Association between cadmium exposure and pulmonary function reduction: Potential mediating role of telomere attrition in chronic obstructive pulmonary disease patients.

BACKGROUND: Environmental cadmium (Cd) exposure is linked to pulmonary function injury in the general population. But, the association between blood Cd concentration and pulmonary function has not been investigated thoroughly in chronic obstructive pulmonary disease (COPD) patients, and the potential mechanisms are unclear. METHODS: All eligible 789 COPD patients were enrolled from Anhui COPD cohort. Blood specimens and clinical information were collected. Pulmonary function test was conducted. The subunit of telomerase, telomerase reverse transcriptase (TERT), was determined through enzyme linked immunosorbent assay (ELISA). Blood Cd was measured via inductively coupled-mass spectrometer (ICP-MS). RESULTS: Blood Cd was negatively and dose-dependently associated with pulmonary function. Each 1-unit increase of blood Cd was associated with 0.861 L decline in FVC, 0.648 L decline in FEV1, 5.938 % decline in FEV1/FVC %, and 22.098 % decline in FEV1 % among COPD patients, respectively. Age, current-smoking, self-cooking and higher smoking amount aggravated Cd-evoked pulmonary function decrease. Additionally, there was an inversely dose-response association between Cd concentration and TERT in COPD patients. Elevated TERT obviously mediated 29.53 %, 37.50 % and 19.48 % of Cd-evoked FVC, FEV1, and FEV1 % declines in COPD patients, respectively. CONCLUSION: Blood Cd concentration is strongly associated with the decline of pulmonary function and telomerase activity among COPD patients. Telomere attrition partially mediates Cd-induced pulmonary function decline, suggesting an underlying mechanistic role of telomere attrition in pulmonary function decline from Cd exposure in COPD patients.

[Risk factors for hemorrhagic cystitis in children with ß-thalassemia major after allogeneic hematopoietic stem cell transplantation]. / 重型ßåœ°ä¸­æµ·è´«è¡€å„¿ç«¥å¼‚åŸºå› é€ è¡€å¹²ç»†èƒžç§»æ¤åŽå¹¶å‘å‡ºè¡€æ€§è†€èƒ±ç‚Žçš„å±é™©å› ç´ åˆ†æž.

OBJECTIVES: To explore the risk factors for hemorrhagic cystitis (HC) in children with ß-thalassemia major (TM) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A retrospective analysis was conducted on clinical data of 247 children with TM who underwent allo-HSCT at Shenzhen Children's Hospital from January 2021 to November 2022. The children were divided into an HC group (91 cases) and a non-HC group (156 cases) based on whether HC occurred after operation. Multivariable logistic regression analysis was used to explore the risk factors for HC, and the receiver operating characteristic curve was used to analyze the predictive efficacy of related factors for HC. RESULTS: Among the 247 TM patients who underwent allo-HSCT, the incidence of HC was 36.8% (91/247). Univariate analysis showed age, incompatible blood types between donors and recipients, occurrence of acute graft-versus-host disease (aGVHD), positive urine BK virus deoxyribonucleic acid (BKV-DNA), and ≥2 viral infections were associated with the development of HC after allo-HSCT (P<0.05). Multivariable analysis revealed that incompatible blood types between donors and recipients (OR=3.171, 95%CI: 1.538-6.539), occurrence of aGVHD (OR=2.581, 95%CI: 1.125-5.918), and positive urine BKV-DNA (OR=21.878, 95%CI: 9.633-49.687) were independent risk factors for HC in children with TM who underwent allo-HSCT. The receiver operating characteristic curve analysis showed that positive urine BKV-DNA alone or in combination with two other risk factors (occurrence of aGVHD, incompatible blood types between donors and recipients) had a certain accuracy in predicting the development of HC after allo-HSCT (area under the curve >0.8, P<0.05). CONCLUSIONS: Incompatible blood types between donors and recipients, occurrence of aGVHD, and positive urine BKV-DNA are risk factors for HC after allo-HSCT in children with TM. Regular monitoring of urine BKV-DNA has a positive significance for early diagnosis and treatment of HC.

Effects and parameters of community-based exercise on motor symptoms in Parkinson's disease: a meta-analysis.

BACKGROUND: Community-based exercise is a continuation and complement to inpatient rehabilitation for Parkinson's disease and does not require a professional physical therapist or equipment. The effects, parameters, and forms of each exercise are diverse, and the effect is affected by many factors. A meta-analysis was conducted to determine the effect and the best parameters for improving motor symptoms and to explore the possible factors affecting the effect of community-based exercise.  METHODS: We conducted a comprehensive search of six databases: PEDro, PubMed/Medline, CENTRAL, Scopus, Embase, and WOS. Studies that compared community-based exercise with usual care were included. The intervention mainly included dance, Chinese martial arts, Nordic walking, and home-based exercise. The primary outcome measure was the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) score. The mean difference (95% CI) was used to calculate the treatment outcomes of continuous outcome variables, and the I2 statistic was used to estimate the heterogeneity of the statistical analysis. We conducted subgroup analysis and meta-regression analysis to determine the optimal parameters and the most important influencing factors of the exercise effect.  RESULTS: Twenty-two studies that enrolled a total of 809 subjects were included in the analysis. Exercise had a positive effect on the UPDRS-III (MD = -5.83; 95% CI, -8.29 to -3.37), Timed Up and Go test (MD = -2.22; 95% CI -3.02 to -1.42), UPDRS ((MD = -7.80; 95% CI -10.98 to -6.42), 6-Minute Walk Test (MD = 68.81; 95% CI, 32.14 to 105.48), and Berg Balance Scale (MD = 4.52; 95% CI, 2.72 to 5.78) scores. However, the heterogeneity of each included study was obvious. Weekly frequency, age, and duration of treatment were all factors that potentially influenced the effect. CONCLUSIONS: This meta-analysis suggests that community-based exercise may benefit motor function in patients with PD. The most commonly used modalities of exercise were tango and tai chi, and the most common prescription was 60 min twice a week. Future studies should consider the influence of age, duration of treatment, and weekly frequency on the effect of exercise. PROSPERO TRIAL REGISTRATION NUMBER: CRD42022327162.

Genetic polymorphisms in metabolic enzymes and transporters have no impact on mycophenolic acid pharmacokinetics in adult kidney transplant patients co-treated with tacrolimus: A population analysis.

WHAT IS KNOWN AND OBJECTIVE: Mycophenolate mofetil, an ester prodrug of mycophenolic acid (MPA), is widely used to prevent graft rejection after kidney transplantation. The pharmacokinetic (PK) of MPA has been extensively studied, which revealed a high degree of variability. An integrated population PK (PopPK) model of MPA and its main metabolite mycophenolic acid glucuronide (MPAG) was developed using the adult patients who underwent kidney transplant and were administered oral mycophenolate mofetil combined with tacrolimus. METHODS: In total, 917 MPA and 740 MPAG concentrations in191 adult patients were analysed via nonlinear mixed-effects modelling. The concentration-time data were adequately described using a chain compartment model, including central and peripheral compartments for MPA and a central compartment for MPAG. Stepwise forward inclusion and backward elimination procedures were used to investigate the effects of genetic polymorphisms, including in UGT1A8, UGT1A9, UGT2B7, ABCB1, ABCC2, ABCG2, SLCO1B1, SLCO1B3, and HNF1α. RESULTS AND DISCUSSION: These genetic polymorphisms in metabolic enzymes and transporters have no obvious impact on the PK of MPA in adult patients who underwent kidney transplant and were co-treated with tacrolimus. The post-transplant time, serum albumin, and creatinine clearance were identified as significant covariates affecting the PK of MPA and MPAG, which should be considered in the clinical use of mycophenolate mofetil. WHAT IS NEW AND CONCLUSION: We established a PopPK model of MPA and MPAG in Chinese adult patients who underwent kidney transplant and were co-treated with tacrolimus. Genetic polymorphisms in metabolic enzymes and transporters showed no obvious impact on MMF PK. A model-informed dosing strategy was proposed by the established model, and MMF dose adjustment should be based on ALB levels and the post-transplantation time.

[Correlations between 6-mercaptopurine treatment-related adverse reactions in children with acute lymphoblastic leukemia and polymorphisms of thiopurine methyltransferase gene].

OBJECTIVE: To explore 6-mercaptopurine (6-MP) treatment-related adverse reactions in children with acute lymphoblastic leukemia (ALL), and to assess the association between the polymorphisms of thiopurine methyltransferase (TPMT) gene and these 6-MP related toxicities. METHODS: Total RNA was extracted from bone marrow samples of 46 children with ALL and was then reversed to cDNA. TPMT(*)1S and (*)3C were screened by denaturing gradient gel electrophoresis (DGGE) combining with DNA sequencing. Drug toxicities were classified according to national cancer institute-common toxicity criteria version 3.0 (NCI CTC 3.0). The relationship between TPMT gene polymorphisms and the adverse reactions of 6-MP treatment was analyzed. RESULTS: During the maintenance treatment period, 22% (10/46) of children discontinued 6-MP treatment because of serious adverse reactions. Two children with TPMT(*)3C genotypes presented severe adverse reactions, including 1 child with homozygotic mutation who had 6-MP dose-related myelosuppression and hepatotoxicity. The main side effects of 6-MP were myelosuppression, hepatotoxicity and gastrointestinal reaction. And there were no significant differences between TPMT(*)1S genotypes and severe myelosuppression or hepatotoxicity caused by 6-MP (P>0.05). CONCLUSIONS: TPMT(*)3C may correlate with severe adverse reactions caused by 6-MP.

Identification of serum exosomal lncRNAs and their potential regulation of characteristic genes of fibroblast-like synoviocytes in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a common autoimmune disease whose pathogenesis is poorly understand. Gaps in laboratory biomarkers cause a lack of clinically available strategies for the early diagnosis and treatment of RA. This study aims to identify serum exosomal lncRNAs as promising biomarkers and to unravel potential mechanisms by which they affect characteristic genes of fibroblast-like synoviocytes (FLSs) to induce RA malignant properties. RNA sequencing datasets of serum exosomes (GSE271161 and PRJNA911001) and FLSs (GSE103578, GSE122616, GSE128813, GSE181614 and GSE83147) were purposively mined. Visualization and functional enrichment of differentially expressed (DE) lncRNAs/protein-coding genes, screening of significant lncRNAs, and construction of competing endogenous RNAs (ceRNAs) and protein-protein interaction (PPI) network were carried out. Quantitative real-time PCR, receiver operating characteristic curve (ROC) and correlation analysis were conducted on the validation cohort. As a result, we screened a total of 131 serum exosomal DElncRNAs and 125 FLSs DEmRNAs, which were predominantly enriched in the proliferative, inflammatory and metabolic pathways. In-depth learning of DElncRNAs expression profiles was performed to identify models with better performance and lncRNAs with higher importance scores using 4 machine learning algorithms (SVM, KNN, RF, Logit), which led to the establishment of ceRNAs network linking serum exosomal lncRNAs and characteristic genes of FLSs. In short, we proposed that 4 RA-representative serum exosomal lncRNAs (DLEU2, FAM13A-AS1, MEG3 and SNHG15) may be applied as valuable indicators for laboratory tests, and their-mediated intercellular communication and ceRNAs network may regulate the characteristic genes of FLSs, thereby generating malignant phenotypes and adaptive synovial microenvironment in RA.

Efficacy and safety of transcranial direct current stimulation in the treatment of fibromyalgia: A systematic review and meta-analysis.

OBJECTIVES: To update a systematic review of the efficacy and safety of transcranial direct current stimulation (tDCS) for analgesia, for antidepressant effects, and to reduce the impact of fibromyalgia (FM), looking for optimal areas of stimulation. METHODS: We searched five databases to identify randomized controlled trials comparing active and sham tDCS for FM. The primary outcome was pain intensity, and secondary outcome measures included FM Impact Questionnaire (FIQ) and depression score. Meta-analysis was conducted using standardized mean difference (SMD). Subgroup analysis was performed to determine the effects of different regional stimulation, over the primary motor cortex (M1), dorsolateral prefrontal cortex (DLPFC), opercular-insular cortex (OIC), and occipital nerve (ON) regions. We analyzed the minimal clinically important difference (MCID) by the value of the mean difference (MD) for an 11-point scale for pain, the Beck Depressive Inventory-II (BDI-II), and the Fibromyalgia Impact Questionnaire (FIQ) score. We described the certainty of the evidence (COE) using the tool GRADE profile. RESULTS: Twenty studies were included in the analysis. Active tDCS had a positive effect on pain (SMD= -1.04; 95 % CI -1.38 to -0.69), depression (SMD= -0.46; 95 % CI -0.64 to -0.29), FIQ (SMD= -0.73; 95 % CI -1.09 to -0.36), COE is moderate. Only group M1 (SD=-1.57) and DLPFC (SD=-1.44) could achieve MCID for analgesia; For BDI-II, only group DLPFC (SD=-5.36) could achieve an MCID change. Adverse events were mild. CONCLUSION: tDCS is a safe intervention that relieves pain intensity, reduces depression, and reduces the impact of FM on life. Achieving an MCID is related to the stimulation site and the target symptom.

[Association of single nucleotide polymorphism of methylenetetrahydrofolate reductase gene with susceptibility to acute leukemia].

OBJECTIVE: To assess whether polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene is associated with susceptibility to acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) in Chinese Han children. METHODS: The study has included 87 patients with ALL, 22 patients with AML and 120 healthy controls. All subjects were analyzed with reverse transcriptase-polymerase chain reaction-denaturing gradient gel electrophoresis and sequencing. RESULTS: A 677CT genotype of the MTHFR gene was associated with decreased risk of ALL (OR=0.23, 95%CI: 0.07-0.79). However, MTHFR A1298C genotypes were not associated with the risk of either disease. 677TT/1298AA and 677CC/1298AC genotypes were associated with increased risk of ALL(OR=3.78, 95% CI: 1.38-10.40; OR=3.17, 95% CI: 1.18-8.53, respectively), whereas the genotype 677CT/1298AA was associated with susceptibility to AML (OR=0.23, 95% CI: 0.06-0.97). CONCLUSION: Our data suggested that C677T polymorphism of MTHFR gene may increase the risk of childhood AML.

[Research progress in hypoxanthine-guanine phosphoribosyltrans-ferase].

Hypoxanthine-guanine phosphoribosyltransferase (HPRT) is a cytoplasmic enzyme which is widely distributed in the body. It not only involves in the purine salvage pathway, but also relates to the metabolism of purine analogues drugs. It is a critical transferase regulating the pharmacological effects and toxicity of purine analogues drugs. The mutations of the gene for HPRT, which influence its activity, may cause metabolic diseases with different clinical symptoms, and influence the metabolism of purine analogues. The HPRT gene, also a housekeeping gene, can serve diagnostic markers for many disorders. This paper reviews the recent progresses on HPRT researches in promoting the individual treatment of analogues drugs and the development of new drugs and improving the diagnosis and therapy of inherited metabolic disease caused by HPRT mutations.

[Relationship between the methylenetetrahydrofolate reductase gene polymorphism and adverse reactions of high-dose methotrexate in children with acute lymphocytic leukemia].

OBJECTIVE: To study the association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and toxicities after high-dose methotrexate (HD-MTX) infusion in children with acute lymphocytic leukemia (ALL). METHODS: MTHFR variants in 52 children with ALL were determined by reverse transcriptase-polymerase chain reaction-denaturing gradient gel electrophoresis and sequencing. Toxicities of children who received HD-MTX chemotherapy were evaluated according to the National Cancer Institute-Common Toxicity Criteria (NCI-CTC). RESULTS: The children carrying MTHFR 1298AC had a higher risk of developing thrombocytopenia compared with the carriers of the 1298 AA genotype (OR=13.7, 95%CI=1.18-159.36, P=0.036). There was no significant difference in HD-MTX chemotherapy-related adverse effects between the patients with different MTHFR C677T or G1793A genotypes. CONCLUSIONS: MTHFR A1298C polymorohism may associate with the toxicity of HD-MTX chemotherapy in children with ALL.

The effectiveness and safety of botulinum toxin injections for the treatment of sialorrhea with Parkinson's disease: a systematic review and meta-analysis.

BACKGROUND: Botulinum toxin (BoNT) injection is an important adjunctive method to treat sialorrhea. The purpose of this systematic review was to analyze the effect and safety of BoNT injections in the intervention of sialorrhea with Parkinson's disease (PD). METHODS: We searched PubMed, Web Of Science (WOS), Scopus, Cochrane CENTRAL, and Embase from inception until April 2022. Randomized controlled trials or randomized crossover trials comparing BoNT with placebo in sialorrhea with PD were eligible. PRISMA guidelines were used to carry out the meta-analysis. The Drooling Severity Frequency Scale (DSFS) score and the number of adverse events (AEs) were the primary and secondary outcomes, respectively. Standardized mean differences (SMDs) and risk differences (RDs) are used to express continuous and categorical outcomes, respectively. Heterogeneity among these studies was evaluated using I2 tests. We used the GRADE tool to assess the certainty of evidence (COE). RESULTS: Eight articles involving 259 patients compared BoNT injections with a placebo for PD with sialorrhea. This meta-analysis showed a significant reduction in DSFS scores between BoNT injections and placebo (SMD=-0.98; 95% CI, -1.27 to 0.70, p<0.001; COE: high). This meta-analysis showed a significant difference in AEs between BoNT injections and placebo (RD=0.15; 95% CI, 0.05 to 0.24, p=0.002; COE: low). CONCLUSIONS: The pooled results suggest that BoNT injections have some effect on DSFS scores with sialorrhea caused by PD. There are also mild adverse events, which generally recover within a week or so. The results indicate that BoNT injection is one of the treatments for sialorrhea caused by PD, but we need to pay attention to adverse events. In addition, the follow-up time was extended to observe oral hygiene, ulceration or dental caries, and digestive function. TRIAL REGISTRATION: Our review protocol was registered on PROSPERO (42021288334).

Corrigendum: Hydroxychloroquine attenuates autoimmune hepatitis by suppressing the interaction of GRK2 with PI3K in T lymphocytes.

[This corrects the article DOI: 10.3389/fphar.2022.972397.].

[Analysis of a 452C/T single nucleotide polymorphism in γ-glutamyl hydrolase gene in children with acute leukemia].

OBJECTIVE: To investigate the distribution of γ-glutamyl hydrolase gene (GGH) 452C/T genotype and allele frequency in children with acute leukemia (AL) and healthy children. METHODS: Bone marrow samples from 92 children with AL and peripheral blood samples from 124 healthy children were obtained to prepare complementary DNAs (cDNAs). The cDNAs were analyzed for a GGH 452C/T polymorphism by reverse transcriptase-polymerase chain reaction-denaturing gradient gel electrophoresis (RT-PCR-DGGE) and direct sequencing. RESULTS: The frequencies of the AL patients with TT, CT and CC genotypes were 2.2%, 13.0% and 84.8%, and the frequencies of the control children were 1.6%, 16.9% and 81.5%, respectively. There was no significant difference in GGH genotype or T allele frequency between the two groups (P> 0.05). However, the T allele frequency in Han Chinese children was significantly different from those reported in Japanese, Mexican and African-American populations. CONCLUSION: The frequency of 452C/T polymorphism of GGH gene in Han Chinese children has been determined. The results suggested that an ethnic difference may exist.

[Magnetic resonance spectroscopy-guided stereotactic biopsy for brain lesion].

OBJECTIVE: To study the clinical value of magnetic resonance spectroscopy (MRS) image in stereotactic biopsy for brain lesion. METHODS: From April 2008 to April 2010, 126 cases (72 male and 54 female, aged from 10 to 82 years, mean 45 years) of brain lesion which were difficult to diagnose were divided into two groups by random number table, 62 cases were executed for MRI-guided frameless stereotactic biopsy (MRI group), 64 cases were executed for MRI and MRS-guided frameless stereotactic biopsy (MRS group). Operation used MRI and Three-dimensional MRS image to locate, and used frameless CAS-R-2 robots to carry out the positioning operating. RESULTS: No surgery-related deaths and infections. Pathological diagnosis was 106 cases of brain tumors, 6 cases of inflammatory disease, 4 cases of tumor-like demyelinating disease and multiple sclerosis, 3 cases of neurodegenerative disease, 7 cases failed to obtain positive pathological diagnosis. The total rate of positive diagnosis was 94.4%, the positive rate in MRS-guided stereotactic biopsy group was 98.4% (63/64), the positive rate of conventional MRI-guided biopsy group was 90.3% (56/62), and there was statistically significant difference between the two groups (χ(2) = 3.92, P = 0.047). Four cases presented with postoperative complications, the complication rate was 3.2% (4/126); the complications were cerebral hemorrhage associated with aphasia, epilepsy, subcutaneous hematoma, gastrointestinal bleeding, which were improved after treatment. CONCLUSIONS: MRS-guided stereotactic biopsy group has a higher positive rate than MRI-guided stereotactic biopsy group, indicating that this method can improve the positive rate of diagnosis, and thus will help to formulate treatment plan for brain lesion.

[A novel missense mutation of folypolyglutamate synthetase gene].

OBJECTIVE: To examine allelic frequencies of coding single nucleotide polymorphisms (cSNPs) of folypolyglutamate synthetase (FPGS) gene in Chinese Han children with acute leukemia (AL), in order to provide a basis for detecting the relationship between FPGS genetic polymorphisms and tumor individualized chemotherapy. METHODS: cSNPs of exon 5 were detected with polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (DGGE) in 91 children with AL and 124 children with upper respiratory infection as controls. Genotypes and allelic frequencies were examined. RESULTS: A novel missense mutation, 502/490 T>C (L151/101P), was found in exon 5 of FPGS from control children. The novel mutation was found in mitochondrial variants in two cases and cytosolic variants in three cases. The cytosolic and mitochondrial variants displayed allelic frequencies of 0.70 % and 0.47 % respectively. The novel mutation was not associated with susceptibility to AL. CONCLUSIONS: A novel missense mutation 502/490 T>C (L151/101P) in exon 5 of FPGS gene is firstly found in Chinese Han children, and the cytosolic and mitochondrial variants display allelic frequencies of 0.70 % and 0.47 % respectively.

[ALK gene mutations in childhood neuroblastoma].

OBJECTIVE: To investigate mutations of anaplastic lymphoma kinase (ALK) in Chinese children with neuroblastoma (NB). METHODS: Genomic DNA was extracted from 22 cases of paraffin-embedding NB tumor tissues. Gene mutations in the exons 20-26 which were mutational hotspots of ALK were analyzed by PCR-DNA direct sequencing. RESULTS: A novel synonymous mutation C3586T (Leu1196Leu) and a known synonymous mutation C3375A (Gly1125Gly) were found and located at exon 23 and exon 21 of ALK respectively. There were 10 cases (46%) of known synonymous mutation C3375A in 22 cases of NB. The C3375A allelic frequency was 27%. No statistically significant correlation was found between mutation C3375A and clinical parameters of NB such as age, sex, metastasis and tumor differentiation. Mutation was not found in the other 5 exons. CONCLUSIONS: A novel ALK gene synonymous mutation C3586T was identified using PCR-DNA sequencing. A known mutation C3375A in ALK was successfully identified in children, and its incidence is not influenced by the clinical features of childhood NB.

Hydroxychloroquine attenuates autoimmune hepatitis by suppressing the interaction of GRK2 with PI3K in T lymphocytes.

Hydroxychloroquine (HCQ) is derivative of the heterocyclic aromatic compound quinoline, which has been used for the treatment of autoimmune diseases. The central purpose of this study was to investigate therapeutic effects and inflammatory immunological molecular mechanism of HCQ in experimental autoimmune hepatitis (AIH). Treatment with HCQ ameliorated hepatic pathologic damage, inflammatory infiltration, while promoted regulatory T cell (Treg) and down-regulated CD8+T cell differentiation in AIH mice induced by S-100 antigen. In vitro, HCQ also suppressed pro-inflammatory cytokine (IFN-γ, TNF-α, and IL-12) secretion, promoted anti-inflammatory cytokine (TGF-ß1) secretion. HCQ mainly impaired T cell lipid metabolism but not glycolysis to promote Treg differentiation and function. Mechanistically, HCQ down-regulated GRK2 membrane translocation in T cells, inhibited GRK2-PI3K interaction to reduce the PI3K recruiting to the membrane, followed by suppressing the phosphorylation of PI3K-AKT-mTOR signal. Pretreating T cells with paroxetine, a GRK2 inhibitor, disturbed HCQ effect to T cells. HCQ also reversed the activation of the PI3K-AKT axis by 740 Y-P (PI3K agonist). Meanwhile, HCQ inhibited the PI3K-AKT-mTOR, JAK2-STAT3-SOCS3 and increased the AMPK signals in the liver and T cells of AIH mice. In conclusion, HCQ exhibited specific and potent therapeutic effects on AIH and attendant liver injury, which was attributed to HCQ acted on GRK2 translocation, inhibited metabolism-related PI3K-AKT and inflammation-related JAK2-STAT3 signal in T lymphocytes, thereby modulating lipid metabolism of T cell function to regulate Treg differentiation and function.

A review on epileptic foci localization using resting-state functional magnetic resonance imaging.

Epilepsy is a brain syndrome caused by synchronous abnormal discharge of brain neurons. As an effective treatment for epilepsy, successful surgical resection requires accurate localization of epileptic foci to avoid iatrogenic disability. Previous studies have demonstrated the potential of restingstate functional magnetic resonance imaging (rs-fMRI) technique to localize epileptic foci though clinical applications of rs-fMRI are still at an early stage of development. fMRI data analysis approaches seek pre-defined regressors modeling contributions to the voxel time series, including the BOLD response following neuronal activation. In present study, localization strategies of epileptic foci in rs-fMRI technology were classified and summarized. To begin with, data-driven approaches attempting to determine the intrinsic structure of the data were discussed in detail. Then, as novel fMRI data analysis methods, deconvolution algorithms such as total activation (TA) and blind deconvolution were discussed, which were applied to explore the underlying activity-inducing signal of the BOLD signal. Lastly, effective connectivity approaches such as autocorrelation function method and Pearson correlation coefficient have also been proposed to identify the brain regions driving the generation of seizures within the epileptic network. In the future, fMRI technology can be used as a supplement of intraoperative subdural electrode method or combined with traditional epileptic focus localization technologies, which is one of the most attractive aspect in clinic. It may also play an important role in providing diagnostic information for epilepsy patients.

Altering Transplantation Time to Avoid Periods of High Temperature Can Efficiently Reduce Bacterial Wilt Disease Incidence with Tomato.

Tomato bacterial wilt caused by Ralstonia solanacearum bacterium is a severe problem in Southern China, where relatively high environmental temperatures commonly prevails during the crop seasons. Previous research has indicated that bacterial wilt disease incidence generally increases during the warm months of summer leading to reduced tomato yield. Moreover, the efficacy of bio-organic fertilizers (BOFs)-organic compost fortified with pathogen-suppressive bacteria-is often lost during the periods of high environmental temperatures. Here we studied if the disease incidence could be reduced and the BOF performance enhanced by simply preponing and postponing the traditional seedling transplantation times to avoid tomato plant development during periods of high environmental temperature. To this end, a continuous, two-year field experiment was conducted to evaluate the performance of BOF in two traditional (late-spring [LS] and early-autumn [EA]) and two alternative (early-spring [ES] and late-autumn [LA]) crop seasons. We found that changing the transplantation times reduced the mean disease incidence from 33.9% (LS) and 54.7% (EA) to 11.1% (ES) and 7.1% (LA), respectively. Reduction in disease incidence correlated with the reduction in R. Solanacearum pathogen density in the tomato plant rhizosphere and stem base. Applying BOF during alternative transplantation treatments improved biocontrol efficiency from 43.4% (LS) and 3.1% (EA) to 67.4% (ES) and 64.8% (LA). On average, the mean maximum air temperatures were positively correlated with the disease incidence, and negatively correlated with the BOF biocontrol efficacy over the crop seasons. Crucially, even though preponing the transplantation time reduced the tomato yield in general, it was still economically more profitable compared to LS season due to reduced crop losses and relatively higher market prices. Preponing and postponing traditional tomato transplantation times to cooler periods could thus offer simple but effective way to control R. solanacearum disease outbreaks.

Regulatory role of tetR gene in a novel gene cluster of Acidovorax avenae subsp. avenae RS-1 under oxidative stress.

Acidovorax avenae subsp. avenae is the causal agent of bacterial brown stripe disease in rice. In this study, we characterized a novel horizontal transfer of a gene cluster, including tetR, on the chromosome of A. avenae subsp. avenae RS-1 by genome-wide analysis. TetR acted as a repressor in this gene cluster and the oxidative stress resistance was enhanced in tetR-deletion mutant strain. Electrophoretic mobility shift assay demonstrated that TetR regulator bound directly to the promoter of this gene cluster. Consistently, the results of quantitative real-time PCR also showed alterations in expression of associated genes. Moreover, the proteins affected by TetR under oxidative stress were revealed by comparing proteomic profiles of wild-type and mutant strains via 1D SDS-PAGE and LC-MS/MS analyses. Taken together, our results demonstrated that tetR gene in this novel gene cluster contributed to cell survival under oxidative stress, and TetR protein played an important regulatory role in growth kinetics, biofilm-forming capability, superoxide dismutase and catalase activity, and oxide detoxicating ability.