Risk factors and outcomes for refeeding syndrome in acute ischaemic stroke patients.

AIM: Patients with acute ischaemic stroke are more likely to develop refeeding syndrome due to increased need for nutritional support when suffering alterations of consciousness and impairment of swallowing. This study aimed to evaluate the incidence, risk factors and outcomes of refeeding syndrome in stroke patients. METHODS: This was a retrospective observational study, using the prospective stroke database from hospital, included all consecutive acute ischaemic stroke patients who received enteral nutrition for more than 72 h from 1 January 2020 and 31 December 2022. Refeeding syndrome was defined as occurrence of new-onset hypophosphataemia within 72 h after enteral feeding. Multiple logistic regression analysis was conducted to evaluate risk factors and relationships between refeeding syndrome and stroke outcomes. RESULTS: 338 patients were included in the study. 50 patients (14.8%) developed refeeding syndrome. Higher scores on National Institutes of Health Stroke Scale and Nutritional Risk Screening 2002, albumin <30 g/L and BMI <18.5 kg/m2 were risk factors for refeeding syndrome. Moreover, refeeding syndrome was independently associated with a 3-month modified Rankin Scale score of >2 and 6-month mortality. CONCLUSIONS: Refeeding syndrome was common in stroke patients and higher baseline National Institutes of Health Stroke Scale, higher Nutritional Risk Screening 2002, albumin <30 g/L and BMI <18.5 kg/m2 were independent risk factors of refeeding syndrome. Occurrence of refeeding syndrome was significantly associated with higher 3-month modified Rankin Scale and 6-month mortality.

Effect of a Declined Plasma Concentration of Valproic Acid Induced by Meropenem on the Antiepileptic Efficacy of Valproic Acid.

OBJECTIVE: This study aimed to indicate whether a declined plasma concentration of valproic acid (VPA) induced by co-administration of meropenem (MEPM) could affect the antiepileptic efficacy of VPA. METHODS: We retrospectively reviewed data of hospitalized patients who were diagnosed with status epilepticus or epilepsy between 2010 and 2019. Patients co-administered VPA and MEPM during hospitalization were screened and assigned to the exposure group, while those co-administerd VPA and other broad-spectrum antibiotics were allocated to the control group. RESULTS: The exposure group and control group included 50 and 11 patients, respectively. With a similar dosage of VPA, the plasma concentration of VPA significantly decreased during co-administration (24.6 ± 4.3 µg/mL) compared with that before co-administration (88.8 ± 13.6 µg/mL, p < 0.0001), and it was partly recovered with the termination of co-administration (39.8 ± 13.2 µg/mL, p = 0.163) in the exposure group. The inverse probability of treatment weighting estimated the treatment efficacy via changes in seizure frequency, seizure duration, and concomitant use of antiepileptic drugs, which were not significantly different between the exposure and control groups. In the exposure group, there was no significant differences in seizure frequency between the periods of before-during and before-after (p = 0.074 and 0.153, respectively). Seizure duration during VPA-MEPM co-administration was not significantly different from that before co-administration (p = 0.291). CONCLUSIONS: In this study, the reduced plasma concentration of VPA induced by the co-administration of MEPM did not affect the antiepileptic efficacy of VPA. This conclusion should be interpreted with caution, and more research is warranted. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2000034567. Registered on 10 July 2020.

Glucosinolate O-methyltransferase mediated callus formation and affected ROS homeostasis in Arabidopsis thaliana.

Auxin-induced callus formation was largely dependent on the function of Lateral Organ Boundaries Domain (LBD) family transcription factors. We previously revealed that two IGMT (Indole glucosinolate oxy-methyl transferase) genes, IGMT2 and IGMT3, may be involved in the callus formation process as potential target genes of LBD29. Overexpression of the IGMT genes induces spontaneous callus formation. However, the details of the IGMT involvement in callus formation process were not well studied. IGMT1-4, but not IGMT5, are targeted and induced by LBD29 during the early stage of callus formation. Cell membrane and nucleus localized IGMT3 was mainly expressed in the elongation and maturation zones tissues of the primary root and lateral root, which could be further accumulated after CIM treatment. The igmts quadruple mutant, which obtained by CRISPR/Cas9 technology, exhibits a phenotype of attenuated callus formation. Enhanced indole glucosinolate anabolic pathway caused by IGMT1-4 overexpression promotes callus formation. In addition, the IGMT genes were involved in the reactive oxygen species homeostasis, which could be responsible for its role on callus formation. This study provides novel insights into the role of IGMTs gene-mediated callus formation. Activation of the Indole glucosinolate anabolic pathway is an inducing factor for plant callus initiation. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01409-2.

Impact of the coronavirus disease 2019 pandemic on the diversity of notifiable infectious diseases: a case study in Shanghai, China.

The outbreak of coronavirus disease 2019 (COVID-19) has not only posed significant challenges to public health but has also impacted every aspect of society and the environment. In this study, we propose an index of notifiable disease outbreaks (NDOI) to assess the impact of COVID-19 on other notifiable diseases in Shanghai, China. Additionally, we identify the critical factors influencing these diseases using multivariate statistical analysis. We collected monthly data on 34 notifiable infectious diseases (NIDs) and corresponding environmental and socioeconomic factors (17 indicators) from January 2017 to December 2020. The results revealed that the total number of cases and NDOI of all notifiable diseases decreased by 47.1% and 52.6%, respectively, compared to the period before the COVID-19 pandemic. Moreover, the COVID-19 pandemic has led to improved air quality as well as impacted the social economy and human life. Redundancy analysis (RDA) showed that population mobility, particulate matter (PM2.5), atmospheric pressure, and temperature were the primary factors influencing the spread of notifiable diseases. The NDOI is beneficial in establishing an early warning system for infectious disease epidemics at different scales. Furthermore, our findings also provide insight into the response mechanisms of notifiable diseases influenced by social and environmental factors.

Ginkgo biloba Extract Drives Gut Flora and Microbial Metabolism Variation in a Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is a complex neurodegenerative disease. Numerous investigations have demonstrated that medications that regulate the "brain-gut" axis can ameliorate disease symptoms of AD. Studies have shown that Ginkgo biloba extract (EGb) is involved in intestinal metabolism to meet the goal of illness treatment. EGb is currently utilized extensively in the clinical prevention and treatment of cardiovascular and cerebrovascular diseases. However, the regulatory effect of EGb on intestinal flora and its metabolites in AD pathology remains largely speculative. In this study, the Morris water maze test showed a significant improvement of spatial memory in the AD mouse model (APP/PS1 mice) after EGb treatment. We next confirmed the positive effects of EGb on the gut flora and metabolites of APP/PS1 mice and further showed that EGb treatment reshaped the disturbed gut microbiome, in particular by reducing the Firmicutes/Bacteroides ratio and increasing the abundance of Bacteroidetes, Uroviricota, Streptophyta, and Spirochaetes. Meanwhile, a non-targeted metabolomics analysis showed that EGb treatment significantly reversed the dysfunction of the microbial metabolic phenotype by altering Limosilactobacillus and Parvibacte, with 300 differential metabolites modulated (131 up-regulated, 169 down-regulated). Our findings highlight the significant regulatory impact of EGb on intestinal microflora and microbial metabolism in AD mice models and provide a potential therapeutic strategy for AD.

Cross-sectional and longitudinal associations of dichlorodiphenyltrichloroethane (DDT) metabolites exposure with lung function alternation in the Chinese general adults.

Exposure of dichlorodiphenyltrichloroethane (DDT) pesticide was suggested to be associated with adverse effects on the respiratory system. However, the effects of DDT exposure on lung function remain unclear. Our objectives were to investigate the potential associations of internal levels of DDT and its metabolites including dichlorodiphenyldichloroethylene (DDE) and dichlorodiphenyldichloroethane (DDD) with lung function. Serum DDT, DDE, and DDD concentrations and lung function were measured among 3968 general adults from the Wuhan-Zhuhai cohort. The cross-sectional and longitudinal associations of serum DDT and its metabolites with lung function were assessed using linear mixed models. The results showed negative dose-response relationships of serum DDT, DDE, and DDD levels with forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). In the cross-sectional analyses, each 1-unit increase in natural log-transformed values of p,p'-DDE, o,p'-DDT, o,p'-DDE, or p,p'-DDD was significantly associated with a 25.77-, 44.84-, 51.13-, or 43.44-mL decrease in FVC, respectively. Each 1-unit increase in natural log-transformed values of o,p'-DDT, o,p'-DDE, o,p'-DDD, or p,p'-DDD was significantly associated with a 35.72-, 31.87-, 29.54-, or 36.80-mL decrease in FEV1, respectively. In the three-year longitudinal analyses, each 1-unit increase in natural log-transformed serum p,p'-DDT and p,p'-DDE was significantly associated with a 35.10 mL and 36.38 mL decrease in FVC, and a 26.32 mL and 32.37 mL decrease in FEV1, respectively. In conclusion, DDT and its metabolites exposure were associated with lung function decline in the general Chinese adult population.

[Risk factors for neonatal asphyxia and establishment of a nomogram model for predicting neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture: a multicenter study]. / æ¹–åŒ—æ©æ–½åœŸå®¶æ—è‹—æ—è‡ªæ²»å·žæ–°ç”Ÿå„¿çª’æ¯å±é™©å› ç´ åˆ†æžåŠåˆ—çº¿å›¾é¢„æµ‹æ¨¡åž‹çš„æž„å»ºï¼šä¸€é¡¹å¤šä¸­å¿ƒç ”ç©¶.

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS: The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.

A Novel Paradigm Defines Functional Molecule Clusters for an Anti-Alzheimer's Disease Recipe from Traditional Chinese Medicine.

Traditional Chinese Medicine (TCM) prescriptions are organically composed of compatible herbs according to the TCM theory. The complex ingredients of TCM could act on multiple targets through various pathways simultaneously to exert pharmacological effects, making TCM an unrivaled gem in the medical world. However, due to a lack of comprehensive and standard study methods, the research of TCM products has been quite limited. A novel paradigm that could aid in the discovery of the material basis and fully clarify the mechanism of TCM prescriptions is urgently needed. In this study, a similarity analysis based on molecular fingerprints was adopted to explore the representative molecules of the Tiaoxin recipe, a Chinese patent formula approved by the National Medical Products Administration (NMPA) for the treatment of mild-to-moderate Alzheimer's disease (AD), and 38 out of 1047 chemicals were finally screened out. Next, we tried to define a new concept of a "functional molecule cluster" for chemicals with similar pharmacological effects to elucidate how the chemical mixture from TCMs produce their therapeutic effects. Four anti-AD functional molecule clusters from the Tiaoxin recipe were identified: an anti-inflammatory cluster, an anti-ROS cluster, an anti-AChE activity cluster, and an anti-A[Formula: see text] aggregation cluster. Furthermore, the chemicals from the anti-inflammatory cluster and anti-ROS cluster were proved to display their multi-target and multi-pathway roles partially or mainly through molecules of the TLR4-MYD88-NF-[Formula: see text]B and Keap1-Nrf2-ARE pathways. The functional molecule clusters may be vital to the explanation of the efficacy of the Tiaoxin recipe, which could give us a more profound understanding of TCM prescriptions. Our paradigm may open a novel path for TCM research.

Ambient temperature exposure causes lung function impairment: The evidence from Controlled Temperature Study in Healthy Subjects (CTSHS).

BACKGROUND: The effect of non-optimal ambient temperatures (low and high temperatures) on lung function and the underlying mechanisms remains unclear. METHODS: Forty-three (20 males, 23 females) healthy non-obese volunteers with an average of 23.9 years participated in the controlled temperature study. All volunteers underwent three temperature exposures in a sequence (moderate [18 °C], low [6 °C], and high [30 °C] temperatures) lasting 12 h with air pollutants controlled. lung function parameters (forced vital capacity [FVC], forced expiratory volume in 1 s [FEV1], and peak expiratory flow [PEF]) were determined in each exposure. Blood and urine samples were collected after each exposure and assayed for inflammatory markers [C-reactive protein (CRP), procalcitonin (PCT), platelet-lymphocyte ratio (PLR), and neutrophil-lymphocyte ratio (NLR)] and oxidative damage markers [protein carbonylation (PCO), 4-hydroxy-2-nominal-mercapturic acid (HNE-MA), 8-iso-prostaglandin-F2α (8-isoPGF2α), and 8-hydroxy-2-deoxyguanosine (8-OHdG)]. Mixed-effects models were constructed to assess the changes of the above indexes under low or high temperatures relative to moderate temperature, and then the repeated measures correlation analyses were performed. RESULTS: Compared with moderate temperature, a 2.20% and 2.59% net decrease in FVC, FEV1, and a 5.68% net increase for PEF were observed under low-temperature exposure, while a 1.59% net decrease in FVC and a 7.29% net increase in PEF under high-temperature exposure were found (all P < 0.05). In addition, low temperature elevated inflammatory markers (PCT, PLR, and NLR) and oxidative damage markers (8-isoPGF2α, 8-OHdG), and high temperature elevated HNE-MA. Repeated measures correlation analyses revealed that PCT (r = -0.33) and NLR (r = -0.31) were negatively correlated with FVC and HNE-MA (r = -0.35) and 8-OHdG (r = -0.31) were negatively correlated with the FEV1 under low-temperature exposure (all P < 0.05). CONCLUSION: Non-optimal ambient temperatures exposure alters lung function, inflammation, and oxidative damage. Inflammation and oxidative damage might be involved in low temperature-related lung function reduction.

Smilagenin induces expression and epigenetic remodeling of BDNF in alzheimer's disease.

BACKGROUND: Smilagenin (SMI) is a lipid-soluble steroidal sapogenin, extracted from traditional Chinses medicinal herbs Radix Asparagi, which is extracted from the dry root of Asparagus cochinchinensis (Lour.) Merr. We previously found that SMI significantly increased brain-derived neurotrophic factor (BDNF) expression in Aß-intoxicated SH-SY5Y cells. METHODS: In this study, we performed behavioral tests to analyze cognitive function of WT and APP/PS1 mice treated with or without SMI, and found that SMI could significantly improve the learning and memory ability of APP/PS1 mice. Moreover, immunofluorescence and ELISA results showed that SMI pretreatment could effectively reduce the deposition of ß-amyloid plaques in the cortex and hippocampus of APP/PS1 mice (26 mg/kg/day for 60 days) and inhibit the secretion of Aß1-42 in N2a/APPswe cells (10 µM concentration for 24 hours). RESULTS: Mechanistically, SMI enhanced BDNF mRNA expression, elevated the global level of H3AC and H4AC, and increased the expression of P300 in AD models. Furthermore, chromatin immunoprecipitation results showed that SMI could increase the levels of H3AC and H4AC at the promoter of BDNF promoter Ⅱ and Ⅳ, indicating that SMI epigenetically regulates BDNF expression through HAT enhancement. To further verify the critical role of P300 by which SMI upregulated histone acetylation in BDNF, AD mice were treated with SMI and C646 simultaneously. Behavioral experiments showed that the improvement effects of SMI on cognitive impairment were abolished after P300 inhibition in APP/PS1 mice. CONCLUSIONS: Our research for the first time demonstrated that SMI showed neuroprotective effects by increasing the expression of P300 protein, thus upregulating histone acetylation levels in the promoter region of BDNF and promoting its transcription. Our findings provide an important theoretical basis for the treatment of Alzheimer's disease with SMI extracted from Asparagus cochinchinensis (Lour.) Merr.

Effects of different types of granular activated carbon on methanogenesis of carbohydrate-rich food waste: Performance, microbial communities and optimization.

Granular activated carbon (GAC) supplementation is an efficient method for enhancing methane production during the anaerobic digestion of food waste, but it remains unclear which type of GAC is optimal and what potential mechanisms are involved with different types of GAC, particularly for the methanogenic system of carbohydrate-rich food waste. This study selected three commercial GAC (GAC#1, GAC#2, GAC#3) with very distinct physical and chemical properties, and investigated their impacts on the methanogenesis of carbohydrate-rich food waste with an inoculation/substrate ratio of 1. Results indicated that Fe-doped GAC#3 had a lower specific surface area but higher conductivity, yet exhibited superior performance in facilitating methanogenesis compared with GAC#1 and GAC#2, which possessed larger specific surface areas. The addition of 10 g/L GAC#3 enhanced the methane yield by 10-folds through regulating pH levels, alleviating volatile fatty acids-induced stress, enhancing key enzymatic activity, as well as enriching direct interspecies electron transfer-mediated syntrophic partner of Syntrophomonas with Methanosarcina. Furthermore, GAC#1, which had the largest specific surface area but exhibited the poorest performance, was chemically modified to enhance its ability in promoting methanogenesis. The resulting material, named MGAC#1 (Fe3O4-loaded GAC#1), exhibited superior electro-conductivity and high methane production efficiency. The methane yield of 588 mL/g-VS showed a remarkable increase of 468 % compared with GAC#1, and a modest increase of 13 % compared with GAC#3, surpassing most values reported in literature. These findings suggested that the Fe3O4-loaded GAC with lager specific surface area, was the optimal choice for the methanogenesis of sole readily acidogenic waste, providing valuable insights for the preparation of superior-quality GAC for application in biogas industry.

Triazine herbicides exposure, natural immunoglobulin M antibodies, and fasting plasma glucose changes: Association and mediation analyses in general Chinese urban adults.

The effects of triazine herbicides on glucose metabolism remain unclear. In this study, we aimed to assess the associations between serum triazine herbicides and glycemia-related risk indicators in general adults, and to evaluate the mediating role of natural immunoglobulin M antibodies (IgM) in the above associations among uninfected participants. We measured the concentrations of atrazine, cyanazine, and IgM in serum, as well as fasting plasma glucose (FPG), and fasting plasma insulin in 4423 adult participants from the Wuhan-Zhuhai cohort baseline population, enrolled in 2011-2012. Generalized linear models were used to evaluate the associations of serum triazine herbicides with glycemia-related risk indicators, and mediation analyses were performed to evaluate the mediating role of serum IgM in the above associations. The median levels of serum atrazine and cyanazine were 0.0237 µg/L and 0.0786 µg/L, respectively. Our study found significant positive associations of serum atrazine, cyanazine, and Σtriazine with FPG levels, risk of impaired fasting glucose (IFG), abnormal glucose regulation (AGR), and type 2 diabetes (T2D). Additionally, serum cyanazine and Σtriazine were found to be significant positive associated with the homeostatic model assessment of insulin resistance (HOMA-IR) levels. Significant negative linear relationships were observed in associations of serum IgM with serum triazine herbicides, FPG, HOMA-IR levels, the prevalence of T2D, and AGR (P < 0.05). Furthermore, we observed a significant mediating role by IgM in the associations of serum triazine herbicides with FPG, HOMA-IR, and AGR, with the proportions ranging from 2.96% to 7.71%. To ensure the stability of our findings, we conducted sensitivity analyses in normoglycemic participants and found that the association of serum IgM with FPG and the mediating role by IgM remained stable. Our results suggest that triazine herbicides exposure is positively associated with abnormal glucose metabolism, and decreasing serum IgM may partly mediate these associations.

Obesity modifies the association of environmental pyrethroid exposure with glucose homeostasis in the US general adults.

Environmental pyrethroids are concerning due to their widespread residues and potential implications on human health. We aimed to assess the association of pyrethroid exposure with glucose homeostasis and examine the interaction between obesity and pyrethroid exposure. A total of 4233 US general adults from the National Health and Nutrition Examination Survey with measured urinary pyrethroid metabolites, fasting plasma glucose (FPG), fasting insulin (FINS), and glycated hemoglobin A1c (HbA1c) were included in the study. The homeostasis model assessment (HOMA2) calculator was utilized to assess insulin resistance (HOMA2-IR), insulin sensitivity (HOMA2-IS), and beta-cell function (HOMA2-ß). We estimated the associations of pyrethroid metabolites with glucose homeostasis parameters (FPG, FINS, HbA1c, HOMA2-IR, HOMA2-IS, and HOMA2-ß) using multivariate linear regression models and restricted cubic spline models and further assessed the interaction between obesity and pyrethroid metabolites on glucose dyshomeostasis. Urinary 3-phenoxybenzoic acid (3-PBA) was the most detected pyrethroid metabolite (81%) with a median concentration of 0.43 (interquartile range 0.20-1.01) µg/g urinary creatinine. Compared with the participants in the lowest quartile, those in the highest quartile of 3-PBA had a 1.93% (95% confidence interval: 0.46%, 3.42%), 6.69% (1.96%, 11.64%), 1.60% (0.64%, 2.57%), 7.06% (2.33%, 12.01%), -6.59% (-10.72%, -2.28%), and 1.10% (-2.69%, 5.04%) alteration in FPG, FINS, HbA1c, HOMA2-IR, HOMA2-IS, and HOMA2-ß, respectively. The restricted cubic spline model displayed a linear positive association between 3-PBA and FPG, FINS, HbA1c, and HOMA2-IR, and a negative association with HOMA2-IS (all P for overall <0.05 and P for non-linear >0.05). Additionally, the association between urinary 3-PBA and FPG was modified by general obesity (P for interaction <0.05), with a more pronounced association observed in obese participants than in non-obese participants. Our findings suggested that pyrethroid exposure was associated with glucose dyshomeostasis. General obesity significantly heightened the association between pyrethroid exposure and increased FPG level.

Community Nurses Are Important Providers of Continuity of Care for Patients With Chronic Diseases: A Qualitative Study.

To clarify the functional orientation of community health nurses in the continuous care of patients with chronic diseases and to encourage community nurses to play their expected roles in extended nursing work. In this study, conducted from May to July 2020, the staff of Shanghai Community Health Service Center were sampled, and representative medical staff were selected for in-depth interviews and focus group discussions. Eighteen community medical staff members participated. The functions of community nurses in the continuous care of patients with chronic diseases are mainly as follows: ① undertaking individualized projects for patients' continuous treatment, nursing and rehabilitation; ② creating "peer education" conditions for patients; ③ providing supportive care to family caregivers; and ④ participating in the whole process of family doctor team health management. The results provide a reminder for nurse managers that under the new mission, community nurses need "one specialty and multiple abilities," appropriate nursing technology and good health management skills. The training of community nurses should better meet the practical needs of patients with chronic diseases.

Arsenic exposure incurs hyperglycemia mediated by oxidative damage in urban adult population: A prospective cohort study with three repeated measures.

The associations and potential mechanisms of low to moderate arsenic exposure with fasting plasma glucose (FPG) and type 2 diabetes mellitus (T2DM) are still unclear. To assess the effects of short-term and long-term arsenic exposure on hyperglycemia and the mediating effect of oxidative damage on such association, three repeated-measures studies with 9938 observations were conducted in the Wuhan-Zhuhai cohort. The levels of urinary total arsenic, FPG, urinary 8-iso-prostaglandin F2alpha (8-iso-PGF2α), urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), and plasma protein carbonyls (PCO) were measured. Generalized linear mixed models were used to evaluate the exposure-response relationships of urinary total arsenic with FPG and the prevalent risks of impaired fasting glucose (IFG), T2DM, and abnormal glucose regulation (AGR). Cox regression models were applied to assess the associations of arsenic exposure with incident risks of IFG, T2DM, and AGR. Mediation analyses were performed to assess the mediating effects of 8-iso-PGF2α, 8-OHdG, and PCO. In cross-sectional analyses, each one-unit increase in natural log-transformed urinary total arsenic was associated with a 0.082 (95% CI: 0.047 to 0.118) mmol/L increase in FPG, as well as a 10.3% (95% CI: 1.4%-20.0%), 4.4% (95% CI: 5.3%-15.2%), and 8.7% (95% CI: 1.2%-16.6%) increase in prevalent risks of IFG, T2DM, and AGR, respectively. In longitudinal analyses, arsenic exposure was further associated with the annual increased rate of FPG with a ß (95% CI) of 0.021 (95% CI: 0.010 to 0.033). The incident risks of IFG, T2DM, and AGR were increased without statistical significance when arsenic levels increased. Mediation analyses showed that 8-iso-PGF2α and PCO mediated 30.04% and 10.02% of the urinary total arsenic-associated FPG elevation, respectively. Our study indicated that arsenic exposure was associated with elevated level and progression rate of FPG among general Chinese adults, where lipid peroxidation and oxidative protein damage might be the potential mechanisms.

Associations of urinary 1,3-butadiene metabolite with glucose homeostasis, prediabetes, and diabetes in the US general population: Role of alkaline phosphatase.

The chemical - 1,3-butadiene (BD) is a volatile organic compound ubiquitous in the environment. However, the relationships and underlying mechanisms between BD exposure and glucose dyshomeostasis and diabetes in the general population remain unclear. We sought to explore the associations of BD exposure with glucose homeostasis, prediabetes, and diabetes, as well as the role of serum alkaline phosphatase (ALP) in these associations. This study included 5092 US general residents from the National Health and Nutrition Examination Survey with measurements of urinary BD metabolite (N-Acetyl-S-(3,4-dihydroxybutyl)-L-cysteine, DHBMA) and serum ALP. Glucose homeostasis was evaluated by fasting plasma glucose (FPG), fasting serum insulin (FINS), glycohemoglobin (HbA1c), and homeostasis model assessment of insulin resistance (HOMA-IR). HOMA-IR>2.6 was considered as insulin resistance (IR). Prediabetes and diabetes were determined according to the recommendations of the American Diabetes Association. The associations of DHBMA with glucose homeostasis, prediabetes, and diabetes were assessed by linear regression models and logistic regression models. The mediating role of ALP was evaluated by mediation analysis. We observed positive dose-response relationships of DHBMA level with glucose homeostasis indices and ALP levels, as well as with the risks of prediabetes and diabetes (all P < 0.05 and/or P for trend <0.05). Each 2-fold increase in DHBMA was associated with a 1.32%, 9.20%, 0.72%, and 10.64% increase in FPG, FINS, HbA1c, and HOMA-IR, respectively (all P < 0.05). And the corresponding odds ratios (ORs) and 95% confidence intervals (CIs) for IR, prediabetes, and diabetes were 1.36 (1.14, 1.61), 1.51 (1.26, 1.83), and 1.20 (0.90, 1.61), respectively. Furthermore, increased ALP significantly mediated 15.29%-41.12% of the associations of DHBMA with glucose dyshomeostasis and increased risks of prediabetes and diabetes. Our findings indicated that BD exposure was associated with glucose dyshomeostasis and increased risks of prediabetes and diabetes. The upregulation of ALP might play a significant role in these associations.

Dynamic changes of neutrophil-to-lymphocyte ratio in brain-dead donors and delayed graft function in kidney transplant recipients.

OBJECTIVES: Neutrophil-to-lymphocyte ratio (NLR) is a simple parameter implying the inflammatory status. We aimed to explore the association of brain-dead donor NLR change with delayed graft function (DGF) in kidney transplant recipients. METHODS: We retrospectively analyzed the data on 102 adult brain-dead donors and their corresponding 199 kidney transplant recipients (2018 - 2021). We calculated ΔNLR by subtracting the NLR before evaluating brain death from the preoperative NLR. Increasing donor NLR was defined as ΔNLR > 0. RESULTS: Forty-four (22%) recipients developed DGF after transplantation. Increasing donor NLR was significantly associated with the development of DGF in recipients (OR 2.8, 95% CI 1.2 - 6.6; p = .018), and remained significant (OR 2.6, 95% CI 1.0 - 6.4; p = .040) after adjustment of confounders including BMI, hypertension, diabetes, and the occurrence of cardiac arrest. When acute kidney injury (AKI) was included in the multivariable analysis, increasing donor NLR lost its independent correlation with DGF, while AKI remained an independent risk factor of recipient DGF (OR 4.5, 95% CI 2.7 - 7.6; p < .001). The area under the curve of combined increasing NLR and AKI in donors (0.873) for predicting DGF was superior to increasing donor NLR (0.625, p = .015) and AKI alone (0.859, p < .001). CONCLUSIONS: Dynamic changes of donor NLR are promising in predicting post-transplant DGF. It will assist clinicians in the early recognition and management of renal graft dysfunction. Validation of this new biomarker in a large study is needed.

A pH-sensitive DNA tetrahedron for targeted release of anthracyclines: Binding properties investigation and cytotoxicity evaluation.

The anticancer efficacy of chemotherapeutic agents can be enhanced by the loading of DNA nanostructures, which is closely related to their interactions. This study achieved pH-responsive and targeted anthracycline delivery using i-motif and MUC1 aptamer co-modified DNA tetrahedron (MUC1-TD). The thermodynamic parameters for the binding of doxorubicin (DOX) and epirubicin (EPI) to MUC1-TD at pHs 7.4 and 5.0 were obtained. The smaller binding constant and the number of binding sites at pH 5.0 than at pH 7.4 indicated that acidic conditions favored the release of DOX and EPI loaded by MUC1-TD. The binding affinity of DOX was stronger than that of EPI at the same pH value due to their different chemical stereostructures. The intercalative binding mechanism was verified. In vitro release experiments revealed that acid pH and deoxyribonuclease I accelerated the release of DOX and EPI. The faster release rate of EPI than DOX was related to their binding affinity. In vitro cytotoxicity and cell uptake experiments revealed that the cytotoxicity of DOX and EPI loaded by MUC1-TD to MCF-7 cells was significantly higher than that to L02 cells. This work will provide theoretical guidance for the application of pH-responsive MUC1-TD nanocarriers in the field of pharmaceutics.

Associations of bifenthrin exposure with glucose homeostasis and type 2 diabetes mellitus in a general Chinese population: Roles of protein carbonylation.

The adverse health effects of pyrethroids exposure have attracted wide concern. We aimed to assess the associations of bifenthrin, a widely used pyrethroid, with glucose homeostasis and risk of type 2 diabetes mellitus (T2DM) and to explore the underlying mechanism. Serum bifenthrin, fasting plasma glucose (FPG), fasting plasma insulin (FPI), and plasma protein carbonyl (PCO) were determined among 3822 participants from the Wuhan-Zhuhai cohort. Glucose homeostasis was evaluated by FPG, FPI, homeostasis model assessment of insulin resistance (HOMA-IR), impaired fasting glucose (IFG), and abnormal glucose regulation (AGR). The associations of serum bifenthrin with glucose homeostasis and risk of T2DM were assessed by generalized linear models and logistic regression models. The role of PCO in the above associations was evaluated by mediation analyses. After adjusting for covariates, each 2-fold increase in serum bifenthrin was associated with a 0.21 mmol/L increase in FPG and a 5.19%, 10.49%, and 12.18% increase in FPI, HOMA-IR, and PCO levels, respectively. Monotonically elevated ORs of IFG and AGR (all P and P for trend <0.05), but not T2DM (P > 0.05) were detected to be associated with increased bifenthrin. Compared with the participants with low bifenthrin and low PCO, participants with high bifenthrin exposure and high PCO showed a 0.40 mmol/L, 11.07%, and 22.50% increase in FPG, FPI, and HOMA-IR, as well as a 119.97% and 48.88% increase in risks of IFG and AGR, respectively (P for trend <0.05). Moreover, PCO mediated 13.61%-24.98% of the serum bifenthrin-associated glucose dyshomeostasis. The study suggested that bifenthrin exposure was dose-dependently associated with glucose dyshomeostasis in the general Chinese urban adults, and these associations were exacerbated and partly mediated by PCO. Given that other pollutants were not included in this study, the effect of co-exposure of pyrethroids with multiple pollutants is necessary to be considered in future studies.

Oyster shell waste as potential co-substrate for enhancing methanogenesis of starch wastewater at low inoculation ratio.

This study evaluated the effect of oyster shells on the methanogenesis of starch wastewater subjected to over-acidification (pH < 4.5) at low inoculum/substrate ratios, and revealed that oyster shells could be used as co-substrates for methane production. The methane yield was improved by approximate 86-folds with optimal dose when compared with that in control. Oyster shells conditioning synchronously improved the acidogenesis and hydrogenotrophic methanogenesis steps, resulting in high methane production. These improvements were attributed to the fact that the oyster shells served as the neutralizing reagent and buffered the sharp pH drop. Carbon dioxide was also released during this process, which was subsequently converted into methane and contributed 17% of the total methane yield. Furthermore, some spheroid and rod microcolonies were observed on the surfaces of the oyster shells. Along with the remarkable enrichment of acetotrophic and methylotrophic methanogens, these microbes benefitted the successful methanogenesis of starch wastewater.