The impact of age and number of mutations on the size of clonal hematopoiesis.

Clonal hematopoiesis (CH) represents the clonal expansion of hematopoietic stem cells and their progeny driven by somatic mutations. Accurate risk assessment of CH is critical for disease prevention and clinical decision-making. The size of CH has been showed to associate with higher disease risk, yet, factors influencing the size of CH are unknown. In addition, the characteristics of CH in long-lived individuals are not well documented. Here, we report an in-depth analysis of CH in longevous (≥90 y old) and common (60~89 y old) elderly groups. Utilizing targeted deep sequencing, we found that the development of CH is closely related to age and the expression of aging biomarkers. The longevous elderly group exhibited a significantly higher incidence of CH and significantly higher frequency of TET2 and ASXL1 mutations, suggesting that certain CH could be beneficial to prolong life. Intriguingly, the size of CH neither correlates significantly to age, in the range of 60 to 110 y old, nor to the expression of aging biomarkers. Instead, we identified a strong correlation between large CH size and the number of mutations per individual. These findings provide a risk assessment biomarker for CH and also suggest that the evolution of the CH is influenced by factor(s) in addition to age.

Aging and comprehensive molecular profiling in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aging-related and heterogeneous hematopoietic malignancy. In this study, a total of 1,474 newly diagnosed AML patients with RNA sequencing data were enrolled, and targeted or whole exome sequencing data were obtained in 94% cases. The correlation of aging-related factors including age and clonal hematopoiesis (CH), gender, and genomic/transcriptomic profiles (gene fusions, genetic mutations, and gene expression networks or pathways) was systematically analyzed. Overall, AML patients aged 60 y and older showed an apparently dismal prognosis. Alongside age, the frequency of gene fusions defined in the World Health Organization classification decreased, while the positive rate of gene mutations, especially CH-related ones, increased. Additionally, the number of genetic mutations was higher in gene fusion-negative (GF-) patients than those with GF. Based on the status of CH- and myelodysplastic syndromes (MDS)-related mutations, three mutant subgroups were identified among the GF- AML cohort, namely, CH-AML, CH-MDS-AML, and other GF- AML. Notably, CH-MDS-AML demonstrated a predominance of elderly and male cases, cytopenia, and significantly adverse clinical outcomes. Besides, gene expression networks including HOXA/B, platelet factors, and inflammatory responses were most striking features associated with aging and poor prognosis in AML. Our work has thus unraveled the intricate regulatory circuitry of interactions among different age, gender, and molecular groups of AML.

Loss of TMCC2 activates endoplasm reticulum stress and causes auditory hair cell death.

As the auditory and balance receptor cells in the inner ear, hair cells are responsible for converting mechanical stimuli into electrical signals, a process referred to as mechano-electrical transduction. Hair cell development and function are tightly regulated, and hair cell deficits are the main reasons for hearing loss and balance disorders. TMCC2 is an endoplasmic reticulum (ER)-residing transmembrane protein whose physiological function largely remains unknown. In the present work, we show that Tmcc2 is specifically expressed in the auditory hair cells of mouse inner ear. Tmcc2 knockout mice were then established to investigate its physiological role in hearing. Auditory brainstem responses measurements show that Tmcc2 knockout mice suffer from congenital hearing loss. Further investigations reveal progressive auditory hair cell loss in the Tmcc2 knockout mice. The general morphology and function of ER are unaffected in Tmcc2 knockout hair cells. However, increased ER stress was observed in Tmcc2 knockout mice and knockdown cells, suggesting that loss of TMCC2 leads to auditory hair cell death through elevated ER stress.

Exosomes derived from umbilical cord-derived mesenchymal stem cells exposed to diabetic microenvironment enhance M2 macrophage polarization and protect against diabetic nephropathy.

The role of mesenchymal-stem-cell-derived exosomes (MSCs-Exo) in the regulation of macrophage polarization has been recognized in several diseases. There is emerging evidence that MSCs-Exo partially prevent the progression of diabetic nephropathy (DN). This study aimed to investigate whether exosomes secreted by MSCs pre-treated with a diabetic environment (Exo-pre) have a more pronounced protective effect against DN by regulating the balance of macrophages. Exo-pre and Exo-Con were isolated from the culture medium of UC-MSCs pre-treated with a diabetic mimic environment and natural UC-MSCs, respectively. Exo-pre and Exo-Con were injected into the tail veins of db/db mice three times a week for 6 weeks. Serum creatinine and serum urea nitrogen levels, the urinary protein/creatinine ratio, and histological staining were used to determine renal function and morphology. Macrophage phenotypes were analyzed by immunofluorescence, western blotting, and quantitative reverse transcription polymerase chain reaction. In vitro, lipopolysaccharide-induced M1 macrophages were incubated separately with Exo-Con and Exo-pre. We performed microRNA (miRNA) sequencing to identify candidate miRNAs and predict their target genes. An miRNA inhibitor was used to confirm the role of miRNAs in macrophage modulation. Exo-pre were more potent than Exo-Con at alleviating DN. Exo-pre administration significantly reduced the number of M1 macrophages and increased the number of M2 macrophages in the kidney compared to Exo-Con administration. Parallel outcomes were observed in the co-culture experiments. Moreover, miR-486-5p was distinctly expressed in Exo-Con and Exo-pre groups, and it played an important role in macrophage polarization by targeting PIK3R1 through the PI3K/Akt pathway. Reducing miR-486-5p levels in Exo-pre abolished macrophage polarization modulation. Exo-pre administration exhibited a superior effect on DN by remodeling the macrophage balance by shuttling miR-486-5p, which targets PIK3R1.

CIB2 and CIB3 Regulate Stereocilia Maintenance and Mechanoelectrical Transduction in Mouse Vestibular Hair Cells.

The mechanoelectrical transduction (MET) protein complex in the inner-ear hair cells is essential for hearing and balance perception. Calcium and integrin-binding protein 2 (CIB2) has been reported to be a component of MET complex, and loss of CIB2 completely abolishes MET currents in auditory hair cells, causing profound congenital hearing loss. However, loss of CIB2 does not affect MET currents in vestibular hair cells (VHCs) as well as general balance function. Here, we show that CIB2 and CIB3 act redundantly to regulate MET in VHCs, as MET currents are completely abolished in the VHCs of Cib2/Cib3 double knock-out mice of either sex. Furthermore, we show that Cib2 and Cib3 transcripts have complementary expression patterns in the vestibular maculae, and that they play different roles in stereocilia maintenance in VHCs. Cib2 transcripts are highly expressed in the striolar region, and knock-out of Cib2 affects stereocilia maintenance in striolar VHCs. In contrast, Cib3 transcripts are highly expressed in the extrastriolar region, and knock-out of Cib3 mainly affects stereocilia maintenance in extrastriolar VHCs. Simultaneous knock-out of Cib2 and Cib3 affects stereocilia maintenance in all VHCs and leads to severe balance deficits. Taken together, our present work reveals that CIB2 and CIB3 are important for stereocilia maintenance as well as MET in mouse VHCs.SIGNIFICANCE STATEMENT Calcium and integrin-binding protein 2 (CIB2) is an important component of mechanoelectrical transduction (MET) complex, and loss of CIB2 completely abolishes MET in auditory hair cells. However, MET is unaffected in Cib2 knock-out vestibular hair cells (VHCs). In the present work, we show that CIB3 could compensate for the loss of CIB2 in VHCs, and Cib2/Cib3 double knock-out completely abolishes MET in VHCs. Interestingly, CIB2 and CIB3 could also regulate VHC stereocilia maintenance in a nonredundant way. Cib2 and Cib3 transcripts are highly expressed in the striolar and extrastriolar regions, respectively. Stereocilia maintenance and balance function are differently affected in Cib2 or Cib3 knock-out mice. In conclusion, our data suggest that CIB2 and CIB3 are important for stereocilia maintenance and MET in mouse VHCs.

Homologous mapping yielded a comprehensive predicted protein-protein interaction network for peanut (Arachis hypogaea L.).

BACKGROUND: Protein-protein interactions are the primary means through which proteins carry out their functions. These interactions thus have crucial roles in life activities. The wide availability of fully sequenced animal and plant genomes has facilitated establishment of relatively complete global protein interaction networks for some model species. The genomes of cultivated and wild peanut (Arachis hypogaea L.) have also been sequenced, but the functions of most of the encoded proteins remain unclear. RESULTS: We here used homologous mapping of validated protein interaction data from model species to generate complete peanut protein interaction networks for A. hypogaea cv. 'Tifrunner' (282,619 pairs), A. hypogaea cv. 'Shitouqi' (256,441 pairs), A. monticola (440,470 pairs), A. duranensis (136,363 pairs), and A. ipaensis (172,813 pairs). A detailed analysis was conducted for a putative disease-resistance subnetwork in the Tifrunner network to identify candidate genes and validate functional interactions. The network suggested that DX2UEH and its interacting partners may participate in peanut resistance to bacterial wilt; this was preliminarily validated with overexpression experiments in peanut. CONCLUSION: Our results provide valuable new information for future analyses of gene and protein functions and regulatory networks in peanut.

FunctanSNP: an R package for functional analysis of dense SNP data (with interactions).

SUMMARY: Densely measured SNP data are routinely analyzed but face challenges due to its high dimensionality, especially when gene-environment interactions are incorporated. In recent literature, a functional analysis strategy has been developed, which treats dense SNP measurements as a realization of a genetic function and can 'bypass' the dimensionality challenge. However, there is a lack of portable and friendly software, which hinders practical utilization of these functional methods. We fill this knowledge gap and develop the R package FunctanSNP. This comprehensive package encompasses estimation, identification, and visualization tools and has undergone extensive testing using both simulated and real data, confirming its reliability. FunctanSNP can serve as a convenient and reliable tool for analyzing SNP and other densely measured data. AVAILABILITY AND IMPLEMENTATION: The package is available at https://CRAN.R-project.org/package=FunctanSNP.

Dynamic N6 -methyladenosine RNA modification regulates peanut resistance to bacterial wilt.

N6 -methyladenosine (m6 A) is the most abundant mRNA modification in eukaryotes and is an important regulator of gene expression as well as many other critical biological processes. However, the characteristics and functions of m6 A in peanut (Arachis hypogea L.) resistance to bacterial wilt (BW) remain unknown. Here, we analyzed the dynamic of m6 A during infection of resistant (H108) and susceptible (H107) peanut accessions with Ralstonia solanacearum (R. solanacearum), the causative agent of BW. Throughout the transcriptome, we identified 'URUAY' as a highly conserved motif for m6 A in peanut. The majority of differential m6 A located within the 3' untranslated region (UTR) of the transcript, with fewer in the exons. Integrative analysis of RNA-Seq and m6 A methylomes suggests the correlation between m6 A and gene expression in peanut R. solanacearum infection, and functional analysis reveals that m6 A-associated genes were related to plant-pathogen interaction. Our experimental analysis suggests that AhALKBH15 is an m6 A demethylase in peanut, leading to decreased m6 A levels and upregulation of the resistance gene AhCQ2G6Y. The upregulation of AhCQ2G6Y expression appears to promote BW resistance in the H108 accession.

Association of Valproic Acid and Its Main Metabolites' Plasma Concentrations with Clinical Outcomes among Epilepsy Patients: A 10-Year Retrospective Study Based on Therapeutic Drug Monitoring.

Valproic acid (VPA) is a first-line antiepileptic drug with broad efficacy. Due to significant individual differences in its metabolism, therapeutic drug monitoring is commonly used. However, the recommended therapeutic range (50-100 µg/mL) is inadequate for predicting clinical outcomes. Additionally, the relationship between VPA metabolites and clinical outcomes remains unclear. In this retrospective study, 485 Chinese Southern Han epilepsy patients receiving VPA monotherapy were analyzed after reaching steady-state levels. Plasma concentrations of VPA and its five main metabolites were determined by liquid chromatography-mass spectrometry (LC-MS). We assessed the relevance of the recommended therapeutic VPA range for clinical outcomes and explored the association between VPA/metabolites levels and treatment efficacy/adverse effects. Vitro experiments were conducted to assess 4-ene-VPA hepatotoxicity. The therapeutic range of VPA exhibited no significant correlation with clinical outcomes, and plasma concentrations of VPA failed to serve as predictive indicators for treatment response/adverse effects. Treatment responders had higher 2-PGA concentrations (median, 26.39 ng/mL versus 13.68 ng/mL), with a threshold of 36.5 ng/mL for optimal epilepsy treatment. Patients with abnormal liver function had a higher 4-ene-VPA median concentration (6.41 µg/mL versus 4.83 µg/mL), and the ratio of 4-ene-VPA to VPA better predicted VPA-induced hepatotoxicity (area under the curve, 0.718) than 4-ene-VPA concentration. Vitro experiments revealed that 4-ene-VPA was more hepatotoxic than VPA in HepaRG and L02 cell lines. Total plasma VPA concentration does not serve as a predictor of clinical outcomes. 2-PGA concentrations may be associated with efficacy, whereas the ratio of 4-ene-VPA to VPA may be considered a better biomarker (threshold 10.03%) for VPA-induced hepatotoxicity. SIGNIFICANCE STATEMENT: This was the first and largest observational cohort in China to explore the relationship between patients' parent and metabolites concentrations of VPA and clinical outcomes during the maintenance of VPA monotherapy in epileptic patients. This study provided feasible references of VPA for epilepsy clinical treatment with a larger sample of patients compared with previous studies for a more definitive conclusion based on real-world situations. We found two potential biomarkers in predicting efficacy and liver injury, respectively. This breakthrough has the potential to assist in the rational use of VPA.

Surface Modification of Gold Nanorods: Multifunctional Strategies and Application Prospects.

Gold nanorods (AuNRs), as an important type of gold nanomaterials, have attracted much attention in the nano field. Compared with gold nanoparticls, AuNRs have broader application potential due to their tunable localized surface plasmon resonance properties and anisotropic shapes. Yet, conventional synthesis methods using surfactants have limited the use of AuNRs in a variety of fields such as biomedical applications, plasma-enhanced fluorescence, optics and optoelectronic devices. To solve this problem and improve the stability and biocompatibility of AuNRs, researchers in recent years have used surface modification and functionalization to modify AuNRs, among which the introduction of organic ligands to prepare organic/gold hybrid nanorods has become an effective strategy. Organic materials have better toughness and easy processing, and by introducing organic ligands into the surface of AuNRs, the molecular-level composite of organic and inorganic materials can be realized, thus obtaining hybrid nanorods with excellent properties. This paper reviews the research progress of hybrid nanocomposites, and introduces the synthesis methods of AuNRs and the development of surface ligand modification, then summaries the applications of a wide variety of ligands. Also, the advantages and disadvantages of different ligands and their roles in further self-assembly processes are discussed.

CD11b maintains West Nile virus replication through modulation of immune response in human neuroblastoma cells.

BACKGROUND: West Nile virus (WNV) is a rapidly spreading mosquito-borne virus accounted for neuroinvasive diseases. An insight into WNV-host factors interaction is necessary for development of therapeutic approaches against WNV infection. CD11b has key biological functions and been identified as a therapeutic target for several human diseases. The purpose of this study was to determine whether CD11b was implicated in WNV infection. METHODS: SH-SY5Y cells with and without MEK1/2 inhibitor U0126 or AKT inhibitor MK-2206 treatment were infected with WNV. CD11b mRNA levels were assessed by real-time PCR. WNV replication and expression of stress (ATF6 and CHOP), pro-inflammatory (TNF-α), and antiviral (IFN-α, IFN-ß, and IFN-γ) factors were evaluated in WNV-infected SH-SY5Y cells with CD11b siRNA transfection. Cell viability was determined by MTS assay. RESULTS: CD11b mRNA expression was remarkably up-regulated by WNV in a time-dependent manner. U0126 but not MK-2206 treatment reduced the CD11b induction by WNV. CD11b knockdown significantly decreased WNV replication and protected the infected cells. CD11b knockdown markedly increased TNF-α, IFN-α, IFN-ß, and IFN-γ mRNA expression induced by WNV. ATF6 mRNA expression was reduced upon CD11b knockdown following WNV infection. CONCLUSION: These results demonstrate that CD11b is involved in maintaining WNV replication and modulating inflammatory as well as antiviral immune response, highlighting the potential of CD11b as a target for therapeutics for WNV infection.

Incidence and risk of remnant gastric cancer after gastrectomy for gastric cancer: a population-based study from the SEER database.

BACKGROUND: Gastric cancer (GC) constitutes a major global health problem, of which remnant gastric cancer (RGC) occurs less frequently. The rate of RGCs after gastrectomy for GC is increasing recently due to improved survival and screening, however, their incidence and risk have not been reported in the U.S. POPULATION: The objective of this study was to evaluate the incidence and elevated risk of RGC after GC gastrectomy in this population, and to identify the risk factors. METHODS: Patients underwent gastrectomy for first primary GC in 2000-2015 and those who developed RGC were identified from Surveillance, Epidemiology and End Results (SEER) database. Fine-Gray regression was used to estimate the cumulative incidence and to identify risk factors. Standardized incidence ratios (SIRs) were calculated by Poisson regression to compare the risk with the general population. RESULTS: Among 21,566 patients included in the cohort, 227 developed RGC. The 20-year cumulative incidence of RGC was 1.88%. Multivariate analysis revealed that older age, invasion depth, male sex, marital status, and lower income are independent risk factors for RGC development. SIR was 7.70 overall and > 4.5 in each stratum. CONCLUSIONS: Cumulative incidence and risk for RGCs increased continuously in patients underwent GC gastrectomy. Close and lifelong endoscopy surveillance should be recommended for patients who received GC gastrectomy, especially those with high-risk factors.

Adverse childhood experiences, sarcopenia, and social participation in older adults: a cohort study.

OBJECTIVES: To examine the relationships between adverse childhood experiences (ACEs) and developing sarcopenia in older adults and the modifying effects of active social participation. METHODS: This prospective cohort study used survey data from the China Health and Retirement Longitudinal Study, including baseline surveys from 2011, follow-up data from 2013, follow-up data from 2015, and information on ACEs from the 2014 Life History Survey. Information concerning 10 ACEs, including five threat-related ACEs and five deprivation-related ACEs before 17 years of age was obtained by questionnaires through face-to-face interviews. Sarcopenia status was assessed according to the Asian Working Group for Sarcopenia 2019 algorithm, consisted of low muscle mass, and low muscle strength, or poor physical performance. The relationship between ACEs, social participation, and sarcopenia was evaluated using Cox proportional hazard regression models. RESULTS: The study population comprised 6859 older adults in main analyses. Having experienced ≥ 3 ACEs led to an increased 31% risk of developing sarcopenia (hazard ratio [HR]:1.31, 95% confidence interval [CI]:1.10-1.56). Participants having experienced ≥ 2 threat-related ACEs (HR:1.22, 95%CI:1.04-1.43) or deprivation-related ACEs (HR:1.22, 95%CI:1.02-1.46) had a 22% higher risk of developing sarcopenia. Active social participation significantly modified the association between ACEs (p < 0.05), especially threat-related ACEs (p < 0.05), and sarcopenia. CONCLUSIONS: ACEs were associated with the development of sarcopenia; however, social participation had a modifying effect. These findings provide insights for early identification of vulnerable groups, advance intervention timing, and highlight the benefits of promoting active social participation among individuals with sarcopenia who have experienced ACEs.

C15:0 and C17:0 partially mediate the association of milk and dairy products with bladder cancer risk.

The relationship between saturated fatty acids (SFA) and bladder cancer (BC) risk has been conflicting. Our aim was to investigate the relationship between erythrocyte membrane SFA and BC risk. A total of 404 participants were enrolled in the study (including 112 cases and 292 controls). A validated food frequency questionnaire was used to assess the food intake. The constitutive composition of fatty acids in the erythrocyte membrane was measured by gas chromatography. After adjustment for BC risk factors, SFA had no significant association with BC risk. However, C18:0 was positively linked with BC risk with an odds ratio (OR; 95% CI) of 2.99 (1.37-6.53). In contrast, very-long-chain saturated fatty acids (VLCSFA), especially C24:0, were negatively related to BC risk with an OR (95% CI) of 0.28 (0.12-0.65) for VLCSFA and 0.33 (0.15-0.75) for C24:0. Higher total odd-chain SFA (C15:0 and C17:0) were associated with a lower risk of BC with OR (95% CI) of 0.18 (0.076-0.44), 0.18 (0.068-0.47), 0.34 (0.14-0.81), respectively. After subgroup analysis, the protective effects C15:0 and C17:0 were still remained. Receiver operating characteristic analysis displayed that the combination of C15:0 and C17:0 indexes increased the accurate predictive rate of BC risk. Further mediation effect analysis showed that C15:0 and C17:0 could be used as partial mediation effectors for milk and dairy products and bladder carcinogenesis. Overall, the combination of odd-chain SFA (C15:0 and C17:0) in the erythrocyte membrane could serve as a reliable mediator and predictor, indicating a relationship between a high intake of milk and dairy products and a lower risk of BC.

Effects of microplastics on dissipation of oxytetracycline and its relevant resistance genes in soil without and with Serratia marcescens: Comparison between biodegradable and conventional microplastics.

The biodegradable (polybutylene adipate terephthalate: PBAT) and conventional (polyethylene: PE) microplastics (MPs) at 0.5 %, 1 %, and 2 % dosages (w/w) were added into soils with and without Serratia marcescens ZY01 (ZY01, a tet-host strain) to understand their different effects on the dissipation of oxytetracycline (OTC) and tet. The results showed that the dosages of PBAT MP exhibited different inhibition degrees of OTC biodegradation in soils regardless of ZY01, while the dosages of PE MP did not change the enhancement degree of OTC biodegradation in soils without ZY01. These differences were due to the higher adsorption capacity of OTC on PBAT MP and the stronger toxicity of PBAT MP to microorganisms. Besides soil organic matter, pH and total phosphorus were important factors regulating specific tet-host bacteria in soils with MPs (e.g., the nitrogen-cycling bacteria Steroidobacter and Nitrospira) and MPs + ZY01 (e.g., the phosphorus-cycling bacteria Saccharimonadales and Haliangium), respectively. Regardless of ZY01, a stronger selective harboring of tet-host bacteria in PE MP treatments than PBAT MP treatments was observed at the MP dosage of 1 % (w/w), while the opposite trend was true at the MP dosages of 0.5 % and 2 % (w/w). Some specific genera belonging to Actinobacteriota strongly associated with the class 1 integron-integrase gene (intI1), playing a critical role in the horizontal gene transfer of tet in soils especially for the co-existence of MPs and ZY01. This study will be helpful for understanding on how biodegradable and conventional MPs as hotspots affect the environmental behavior of antibiotics and ARGs in soil.

A case-series study of hepatic left lateral segment inversion for surgical field exposure in laparoscopic gastrectomy.

PURPOSE: Retraction of the hepatic left lateral segment (HLLS) is a crucial maneuver for surgical field exposure during laparoscopic gastrectomy with systematic lymphadenectomy. Though various methods of retraction are available, there is no perfect solution. Here, we report the results of our initial 42 cases with HLLS inversion method and discuss the feasibility, safety, effectiveness and technical aspects of this method. METHODS: The intraoperative and postoperative short-term outcomes of 42 patients who underwent HLLS inversion during laparoscopic total gastrectomy and proximal gastrectomy in our department September, 2023 to January, 2024 were reviewed. HLLS inversion was performed by mobilizing the HLLS and inverting it to the right supra-hepatic space through an incision at the falciform ligament. RESULTS: 42 patients underwent HLLS inversion successfully with an average time of 13.9 min. 7 patients needed re-inversion due to slipping back of the HLLS during operation. Optimal exposure of the surgical field was achieved in all patients. No intra-operative complications occurred, except for 1 patient presented with mild intraoperative hepatic hemorrhage requiring electrocoagulation for hemostasis. Alanine aminotransferase and glutamine aminotransferase elevated in some patients on postoperative day 1(POD1), but declined to preoperative levels on the 7th postoperative day. There were no Clavien-Dindo II grade or higher digestive complications after surgery. In 5 patients with preservation the hepatic branch of the vagus nerve, the contractile function of the gall bladder was intact or slightly impaired 2 weeks after operation. CONCLUSION: For laparoscopic proximal gastrectomy (LPG) and laparoscopic total gastrectomy (LTG), HLLS inversion is a feasible method for optimizing visualization of the surgical field with preservation of the function of the hepatic branch of the vagus nerve. It is safe and acceptable as to the manipulation time. Re-inversion is easy and effective even in case of failure of inversion. HLLS inversion seems to be a promising technique for retraction of the liver during laparoscopic gastrectomy.

Regulating pathway for bacterial diversities toward improved ecological benefits of thiencarbazone-methyl·isoxaflutole application: A field experiment.

Herbicide abuse has a significantly negative impact on soil microflora and further influences the ecological benefit. The regulating measures and corresponding mechanisms mitigating the decreased bacterial diversity due to herbicide use have rarely been studied. A field experiment containing the application gradient of an efficient maize herbicide thiencarbazone-methyl·isoxaflutole was performed. The relationship between soil bacterial community and thiencarbazone-methyl·isoxaflutole use was revealed. Modified attapulgite was added to explore its impacts on soil microflora under the thiencarbazone-methyl·isoxaflutole application. Based on the analytic network process-entropy weighting method-TOPSIS method model, the ecological benefit focusing on microbial responses was quantitatively estimated along with technical effectiveness and economic benefit. The results showed that the diversity indices of soil microflora, especially the Inv_Simpson index, were reduced at the recommended, 5 and 10 times the recommended dosages of thiencarbazone-methyl·isoxaflutole use. The Flavisolibacter bacteria was negatively correlated with the residues in soils based on the random forest model and correlation analysis, indicating a potential degrader of thiencarbazone-methyl·isoxaflutole residues. The structural equation model further confirmed that the high soil water content and soil pH promoted the function of Flavisolibacter bacteria, facilitated the dissipation of thiencarbazone-methyl·isoxaflutole residues and further improved the diversity of soil microflora. In addition, the presence of modified attapulgite was found to increase the soil pH, which may improve bacterial diversity through the regulating pathway. This explained the high ecological benefits of the treatment where the thiencarbazone-methyl·isoxaflutole was applied at the recommended dosage rates in conjunction with modified attapulgite addition. Therefore, the comprehensive benefits of thiencarbazone-methyl·isoxaflutole application with a focus on ecological benefits can be improved by regulating the soil pH with modified attapulgite.

Steroidal Saponins from Water Eggplant (Fruits of Solanum torvum) Exhibit Anti-Epileptic Activity against Pentylenetetrazole-Induced Seizure Model in Zebrafish.

The fruits of Solanum torvum Swartz, a wild relative of eggplant, are consumed as a wild vegetable in tropical regions of Africa, Asia, and South America. In traditional Chinese medicine, it is believed to have anti-inflammatory and sedative effects. In the Philippines, water decoction is used to treat hyperactivity disorder. Twenty-two steroidal saponins were isolated and purified from the fruits grown in Yunnan, China, including six new compounds: torvosides U-Z (1-6). During drying and cooking, the saponins may undergo transformation, resulting in small amounts of sapogenins. These transformations can include dehydration of hydroxyl groups at position C22, formation of double bonds at position 20, 22 or 22, 23, and even formation of peroxide products. Saponin compounds torvoside X (4), torvoside Y (5), torvoside A (7), and (25S)-3-oxo-5α-spirostan-6α-yl-O-ß-d-xylopyranoside (20), which are glycosylated at C-6, showed certain anti-epileptic activity in a pentylenetetrazole-induced zebrafish seizure model. No antiproliferative activity was detected when tested on the cancer cell line HepG2, and no hepatotoxic effect was noted on normal liver cell line LO2.

Genome-wide identification of GRF transcription factors and their expression profile in stem meristem of broomcorn millet (Panicum miliaceum L.).

To understand the genome-wide information of the GRF family genes in broomcorn millet and their expression profile in the vegetative meristems, bioinformatic methods and transcriptome sequencing were used to analyze the characteristics, physical and chemical properties, phylogenetic relationship, chromosome distribution, gene structure, cis-acting elements and expression profile in stem meristem for the GRF family members. The results showed that the GRF gene family of millet contains 21 members, and the PmGRF gene is unevenly distributed on 12 chromosomes. The lengths of PmGRF proteins vary from 224 to 618 amino acids, and the isoelectric points are between 4.93-9.69. Each member of the family has 1-4 introns and 2-5 exons. The protein PmGRF13 is localized in both the nucleus and chloroplast, and the rest PmGRF proteins are located in the nucleus. Phylogenetic analysis showed that the 21 GRF genes were divided into 4 subfamilies (A,B,C and D) in broomcorn millet. The analysis of cis-acting elements showed that there were many cis-acting elements involved in light response, hormone response, drought induction, low temperature response and other environmental stress responses in the 2000 bp sequence upstream of the GRF genes. Transcriptome sequencing and qRT-PCR analyses showed that the expression levels of PmGRF3 and PmGRF12 in the dwarf variety Zhang778 were significantly higher than those of the tall variety Longmi12 in the internode and node meristems at the jointing stage, while the expression patterns of PmGRF4, PmGRF16 and PmGRF21 were reverse. In addition, the expression levels of PmGRF2 and PmGRF5 in the internode of Zhang778 were significantly higher than Longmi12. The other GRF genes were not or insignificantly expressed. These results indicated that seven genes, PmGRF2, PmGRF3, PmGRF4, PmGRF5, PmGRF12, PmGRF16 and PmGRF21, were related to the formation of plant height in broomcorn millet.

[Construction and Evaluation of a Prognostic Risk Prediction Model of Pancreatic Ductal Adenocarcinoma Based on Immune-Related Genes].

Objective To construct a risk prediction model by integrating the molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) and immune-related genes.Methods With GSE71729 data set (n=145) as the training set,the differentially expressed genes and differential immune-related genes between the squamous and non-squamous subtypes of PDAC were integrated to construct a regulatory network,on the basis of which five immune marker genes regulating the squamous subtype were screened out.An integrated immune score (IIS) model was constructed based on patient survival information and immune marker genes to predict the clinical prognosis of PDAC patients,and its predictive performance was tested with 5 validation sets (n=758).Results PDAC patients were assigned into high risk and low risk groups according to the IIS.In both training and validation sets,the overall survival of patients in the high risk group was shorter than that in the low risk group (both P<0.001).The multivariable Cox regression showed that IIS was an independent prognostic factor for PDAC (HR=2.16,95%CI=1.50-3.10,P<0.001).Conclusion IIS can be used for risk stratification of PDAC patients and may become a potential prognostic marker for PDAC.