Strong associations between dissolved organic matter and microbial communities in the sediments of Qinghai-Tibetan Plateau lakes depend on salinity.

In aquatic ecosystems, dissolved organic matter (DOM) plays a vital role in microbial communities and the biogeochemical cycling of elements. However, little is known about the associations between DOM and microbial communities in lake sediments. This study investigated the composition of water-extractable organic matter and microbial communities in surface sediments of lakes with different salinities on the Qinghai-Tibet Plateau. Ultrahigh-resolution mass spectrometry and high-throughput microbial sequencing techniques were employed to assess the associations between molecular diversity and microbial diversity and the effects of salinity in 19 lakes spanning a salinity range from 0.22 ‰ to 341.87 ‰. Our results show that increasing salinity of lake water led to higher molecular diversity of DOM in surface sediments. High-salinity lakes exhibited distinct DOM characteristics, such as lower aromaticity, smaller molecular weight, and higher oxidation degree, compared to freshwater lakes. The complexity of the microbial network composition of sediments first increased and then decreased with the increase of salinity. Moreover, as salinity increases, the dominant species transitioned from Gammaproteobacteria to Bacteroidia, and this transition was accompanied by a decrease in microbial diversity and an increase in molecular diversity. Microbial factors accounted for 34.68 % of the variation in the molecular composition of DOM. Overall, this study emphasizes the significant effects of salinity on both molecular and microbial diversity in lake sediments. Furthermore, our findings underscore the importance of microbes in controlling the range of organic compounds present in lakes and deepen our knowledge of the biogeochemical cycling of DOM.

Effects of tumor necrosis factor-alpha inhibitors on lipid profiles in patients with psoriasis: a systematic review and meta-analysis.

Background: There is no consensus on the effect of tumor necrosis factor-alpha (TNF-alpha) inhibitors on lipid profiles in patients with psoriasis. This study aimed to investigate the effects of TNF-alpha inhibitors on lipid profiles (triglycerides, total cholesterol, low-density lipoprotein, or high-density lipoprotein) in patients with psoriasis. Methods: We searched PubMed, Embase, and Cochrane Library databases for articles published before October 17, 2023. Four TNF-alpha inhibitors (infliximab, etanercept, adalimumab, and certolizumab) were included in our study. (PROSPERO ID: CRD42023469703). Results: A total of twenty trials were included. Overall results revealed that TNF-alpha inhibitors elevated high-density lipoprotein levels in patients with psoriasis (WMD = 2.31; 95% CI: 0.96, 3.67; P = 0.001), which was supported by the results of sensitivity analyses excluding the effect of lipid-lowering drugs. Subgroup analyses indicated that high-density lipoprotein levels were significantly increased in the less than or equal to 3 months group (WMD = 2.88; 95% CI: 1.37, 4.4; P < 0.001), the etanercept group (WMD = 3.4; 95% CI = 1.71, 5.09, P < 0.001), and the psoriasis group (WMD = 2.52; 95% CI = 0.57, 4.48, P = 0.011). Triglyceride levels were significantly increased in the 3 to 6-month group (WMD = 4.98; 95% CI = 1.97, 7.99, P = 0.001) and significantly decreased in the 6-month and older group (WMD = -19.84; 95% CI = -23.97, -15.7, P < 0.001). Additionally, Triglyceride levels were significantly increased in the psoriasis group (WMD = 5.22; 95% CI = 2.23, 8.21, P = 0.001). Conclusion: Our results revealed that TNF-alpha inhibitors might temporarily increase high-density lipoprotein levels in patients with psoriasis. However, changes in triglycerides were not consistent among the different durations of treatment, with significant increases after 3 to 6 months of treatment. Future prospective trials with long-term follow-up contribute to confirming and extending our findings. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023469703.

Nocardia colli sp. nov., a new pathogen isolated from a patient with primary cutaneous nocardiosis.

A novel nocardioform strain, CICC 11023T, was isolated from a tissue biopsy of neck lesions of a patient with primary cutaneous nocardiosis and characterized to establish its taxonomic position. The morphological, biochemical, physiological and chemotaxonomic properties of strain CICC 11023T were consistent with classification in the genus Nocardia. Whole-cell hydrolysates were rich in meso-diaminopimelic acid, galactose, arabinose and fructose. Mycolic acids were present. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, one unidentified phospholipid and two unidentified lipids, and the predominant menaquinone was cyclo MK-8 (H4, ω-cyclo). The main fatty acids (>5 %) were C18 : 0 10-methyl (TBSA), C16 : 0, summed feature 4 (C16 : 1 trans 9/C15 : 0 iso 2OH), C15 : 0 and C17 : 0 10-methyl. Phylogenetic analyses based on 16S rRNA gene sequences revealed that the isolate is most closely related (>98 % similarity) to the type strains Nocardia ninae OFN 02.72T, Nocardia iowensis UI 122540T and Nocardia alba YIM 30243T, and phylogenetic analysis of gyrB gene sequences showed similarity (89.1-92.2 %) to Nocardia vulneris NBRC 108936T, Nocardia brasiliensis IFM 0236T and Nocardia exalbida IFM 0803T. DNA-DNA hybridization results for strain CICC 11023T compared to Nocardia type strains ranged from 20.4 to 35.4 %. The genome of strain CICC 11023T was 8.78 Mbp with a G+C content of 67.4 mol% overall. The average nucleotide identity (ANI) values between strain CICC 11023T and N. alba YIM 30243T were low (OrthoANIu=77.47 %), and the ANI values between strain CICC 11023T and N. vulneris NBRC 108936 T were low (OrthoANIu=83.75 %). Consequently, strain CICC 11023T represents a novel Nocardia species on the basis of this polyphasic study, for which the name Nocardia colli sp. nov. is proposed. The type strain is CICC 11023T (=KCTC 39837T).

ZEB1 Promotes Chemoresistance to Cisplatin in Ovarian Cancer Cells by Suppressing SLC3A2.

Ovarian cancer is one of the deadliest gynecological malignancies in women. Chemoresistance has been a major obstacle for ovarian cancer treatment. Zinc finger E-box-binding homeobox 1 (ZEB1) is an important regulator of tumor development in various types of cancer. Abnormal expression of SLC3A2 (CD98hc), a type 2 transmembrane cell surface molecule, has been described in several cancers. This study was designed to investigate the role of ZEB1 and SLC3A2 in the chemoresistance to cisplatin in ovarian cancer cells. We found that ZEB1 was increased in cisplatin-resistant SKOV3/DPP cells. Downregulation of ZEB1 significantly decreased cell viability in response to cisplatin, increased cis-platin-induced apoptosis, and decreased migration and invasion in the presence of cisplatin. In addition, downregulation of ZEB1 decreased the volume and weight of implanted tumors. SLC3A2 was decreased in cisplatin-resistant SKOV3/DPP cells. Upregulation of SLC3A2 significantly decreased cell viability in response to cisplatin, increased cisplatin-induced apoptosis, and decreased migration and invasion in the presence of cisplatin. Moreover, upregulation of SLC3A2 decreased the volume and weight of implanted tumors. Downregulation of ZEB1 resulted in a significant increase of SLC3A2 expression. Moreover, downregulation of SLC3A2 significantly inhibited ZEB1 knockdown-mediated inhibition of cisplatin-resistance. ZEB1-mediated regulation of SLC3A2 was involved in the chemoresistance to cisplatin in ovarian cancer cells. Overall, we provide new insights into the mechanism of chemoresistance to cisplatin in ovarian cancer cells. ZEB1/SLC3A2 may be promising therapeutic targets for enhancement of the sensitivity of ovarian cancer cells to cisplatin-mediated chemotherapy.

miR-199a-3p enhances cisplatin sensitivity of ovarian cancer cells by targeting ITGB8.

Drug resistance remains a large obstacle for the treatment of ovarian cancer. miRNAs have been reported to be involved in cisplatin (CDDP) resistance in ovarian cancer. The aim of the present study was to investigate the function and mechanism of miR-199a-3p in the CDDP resistance in ovarian cancer. We found that miR-199a-3p was significantly downregulated in chemoresistant ovarian cancer tissues, as well as CDDP-resistant SKOV3/CDDP cells, compared to chemosensitive carcinomas and SKOV3 cells. Restoration of miR-199a-3p in SKOV3/CDDP cells reduced cell proliferation, G1 phase cell cycle arrest, cell invasion, and increased cell apoptosis, resulting in enhanced CDDP sensitivity, while miR-199a-3p inhibition resulted in the opposite effects. Luciferase reporter assay showed that integrin ß8 (ITGB8), one of the integrins that is involved in the regulation of cell cycle and motility, was a direct target of miR-199a-3p. Overexpression of miR-199a-3p downregulated ITGB8 expression via binding to its 3'-UTR. In addition, overexpression of ITGB8 restored CDDP resistance inhibited by miR-199a-3p. Moreover, orthotopic ovarian cancer mouse model showed that miR­199a-3p enhanced CDDP sensitivity of ovarian cancer in vivo. Therefore, our results indicate that miR-199a-3p enhances CDDP sensitivity of ovarian cancer cells through downregulating ITGB8 expression, and miR-199a-3p may serve as a therapeutic target for the treatment of ovarian cancer patients with CDDP-resistance.

A randomised double-blind, placebo-controlled trial of allogeneic umbilical cord-derived mesenchymal stem cell for lupus nephritis.

OBJECTIVE: We evaluate the efficacy of human umbilical cord-derived mesenchymal stem cell (hUC-MSC) for the treatment of lupus nephritis (LN). Previous reports showed hUC-MSC could have dramatic treatment effect. METHODS: Eighteen patients with WHO class III or IV LN were randomly assigned to hUC-MSC (dose 2×108 cells) or placebo. All patients received standard immunosuppressive treatment, which consisted of intravenous methylprednisolone and cyclophosphamide, followed by maintenance oral prednisolone and mycophenolate mofetil. RESULTS: Remission occurred in 9 of 12 patients (75%) in the hUC-MSC group and 5 of 6 patients (83%) in the placebo group. Remission was defined as stabilisation or improvement in renal function, reduction in urinary red cells and protein. A similar proportion of patients on hUC-MSC and placebo achieved complete remission. Improvements in serum albumin, complement, renal function, Systemic Lupus Erythematosus Disease Activity Index and British Isles Lupus Assessment Group scores were similar in both groups. One patient on placebo had a stroke and another had ascites. One patient on hUC-MSC had leucopenia, pneumonia and subcutaneous abscess and another died of severe pneumonia. The trial was abandoned after 18 patients were enrolled when it had become obvious it would not demonstrate a positive treatment effect. CONCLUSION: hUC-MSC has no apparent additional effect over and above standard immunosuppression. TRIAL REGISTRATION NUMBER: NCT01539902; Results.

Cryptococcal meningitis in systemic lupus erythematosus patients: pooled analysis and systematic review.

Cryptococcal meningitis is an important fungal infection among systemic lupus erythematosus patients. We conducted a pooled analysis and systematic review to describe the epidemiological and clinical profile of cryptococcal meningitis in systemic lupus erythematosus patients. From two hospitals in China and nine literature databases, cases and prevalence data were collected for pooled analysis and meta-analysis, respectively. Categorical variables of cases were compared using a χ(2)-test on the statistical program of SAS. A multiple regression analysis was performed to ascertain independent predictors significantly correlated with prognosis. Meta-analysis was conducted by the statistical program of R. The prevalence of cryptococcal meningitis in systemic lupus erythematosus patients was 0.5%. Patients were predominantly females and adults. A prednisone equivalent of more than 30 mg/day before infection was associated with higher mortality (odds ratio (OR)=9.69 (1.54, 60.73)). In all, 36.8-38.9% patients showed low lupus activity when they developed the crytococcal infection. Moreover, 38.2% of the patients were misdiagnosed. The estimated case-fatality rate was 23.6%. Our results suggest that more emphasis should be placed to further understand lupus-related cryptococcal meningitis and to develop better prophylaxis and management strategies to combat this condition.

miR-146a Inhibits Proliferation and Enhances Chemosensitivity in Epithelial Ovarian Cancer via Reduction of SOD2.

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, accounting for 90% of all ovarian cancer. Dysregulation of miRNAs is associated with several types of EOC. In the current research, we aimed to study the role of abnormal expression of miR-146a in the development of EOC and to elucidate the possible molecular mechanisms. Compared with control samples, mRNA expression of miR-146a was significantly decreased in EOC tissues and cell lines. Overexpression of miR-146a prohibited cell proliferation, enhanced apoptosis, and increased sensitivity to chemotherapy drugs in EOC cells. In contrast, downregulation of miR-146a promoted cell proliferation, suppressed apoptosis, and decreased sensitivity to chemotherapy drugs in EOC cells. Overexpression of miR-146a increased the reactive oxygen species (ROS) level and decreased SOD2 mRNA and protein expression. Downregulation of miR-146a increased SOD2 mRNA and protein expression. Overexpression of SOD2 significantly inhibited miR-146a mimics-induced suppression of cell proliferation and the increase of apoptosis and chemosensitivity. In conclusion, we identify miR-146a as a potential tumor suppressor in patients with EOC. miR-146a downregulates the expression of SOD2 and enhances ROS generation, leading to increased apoptosis, inhibition of proliferation, and enhanced sensitivity to chemotherapy. The data demonstrate that the miR-146a/SOD2/ROS pathway may serve as a novel therapeutic target and prognostic marker in patients with EOC.

Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus.

We performed a genome-wide association study (GWAS) of systemic lupus erythematosus (SLE) in a Chinese Han population by genotyping 1,047 cases and 1,205 controls using Illumina Human610-Quad BeadChips and replicating 78 SNPs in two additional cohorts (3,152 cases and 7,050 controls). We identified nine new susceptibility loci (ETS1, IKZF1, RASGRP3, SLC15A4, TNIP1, 7q11.23, 10q11.22, 11q23.3 and 16p11.2; 1.77 x 10(-25) < or = P(combined) < or = 2.77 x 10(-8)) and confirmed seven previously reported loci (BLK, IRF5, STAT4, TNFAIP3, TNFSF4, 6q21 and 22q11.21; 5.17 x 10(-42) < or = P(combined) < or = 5.18 x 10(-12)). Comparison with previous GWAS findings highlighted the genetic heterogeneity of SLE susceptibility between Chinese Han and European populations. This study not only advances our understanding of the genetic basis of SLE but also highlights the value of performing GWAS in diverse ancestral populations.

[A study on the relationship between insulin-like growth factor, insulin-like growth factor-binding protein-3 and fetal growth retardation].

OBJECTIVE: To explore the effect of insulin-like growth factor-I (IGF-I), insulin-like growth factor-II (IGF-II) and insulin-like growth factor-binding protein-3 (IGFBP-3) on the fetal growth. METHODS: Samples of maternal blood and matched umbilical cord blood were collected at time of delivery from twenty pairs of mothers and newborns with normal birth weight (control group) twenty pairs with fetal growth restriction (FGR group) and ten pairs with macrosomia (macrosomia group). Serum IGF-I, IGF-II and IGFBP-3 were measured by radioimmunoassay (RIA) and immunoradiometric analysis (IRMA). RESULTS: (1) Levels of maternal serum IGF-I, IGF-II and IGFBP-3 in GFR group were (130.5 +/- 26.0) microgram/L, (2.40 +/- 0.42) microgram/L, (5 579 +/- 848) microgram/L respectively; IGF-I, IGF-II and IGFBP-3 levels of fetal serum in this group were (6.6 +/- 1.7) microgram/L, (1.54 +/- 0.31) microgram/L, (869 +/- 183) microgram/L respectively. (2) In macrosomia group the levels of maternal serum IGF-I, IGF-II and IGFBP-3 were (309.7 +/- 44.6) microgram/L, (2.43 +/- 0.25) microgram/L, (5 562 +/- 742) microgram/L respectively. In fetal serum that were (69.6 +/- 23.9) microgram/L, (2.19 +/- 0.29) microgram/L, (1 682 +/- 130) microgram/L respectively. (3) In control group the levels of maternal serum IGF-I, IGF-II and IGFBP-3 were (307.9 +/- 70.7) microgram/L, (2.41 +/- 0.36) microgram/L, (5 586 +/- 678) microgram/L respectively;That were (68.9 +/- 32.9) microgram/L, (1.95 +/- 0.26) microgram/L, (1 624 +/- 296) microgram/L in fetal serum respectively. (4) In three group the levels of maternal IGF-I, IGF-II and IGFBP-3 were significantly higher than that of fetal levels (P < 0.01). The fetal IGF-I, IGF-II and IGFBP-3 levels in FGR group were significantly lower than those in control group (P < 0.01). (5) The levels of fetal IGF-I, IGF-II, IGFBP-3 were positively correlated with birth weight (r = 0.61, r = 0.51 and 0.63, P < 0.01) and placental weight (r = 0.47, r = 0.56 and 0.48, P < 0.01). The levels of fetal IGF-I, IGF-II and IGFBP-3 were no different between macrosomia group and control group. CONCLUSIONS: This study suggest that (1) IGF-I, IGF-II and IGFBP-3 cannot pass through the placenta. (2) The betal IGF-I, IGF-II and IGFBP-3 may have the close relationship with the fetal growth. The decrease of IGF-I, IGF-II and IGFBP-3 may be one of the causes of FGR.