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Recent studies have shown that the use of mesenchymal stem/stromal cells (MSCs) may be a promising strategy for treating spinal cord injury (SCI). This study aimed to explore the effectiveness of human umbilical cord-derived MSCs (hUC-MSCs) with different administration routes and dosages on SCI rats. Following T10-spinal cord contusion in Sprague-Dawley rats (N = 60), three different dosages of hUC-MSCs were intrathecally injected into rats (SCI-ITH) after 24 h. Intravenous injection of hUC-MSCs (SCI-i.v.) and methylprednisolone reagent (SCI-PC) were used as positive controls (N = 10/group). A SCI control group without treatment and a sham operation group were injected with Multiple Electrolyte Injection solution. The locomotor function was assessed by Basso Beattie Bresnahan (BBB) rating score, magnetic resonance imaging (MRI), histopathology, and immunofluorescence. ELISA was conducted to further analyze the nerve injury and inflammation in the rat SCI model. Following SCI, BBB scores were significantly lower in the SCI groups compared with the sham operation group, but all the treated groups showed the recovery of hind-limb motor function, and rats receiving the high-dose intrathecal injection of hUC-MSCs (SCI-ITH-H) showed improved outcomes compared with rats in hUC-MSCs i.v. and positive control groups. Magnetic resonance imaging revealed significant edema and spinal cord lesion in the SCI groups, and significant recovery was observed in the medium and high-dose hUC-MSCs ITH groups. Histopathological staining showed that the necrotic area in spinal cord tissue was significantly reduced in the hUC-MSCs ITH-H group, and the immunofluorescence staining confirmed the neuroprotection effect of hUC-MSCs infused on SCI rats. The increase of inflammatory cytokines was repressed in hUC-MSCs ITH-H group. Our results confirmed that hUC-MSC administered via intrathecal injection has dose-dependent neuroprotection effect in SCI rats.

Abstract We aimed to determine disseminated intravascular coagulation (DIC)-associated organ failure and underlying diseases based on data from three ICU wards in tertiary hospitals in China from 2008 to 2016. The diagnosis of DIC was confirmed by an International Society of Thrombosis and Hemostasis score greater than or equal to 5. The maternal outcomes included the changes in organ function 24 h after ICU admission. The durations of hospital stay and ICU stay were recorded as secondary outcomes. Among 297 ICU admissions (median Sequential Organ Failure Assessment score, 4) for obstetric diseases, there were 87 DIC cases, with an estimated DIC incidence of 87 per 87,580 deliveries. Postpartum hemorrhage was the leading disease associated with DIC (71, 81.6%), followed by hypertensive disorders (27, 31.0%), sepsis (15, 17.2%), acute fatty liver of pregnancy (11, 12.6%) and amniotic fluid embolism (10, 11.5%). Compared with patients without DIC, those with DIC had higher rates of multiple organ dysfunction syndrome/death (27.6% vs 4.8%, p = 0.000), organ failure (36.8% vs 24.3%, p = 0.029), among which organ failure included acute renal failure (32.2% vs 10.0%, p = 0.000), respiratory failure (16.1% vs 8.6%, p = 0.057), disturbance of consciousness (12.6% vs 2.4%, p = 0.000) and DIC group also had higher rates of massive transfusion (52.9% vs 21.9%, p = 0.000), hysterectomy (32.2% vs 15.7%, p = 0.001), longer ICU (4 days vs 2 days, p = 0.000) and hospital stays (14 days vs 11 days, p = 0.005). DIC and amniotic fluid embolism were independent risk factors for organ failure in patients admitted to the ICU. Postpartum hemorrhage was the leading cause of DIC associated organ failure in obstetrics admitted to the ICU. The control of obstetric bleeding in a timely manner may improve obstetric prognoses.

Abstract This study aims to investigate the potential relationships between the systemic immune-inflammation index (SII) and body mass index (BMI), waist circumference, and the prevalence of obesity. A cross-sectional analysis was conducted on 7,645 individuals aged 20 and above from the NHANES 2017–2020. Multivariate linear regression analyses were conducted to evaluate the association of the logarithmically transformed SII (lgSII) with BMI and waist circumference. Additionally, multivariable logistic regression was utilized to explore the relationship between lgSII and the prevalence of obesity. Fitted smoothing curves and threshold-effect analysis were applied to elucidate nonlinear relationships. In the fully adjusted model, a positive relationship was observed between lgSII and BMI, waist circumference, and obesity prevalence (β = 3.13, 95% CI 2.10–4.16; β = 7.81, 95% CI 5.50–10.13; OR = 1.44, 95% CI 1.12–1.86). The variables of gender, age, race, education, marital status, poverty income ratio (PIR), energy intake, sleep disorder, smoking status, and alcohol use did not significantly modify the positive association between lgSII and obesity. However, physical activity appeared to influence the positive correlation between lgSII and obesity. Using a two-segment linear regression model, an inverted U-shaped relationship was observed between lgSII and both BMI and waist circumference. Furthermore, lgSII demonstrated a linear positive correlation with obesity prevalence. When stratified by physical activity, lgSII showed a non-significant negative correlation with obesity in the physically active group. Our findings underscore a robust association between the logarithmically transformed SII and BMI, waist circumference, and the prevalence of obesity.

Abstract Background Whole exome sequencing (WES) has been recommended to investigate the genetic cause of fetal structural anomalies. In this retrospective study, we aimed to evaluate the diagnostic yield of WES in our cohort of families with pregnancy loss or termination of pregnancy due to structural anomalies. Methods As aneuploidy, triploidy and copy number variations (CNVs) could be detected by exome-based CNV analysis, only WES is performed in this study. And the results of 375 cases assessed by WES were analyzed. Results The overall detection rate was 32.3% (121/375), including aneuploidy and triploidy (7.5%, 28/375), CNVs (5.1%, 19/375) and single-nucleotide variants (SNVs) /insertions or deletions (Indels) (19.7%, 74/375). Among these, the diagnostic yield for likely pathogenic (LP) or pathogenic (P) CNVs is 4.8% (18/375), and the diagnostic yield for LP or P SNVs/Indels is 15.2% (57/375). And an additional 4.8% (18/375) of cases had CNVs or SNVs/Indels classified as variants of uncertain significance (VUS) with potential clinical significance. Conclusions Our findings expand the known mutation spectrum of genetic variants related to fetal abnormalities, increase our understanding of prenatal phenotypes, and enable more accurate counseling of recurrence risk for future pregnancies.

Breast cancer is rare in men and is managed using strategies similar to those for breast cancer in women. This study retrospectively analyzed the clinicopathological features, treatment, and survival of male breast cancer (MBC). A total of 66 patients with MBC admitted into Xijing Hospital from August 2006 to March 2024 were reviewed. Data were collected from patients’ hospital records and breast cancer database of Xijing Hospital. The incidence of MBC tended to increase from 2018, with affected individuals being older than those with female breast cancer (FBC). The most common histological type of MBC was invasive carcinoma, with positive hormone receptor status. A total of 62 (93.9%) patients with MBC underwent modified radical mastectomy. Chemotherapy was administered to 39 (59.1%) patients, while endocrine therapy was received by 14 patients (21.2%) and radiotherapy by nine patients (13.6%). Survival analysis indicated that the median overall survival (OS) of patients with MBC was 46.7 months (0.9–184.8 months). As of the latest data, 58 patients (87.9%) with MBC are alive. Factors significantly associated with survival included age (χ 2 = 3.856, p = .050), estrogen receptor (χ 2 = 10.427, p = .005), molecular types (χ 2 = 10.641, p = .031), P63 (χ 2 = 2.631, p

Objective This study investigated the correlation between uncertainty stress (US) and depression among healthcare professionals (HCPs) in China.Design, settings and participants A cross-sectional online survey was conducted by recruiting HCPs from three provinces in China (central, eastern and western) through purposive sampling between 29 September 2022 and 18 January 2023. US was measured using the Life Stress Questionnaire and depression was measured using the Patient Health Questionnaire-9. In total, 2976 questionnaires were deemed valid.Primary and secondary outcome This study examined the prevalence of US and depression among HCPs in China; the correlating sociodemographic traits; and the correlation between US and depression.Results The prevalence of US and depression among HCPs in China was 26.54% (790 out of 2976) and 71.63% (2132 out of 2976). Binary logistic analysis revealed that individuals with graduate degrees (OR: 1.83; 95% CI 1.07 to 3.11; p

Abstract Currently, the precise and detailed anatomical data of the normal uterus, especially the myometrium thickness in various parts of the uterus, are lacking. This study aims to provide normal references for uterine size in healthy reproductive-aged Chinese women to facilitate the application of hysteroscopic surgery. A total of 298 women of reproductive age with normal uterine were included. Parity was significantly correlated with uterine measurements (P 0.05). There was a positive correlation between body mass index (BMI) and extrauterine measurements as well as myometrial thickness (P

Abstract To evaluate the safety and effectiveness of epigallocatechin-3-gallate (EGCG) solution treating the acute severe dermatitis in patients receiving radiotherapy. This phase I research enrolled patients with thoracic cancer receiving radiotherapy at Shandong Cancer Hospital and Institute in Shandong, China. EGCG solution was sprayed to the radiation field when grade III radiation-induced dermatitis (RID) first appearance. EGCG concentration escalated from 660 to 2574 μmol/L using modified-Fibonacci dose-escalation. RID and related symptoms were followed up every day. Between March 2021 and November 2021, 19 patients were enrolled in this phase I research. The median dose of grade III RID first observation was 44 Gy (30.6–52 Gy). As the EGCG treatment was performed continuously, all these grade III RID reactions were significantly decreased to grade I or grade II RID at three days after use of EGCG (p

N6-methyladenosine (m6A) methylation of RNA by the methyltransferase complex (MTC), with core components including METTL3–METTL14 heterodimers and Wilms’ tumor 1-associated protein (WTAP), contributes to breast tumorigenesis, but the underlying regulatory mechanisms remain elusive. Here, we identify a novel cleaved form METTL3a (residues 239–580 of METTL3). We find that METTL3a is required for the METTL3–WTAP interaction, RNA m6A deposition, as well as cancer cell proliferation. Mechanistically, we find that METTL3a is essential for the METTL3–METTL3 interaction, which is a prerequisite step for recruitment of WTAP in MTC. Analysis of m6A sequencing data shows that depletion of METTL3a globally disrupts m6A deposition, and METTL3a mediates mammalian target of rapamycin (mTOR) activation via m6A-mediated suppression of TMEM127 expression. Moreover, we find that METTL3 cleavage is mediated by proteasome in an mTOR-dependent manner, revealing positive regulatory feedback between METTL3a and mTOR signaling. Our findings reveal METTL3a as an important component of MTC, and suggest the METTL3a–mTOR axis as a potential therapeutic target for breast cancer.

Abstract Background Genome-wide association studies (GWAS) have identified some variants associated with subclinical atherosclerosis (SCA) in general population but lacking sufficient validation. Besides traditional risk factors, whether and how would genetic variants associate with SCA among people with HIV (PWH) remains to be elucidated. Method A large original GWAS and gene-environment interaction analysis of SCA were conducted among Chinese PWH (n = 2850) and age/sex-matched HIV-negative controls (n = 5410). Subgroup analyses by age and functional annotations of variants were also performed. Results Different from HIV-negative counterparts, host genome had a greater impact on young PWH rather than the elders: one genome-wide significant variant (rs77741796, P = 2.20 × 10−9) and eight suggestively significant variants (P

Objectives This study aimed to screen the potential risk factors for academic burnout among adolescents during the COVID-19 pandemic, develop and validate a predictive tool based on the risk factors for predicting academic burnout.Design This article presents a cross-sectional study.Setting This study surveyed two high schools in Anhui Province, China.Participants A total of 1472 adolescents were enrolled in this study.Outcome measures The questionnaires included demographic characteristic variables, living and learning states and adolescents’ academic burnout scale. Least absolute shrinkage and selection operator and multivariate logistic regression analyses were employed to screen the risk factors for academic burnout and develop a predictive model. The receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to assess the accuracy and discrimination of the nomogram.Results In this study, 21.70% of adolescents reported academic burnout. Multivariable logistic regression analysis showed that single-child family (OR=1.742, 95% CI: 1.243 to 2.441, p=0.001), domestic violence (OR=1.694, 95% CI: 1.159 to 2.476, p=0.007), online entertainment (>8 hours/day, OR=3.058, 95% CI: 1.634 to 5.720, p

Objective To analyze the causes and treatments for the incompatible crossmatching between a patient, who underwent the minor ABO mismatches lung transplantation, and the blood donor with ABO-compatible blood. Methods A patient, who underwent the minor ABO mismatches (donor group O; recipient group A) lung transplantation developed a continuous decrease in Hb for 13 days after surgery, The blood sample of the patient presented major crossmatching incompatibility with the blood donors and the causes of it were analyzed by the recipient′s blood type reviewing, direct antiglobulin test, antibody screening and erythrocyte elution. Results The patient’s serum reacted with A1 erythrocyte reagent with agglutination strength at ±, and enhanced to 1+ at 4℃ after 10 min incubation.Antibodies were not detected by 10-cell panel and the effects of unexpected antibodies were excluded.The results of direct antiglobulin test and elution test were positive, and eluted anti-A antibody was detected.Combined with the patient′s continuous decline in Hb and elevated total bilirubin, passenger lymphocyte syndrome (PLS) was clinically diagnosed.After the transfusion of 6 U of O-type washed RBCs, the symptoms of anemia were improved and no adverse reactions occurred. Conclusion PLS may occur after an ABO mismatched solid organ transplantation.Most of the hemolytic symptoms are not obvious and easy to ignore, therefore clinical indicators of direct antiglobulin test results, Hb and total bilirubin should be continuously monitored after transplantation for early detection and timely treatment of PLS to avoid major adverse consequences.

Abstract. Introduction:. When initiating urate-lowering therapy, using anti-inflammatory prophylaxis therapy for at least 3 to 6 months is strongly recommended. Previous studies have found that zhengqing fengtongning sustained-release tablets (sinomenine) can improve inflammation in the acute phase of gout; however, the efficacy of urate-lowering therapy in reducing frequency of acute flares still needs to be investigated. The aim of the present study is to explore the efficacy and safety of sinomenine for prophylaxis of acute flares when initiating urate-lowering therapy. Methods and analysis:. This randomized, placebo-controlled, double-blinded trial will include a total of 210 gout patients who meet the study criteria. The patients will be randomized (1:1) to the test group and the control group. The intervention is planned to be performed for 12 weeks with a follow-up of 12 weeks. All patients would be administered febuxostat (40 mg/d) and concomitant anti-inflammatory prophylaxis therapy. Sinomenine and colchicine placebo are administered in the sinomenine group, sinomenine placebo and colchicine are administered in the colchicine group. The primary outcome is the rate of acute gout flares in subjects within 12 weeks of the treatment period. The secondary outcomes include the times of acute gout flares and the duration of each acute flares within 12 weeks; the compliance rate in patients whose UA levels ≤6.0 mg/dL (360 μmol/L) at the weekend of 2nd, 4th, 8th, and 12th week in each group; the proportion of patients with ≥1 and ≥2 gout flares within 12 weeks; average visual analogue scale/score pain score during gout flares; and the oral dose of etoricoxib will be used to control the onset of acute flares within 12 weeks. Ethics and dissemination:. The Institutional Medical Ethics Committee have approved the trial protocol. We plan to publish the results of this study in a peer-reviewed journal. Trial registration:. ChiCTR, ChiCTR2100045114, Registered 8 April 2021 http://www.chictr.org.cn/showproj.aspx?proj=124688

Abstract Background Understanding the roles of miRNAs in cardiovascular disease remains a challenge. Genomic linkage indicates a functional relationship between intronic miRNAs and their host genes. However, few studies have shown functional association between intronic miRNAs and their host coding genes that are genetically associated with cardiovascular disease. Methods In this study, we investigated functional relationship between three protein-coding genes genetically associated with cardiovascular disease, i.e., CDH13, SLC12A3, and CKAP5, and their intronic miRNAs using a data-driven approach. Results We found that the three protein-coding genes functionally interact with targets of their intronic miRNAs, i.e., miR-3182, miR-6863, and miR-5582, in a tissue-specific pattern. The intronic miRNAs preferentially impact important genes for the three host genes in the network, indicating their roles in maintaining the integrity of the interactome where the host genes are involved. Targets of the intronic miRNAs display functional similarity to the host genes. We furthermore present sets of target genes for future investigation on the possible miRNA-target interactions that potentially contribute to cardiovascular diseases. Conclusions Our work provides new insight into the regulatory network of the cardiovascular-associated pathways and opens the possibility for future experimental research.

Background Lower respiratory tract infection (LRTI) is one of the leading cause of death in children under 5 years old around the world between 1980 and 2016. Distinguishing between viral and bacterial infection is challenging when children suffered from LRTI in the absence of pathogen detection. The aim of our study is to analyze the difference of serum β2-microglobulin (β2-MG) between viral LRTI and bacterial LRTI in children. Methods This retrospective study included children with LRTI caused by a single pathogen from Yancheng Third People’s Hospital, Yancheng, China, between January 1, 2016 and December 31, 2019. Participants were divided into the younger group (1 year old ≤ age < 3 years old) and the older group (3 years old ≤ age < 5 years old) for subgroup analysis. Results A total of 475 children with LRTI caused by common respiratory pathogens were identified. In the younger group as well as the older group, the serum level of β2-MG in respiratory syncytial virus, influenza A virus and influenza B virus groups were significantly increased compared to that in the Mycoplasma pneumoniae group. Compared with Streptococcus pneumoniae infection group, the serum β2-MG level of respiratory syncytial virus, influenza A virus and influenza B virus groups were significantly higher in children between 1 and 3 years old. Conclusions The serum β2-MG may distinguish viral infection from bacterial infection in children with LRTI.

To develop and validate a radiomics signature for the prediction of gastric cancer (GC) survival and chemotherapeutic benefits. In this multicenter retrospective analysis, we analyzed the radiomics features of portal venous-phase computed tomography in 1591 consecutive patients. A radiomics signature was generated by using the Lasso-Cox regression model in 228 patients and validated in internal and external validation cohorts. Radiomics nomograms integrating the radiomics signature were constructed, demonstrating the incremental value of the radiomics signature to the traditional staging system for individualized survival estimation. The performance of the nomograms was assessed with respect to calibration, discrimination, and clinical usefulness. The radiomics signature consisted of 19 selected features and was significantly associated with DFS (disease-free survival) and OS (overall survival). Multivariate analysis demonstrated that the radiomics signature was an independent prognostic factor. Incorporating the radiomics signature into the radiomics-based nomograms resulted in better performance for the estimation of DFS and OS than the clinicopathological nomograms and TNM staging system, with improved accuracy of the classification of survival outcomes. Further analysis showed that stage II and III patients with higher radiomics scores exhibited a favorable response to chemotherapy. In conclusion, the newly developed radiomics signature is a powerful predictor of DFS and OS, and it may predict which patients with stage II and III GC benefit from chemotherapy. Keywords: Gastric cancer, Radiomics signature, Prognosis, Chemotherapy

Abstract A reduction in the particle size is expected to improve the properties and increase the application potential of high-entropy alloys. Therefore, in this study, a novel sol–gel autocombustion technique was first used to synthesize high-entropy alloys. The average grain size of the prepared nanocrystalline CoCrCuNiAl high-entropy alloys showed was 14 nm with an excellent and uniform dispersion, exhibiting a distinct magnetic behavior similar to the superparamagnetic behavior. We show that the metal nitrates first form (Co,Cu,Mg,Ni,Zn)O high-entropy oxides, and then in situ reduce to CoCrCuNiAl high-entropy alloys by the reducing gases, and the chelation between citric acid and the metal ions and the in situ chemical reactions are the dominant reaction mechanisms. We demonstrate that the sol–gel autocombustion process is an efficient way to synthesize solid solution alloys eluding the restriction of a high mixing entropy.

BACKGROUND:Vascular endothelial growth factor (VEGF) is commonly overexpressed in a variety of tumor types including lung cancer. As a key regulator of angiogenesis, it promotes tumor survival, growth, and metastasis through the activation of the downstream protein kinase B (AKT) and extracellular signal-regulated kinase (ERK 1/2) activation. The VEGF promoter contains a 36 bp guanine-rich sequence (VEGFq) which is capable of forming quadruplex (four-stranded) DNA. This sequence has been implicated in the down-regulation of both basal and inducible VEGF expression and represents an ideal target for inhibition of VEGF expression. RESULTS:Our experiments demonstrate sequence-specific interaction between a G-rich quadruplex-forming oligonucleotide encoding a portion of the VEGFq sequence and its double stranded target sequence, suggesting that this G-rich oligonucleotide binds specifically to its complementary C-rich sequence in the genomic VEGF promoter by strand invasion. We show that treatment of A549 non-small lung cancer cells (NSCLC) with this oligonucleotide results in decreased VEGF expression and growth inhibition. The VEGFq oligonucleotide inhibits proliferation and invasion by decreasing VEGF mRNA/protein expression and subsequent ERK 1/2 and AKT activation. Furthermore, the VEGFq oligonucleotide is abundantly taken into cells, localized in the cytoplasm/nucleus, inherently stable in serum and intracellularly, and has no effect on non-transformed cells. Suppression of VEGF expression induces cytoplasmic accumulation of autophagic vacuoles and increased expression of LC3B, suggesting that VEGFq may induce autophagic cell death. CONCLUSION:Our data strongly suggest that the G-rich VEGFq oligonucleotide binds specifically to the C-rich strand of the genomic VEGF promoter, via strand invasion, stabilizing the quadruplex structure formed by the genomic G-rich sequence, resulting in transcriptional inhibition. Strand invading oligonucleotides represent a new approach to specifically inhibit VEGF expression that avoids many of the problems which have plagued the therapeutic use of oligonucleotides. This is a novel approach to specific inhibition of gene expression.

Massively parallel sequencing (MPS) combined with bioinformatic analysis has been widely applied to detect fetal chromosomal aneuploidies such as trisomy 21, 18, 13 and sex chromosome aneuploidies (SCAs) by sequencing cell-free fetal DNA (cffDNA) from maternal plasma, so-called non-invasive prenatal testing (NIPT). However, many technical challenges, such as dependency on correct fetal sex prediction, large variations of chromosome Y measurement and high sensitivity to random reads mapping, may result in higher false negative rate (FNR) and false positive rate (FPR) in fetal sex prediction as well as in SCAs detection. Here, we developed an optimized method to improve the accuracy of the current method by filtering out randomly mapped reads in six specific regions of the Y chromosome. The method reduces the FNR and FPR of fetal sex prediction from nearly 1% to 0.01% and 0.06%, respectively and works robustly under conditions of low fetal DNA concentration (1%) in testing and simulation of 92 samples. The optimized method was further confirmed by large scale testing (1590 samples), suggesting that it is reliable and robust enough for clinical testing.

Congenital contractural arachnodactyly (CCA, OMIM 121050), also known as Beals-Hecht syndrome, is an autosomal dominant disorder of connective tissue. CCA is characterized by arachnodactyly, dolichostenomelia, pectus deformities, kyphoscoliosis, congenital contractures and a crumpled appearance of the helix of the ear. The aim of this study is to identify the genetic cause of a 4-generation Chinese family of Tujia ethnicity with congenital contractural arachnodactyly by exome sequencing. The clinical features of patients in this family are consistent with CCA. A novel missense mutation, c.3769T>C (p.C1257R), in the fibrillin 2 gene (FBN2) was identified responsible for the genetic cause of our family with CCA. The p.C1257R mutation occurs in the 19th calcium-binding epidermal growth factor-like (cbEGF) domain. The amino acid residue cysteine in this domain is conserved among different species. Our findings suggest that exome sequencing is a powerful tool to discover mutation(s) in CCA. Our results may also provide new insights into the cause and diagnosis of CCA, and may have implications for genetic counseling and clinical management.

Abscisic acid (ABA) has an important role in the responses of plants to pathogens due to its ability to induce stomatal closure and interact with salicylic acid (SA) and jasmonic acid (JA). WRKY transcription factors serve as antagonistic or synergistic regulators in the response of plants to a variety of pathogens. Here, we demonstrated that CmWRKY15, a group IIa WRKY family member, was not transcriptionally activated in yeast cells. Subcellular localization experiments in which onion epidermal cells were transiently transfected with CmWRKY15 indicated that CmWRKY15 localized to the nucleus in vivo. The expression of CmWRKY15 could be markedly induced by the presence of Alternaria tenuissima inoculum in chrysanthemum. Furthermore, the disease severity index (DSI) data of CmWRKY15-overexpressing plants indicated that CmWRKY15 overexpression enhanced the susceptibility of chrysanthemum to A. tenuissima infection compared to controls. To illustrate the mechanisms by which CmWRKY15 regulates the response to A. tenuissima inoculation, the expression levels of ABA-responsive and ABA signaling genes, such as ABF4, ABI4, ABI5, MYB2, RAB18, DREB1A, DREB2A, PYL2, PP2C, RCAR1, SnRK2.2, SnRK2.3, NCED3A, NCED3B, GTG1, AKT1, AKT2, KAT1, KAT2, and KC1were compared between transgenic plants and controls. In summary, our data suggest that CmWRKY15 might facilitate A. tenuissima infection by antagonistically regulating the expression of ABA-responsive genes and genes involved in ABA signaling, either directly or indirectly.

Heat stress due to high environmental temperature negatively influences animal performances. To better understand the biological impact of heat stress, laying broiler breeder chickens were subjected either to acute (step-wisely increasing temperature from 21 to 35°C within 24 hours) or chronic (32°C for 8 weeks) high temperature exposure. High temperature challenges significantly elevated body temperature of experimental birds (P

Autosomal recessive cerebellar ataxias are a group of neurodegenerative disorders that are characterized by complex clinical and genetic heterogeneity. Although more than 20 disease-causing genes have been identified, many patients are still currently without a molecular diagnosis. In a two-generation autosomal recessive cerebellar ataxia family, we mapped a linkage to a minimal candidate region on chromosome 16p13.3 flanked by single-nucleotide polymorphism markers rs11248850 and rs1218762. By combining the defined linkage region with the whole-exome sequencing results, we identified a homozygous mutation (c.493CT) in CHIP (NM_005861) in this family. Using Sanger sequencing, we also identified two compound heterozygous mutations (c.389AT/c.441GT; c.621C>G/c.707GC) in CHIP gene in two additional kindreds. These mutations co-segregated exactly with the disease in these families and were not observed in 500 control subjects with matched ancestry. CHIP colocalized with NR2A, a subunit of the N-methyl-D-aspartate receptor, in the cerebellum, pons, medulla oblongata, hippocampus and cerebral cortex. Wild-type, but not disease-associated mutant CHIPs promoted the degradation of NR2A, which may underlie the pathogenesis of ataxia. In conclusion, using a combination of whole-exome sequencing and linkage analysis, we identified CHIP, encoding a U-box containing ubiquitin E3 ligase, as a novel causative gene for autosomal recessive cerebellar ataxia.