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The long noncoding RNASBF2-AS1 can promote the occurrence and development of many kinds of tumours, but its role in oesophageal squamous cell carcinoma (ESCC) is unknown. We found that SBF2-AS1 was up-regulated in ESCC, and its expression was positively correlated with tumor size (P = 0.0001), but was not related to gender, age, TNM stage, histological grade, and lymphnode metastasis (P > 0.05). It was further found that the higher the expression of SBF2-AS1, the lower the survival rate. COX multivariate analysis showed that the expression of SBF2-AS1 was an independent prognostic factor. Functional experiments show that inhibition of SBF2-AS1 can inhibit the proliferation of ESCC through in vivo and in vitro, and overexpression of SBF2-AS1 can promote the proliferation of ESCC and inhibit its apoptosis. In mechanism, SBF2-AS1/miR-338-3P, miR-362-3P/E2F1 axis are involved in the regulation of ESCC growth. In general, SBF2-AS1 may be used as ceRNA to combine with miR-338-3P and miR-362-3P to up-regulate the expression ofE2F1, and ultimately play a role in promoting cancer. It may be used as a therapeutic target and a biomarker for prognosis.

The metabolism of flavone C-glucosides and p-coumaric acid from antioxidant of bamboo leaves (AOB) in rats is discussed systematically in the present study. Following single oral administration of AOB, p-coumaric acid was detected in plasma but not in gastrointestinal tract extracts and faeces, and the corresponding absorption pharmacokinetic curve at different time points showed a prolonged elimination phase with p-coumaric acid being detected in the kidneys and excreted as its original form (1·80 (sd 0·24) % and 1·90 (sd 0·26) % at 12 and 24 h, respectively). However, the four flavone C-glucosides orientin, homoorientin, vitexin and isovitexin were poorly absorbed in the gastrointestinal tract. More than 50 % recovery of flavone C-glucosides was determined at 12 h and faeces containing these four analytes (21·23 (sd 1·92) %) were excreted at 24 h. These data suggested that the effective time these compounds were in the colon was long enough so that they could exert their antioxidant activity and scavenge free radicals. Besides the excretion of the original forms, moieties of the flavone C-glucosides were hydrolysed by deglycosylation and the opening of the heterocyclic C ring. Some small molecules such as phloroglucinol (PG), hydrocaffeic acid (HCA) and phloretic acid (PA) were detected and identified as metabolites of the flavone C-glucosides. In the present work, we compared the metabolic fate of flavone C-glucosides to that of flavone O-glucosides in rats, and evaluated the absorption, tissue distribution and excretion of flavone C-glucosides in AOB on their metabolism for the first time.

Environmental context Environmental estrogens can disrupt the normal functioning of endocrine systems, and their occurrence in drinking water sources could cause potential health risk. We investigated concentrations of four estrogens in the lakes from the Taihu Basin, and found that BPA and EE2 were elevated in some sites. However, concentrations of all four environmental estrogens were below the national standards, and caused no health threat to local population. Rationale The Taihu Basin is a critical freshwater ecosystem susceptible to contamination from various anthropogenic activities. Environmental estrogens (also known as endocrine disrupting chemicals, EDCs) are exogenous substances that can disrupt the normal functioning of endocrine systems. The contamination of water by EDCs is primarily caused by effluents from sewage treatment plants and livestock poultry farms. In this study, we assessed the spatial distribution and potential risks of environmental estrogens in surface water in the Taihu basin. Various statistical evaluations were employed to establish connections between measured concentration of heavy elements, estrogens and physicochemical parameters, to identify potential sources of these contaminants. Methodology Water samples from 44 sampling points in five lakes in Suzhou were taken for evaluation of environmental estrogens. Gas chromatography–mass spectrometry was used for identification of concentrations of estrone (E1), estradiol (E2), ethinyl estradiol (EE2) and bisphenol A (BPA). Inductively coupled plasma–mass spectrometry was employed to identify heavy element concentrations in water samples. Results Environmental estrogen concentrations were detected ranging from 0.001 to 209 ng L–1, with the highest attributed to BPA, whereas E1, E2 and EE2 were comparatively lower. Correlation evaluation between environmental estrogens, physicochemical parameters and heavy element contents revealed a positive correlation (P < 0.05) between the total chromium and environmental estrogen contents. Consequently, the risk entropy value of Shanghu Lake exceeded 0.5, indicating a potentially high risk of estrogenic activity. Discussion The widespread distribution and high concentrations of BPA in freshwater raise urgent concerns, highlighting the need for frequent monitoring of environmental estrogens in surface waters throughout the year to mitigate potential risks in the future. Our results suggest that a potential estrogen risk exists in the Shanghu Lake in the Taihu basin. Potential treatment methods for endocrine disruptors have been proposed, which could provide actionable plans for stakeholders.

HighlightsA novel strategy was developed to construct ultrathin microfiber composite hydrogel films (< 5 μm) by embedding an electrospun fiber network into a hydrogel.The microfiber composite hydrogel offers tunable modulus in a broad range (from ~ 5 kPa to tens of MPa), which matches the modulus of most biological tissues and organs.The ultrathin configuration and ultrasoft nature allow the microfiber composite hydrogel seamlessly attaching to various rough surfaces.Hydrogels offer tissue-like softness, stretchability, fracture toughness, ionic conductivity, and compatibility with biological tissues, which make them promising candidates for fabricating flexible bioelectronics. A soft hydrogel film offers an ideal interface to directly bridge thin-film electronics with the soft tissues. However, it remains difficult to fabricate a soft hydrogel film with an ultrathin configuration and excellent mechanical strength. Here we report a biological tissue-inspired ultrasoft microfiber composite ultrathin (< 5 μm) hydrogel film, which is currently the thinnest hydrogel film as far as we know. The embedded microfibers endow the composite hydrogel with prominent mechanical strength (tensile stress ~ 6 MPa) and anti-tearing property. Moreover, our microfiber composite hydrogel offers the capability of tunable mechanical properties in a broad range, allowing for matching the modulus of most biological tissues and organs. The incorporation of glycerol and salt ions imparts the microfiber composite hydrogel with high ionic conductivity and prominent anti-dehydration behavior. Such microfiber composite hydrogels are promising for constructing attaching-type flexible bioelectronics to monitor biosignals.

The current pandemic of COVID-19 is fueled by more infectious emergent Omicron variants. Ongoing concerns of emergent variants include possible recombinants, as genome recombination is an important evolutionary mechanism for the emergence and re-emergence of human viral pathogens. In this study, we identified diverse recombination events between two Omicron major subvariants (BA.1 and BA.2) and other variants of concern (VOCs) and variants of interest (VOIs), suggesting that co-infection and subsequent genome recombination play important roles in the ongoing evolution of SARS-CoV-2. Through scanning high-quality completed Omicron spike gene sequences, 18 core mutations of BA.1 (frequency >99%) and 27 core mutations of BA.2 (nine more than BA.1) were identified, of which 15 are specific to Omicron. BA.1 subvariants share nine common amino acid mutations (three more than BA.2) in the spike protein with most VOCs, suggesting a possible recombination origin of Omicron from these VOCs. There are three more Alpha-related mutations in BA.1 than BA.2, and BA.1 is phylogenetically closer to Alpha than other variants. Revertant mutations are found in some dominant mutations (frequency >95%) in the BA.1. Most notably, multiple characteristic amino acid mutations in the Delta spike protein have been also identified in the “Deltacron”-like Omicron Variants isolated since November 11, 2021 in South Africa, which implies the recombination events occurring between the Omicron and Delta variants. Monitoring the evolving SARS-CoV-2 genomes especially for recombination is critically important for recognition of abrupt changes to viral attributes including its epitopes which may call for vaccine modifications.

Atrial fibrillation (AF) is the most common cardiac arrhythmia at the clinic. Recent GWAS identified several variants associated with AF, but they account for <10% of heritability. Gene-gene interaction is assumed to account for a significant portion of missing heritability. Among GWAS loci for AF, only three were replicated in the Chinese Han population, including SNP rs2106261 (G/A substitution) in ZFHX3, rs2200733 (C/T substitution) near PITX2c, and rs3807989 (A/G substitution) in CAV1. Thus, we analyzed the interaction among these three AF loci. We demonstrated significant interaction between rs2106261 and rs2200733 in three independent populations and combined population with 2,020 cases/5,315 controls. Compared to non-risk genotype GGCC, two-locus risk genotype AATT showed the highest odds ratio in three independent populations and the combined population (OR=5.36 (95% CI 3.87-7.43), P=8.00×10-24). The OR of 5.36 for AATT was significantly higher than the combined OR of 3.31 for both GGTT and AACC, suggesting a synergistic interaction between rs2106261 and rs2200733. Relative excess risk due to interaction (RERI) analysis also revealed significant interaction between rs2106261 and rs2200733 when exposed two copies of risk alleles (RERI=2.87, P<1.00×10-4) or exposed to one additional copy of risk allele (RERI=1.29, P<1.00×10-4). The INTERSNP program identified significant genotypic interaction between rs2106261 and rs2200733 under an additive by additive model (OR=0.85, 95% CI: 0.74-0.97, P=0.02). Mechanistically, PITX2c negatively regulates expression of miR-1, which negatively regulates expression of ZFHX3, resulting in a positive regulation of ZFHX3 by PITX2c; ZFHX3 positively regulates expression of PITX2C, resulting in a cyclic loop of cross-regulation between ZFHX3 and PITX2c. Both ZFHX3 and PITX2c regulate expression of NPPA, TBX5 and NKX2.5. These results suggest that cyclic cross-regulation of gene expression is a molecular basis for gene-gene interactions involved in genetics of complex disease traits.

Microsporidia are obligate intracellular parasites, and a derivative of fungi, which harbor a rigid spore wall to resist adverse environmental pressures. The spore wall protein, which is thought to be the first and direct protein interacting with the host cell, may play a key role in the process of microsporidia infection. In this study, we report a protein, NbHSWP11, with a dnaJ domain. The protein also has 6 heparin-binding motifs which are known to interact with extracellular glycosaminoglycans. Syntenic analysis indicated that gene loci of Nbhswp11 are conserved and syntenic between Nosema bombycis and Nosema ceranae. Phylogenetic tree analysis showed that Nbhswp11 clusters with fungal dnaJ proteins and has 98% identity with an N. bombycis dnaJ protein. Nbhswp11 was transcribed throughout the entire life stages, and gradually increased during 1–7 days, in a silkworm that was infected by N. bombycis, as determined by reverse-transcription PCR (RT-PCR). The recombinant protein NbHSWP11 (rSWP11-HIS) was obtained and purified using gene cloning and prokaryotic expression. Western blotting analysis displayed NbHSWP11 expressed in the total mature spore proteins and spore coat proteins. Indirect immunofluorescence assay revealed NbHSWP11 located at the spore wall of mature spores and the spore coats. Furthermore, immune electron microscopy showed that NbHSWP11 localized in the cytoplasm of the sporont. Within the developmental process of N. bombycis, a portion of NbHSWP11 is targeted to the spore wall of sporoblasts and mature spores. However, most of NbHSWP11 distributes on the membraneous structures of the sporoblast and mature spore. In addition, using a host cell binding assay, native protein NbHSWP11 in the supernatant of total soluble mature spore proteins is shown to bind to the host cell BmE surface. Finally, an antibody blocking assay showed that purified rabbit antibody of NbHSWP11 inhibits spore adherence and decreases the adherence rate of spores by 20% compared to untreated spores. Collectively, the present results suggest that NbHSWP11 is involved in host cell adherence in vitro. Therefore NbHSWP11, which has a dnaJ domain, may modulate protein assembly, disassembly, and translocation in N. bombycis.

IntroductionThis phase III trial (NCT04178850) evaluated the efficacy, safety, and immunogenicity of GB242, an infliximab biosimilar, vs. infliximab (Remicade®) reference product in patients with moderate-to-severe active rheumatoid arthritis (RA) combination with methotrexate (MTX) therapy.MethodsPatients were randomized in a 1:1 ratio to receive either GB242 or INF (3 mg/kg). Therapeutic equivalence of clinical response according to the American College of Rheumatology 20% (ACR20) response rate at week 30 was declared if the two-sided 95% CI for the treatment difference was within ± 14%. The comparison of GB242 with INF also included the proportion of patients achieving a week 30 ACR 50 response, ACR70 response, change in Disease Activity Score 28 (DAS28), as well as safety and immunogenicity.ResultsA total of 570 subjects were randomized into GB242 (N = 285) or INF (N = 285) and 283 subjects in each group were analyzed. At week 30, the ACR20 was 62.54% for the GB242 group (95% CI 56.62–68.20%) and 56.89% for the INF group (95% CI 50.90–62.74%). The difference between the two groups was 5.65% with a 95% CI of – 2.48 to 13.74. ACR50 response was 37.12% for GB242 and 32.86% for INF at week 30. ACR70 response was 19.79% for GB242 and 16.96% for INF at week 30, respectively. The incidence of treatment-emergent adverse events was comparable (77.4% in GB242 vs. 80.2% in INF) and detection of antidrug antibodies (ADA) to infliximab up to week 30 (60.8% in GB242 vs. 59.4% in INF) was comparable.ConclusionsGB242 demonstrated equivalent efficacy to INF at week 30. Moreover, GB242 was well tolerated, with a similar immunogenicity and safety profile comparable to INF.

Reactive power voltage partition control is an important part of AVC secondary voltage control. Aiming at the current status of secondary voltage control, based on the voltage/reactive sensitivity and modularity function, an adaptive dynamic partitioning method is proposed, which changes with the operating conditions of the grid. With each reactive power source partition center, the load nodes are mapped to the corresponding reactive power sources according to the voltage/reactive sensitivity, and the regional merging automatically forms the optimal partition by using the modularity function as a measure. Finally, the proposed method is verified by the IEEE-39 system.

Atrial fibrillation (AF) is the most common cardiac arrhythmia at the clinic. Recent GWAS identified several variants associated with AF, but they account for <10% of heritability. Gene-gene interaction is assumed to account for a significant portion of missing heritability. Among GWAS loci for AF, only three were replicated in the Chinese Han population, including SNP rs2106261 (G/A substitution) in ZFHX3, rs2200733 (C/T substitution) near PITX2c, and rs3807989 (A/G substitution) in CAV1. Thus, we analyzed the interaction among these three AF loci. We demonstrated significant interaction between rs2106261 and rs2200733 in three independent populations and combined population with 2,020 cases/5,315 controls. Compared to non-risk genotype GGCC, two-locus risk genotype AATT showed the highest odds ratio in three independent populations and the combined population (OR=5.36 (95% CI 3.87-7.43), P=8.00×10-24). The OR of 5.36 for AATT was significantly higher than the combined OR of 3.31 for both GGTT and AACC, suggesting a synergistic interaction between rs2106261 and rs2200733. Relative excess risk due to interaction (RERI) analysis also revealed significant interaction between rs2106261 and rs2200733 when exposed two copies of risk alleles (RERI=2.87, P<1.00×10-4) or exposed to one additional copy of risk allele (RERI=1.29, P<1.00×10-4). The INTERSNP program identified significant genotypic interaction between rs2106261 and rs2200733 under an additive by additive model (OR=0.85, 95% CI: 0.74-0.97, P=0.02). Mechanistically, PITX2c negatively regulates expression of miR-1, which negatively regulates expression of ZFHX3, resulting in a positive regulation of ZFHX3 by PITX2c; ZFHX3 positively regulates expression of PITX2C, resulting in a cyclic loop of cross-regulation between ZFHX3 and PITX2c. Both ZFHX3 and PITX2c regulate expression of NPPA, TBX5 and NKX2.5. These results suggest that cyclic cross-regulation of gene expression is a molecular basis for gene-gene interactions involved in genetics of complex disease traits.