Drug-drug interaction and initial dosage optimization of aripiprazole in patients with schizophrenia based on population pharmacokinetics.

Background: The present study aimed to investigate the drug-drug interaction and initial dosage optimization of aripiprazole in patients with schizophrenia based on population pharmacokinetics. Research design and methods: A total of 119 patients with schizophrenia treated with aripiprazole were included to build an aripiprazole population pharmacokinetic model using nonlinear mixed effects. Results: The weight and concomitant medication of fluoxetine influenced aripiprazole clearance. Under the same weight, the aripiprazole clearance rates were 0.714:1 in patients with or without fluoxetine, respectively. In addition, without fluoxetine, for the once-daily aripiprazole regimen, dosages of 0.3 and 0.2 mg kg-1 day-1 were recommended for patients with schizophrenia weighing 40-95 and 95-120 kg, respectively, while for the twice-daily aripiprazole regimen, 0.3 mg kg-1 day-1 was recommended for those weighing 40-120 kg. With fluoxetine, for the once-daily aripiprazole regimen, a dosage of 0.2 mg kg-1 day-1 was recommended for patients with schizophrenia weighing 40-120 kg, while for the twice-daily aripiprazole regimen, 0.3 and 0.2 mg kg-1 day-1 were recommended for those weighing 40-60 and 60-120 kg, respectively. Conclusion: This is the first investigation of the effects of fluoxetine on aripiprazole via drug-drug interaction. The optimal aripiprazole initial dosage is recommended in patients with schizophrenia.

Efficacy and safety of topical minocycline foam (FMX101 4%) in treatment of Chinese subjects with moderate-to-severe facial acne vulgaris: A phase 3, multi-centre, randomized, double-blind, vehicle-controlled study.

BACKGROUND: FMX101 4%, as a topical foam formulation of minocycline, has been approved by US Food and Drug Administration for the treatment of moderate-to-severe acne vulgaris (AV). OBJECTIVE: To evaluate the efficacy and safety of FMX101 4% in treating Chinese subjects with moderate-to-severe facial AV. METHODS: This was a multi-centre, randomized, double-blind, vehicle-controlled phase 3 study in Chinese subjects with moderate-to-severe AV. Eligible subjects were randomized 2:1 to receive either FMX101 4% or vehicle foam treatment for 12 weeks. The primary efficacy endpoint was the change in inflammation lesion count (ILC) from baseline at week 12. The key secondary endpoint was the treatment success rate according to Investigator's Global Assessment (IGA) at week 12. RESULTS: In total, 372 subjects were randomized into two groups (FMX101 4% group, n = 248; vehicle group, n = 124). After 12 weeks treatment, the reduction in ILC from baseline was statistically significant in favour of FMX101 4%, compared with vehicle foam (-21.0 [0.08] vs. -12.3 [1.14]; LSM [SE] difference, -8.7 [1.34]; 95% CI [-11.3, -6.0]; p < 0.001). FMX101 4% treatment yielded significantly higher IGA treatment success rate at week 12 as compared to the control treatment (8.06% vs. 0%). Applying FMX101 4% also resulted in significant reduction in noninflammatory lesion count (nILC) versus vehicle foam at week 12 (-19.4 [1.03] vs. -14.9 [1.47]; LSM [SE] difference, -4.5 [1.74]; 95% CI [-8.0, -1.1]; p = 0.009). Most treatment-emergent adverse events (TEAEs) were mild-to-moderate in severity, and no treatment-related treatment-emergent serious adverse event (TESAE) occurred. Thus, FMX101 4% was considered to be a safe and well-tolerated product during the 12-week treatment period. CONCLUSION: FMX101 4% treatment for 12 weeks could lead to significantly reduced ILC and nILC, and improved IGA treatment success rate in Chinese subjects with moderate-to-severe facial AV. It also showed a well acceptable safe and tolerability profile.

The flavour of wheat gluten hydrolysate after Corynebacterium Glutamicum fermentation: Effect of degrees of hydrolysis and fermentation time.

Corynebacterium glutamicum was used to ferment wheat gluten hydrolysates (WGHs) to prepare flavour base. This study investigated the effect of hydrolysis degrees (DHs) and fermentation time on flavour of WGHs. During fermentation, the contents of amino nitrogen, total acid and small peptides increased, while the protein and pH value decreased. Succinic acid, GMP, and Glu were the prominent umami substances in fermented WGHs. The aromas of WGHs with different DHs could be distinguished by electronic nose and GC-IMS. Based on OAV of GC-MS, hexanal was the main compound in WGHs, while phenylethyl alcohol and acetoin were dominant after fermentation. WGHs with high DHs accumulated more flavour metabolites. Correlation analysis showed that small peptides (<1 kDa) could promote the formation of flavour substances, and Asp was potentially relevant flavour precursor. This study indicated that fermented WGHs with different DHs can potentially be used in different food applications based on flavour profiles.

Prenatal exposure to polycyclic aromatic hydrocarbons and phthalate acid esters and gestational diabetes mellitus: A prospective cohort study.

BACKGROUND: Polycyclic aromatic hydrocarbons and phthalate acid esters (PAHs & PAEs), known as endocrine disrupting chemicals (EDCs), widely exist in daily life and industrial production. Previous studies have suggested that PAHs & PAEs may modify the intrauterine homeostasis and have adverse effects on fetal development. However, epidemiological evidence on the associations between PAHs & PAEs and gestational diabetes mellitus (GDM) is still limited. OBJECTIVE: To investigate the effects of prenatal PAHs &PAEs exposure on the risk of GDM and hyperglycemia in pregnant women. METHODS: The study population was a total of 725 pregnant women from a prospective birth cohort study conducted from December 2019 to December 2021. Blood glucose levels were collected by the hospital information system. Urinary PAHs & PAEs concentrations were determined by gas chromatography tandem mass spectrometry. The Poisson regression in a generalized linear model (GLM), multiple linear regression, quantile-based g-computation method (qgcomp), and Bayesian kernel machine regression (BKMR) were applied to explore and verify the individual and overall effects of PAHs & PAEs on glucose homeostasis. Potential confounders were adjusted in all statistical models. RESULTS: A total of 179 (24.69%) women were diagnosed with GDM. The Poisson regression suggested that a ln-unit increment of 4-OHPHE (4-hydroxyphenanthrene) (adjusted Risk Ratio (aRR) = 1.13; 1.02-1.26) was associated with the increased GDM risk. Mixed-exposure models showed similar results. We additionally found that MBZP (mono-benzyl phthalate) (aRR = 1.19; 1.02-1.39) was positively related to GDM risk in qgcomp model. Although neither model demonstrated that 2-OHNAP (2-hydroxynaphthalene) and 9-OHFLU (9-hydroxyfluorene) increased the risk of GDM, 2-OHNAP and 9-OHFLU exposure significantly increased blood glucose levels. BKMR model further confirmed that overall effects of PAHs & PAEs were significantly associated with the gestational hyperglycemia and GDM risk. CONCLUSIONS: Our study presents that environmental exposure to PAHs & PAEs was positively associated with gestational glucose levels and the risks of developing GDM. In particular, 2-OHNAP, 9-OHFLU, 4-OHPHE and MBZP may serve as important surveillance markers to prevent the development of GDM.

Mapping the distribution of Nipah virus infections: a geospatial modelling analysis.

BACKGROUND: Nipah virus is a zoonotic paramyxovirus responsible for disease outbreaks with high fatality rates in south and southeast Asia. However, knowledge of the potential geographical extent and risk patterns of the virus is poor. We aimed to establish an integrated spatiotemporal and phylogenetic database of Nipah virus infections in humans and animals across south and southeast Asia. METHODS: In this geospatial modelling analysis, we developed an integrated database containing information on the distribution of Nipah virus infections in humans and animals from 1998 to 2021. We conducted phylodynamic analysis to examine the evolution and migration pathways of the virus and meta-analyses to estimate the adjusted case-fatality rate. We used two boosted regression tree models to identify the potential ecological drivers of Nipah virus occurrences in spillover events and endemic areas, and mapped potential risk areas for Nipah virus endemicity. FINDINGS: 749 people and eight bat species across nine countries were documented as being infected with Nipah virus. On the basis of 66 complete genomes of the virus, we identified two clades-the Bangladesh clade and the Malaysia clade-with the time of the most recent common ancestor estimated to be 1863. Adjusted case-fatality rates varied widely between countries and were higher for the Bangladesh clade than for the Malaysia clade. Multivariable meta-regression analysis revealed significant relationships between case-fatality rate estimates and viral clade (p=0·0021), source country (p=0·016), proportion of male patients (p=0·036), and travel time to health-care facilities (p=0·036). Temperature-related bioclimate variables and the probability of occurrence of Pteropus medius were important contributors to both the spillover and the endemic infection models. INTERPRETATION: The suitable niches for Nipah virus are more extensive than previously reported. Future surveillance efforts should focus on high-risk areas informed by updated projections. Specifically, intensifying zoonotic surveillance efforts, enhancing laboratory testing capacity, and implementing public health education in projected high-risk areas where no human cases have been reported to date will be crucial. Additionally, strengthening wildlife surveillance and investigating potential modes of transmission in regions with documented human cases is needed. FUNDING: The Key Research and Development Program of China.

Establishment and application of a rapid visualization method for detecting Vibrio parahaemolyticus nucleic acid.

Background: Swift and accurate detection of Vibrio parahaemolyticus, which is a prominent causative pathogen associated with seafood contamination, is required to effectively combat foodborne disease and wound infections. The toxR gene is relatively conserved within V. parahaemolyticus and is primarily involved in the expression and regulation of virulence genes with a notable degree of specificity. The aim of this study was to develop a rapid, simple, and constant temperature detection method for V. parahaemolyticus in clinical and nonspecialized laboratory settings. Methods: In this study, specific primers and CRISPR RNA were used to target the toxR gene to construct a reaction system that combines recombinase polymerase amplification (RPA) with CRISPR‒Cas13a. The whole-genome DNA of the sample was extracted by self-prepared sodium dodecyl sulphate (SDS) nucleic acid rapid extraction reagent, and visual interpretation of the detection results was performed by lateral flow dipsticks (LFDs). Results: The specificity of the RPA-CRISPR/Cas13a-LFD method was validated using V. parahaemolyticus strain ATCC-17802 and six other non-parahaemolytic Vibrio species. The results demonstrated a specificity of 100%. Additionally, the genomic DNA of V. parahaemolyticus was serially diluted and analysed, with a minimum detectable limit of 1 copy/µL for this method, which was greater than that of the TaqMan-qPCR method (102 copies/µL). The established methods were successfully applied to detect wild-type V. parahaemolyticus, yielding results consistent with those of TaqMan-qPCR and MALDI-TOF MS mass spectrometry identification. Finally, the established RPA-CRISPR/Cas13a-LFD method was applied to whole blood specimens from mice infected with V. parahaemolyticus, and the detection rate of V. parahaemolyticus by this method was consistent with that of the conventional PCR method. Conclusions: In this study, we describe an RPA-CRISPR/Cas13a detection method that specifically targets the toxR gene and offers advantages such as simplicity, rapidity, high specificity, and visual interpretation. This method serves as a valuable tool for the prompt detection of V. parahaemolyticus in nonspecialized laboratory settings.

Utilizing machine learning for early screening of thyroid nodules: a dual-center cross-sectional study in China.

Background: Thyroid nodules, increasingly prevalent globally, pose a risk of malignant transformation. Early screening is crucial for management, yet current models focus mainly on ultrasound features. This study explores machine learning for screening using demographic and biochemical indicators. Methods: Analyzing data from 6,102 individuals and 61 variables, we identified 17 key variables to construct models using six machine learning classifiers: Logistic Regression, SVM, Multilayer Perceptron, Random Forest, XGBoost, and LightGBM. Performance was evaluated by accuracy, precision, recall, F1 score, specificity, kappa statistic, and AUC, with internal and external validations assessing generalizability. Shapley values determined feature importance, and Decision Curve Analysis evaluated clinical benefits. Results: Random Forest showed the highest internal validation accuracy (78.3%) and AUC (89.1%). LightGBM demonstrated robust external validation performance. Key factors included age, gender, and urinary iodine levels, with significant clinical benefits at various thresholds. Clinical benefits were observed across various risk thresholds, particularly in ensemble models. Conclusion: Machine learning, particularly ensemble methods, accurately predicts thyroid nodule presence using demographic and biochemical data. This cost-effective strategy offers valuable insights for thyroid health management, aiding in early detection and potentially improving clinical outcomes. These findings enhance our understanding of the key predictors of thyroid nodules and underscore the potential of machine learning in public health applications for early disease screening and prevention.

Complex Hand Reconstruction using a Novel Two-stage Temporary Ectopic Implantation of the Contralateral Upper Limb.

Ectopic transplantation of the hand remains a rare, innovative yet valuable operation in select cases of trauma and amputation. We aim to describe a novel technique of complex hand reconstruction using a two-stage ectopic implantation of the contralateral upper limb. A male patient with a near complete avulsion amputation of the right upper limb at the level of the mid-forearm and a crushing injury to his left hand was admitted after a farming accident. The right palm was ectopically transplanted to the left lower limb and both upper limbs underwent debridement with vacuum assisted dressings (VACs). There was eventual dieback of the left thumb, ring and little finger with a large palmar soft tissue defect that was eventually reconstructed using segments of the ectopically transplanted limb in two separate operations. The patient made an uneventful postoperative recovery and managed to regain protective sensation and gross motor function of his reconstructed hand.

Study on botulinum toxin in dermatology from 2000 to 2023: A CiteSpace-based bibliometric analyses.

OBJECTIVE: Using bibliometric methods, this study analyzed and summarized the current situation and development of the global application of botulinum toxin in dermatology. METHODS: Literature published in the Web of Science Core Collection database from January 1, 2000 to October 28, 2023 was searched for topics such as "Botulinum toxin," "Dermatology," and so forth. The number of publications, countries, institutions, journals, authors, cited literature, keywords, and so forth, were analyzed and a visual knowledge map was created using scientometric tools such as CiteSpace, VOSviewer, and Scimago Graphica. RESULTS: A total of 2039 documents were retrieved and 1877 documents were included after de-duplication and transformation. The country with the highest number of published periodical articles was the United States; the main research institution was Yonsei University; the author with the highest number of published periodical articles was Kim, Hee Jin; and the high-frequency keywords mainly related to indications, combination therapy, and safety optimization. CONCLUSION: The results of this study provide information on the current status and trends in clinical studies of botulinum toxin in dermatology, which will help researchers identify hotspots and explore new research directions in this field.

Preclinical Therapeutic Efficacy of RAF/MEK/ERK and IGF1R/AKT/mTOR Inhibition in Neuroblastoma.

Activating mutations in the RAS/MAPK pathway are observed in relapsed neuroblastoma. Preclinical studies indicate that these tumors have an increased sensitivity to inhibitors of the RAS/MAPK pathway, such as MEK inhibitors. MEK inhibitors do not induce durable responses as single agents, indicating a need to identify synergistic combinations of targeted agents to provide therapeutic benefit. We previously showed preclinical therapeutic synergy between a MEK inhibitor, trametinib, and a monoclonal antibody specific for IGF1R, ganitumab in RAS-mutated rhabdomyosarcoma. Neuroblastoma cells, like rhabdomyosarcoma cells, are sensitive to the inhibition of the RAS/MAPK and IGF1R/AKT/mTOR pathways. We hypothesized that the combination of trametinib and ganitumab would be effective in RAS-mutated neuroblastoma. In this study, trametinib and ganitumab synergistically suppressed neuroblastoma cell proliferation and induced apoptosis in cell culture. We also observed a delay in tumor initiation and prolongation of survival in heterotopic and orthotopic xenograft models treated with trametinib and ganitumab. However, the growth of both primary and metastatic tumors was observed in animals receiving the combination of trametinib and ganitumab. Therefore, more preclinical work is necessary before testing this combination in patients with relapsed or refractory RAS-mutated neuroblastoma.

The mechano-chemical circuit in fibroblasts and dendritic cells drives basal cell proliferation in psoriasis.

Psoriasis is an intractable immune-mediated disorder that disrupts the skin barrier. While studies have dissected the mechanism by which immune cells directly regulate epidermal cell proliferation, the involvement of dermal fibroblasts in the progression of psoriasis remains unclear. Here, we identified that signals from dendritic cells (DCs) that migrate to the dermal-epidermal junction region enhance dermal stiffness by increasing extracellular matrix (ECM) expression, which further promotes basal epidermal cell hyperproliferation. We analyzed cell-cell interactions and observed stronger interactions between DCs and fibroblasts than between DCs and epidermal cells. Using single-cell RNA (scRNA) sequencing, spatial transcriptomics, immunostaining, and stiffness measurement, we found that DC-secreted LGALS9 can be received by CD44+ dermal fibroblasts, leading to increased ECM expression that creates a stiffer dermal environment. By employing mouse psoriasis and skin organoid models, we discovered a mechano-chemical signaling pathway that originates from DCs, extends to dermal fibroblasts, and ultimately enhances basal cell proliferation in psoriatic skin.

Theoretical study on the H-atom abstraction reactions of pentanol + HȮ2, part I: five branched pentanol isomers.

The chemical kinetic studies of hydrogen atom (H-atom) abstraction reactions by hydroperoxyl (HȮ2) radicals from five branched pentanol isomers, including 3-methyl-1-butanol, 2-methyl-1-butanol, 1,1-dimethyl-1-propanol, 1,2-dimethyl-1-propanol, and 2,2-dimethyl-1-propanol were investigated systematically through high-level ab initio calculations. Geometry optimization, frequency analysis, and zero-point energy (ZPE) corrections were performed for six reactants, twenty-three transition states (TSs), and twenty-four products at the M06-2X/6-311++G(d,p) level of theory. The intrinsic reaction coordinate calculation was performed at the same level of theory to confirm the transition state connection. The one-dimensional hindered rotor treatment for low-frequency torsional modes was also treated at the M06-2X/6-311++G(d,p) level of theory. The QCISD(T)/CBS level of theory was used to calculate the single-point energies for the species whose T1 diagnostic value was lower than 0.035. At the same time, the CASPT2/CBS level of theory was used to calculate the single-point energies for the channel in which the T1 diagnostic value of transition states was greater than 0.035. Rate constants for the H-atom abstraction reactions from the five branched pentanol isomers by HȮ2 radicals were calculated by using conventional transition state theory with asymmetric Eckart tunneling corrections in the temperature range of 500-2000 K. Rate constants and branching ratios for the title reactions and the rate rules for ten different H-atom abstraction types were investigated. Temperature-dependent thermochemistry properties for all reactants and products were calculated by the composite methods of G3/G4/CBS-QB3/CBS-APNO, which were in good agreement with the data available in the literature. Rate constants for the H-atom abstraction reactions by HȮ2 radical from branched pentanol isomers were investigated in this work as part I, and those for linear pentanol isomers will be analyzed in part II. All the calculated kinetics and thermochemistry data can be utilized in the model development for branched pentanol isomers oxidation.

Use of Period Analysis to Timely Assess Five-Year Relative Survival for the Patients With Bone Cancer.

Background: While timely assessment of long-term survival for patients with bone cancer is essential for evaluation on early detection and prognosis level of treatment of bone cancer, those data are extremely scarce in China. We aimed to timely and accurately assess long-term survival for patients with bone cancer in Eastern China. Methods: Patients diagnosed with bone cancer during 2004 - 2018 from four cancer registries with high-quality data from Taizhou, Eastern China were included. Five-year relative survival (RS) of bone cancer patients was calculated by period analysis for overall and the stratification. We further predicted 5-year RS during upcoming 2019 - 2023 using a model-based period analysis and survival data during 2004 - 2018. Results: Overall, 5-year RS for patients with bone cancer during 2014 - 2018 reached 46.6%, being 40.8% for male and 51.0% for female. Five-year RS declined along with aging, decreasing from 58.9% for age < 45 years to 41.5% for age > 60 years, while 5-year RS for urban area was higher compared to rural area (59.1% vs. 44.3%). The 5-year RS during upcoming 2019 - 2023 reached 48.3%. We found a clear upward trend in 5-year RS during 2004 - 2023 for overall and the stratification by sex, age at diagnosis, and region. Conclusions: We found that, for first time in China using period analysis, most up-to-date 5-year RS for patients with bone cancer reached 46.6% during 2014 - 2018, and is projected to reach 48.3% for the period 2019 - 2023, which has important implications for timely evaluation on early detection and prognosis level of treatment for patients with bone cancer in Eastern China.

Predictive value of preoperative routine examination for the prognosis of patients with pT2N0M0 or pT3N0M0 colorectal cancer.

BACKGROUND: In recent years, the incidence of colorectal cancer (CRC) has been increasing. With the popularization of endoscopic technology, a number of early CRC has been diagnosed. However, despite current treatment methods, some patients with early CRC still experience postoperative recurrence and metastasis. AIM: To search for indicators associated with early CRC recurrence and metastasis to identify high-risk populations. METHODS: A total of 513 patients with pT2N0M0 or pT3N0M0 CRC were retrospectively enrolled in this study. Results of blood routine test, liver and kidney function tests and tumor markers were collected before surgery. Patients were followed up through disease-specific database and telephone interviews. Tumor recurrence, metastasis or death were used as the end point of study to find the risk factors and predictive value related to early CRC recurrence and metastasis. RESULTS: We comprehensively compared the predictive value of preoperative blood routine, blood biochemistry and tumor markers for disease-free survival (DFS) and overall survival (OS) of CRC. Cox multivariate analysis demonstrated that low platelet count was significantly associated with poor DFS [hazard ratio (HR) = 0.995, 95% confidence interval (CI): 0.991-0.999, P = 0.015], while serum carcinoembryonic antigen (CEA) level (HR = 1.008, 95%CI: 1.001-1.016, P = 0.027) and serum total cholesterol level (HR = 1.538, 95%CI: 1.026-2.305, P = 0.037) were independent risk factors for OS. The cutoff value of serum CEA level for predicting OS was 2.74 ng/mL. Although the OS of CRC patients with serum CEA higher than the cutoff value was worse than those with lower CEA level, the difference between the two groups was not statistically significant (P = 0.075). CONCLUSION: For patients with T2N0M0 or T3N0M0 CRC, preoperative platelet count was a protective factor for DFS, while serum CEA level was an independent risk factor for OS. Given that these measures are easier to detect and more acceptable to patients, they may have broader applications.

Elevated expression of ECT2 as a diagnostic marker and prognostic indicator in endometrial cancer.

OBJECTIVES: The study aims to investigate genes associated with endometrial cancer (EC) progression to identify new biomarkers for early detection. METHODS: Differentially expressed genes (DEGs), Series test of cluster (STC) and protein-protein interaction analyses identified hub genes in EC. Clinical samples were utilized to examine the expression pattern of ECT2, assess its prognostic value, and evaluate its diagnostic potential. RESULTS: Upregulated DEGs were significantly enriched in cancer-related processes and pathways. Validations across databases identified ASPM, ATAD2, BUB1B, ECT2, KIF14, NUF2, NCAPG, and SPAG5 as potential hub genes, with ECT2 exhibiting the highest diagnostic efficacy. The expression levels of ECT2 varied significantly across different clinical stages, pathological grades, and metastasis statuses in UCEC. Furthermore, ECT2 mRNA was upregulated in the p53abn group, indicating a poorer prognosis, and downregulated in the MMRd and NSMP groups, suggesting a moderate prognosis. In clinical samples, ECT2 expression increased from normal endometria and endometrial hyperplasia without atypia (EH) to atypical endometrial hyperplasia (AH) and EC, effectively distinguishing between benign and malignant endometria. High ECT2 expression was associated with an unfavourable prognosis. CONCLUSIONS: ECT2 expression significantly rises in AH and EC, showing high accuracy in distinguishing between benign and malignant endometria. ECT2 emerges as a promising biomarker for diagnosing endometrial neoplasia and as a prognostic indicator in EC.

Defense of cabbages against herbivore cutworm Spodoptera litura under Cd stress and insect herbivory stress simultaneously.

Biotic (e.g., heavy metal) and abiotic stress (e.g., insect attack) can affect plant chemical defense, but little is known about the changes in plant defense when they occur concurrently. Herein, the impacts of heavy metal cadmium (Cd) stress and insect herbivory stress on the direct and indirect defense of two cultivar cabbages of Brassica campestris, the low-Cd cultivar Lvbao701 and the high-Cd cultivar Chicaixin No.4, against the herbivore cutworm Spodoptera litura were investigated. Although 10 mg kg-1 Cd stress alone inhibited leaf secondary metabolites (total phenolics, flavonoids), it reduced the feeding rate and odor selection of S. litura towards both cultivar cabbages, especially for Lvbao701, by increasing leaf Cd content and repellent volatile organic compounds (VOCs) (6-methyl-5-hepten-2-one, 7,9-di-tert-butyl-1-oxaspiro (4,5)deca-6,9-diene-2,8-dione), and reducing soluble sugar and attractive VOCs (3-methyl-3-pentanol, 2,5-hexanedione, tetradecanal). Under 2.5 mg kg-1 Cd and herbivory stress, although leaf total phenolics and flavonoids increased significantly, the feeding rate and odor selection of S. litura towards both cultivar cabbages increased, especially for Chicaixin No.4, indicating that the chemical defense of cabbages was depressed. Therefore, Cd stress alone improved the insect resistance of cabbages, whereas herbivory stress weakened the enhanced cabbages defence by Cd stress. The low-Cd cultivar Lvbao701 presented stronger insect resistance than Chicaixin No.4, suggesting that Lvbao701 application in Cd-polluted soil can not only decrease Cd transmission to higher levels in the food chain but also reduce pest occurrence.

A novel OsGST gene encoding 9glutathione reductase negatively regulates cadmium accumulation in rice.

Cadmium (Cd) accumulates in rice and then moves up the food chain, causing serious health problems for humans. Glutathione S-transferase (GST) binds exogenous hazardous compounds to glutathione (GSH), which performs a variety of roles in plant responses to Cd stress. Here, Cd stimulated the transcripts of a novel OsGST gene, and the OsGST protein, which was localized in the nucleus and cytoplasm, was also induced by Cd. In OsGST deletion mutant lines generated by CRISPR/Cas9, more Cd was accumulated, and Cd hypersensitive phenotypes were observed, while transgenic lines overexpressing OsGST exhibited enhanced Cd tolerance and less Cd accumulation. Further analysis indicated that the osgst mutants exhibited considerably greater reactive oxygen species (ROS) and higher GSH level, and the antioxidant activity associated genes' expression were down-regulated, imply that OsGST controlled rice Cd accumulation and resistance through preserving the equilibrium of the GSH and redox in rice.

[Antibiotic Contamination Characteristics and Ecological Risk Assessment in Soils of Large-scaled Culturing Farms].

The soils of different land use types in large-scaled culturing farms were collected for detecting the contents of antibiotics in these soils by applying high-performance liquid chromatography, analyzing the relationship between antibiotics and physicochemical properties of soils, as well as performing the ecological risk assessment of antibiotics in the soils of culturing farms by using the risk quotient method. The results showed that the surrounding soils of the culturing farm were contaminated by antibiotics to varying degrees, in which tetracycline had the highest detection rate and average content. Among the soils of different land use types, the average contents of antibiotics were ranked as corn field （1.48 µg·kg-1）>0.5 meters outside the farm fence （1.27 µg·kg-1）>yam field （1.03 µg·kg-1）>pasture （0.69 µg·kg-1）>woodland （0.18 µg·kg-1）. According to the redundancy analysis results, the total nitrogen, total phosphorus, and cellulase had a great impact on the antibiotic content in soil samples. It can be concluded from the ecological risk assessment that oxytetracycline （OTC）, chlortetracycline （CTC）, doxycycline （DOC）, ciprofloxacin （CIP）, and tetracycline （TC） were categorized in the low risk level. Sulfadiazine （SM） and sulfadimidine （SM2） were categorized in the medium and high risk levels. It is of the upmost importance to control the antibiotic contamination in surrounding soils of culturing farms and to strengthen the management of veterinary antibiotics.

Association of ambient temperature on acute ischemic stroke in Yancheng, China.

BACKGROUND: Acute ischemic stroke (AIS) is a major global public health issue. There is limited research on the relationship between ambient temperature and AIS hospital admissions, and the results are controversial. Our objective is to assess the short-term impact of ambient temperature on the risk of AIS hospital admissions in Yancheng, China. METHODS: We collected data on daily AIS hospital admissions, meteorological factors, and air quality in Yancheng from 2014 to 2019. We used Poisson regression to fit generalized linear models and distributed lag non-linear models to explore the association between ambient temperature and AIS hospital admissions. The effects of these associations were evaluated by stratified analysis by sex and age. RESULTS: From 2014 to 2019, we identified a total of 13,391 AIS hospital admissions. We observed that the influence of extreme cold and heat on admissions for AIS manifests immediately on the day of exposure and continues for a duration of 3-5 days. Compared to the optimal temperature (24.4 °C), the cumulative relative risk under extreme cold temperature (-1.3 °C) conditions with a lag of 0-5 days was 1.88 (95%CI: 1.28, 2.78), and under extreme heat temperature (30.5 °C) conditions with a lag of 0-5 days was 1.48 (95%CI: 1.26, 1.73). CONCLUSIONS: There is a non-linear association between ambient temperature and AIS hospital admission risk in Yancheng, China. Women and older patients are more vulnerable to non-optimal temperatures. Our findings may reveal the potential impact of climate change on the risk of AIS hospital admissions.

Mapping the distribution of sandflies and sandfly-associated pathogens in China.

BACKGROUND: Understanding and mapping the distribution of sandflies and sandfly-associated pathogens (SAPs) is crucial for guiding the surveillance and control effort. However, their distribution and the related risk burden in China remain poorly understood. METHODS: We mapped the distribution of sandflies and SAPs using literature data from 1940 to 2022. We also mapped the human visceral leishmaniasis (VL) cases using surveillance data from 2014 to 2018. The ecological drivers of 12 main sandfly species and VL were identified by applying machine learning, and their distribution and risk were predicted in three time periods (2021-2040, 2041-2060, and 2061-2080) under three scenarios of climate and socioeconomic changes. RESULTS: In the mainland of China, a total of 47 sandfly species have been reported, with the main 12 species classified into three clusters according to their ecological niches. Additionally, 6 SAPs have been identified, which include two protozoa, two bacteria, and two viruses. The incidence risk of different VL subtypes was closely associated with the distribution risk of specific vectors. The model predictions also revealed a substantial underestimation of the current sandfly distribution and VL risk. The predicted areas affected by the 12 major species of sandflies and the high-risk areas for VL were found to be 37.9-1121.0% and 136.6% larger, respectively, than the observed range in the areas. The future global changes were projected to decrease the risk of mountain-type zoonotic VL (MT-ZVL), but anthroponotic VL (AVL) and desert-type zoonotic VL (DT-ZVL) could remain stable or slightly increase. CONCLUSIONS: Current field observations underestimate the spatial distributions of main sandfly species and VL in China. More active surveillance and field investigations are needed where high risks are predicted, especially in areas where the future risk of VL is projected to remain high or increase.