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In areas with high incidence of tuberculosis (TB), there are more infertile women who underwent in vitro fertilization (IVF) and have latent TB infection (LTBI), and thus, their potential risks should be paid enough attention. The purpose of our study aimed to analyze the relationship between LTBI and clinical pregnancy outcomes of IVF and fresh embryo transfer (IVF–FET). This was a retrospective study of 628 infertile women who had undergone IVF–FET in the Fourth Affiliated Hospital of Hebei Medical University from January 2019 to December 2021. The women experienced no clinical symptoms, negative imaging, and T-SPOT.TB-positive diagnosis of LTBI. We divided the study population into the LTBI group and the non-LTBI group. The clinical pregnancy rate in the LTBI group was significantly lower than that in the non-LTBI group (40.54% vs 49.51%, P = 0.031), and there was no significant difference in live birth rate and miscarriage rate between the two groups. Logistic regression analysis showed that LTBI was an independent risk factor for decreased clinical pregnancy rate in infertile women undergoing IVF–FET. In conclusion, LTBI affects clinical pregnancy rate of IVF–FET in infertile women, and therefore, clinicians (especially in countries with a high TB burden) need to pay attention to LTBI before IVF and embryo transfer.

The miR-141-3p has been reported to participate in regulating autophagy and tumor-stroma interactions in ovarian cancer (OC). We aim to investigate whether miR-141-3p accelerates the progression of OC and its effect on macrophage 2 polarization by targeting the Kelch-like ECH-associated protein1-Nuclear factor E2-related factor2 (Keap1-Nrf2) pathway. SKOV3 and A2780 cells were transfected with miR-141-3p inhibitor and negative control to confirm the regulation of miR-141-3p on OC development. Moreover, the growth of tumors in xenograft nude mice treated by cells transfected with miR-141-3p inhibitor was established to further testify the role of miR-141-3p in OC. The expression of miR-141-3p was higher in OC tissue compared with non-cancerous tissue. Downregulation of miR-141-3p inhibited the proliferation, migration, and invasion of ovarian cells. Furthermore, miR-141-3p inhibition also suppressed M2-like macrophage polarization and in vivo OC progression. Inhibition of miR-141-3p significantly enhanced the expression of Keap1, the target gene of miR-141-3p, and thus downregulated Nrf2, while activation of Nrf2 reversed the reduction in M2 polarization by miR-141-3p inhibitor. Collectively, miR-141-3p contributes to tumor progression, migration, and M2 polarization of OC by activating the Keap1-Nrf2 pathway. Inhibition of miR-141-3p attenuates the malignant biological behavior of ovarian cells by inactivating the Keap1-Nrf2 pathway.

The regulatory mechanisms involved in embryonic development are complex and yet remain unclear. SCP4 represents a novel nucleus‐resident phosphatase identified in our previous study. The primary aim of this study was to elucidate the function of SCP4 in the progress of cartilage development and endochondral osteogenesis. SCP4−/− and SCP4Col2ER mice were constructed to assess differences in bone formation using whole skeleton staining. ABH/OG staining was used to compare chondrocyte differentiation and cartilage development. Relevant biological functions were analysed using RNA‐sequencing and GO enrichment, further validated by immunohistochemical staining, Co‐IP and Western Blot. Global SCP4 knockout led to abnormal embryonic development in SCP4−/− mice, along with delayed endochondral osteogenesis. In parallel, chondrocyte‐specific removal of SCP4 yielded more severe embryonic deformities in SCP4Col2ER mice, including limb shortening, reduced chondrocyte number in the growth plate, disorganisation and cell enlargement. Moreover, RNA‐sequencing analysis showed an association between SCP4 and chondrocyte apoptosis. Notably, Tunnel‐positive cells were indeed increased in the growth plates of SCP4Col2ER mice. The deficiency of SCP4 up‐regulated the expression levels of pro‐apoptotic proteins both in vivo and in vitro. Additionally, phosphorylation of FoxO3a (pFoxO3a), a substrate of SCP4, was heightened in chondrocytes of SCP4Col2ER mice growth plate, and the direct interaction between SCP4 and pFoxO3a was further validated in chondrocytes. Our findings underscore the critical role of SCP4 in regulating cartilage development and endochondral osteogenesis during embryonic development partially via inhibition of chondrocytes apoptosis regulated by FoxO3a dephosphorylation. [ABSTRACT FROM AUTHOR]

The antioxidant activity of chitosan (CS) and three water-soluble derivatives was analyzed comparatively by in vitro and in vivo experiments, including hydroxypropyl chitosan (HPCS), quaternary ammonium salt of chitosan (HACC), and carboxymethyl chitosan (CMCS). The results show that chitosan and its water-soluble derivatives have a scavenging ability on DPPH radicals, superoxide radicals, and hydroxyl radicals, and a reducing ability. A remarkable difference (p < 0.05) was found for HACC and HPCS compared with CS on DPPH radicals, hydroxyl radicals, and reducing ability. The antioxidant ability of the four chitosan samples was in the order of HPCS > HACC > CMCS > CS. Furthermore, antioxidant activity of all samples increased gradually in a concentration-dependent manner. The in vivo result indicates that oral CS and its derivatives samples result in a decrease in lipid peroxides (LPO) and free fatty acids (FFA) levels in serum with an increase in superoxide dismutase (SOD) activity. Especially for the HPCS and HACC groups, the LPO, FFA, and SOD activity in serum was different significantly in comparison with the high-fat controlgroup (HF) (p < 0.05). These results indicate that chitosan and its derivatives can be used as good antioxidants, and the antioxidant activity might be related to the molecular structure of chitosan derivatives. [ABSTRACT FROM AUTHOR]

Autosomal dominant polycystic kidney disease (ADPKD), caused by mutations in PKD1 and PKD2 (PKD1/2), has unexplained phenotypic variability likely affected by environmental and other genetic factors. Approximately 10% of individuals with ADPKD phenotype have no causal mutation detected, possibly due to unrecognized risk variants of PKD1/2. This study was designed to identify risk variants of PKD genes through population genetic analyses. We used Wright's F‐statistics (Fst) to evaluate common single nucleotide variants (SNVs) potentially favored by positive natural selection in PKD1 from 1000 Genomes Project (1KG) and genotyped 388 subjects from the Rogosin Institute ADPKD Data Repository. The variants with >90th percentile Fst scores underwent further investigation by in silico analysis and molecular genetics analyses. We identified a deep intronic SNV, rs3874648G> A, located in a conserved binding site of the splicing regulator Tra2‐β in PKD1 intron 30. Reverse‐transcription PCR (RT‐PCR) of peripheral blood leukocytes (PBL) from an ADPKD patient homozygous for rs3874648‐A identified an atypical PKD1 splice form. Functional analyses demonstrated that rs3874648‐A allele increased Tra2‐β binding affinity and activated a cryptic acceptor splice‐site, causing a frameshift that introduced a premature stop codon in mRNA, thereby decreasing PKD1 full‐length transcript level. PKD1 transcript levels were lower in PBL from rs3874648‐G/A carriers than in rs3874648‐G/G homozygotes in a small cohort of normal individuals and patients with PKD2 inactivating mutations. Our findings indicate that rs3874648G > A is a PKD1 expression modifier attenuating PKD1 expression through Tra2‐β, while the derived G allele advantageously maintains PKD1 expression and is predominant in all subpopulations. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OC) is a gynecological malignancy that ranks among the most common female cancers worldwide and notably reduces a patient's quality of life. Mitochondrial carrier homology 2 (MTCH2) is a mitochondrial outer membrane protein that serves a regulatory role in mitochondrial metabolism and cell death. The precise contribution and underlying molecular pathways of MTCH2 in the context of OC development is currently unclear. The present study aimed to investigate the roles of MTCH2 in the energy metabolism, cell proliferation and metastatic potential of OC cells and evaluate the regulatory relationship between MTCH2, aminoacyl transfer RNA synthetase-interacting multifunctional protein 2 (AIMP2) and claudin-3. An analysis of 67 patients with high-grade serous OC demonstrated increased expression levels of MTCH2, AIMP2 and claudin-3 in OC tumor tissue samples compared with in corresponding normal tissues adjacent to OC tissue samples. MTCH2 overexpression was significantly associated with the International Federation of Gynecology and Obstetrics stage and tumor differentiation of the OC tumor samples. In vitro experiments using the SK-OV-3 OC cell line demonstrated that MTCH2 exerts a regulatory effect on the cell proliferation, invasion and migratory capabilities of these cells. Knockdown of MTCH2 reduced ATP production, induced mitochondrial dysfunction and promoted cytoskeleton remodeling and apoptosis in SK-OV-3 OC cells. In addition, MTCH2 knockdown downregulated the expression levels of both claudin-3 and AIMP2 proteins. Knockdown of AIMP2 inhibited the regulatory effect of MTCH2. Co-immunoprecipitation experiments demonstrated that MTCH2 interacts with AIMP2 and claudin-3. The present study provides novel insights into the treatment of OC metastasis, as MTCH2 was demonstrated to serve roles in the progression of OC cells through the regulation of claudin-3 via AIMP2, which could provide novel insights into the treatment of ovarian cancer metastasis. [ABSTRACT FROM AUTHOR]