Dexamethasone promotes renal fibrosis by upregulating ILT4 expression in myeloid-derived suppressor cells.

Studies have shown that adoptive transfer of myeloid-derived suppressor cells (MDSCs) can alleviate various inflammatory diseases, including glomerulonephritis, but the long-term effects of the transferred MDSCs are still unclear. In addition, although glucocorticoids exert immunosuppressive effects on inflammatory diseases by inducing the expansion of MDSCs, the impact of glucocorticoids on the immunosuppressive function of MDSCs and their molecular mechanisms are unclear. In this study, we found that adoptive transfer of MDSCs to doxorubicin-induced focal segmental glomerulosclerosis (FSGS) mice for eight consecutive weeks led to an increase in serum creatinine and proteinuria and aggravation of renal interstitial fibrosis. Similarly, 8 weeks of high-dose dexamethasone administration exacerbated renal interstitial injury and interstitial fibrosis in doxorubicin-induced mice, manifested as an increase in serum creatinine and proteinuria, collagen deposition and α-SMA expression. On this basis, we found that dexamethasone could enhance MDSC expression and secretion of the fibrosis-related cytokines TGF-ß and IL-10. Mechanistically, we revealed that dexamethasone promotes the expression of immunoglobulin-like transcription factor 4 (ILT4), which enhances the T-cell inhibitory function of MDSCs and promotes the activation of STAT6, thereby strengthening the expression and secretion of TGF-ß and IL-10. Knocking down ILT4 alleviated renal fibrosis caused by adoptive transfer of MDSCs. Therefore, our findings demonstrate that the role and mechanism of dexamethasone mediate the expression and secretion of TGF-ß and IL-10 in MDSCs by promoting the expression of ILT4, thereby leading to renal fibrosis.

Effects of one-week bilateral cerebellar iTBS on resting-state functional brain network and multi-task attentional performance in healthy individuals: A randomized, sham-controlled trial.

BACKGROUND: Cerebellar intermittent theta burst stimulation (iTBS) modulates the excitability of the cerebral cortex and may enhance attentional performance. To date, few studies have conducted iTBS on healthy subjects for one week and used electroencephalography (EEG) to investigate the effect of multiple stimulation sessions on resting-state functional brain networks and the daily stimulation effect on attentional performance. METHODS: 16 healthy subjects participated in a one-week experiment, receiving bilateral cerebellar iTBS or sham stimulation and engaging in multi-task attentional training. The primary measures were the one-week attentional performance and pre- and post-experiment resting-state EEG activities. Amplitude Envelope Correlation (AEC) was used to construct the functional connectivity in the eye-open (EO) and eye-closed (EC) phases. RESULTS: At least three sessions of iTBS were required to enhance multi-task performance significantly, whereas only one or two sessions failed to elicit the improvement. Compared with the control group, iTBS induced significant changes in PSD, AEC functional connectivity, and AEC network properties during the EO phase, while it had little effect during the EC phase. During the EO phase, the network property changes of the iTBS subject were correlated with improved attentional performance. CONCLUSION: The multi-task performance requires multiple stimulations to enhance. iTBS affects the resting-state alpha band brain activities during the EO rather than the EC phase. The AEC network properties may serve as a biomarker to assess the attentional potential of healthy subjects.

Soybean-mediated suppression of BjaI/BjaR1 quorum sensing in Bradyrhizobium diazoefficiens impacts symbiotic nitrogen fixation.

The acyl-homoserine lactones (AHLs)-mediated LuxI/LuxR quorum sensing (QS) system orchestrates diverse bacterial behaviors in response to changes in population density. The role of the BjaI/BjaR1 QS system in Bradyrhizobium diazoefficiens USDA 110, which shares homology with LuxI/LuxR, remains elusive during symbiotic interaction with soybean. Here this genetic system in wild-type (WT) bacteria residing inside nodules exhibited significantly reduced activity compared to free-living cells, potentially attributed to soybean-mediated suppression. The deletion mutant strain ΔbjaR1 showed significantly enhanced nodulation induction and nitrogen fixation ability. Nevertheless, its ultimate symbiotic outcome (plant dry weight) in soybeans was compromised. Furthermore, comparative analysis of the transcriptome, proteome, and promoter activity revealed that the inactivation of BjaR1 systematically activated and inhibited genomic modules associated with nodulation and nitrogen metabolism. The former appeared to be linked to a significant decrease in the expression of NodD2, a key cell-density-dependent repressor of nodulation genes, while the latter conferred bacterial growth and nitrogen fixation insensitivity to environmental nitrogen. In addition, BjaR1 exerted a positive influence on the transcription of multiple genes involved in a so-called central intermediate metabolism within the nodule. In conclusion, our findings highlight the crucial role of the BjaI/BjaR1 QS circuit in positively regulating bacterial nitrogen metabolism and emphasize the significance of the soybean-mediated suppression of this genetic system for promoting efficient symbiotic nitrogen fixation by B. diazoefficiens.IMPORTANCEThe present study demonstrates, for the first time, that the BjaI/BjaR1 QS system of Bradyrhizobium diazoefficiens has a significant impact on its nodulation and nitrogen fixation capability in soybean by positively regulating NodD2 expression and bacterial nitrogen metabolism. Moreover, it provides novel insights into the importance of suppressing the activity of this QS circuit by the soybean host plant in establishing an efficient mutual relationship between the two symbiotic partners. This research expands our understanding of legumes' role in modulating symbiotic nitrogen fixation through rhizobial QS-mediated metabolic functioning, thereby deepening our comprehension of symbiotic coevolution theory. In addition, these findings may hold great promise for developing quorum quenching technology in agriculture.

Expression of plasma IFN signaling-related miRNAs during acute SARS-CoV-2 infection and its association with RBD-IgG antibody response.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a huge challenge worldwide. Although previous studies have suggested that type I interferon (IFN-I) could inhibit the virus replication, the expression characteristics of IFN-I signaling-related miRNAs (ISR-miRNAs) during acute severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and its relationship with receptor-binding domain (RBD) IgG antibody response at the recovery phase remain unclear. METHODS: Expression profiles of 12 plasma ISR-miRNAs in COVID-19 patients and healthy controls were analyzed using RT-qPCR. The level of RBD-IgG antibody was determined using the competitive ELISA. Spearman correlation was done to measure the associations of plasma ISR-miRNAs with clinical characteristics during acute SARS-CoV-2 infection and RBD-IgG antibody response at the recovery phase. RESULTS: Compared with the healthy controls, COVID-19 patients exhibited higher levels of miR-29b-3p (Z = 3.15, P = 0.002) and miR-1246 (Z = 4.98, P < 0.001). However, the expression of miR-186-5p and miR-15a-5p were significantly decreased. As the results shown, miR-30b-5p was negatively correlated with CD4 + T cell counts (r = - 0.41, P = 0.027) and marginally positively correlated with fasting plasma glucose in COVID-19 patients (r = 0.37, P = 0.052). The competitive ELISA analysis showed the plasma level of miR-497-5p at the acute phase was positively correlated with RBD-IgG antibody response (r = 0.48, P = 0.038). CONCLUSIONS: Our present results suggested that the expression level of ISR-miRNAs was not only associated with acute SARS-CoV-2 infection but also with RBD-IgG antibody response at the recovery phase of COVID-19. Future studies should be performed to explore the biological significance of ISR-miRNAs in SARS-CoV-2 infection.

Influence of diabetes mellitus on the severity and fatality of SARS-CoV-2 (COVID-19) infection.

AIM: To evaluate the influence of diabetes on the severity and fatality of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. MATERIALS AND METHODS: The medical records of 66 hospitalized coronavirus disease 2019 (COVID-19) patients were collected and classified into non-severe (mild/moderate cases) and severe (severe/critical cases) groups. Logistic regression analysis was used to estimate the risk of severe COVID-19 (severe/critical infection). In addition, a meta-analysis including published studies reported the impact of diabetes on the severity and fatality of COVID-19. The current study was conducted using fixed effects models. RESULTS: There were 22 diabetes and 44 non-diabetes cases among the 66 hospitalized COVID-19 patients. Seven patients with diabetes (31.82%) were diagnosed as severe COVID-19 cases, which was significantly higher than that in the non-diabetes group (4/44, 9.09%, P = .033). After adjustment for age and gender, diabetes was significantly associated with COVID-19 severity (OR: 5.29, 95% CI: 1.07-26.02). A meta-analysis further confirmed the positive association between diabetes and COVID-19 severity (pooled OR = 2.58, 95% CI: 1.93-3.45). Moreover, the patients with diabetes infected with SARS-CoV-2 had a 2.95-fold higher risk of fatality compared with those patients without diabetes (95% CI: 1.93-4.53). CONCLUSIONS: Our findings provide new evidence that diabetes is associated with a higher risk of severity and fatality of COVID-19. Therefore, intensive monitoring and antidiabetic therapy should be considered in patients with diabetes with SARS-CoV-2 infection.

Evaluation of candidate genes associated with hepatitis A and E virus infection in Chinese Han population.

BACKGROUND: Recent GWAS-associated studies reported that single nucleotide polymorphisms (SNPs) in ABCB1, TGFß1, XRCC1 genes were associated with hepatitis A virus (HAV) infection, and variants of APOA4 and APOE genes were associated with and hepatitis E virus (HEV) infection in US population. However, the associations of these loci with HAV or HEV infection in Chinese Han population remain unclear. METHODS: A total of 3082 Chinese Han persons were included in this study. Anti-HAV IgG and anti-HEV IgG were detected by enzyme-linked immunosorbent assay (ELISA). Genotypes in ABCB1, TGFß1, XRCC1, APOA4 and APOE SNPs were determined by TaqMan MGB technology. RESULTS: In Chinese Han population, rs1045642 C to T variation in ABCB1 was significantly associated with the decreased risk of HAV infection (P < 0.05). However, the effect direction was different with the previous US study. Rs1001581 A to G variation in XRCC1, which was not identified in US population, was significantly associated with the protection against HAV infection in our samples (P < 0.05). In addition, our results suggested that rs7412 C to T variation in APOE was significantly associated with lower risk of HEV infection in males (adjusted OR < 1.0, P < 0.05) but not in females. CONCLUSIONS: ABCB1 and XRCC1 genes variants are significantly associated with the protection against HAV infection. Additionally, Chinese Han males with rs7412 C to T variation in APOE gene are less prone to be infected by HEV.

Risk of reduced platelet counts in patients with nonalcoholic fatty liver disease (NAFLD): a prospective cohort study.

BACKGROUND: The production of peripheral platelet is mainly regulated by thrombopoietin, which is a glycoprotein hormone predominantly synthesized in the liver. Previously, many studies have reported that there was an inverse correlation between the degree of chronic viral hepatitis and the peripheral platelet count. However, the effect of nonalcoholic fatty liver disease (NAFLD) on the peripheral platelet counts remains unclear. METHODS: With 1303 participants from "The prevention of MS and multi-metabolic disorders in Jiangsu province of China (PMMJS)" cohort study, we investigated the associations between NAFLD and the risk of platelet counts reduction in Chinese adults. The paired-samples T test was used to explore the platelet counts changes between baseline and follow-up. Multivariate logistic regression was used to examine the association between presence of NAFLD and the risk of platelet reduction by calculating the odds ratios (ORs) and 95% confidence interval (CI). RESULTS: After five years of follow-up, platelet counts were markedly reduced from 220.6 ± 42.22 (109/L) at baseline to 208.41 ± 40.70 (109/L) at follow-up in NAFLD group (P < 0.0001). However, platelet counts were slightly lowered from 213.2 ± 43.26(109/L) at baseline to 211.8 ± 41.65 (109/L) at follow-up in non-NAFLD people (P = 0.2349). Meanwhile, there was a significant association between NAFLD and the risks of platelet count reduction, even after adjustment for confounding variables (OR: 1.68, 95% CI: 1.06-2.67). Additionally, among the participants with BMI ≤ 23 kg/m2 and SUA ≤ 344.3 µmol/L, the NAFLD participants have an increased risk of platelet count reduction compared to the persons in non-NAFLD group. CONCLUSIONS: Our present results suggested that NAFLD individuals have an increased risk of platelet counts reduction.

[Efficacy and safety of telbivudine treatment to block mother-to-child transmission of hepatitis B virus: a meta-analysis].

OBJECTIVE: To evaluate the efficacy and safety of telbivudine treatment in pregnant patients with chronic hepatitis B to block mother-to-child transmission of hepatitis B virus (HBV). METHODS: Medline and the Chinese Biomedical Literature Database were searched for studies of HBV, mother-to-child transmission, and telbivudine. Of the 68 potentially relevant publications, eight randomized controlled trials (RCTs) conformed to the inclusion and exclusion criteria. Following data extraction, a meta-analysis was carried out with RevMan5.1 software. RESULTS: Seven of the eight RCTs were in Chinese, and the remaining study was in English but carried out at a Chinese site. The RCTs comprised a total of 678 subjects, including 352 cases and 326 controls. Infants born to telbivudine-treated mothers had a significantly lower rate of HBsAg positivity and HBV DNA positivity at birth than the control group of infants (odds ratio (OR) = 0.27, 95% confidence interval (CI): 0.17, 0.43, P less than 0.00001; OR = 0.14, 95% CI: 0.06, 0.32, P less than 0.00001). Infants born to telbivudine-treated mothers also had significantly lower rates of mother-to-child transmitted HBV at 6 months (OR = 0.06, 95% CI: 0.02, 0.22, P less than 0.00001; OR = 0.05, 95% CI: 0.01, 0.25, P = 0.0003) and 12 months (OR = 0.13, 95% CI: 0.03, 0.56, P = 0.007; OR = 0.08, 95% CI: 0.02, 0.37, P = 0.001) after birth. The pre-telbivudine treatment levels of HBV DNA were not significantly different between pregnant women in the telbivudine-treated group and the control group (OR = 0.12, 95% CI: 0.00, 0.24, P = 0.04), but the HBV DNA levels were significantly lower in the telbivudine-treated group of pregnant women prior to delivery (OR = -3.92, 95% CI: -4.90, -2.95, P less than 0.00001). There was no evidence of telbivudine treatment being associated with more adverse side effects or complications during pregnancy or in the infant (OR = 1.72, 95% CI: 0.68, 4.38, P = 0.25; OR=0.69, 95% CI: 0.04, 11.24, P = 0.80). CONCLUSION: Telbivudine treatment effectively and safely prevents mother-to-child transmission of HBV from chronically infected mothers with a high degree of infectivity late in pregnancy.

Sequential and Dynamic Variations of IL-6, CD18, ICAM, TNF-α, and Microstructure in the Early Stage of Diabetic Retinopathy.

OBJECTIVE: The purpose of this project is to make sequential and indepth observation of the variations of retinal microvascular, microstructure, and inflammatory mediators at the early stage of diabetic retinopathy (DR) in streptozotocin-induced diabetes mellitus (DM) rats. METHODS: DM was induced by a single intraperitoneal injection of 60 mg/kg body weight streptozotocin (STZ). The fluorescein fundus angiography, hematoxylin and eosin staining, periodic acid-Schiff staining, fluorescence imaging techniques, quantitative real-time PCR, and vascular endothelial growth factor- (VEGF-) A ELISA were performed on the 8th day, at the 4th week, 6th week, 8th week, and 10th week after DM induction, respectively. RESULTS: In this study, we observed not only the decrease of retinal ganglion cells (RGCs) and the increase of endotheliocytes to pericytes (E/P) ratio, acellular capillaries, and type IV collagen-positive strands began to occur on the 8th day after induction but the vascular permeability and new vessel buds began to appear in the diabetes group at the 8th week, while the expression of VEGF-A, VEGF mRNA, IL-6 mRNA, ICAM mRNA, and TNF-α mRNA were significantly higher in the diabetes group compared with the normal group(P < 0.01) on the 8th day after induction and maintained a high expression level throughout the 10-week observation period. However, the expression of CD18 mRNA began to increase significantly at the 4th week after induction and reached a peak at the 6th week. CONCLUSION: Our study indicated the abnormal alterations of microvessels, microstructure, and inflammatory mediators at the early stage of DR, which confirms and supplements the previous research, and also promotes an indepth understanding and exploration of the pathophysiology and underlying pathogenesis of DR.

Radical modulated regioselective difunctionalization of vinyl enynes: tunable access to naphthalen-1(2H)-ones and allenic alcohols.

A novel and efficient radical-modulated difunctionalization of vinyl enynes has been disclosed using TEMPO as a radical regulator. Facile access to structurally diverse 3-bromo-naphthalen-1(2H)-ones and 4-bromo-allenic alcohols was realized via 1,2-addition/1,2-migration or 1,4-addition, respectively. This protocol represents the first example of radical-modulated metal-free difunctionalization of 1,3-enynes with high regioselectivity.

Characterization of complete chloroplast genome of Malus sylvestris L.

The European wild apple (Malus sylvestris L.) is an important economical fruit crop. In this present study, we characterized the complete chloroplast (cp) genome sequence of Malus sylvestris L. The complete cp genome is 159,926 bp in length with a typical quadripartite structure, containing a large single-copy region (88,064 bp), a small single-copy region (26,353 bp) and a pair of inverted repeat regions (19,157 bp each). A total of 110 unique genes were found in the newly sequenced genome, including 78 protein-coding genes, 28 tRNA genes, and 4 rRNA genes. Of these, 6 protein-coding genes, 7 tRNA genes, and all 4 rRNA genes are duplicated in the inverted regions. A phylogenetic tree was reconstructed using the neighbor-joining method based on the full length of cp genomes within genus Malus. The result showed that M. sylvestris L. was clustered together with the cultivated apple. The complete cp genome could provide valuable information for understanding the phylogenetic relationships within the genus Malus.

The complete chloroplast genome sequence of Chimonanthus praecox cv. concolor.

Calycanthaceae is a perennial shrub endemic to China with important ornamental and medicinal values. In this study, Chimonanthus praecox cv. concolor chloroplast (cp) genome was characterized using Illumina paired-end reads data. In total, whole cp genome is 153,254 bp long and contains a small single-copy region of 19,769 bp, a pair of repeat (IRa and IRb) regions of 23,286 bp each, and a large single-copy region of 86,913 bp. This genome contains 129 genes, including 84 protein-genes, 8 rRNA genes, and 37 tRNA genes. Phylogenetic analysis based on 19 cp genomes showed that C. praecox cv. concolor is closely related to Chimonanthus praecox and Chimonanthus nitens.

Associations between fatty liver index and asymptomatic intracranial vertebrobasilar stenosis in Chinese population.

Metabolic diseases such as type 2 diabetes mellitus (T2DM) and metabolic syndromes (MetS) have been recognized as the important risk factors for asymptomatic intracranial vertebrobasilar stenosis (IVBS). Although fatty liver index (FLI) is significantly related with these diseases, the association between FLI and IVBS remains unclear. In the present study, 2368 participants (30-75 years) were recruited from a Chinese prospective cohort study of PMMJS. Amongst them, 2281 individuals who did not have IVBS at baseline were enrolled in the 6-year following-up study. In cross-sectional analysis based on the baseline characteristics, the results showed that FLI was positively related with IVBS prevalence. Compared to the participants with FLI < 30, the adjusted OR (95% CI) of IVBS was 2.07 (1.18, 3.62) and 2.85 (1.39, 5.18) in the groups of 30 ≤ FLI < 60 and FLI ≥ 60, respectively. In longitudinal analysis, the results showed that the participants with FLI ≥ 60 had an increased risk of asymptomatic IVBS compared to those with FLI < 30 [adjusted HR (95%CI): 1.65 (1.05, 2.60)]. Moreover, exclusion of persons with hypertension, T2DM and MetS did not alter the associations between FLI and asymptomatic IVBS. Therefore, our results suggest that elevated FLI is an independent risk factor for asymptomatic IVBS in Chinese adults.

Associations between Serum Uric Acid and the Remission of Non-Alcoholic Fatty Liver Disease in Chinese Males.

Epidemiological studies suggest that higher serum uric acid (sUA) level is significantly associated with nonalcoholic fatty liver disease (NAFLD) development. However, little information is available on the relationships between sUA and NAFLD remission. In the present study, 841 NAFLD males (30-75 years) were recruited from a Chinese prospective cohort study (PMMJS) and followed up for five years. The baseline sUA levels of participants were categorized into four quartiles: 191 µmol/L≤ sUA ≤ 347 µmol/L, 347 µmol/L < sUA ≤ 392 µmol/L, 392 µmol/L < sUA ≤ 441 µmol/L and 441 µmol/L

Serological and molecular analysis on the relationships between type 2 diabetes mellitus and hepatitis B virus infection.

INTRODUCTION: This study aimed to further analyze the associations between type 2 diabetes mellitus (T2DM) and hepatitis B virus (HBV) infection, and to investigate the relationships between T2DM and the mutations within the HBV major hydrophilic region (MHR). METHODOLOGY: In this cross-sectional study, 3,377 persons (338 T2DM patients and 3,039 non-diabetics) were randomly selected. HBsAg detection was performed by enzyme-linked immunosorbent assay. The HBV MHR was amplified, sequenced, and analyzed by nested PCR. RESULTS: The seroprevalence of HBsAg was 21.30% in T2DM patients (72/338), which was significantly higher than in non-diabetics (15.53%). Compared to persons without T2DM, the proportion of T2DM patients positive for HBsAg was significantly elevated in males, people > 55 years (p = 0.039), and people with a body mass index (BMI) ≥ 24 kg/m2. Totally, 112 genotype B and 111 genotype C HBV sequences were isolated. No significant difference in HBV genotype distribution was observed between T2DM patients and non-diabetics. Compared to genotype C HBV-infected cases in non-diabetics, the amino acid substitution rates in the MHR were significantly higher in T2DM patients (p = 0.003). Moreover, seven HBV strains with stop codon mutations within the HBV S gene were identified: three from T2DM patients (5.45%) and four from non-diabetics (2.38%). CONCLUSIONS: In China, T2DM is significantly associated with chronic HBV infections and genotype C HBV MHR mutations. Being males, > 55 years of age, and ≥ 24 kg/m2 of BMI are the risk factors of HBV infection in T2DM patients.

Role of maternal viremia and placental infection in hepatitis B virus intrauterine transmission.

The mechanism of intrauterine hepatitis B virus infection has not been established. In this study, venous blood, cord blood, and placental tissues from 171 chronic hepatitis B virus infected pregnant women were tested for hepatitis B surface antigen, hepatitis B core antigen, and hepatitis B virus DNA. We found that residence, mode of delivery, age, and number of gestational weeks of pregnant women were not correlated with intrauterine hepatitis B virus infection, while neonates of mothers who were hepatitis B s antigen positive and hepatitis B e antigen positive (P < 0.01) or who had high hepatitis B virus DNA levels (≥10(6) copies/ml) were more likely to get an intrauterine infection (P < 0.01). The hepatitis B virus infection rate in placental cell layers gradiently decreased from the mother's side to the fetus's side of the placenta, but the odds ratio value of correlation between placental hepatitis B virus infection and intrauterine infection gradiently increased. The way of intrauterine hepatitis B virus infection may be through a layer-layer transmission pathway, although the possibility of placental leakage cannot be excluded.