partial nitrification, endogenous denitrification and phosphorus removal (SPNEDpr) system was operated for 213 days in a sequencing batch reactor to treat real domestic sewage. The nutrient removal was achieved under an operation mode of intermittent aeration at unequal intervals with low oxygen concentrations. Through optimizing intermittent aeration conditions, the removal efficiencies of total inorganic nitrogen (TIN), PO43-P and chemical oxygen demand (COD) reached 78.40%, 98.13% and 84%, respectively. Low-oxygen (0.1-0.7 mg/L) and intermittent aeration effectively inhibited nitrite oxidation bacteria (NOB), maintaining stable partial nitrification with nitrite accumulation ratio of 96.45%. Notably, intermittent aeration promoted the formation of aerobic granular sludge, with the sludge particle size increasing from 217.2 ± 5.3 to 351.8 ± 4.8 µm, thereby enhancing the TIN loss efficiency (81.3%). The predominant genus was Candidatus_Competibacter (11.6%), which stored COD as intracellular carbon source and performed the endogenous denitrification. The SPNEDpr process provided a highly efficient and economical method for treating urban sewage.