Correlative analysis of different treatments of persistent occipitotransverse position on the outcome for mother and infant.

OBJECTIVE: To explore the clinical feasibility of different treatment methods for persistent occipitotransverse position and the influence on maternal and infant complications. METHOD: During the trial of vaginal delivery from April 2020 to March 2023 in our hospital, the cervix was fully dilated and the presentation was located at +2 station. Ninety-six pregnant women with fetal presentation at +4 station, occipitotransverse fetal position, maternal complications, abnormalities in the second stage of labor, and or fetal distress were divided into two groups: 65 patients with Kielland forceps vaginal delivery and 31 patients underwent emergency cesarean section. The delivery time, vaginal laceration rate, postpartum blood loss volume, puerperal infection rate, neonatal birth injury rate, and neonatal 1 min Apgar scores were analyzed. RESULTS: The delivery outcomes and maternal and neonatal complications of 96 pregnant women were analyzed: the application of Kielland forceps delivery time was shorter, while the vaginal laceration rate, postpartum hemorrhage, puerperal infection rate were significantly lower than that of patients undergoing emergency cesarean section and the neonatal 1 min Apgar score was higher than that of emergency cesarean section group (p < 0.05). CONCLUSION: It was clinically appropriate to use Kielland forceps in vaginal delivery when the persistent occipitotransverse position was present and delivery needed to be expediated. Use of Kielland forceps can shorten the delivery time, improve the success rate of vaginal delivery and reduce the complications of mothers and infants.

Buried Interface Regulation by Bio-Functional Molecules for Efficient and Stable Planar Perovskite Solar Cells.

Among the factors that lead to the reduction of the efficiency of perovskite solar cells (PSCs) the difficulty involved in realizing a high-quality film and the efficient charge transfer that takes place at the interface between electron-transport layer (ETL) and perovskite is worth mentioning. Here, a strategy for planar-type devices by natural bio-functional interfaces that uses a buried electron-transport layer made of cobalamin complexed tin oxide (SnO2 @B12 ) is demonstrated. Having systematically investigated the effects of SnO2 @B12 interfacial layer in perovskite solar cells, it can be concluded that cobalamin can chemically link the SnO2 layer and the perovskite layer, resulting in improved perovskite film quality and interfacial defect passivation. Utilizing SnO2 @B12 improves the efficiency of planar-type PSCs by 20.60 %. Furthermore, after 250 h of exposure to an ambient atmosphere, unsealed PSCs containing SnO2 @B12 degrade by 10 %. This research provides a viable method for developing bio-functional molecules that will increase the effectiveness and durability of planar-perovskite solar cells.

miR-204-5p inhibits cell proliferation and induces cell apoptosis in esophageal squamous cell carcinoma by regulating Nestin.

Esophageal cancer (EC) is a highly malignant gastrointestinal tumor, and esophageal squamous cell carcinoma (ESCC) is one of the most common histological types of EC. MicroRNAs (miRNAs) are small noncoding RNAs closely related to tumorigenesis and tumor progression. In addition, Nestin is an intermediate filament protein (class VI) and contributes to the progression of numerous tumors. However, the correlation between miRNAs and Nestin in ESCC remains unclear. This study aimed to investigate the relationship between miR-204-5p and Nestin in ESCC. First, Nestin-related miRNAs in ESCC were explored using RNA sequencing. In ESCC tissues and cell lines, the expression of miR-204-5p was decreased detected by quantitative real-time polymerase chain reaction (qPCR), whereas Nestin protein level was upregulated identified by Western blotting (WB). Besides, Nestin was the direct target of miR-204-5p in ESCC determined via the luciferase reported assay. Moreover, miR-204-5p regulated Nestin to inhibit ESCC cell proliferation detected by the colony formation assay and promote ESCC cell apoptosis identified using the flow cytometry and TUNEL assay. Furthermore, miR-204-5p suppressed tumorigenesis in vivo evaluated by the murine xenograft tumor model. In conclusion, these results indicated that miR-204-5p inhibited cell proliferation and induced cell apoptosis in ESCC through targeting Nestin, which might provide novel therapeutic targets for ESCC therapy.

A Child Infected with COVID-19 in China-A Case Report.

A 16-month-old boy was admitted with cough for 2 days and fever for 1 day. Chest computed tomography (CT) scan of the child revealed large areas of ground-glass opacities in both lungs. Nucleic acid amplification tests (NAATs) were performed repeatedly to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the results were all negative. On day 13 of hospitalization, no clinical symptoms except diarrhea were present in the patient, and re-examination by chest CT revealed lesion shrinkage, but the NAAT on throat swabs was positive. On day 22 of hospitalization, the NAAT on throat swabs was negative and the fecal samples were positive. Positive fecal samples nucleic acid lasted for 62 days. Suggesting that pediatric patients may be important sources of infection during the recovery phase of clinical symptoms and whether SARS-CoV-2 has fecal-oral transmission needs further study.

FUNDC1 regulates mitochondrial dynamics at the ER-mitochondrial contact site under hypoxic conditions.

In hypoxic cells, dysfunctional mitochondria are selectively removed by a specialized autophagic process called mitophagy. The ER-mitochondrial contact site (MAM) is essential for fission of mitochondria prior to engulfment, and the outer mitochondrial membrane protein FUNDC1 interacts with LC3 to recruit autophagosomes, but the mechanisms integrating these processes are poorly understood. Here, we describe a new pathway mediating mitochondrial fission and subsequent mitophagy under hypoxic conditions. FUNDC1 accumulates at the MAM by associating with the ER membrane protein calnexin. As mitophagy proceeds, FUNDC1/calnexin association attenuates and the exposed cytosolic loop of FUNDC1 interacts with DRP1 instead. DRP1 is thereby recruited to the MAM, and mitochondrial fission then occurs. Knockdown of FUNDC1, DRP1, or calnexin prevents fission and mitophagy under hypoxic conditions. Thus, FUNDC1 integrates mitochondrial fission and mitophagy at the interface of the MAM by working in concert with DRP1 and calnexin under hypoxic conditions in mammalian cells.

MicroRNA-495 regulates starvation-induced autophagy by targeting ATG3.

The functions of some essential autophagy genes are regulated by microRNAs. However, an ATG3-modulating microRNA has never been reported. Here we show that the transcription of miR-495 negatively correlates with the translation of ATG3 under nutrient-deprived or rapamycin-treated conditions. miR-495 targets ATG3 and regulates its protein levels under starvation conditions. miR-495 also inhibits starvation-induced autophagy by decreasing the number of autophagosomes and by preventing LC3-I-to-LC3-II transition and P62 degradation. These processes are reversed by the overexpression of an endogenous miR-495 inhibitor. Re-expression of Atg3 without miR-495 response elements restores miR-495-inhibited autophagy. miR-495 sustains cell viability under starvation conditions but has no effect under hypoxia. Moreover, miR-495 inhibits etoposide-induced cell death. In conclusion, miR-495 is involved in starvation-induced autophagy by regulating Atg3.

Phosphorylation of ULK1 by AMPK regulates translocation of ULK1 to mitochondria and mitophagy.

UNC-51 like kinase (ULK1) translocates to dysfunctional mitochondria and is involved in mitophagy, but the mechanisms responsible for ULK1 activation and translocation remain unclear. Here, we found that hypoxia induces phosphorylation of ULK1 at Serine-555 by Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK). Unlike wild-type ULK1, an ULK1 (S555A) mutant cannot translocate to mitochondria in response to hypoxia. Inhibition or knockdown of AMPK prevents ULK1 translocation and inhibits mitophagy. Finally, the phospho-mimic ULK1 (S555D) mutant, but not ULK1 (S555A), rescues mitophagy in AMPK-knockdown cells. Thus, we conclude that AMPK-dependent phosphorylation of ULK1 is critical for translocation of ULK1 to mitochondria and for mitophagy in response to hypoxic stress.

Association between HTR2A T102C polymorphism and major depressive disorder: a meta-analysis in the Chinese population.

Although a number of studies have been conducted on the association between HTR2A T102C polymorphism and major depressive disorder (MDD) in Chinese, this association remains elusive and controversial. To clarify the effects of HTR2A T102C polymorphism on the risk of MDD, a meta-analysis was performed in the Chinese population. Related studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) till 5 May 2015. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of the associations. Statistical analyses were conducted with Version 10.0 STATA statistical software. A total of 12 case-control studies including 1444 MDD cases and 1445 controls were involved in this meta-analysis. Overall, no significant association with MDD risk was provided in the Chinese population (C vs. T: OR=0.97, 95% CI: 0.81-1.17, 95%; CC vs. TT: OR=0.95, 95% CI: 0.65-1.37; CC+TC vs. TT: OR=0.96, 95% CI: 0.75-1.12; CC vs. TT+TC: OR=0.94, 95% CI: 0.78-1.12). In subgroup analyses stratified by geographic area and source of controls, no significant association was found in any of the subgroups. In conclusion, this meta-analysis indicate that the HTR2A T102C polymorphism is not associated with susceptibility to MDD in Chinese population.

Prevention of aortic fibrosis by N-acetyl-seryl-aspartyl-lysyl-proline in angiotensin II-induced hypertension.

Fibrosis is an important component of large conduit artery disease in hypertension. The endogenous tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) has anti-inflammatory and antifibrotic effects in the heart and kidney. However, it is not known whether Ac-SDKP has an anti-inflammatory and antifibrotic effect on conduit arteries such as the aorta. We hypothesize that in ANG II-induced hypertension Ac-SDKP prevents aortic fibrosis and that this effect is associated with decreased protein kinase C (PKC) activation, leading to reduced oxidative stress and inflammation and a decrease in the profibrotic cytokine transforming growth factor-beta1 (TGF-beta1) and phosphorylation of its second messenger Smad2. To test this hypothesis we used rats with ANG II-induced hypertension and treated them with either vehicle or Ac-SDKP. In this hypertensive model we found an increased collagen deposition and collagen type I and III mRNA expression in the aorta. These changes were associated with increased PKC activation, oxidative stress, intercellular adhesion molecule (ICAM)-1 mRNA expression, and macrophage infiltration. TGF-beta1 expression and Smad2 phosphorylation also increased. Ac-SDKP prevented these effects without decreasing blood pressure or aortic hypertrophy. Ac-SDKP also enhanced expression of inhibitory Smad7. These data indicate that in ANG II-induced hypertension Ac-SDKP has an aortic antifibrotic effect. This effect may be due in part to inhibition of PKC activation, which in turn could reduce oxidative stress, ICAM-1 expression, and macrophage infiltration. Part of the effect of Ac-SDKP could also be due to reduced expression of the profibrotic cytokine TGF-beta1 and inhibition of Smad2 phosphorylation.

Role of cardiac overexpression of ANG II in the regulation of cardiac function and remodeling postmyocardial infarction.

ANG II has a clear role in development of cardiac hypertrophy, fibrosis, and dysfunction. It has been difficult, however, to determine whether these actions are direct or consequences of its systemic hemodynamic effects in vivo. To overcome this limitation, we used transgenic mice with cardiac-specific expression of a transgene fusion protein that releases ANG II from cardiomyocytes (Tg-ANG II-cardiac) without involvement of the systemic renin-angiotensin system and tested whether increased cardiac ANG II accelerates remodeling and dysfunction postmyocardial infarction (MI), whereas those mice show no evidence of cardiac hypertrophy under the basal condition. Male 12- to 14-wk-old Tg-ANG II-cardiac mice and their wild-type littermates (WT) were subjected to sham-MI or MI by ligating the left anterior descending coronary artery for 8 wk. Cardiac ANG II levels were approximately 10-fold higher in Tg-ANG II-cardiac mice than their WT, whereas ANG II levels in plasma and other tissues did not differ between strains. Systolic blood pressure and heart rate were similar between groups with or without MI. In sham-MI, Tg-ANG II-cardiac mice had increased collagen deposition and decreased capillary density. The differences between strains became more pronounced after MI. Although cardiac function was well preserved in the Tg-ANG II-cardiac mice with sham-MI, cardiac remodeling and dysfunction post-MI were more severe than WT. Our results demonstrate that, independent of systemic hemodynamic effects, cardiac ANG II may act locally in the heart, causing interstitial fibrosis in sham-MI and accelerating deterioration of cardiac dysfunction and remodeling post-MI.

Lack of inducible NO synthase reduces oxidative stress and enhances cardiac response to isoproterenol in mice with deoxycorticosterone acetate-salt hypertension.

Although NO derived from endothelial NO synthase (eNOS) is thought to be cardioprotective, the role of inducible NO synthase (iNOS) remains controversial. Using mice lacking iNOS (iNOS-/-), we studied (1) whether development of hypertension, cardiac hypertrophy, and dysfunction after deoxycorticosterone acetate (DOCA)-salt would be less severe compared with wild-type controls (WT; C57BL/6J), and (2) whether the cardioprotection attributable to lack of iNOS is mediated by reduced oxidative stress. Mice were uninephrectomized and received either DOCA-salt (30 mg/mouse SC and 1% NaCl+0.2% KCl in drinking water) or vehicle (tap water) for 12 weeks. Systolic blood pressure (SBP) was measured weekly. Left ventricular (LV) ejection fraction (EF) by echocardiography and cardiac response to isoproterenol (50 ng/mouse IV) were studied at the end of the experiment. Expression of eNOS and iNOS as well as the oxidative stress markers 4-hydroxy-2-nonenal (4-HNE, a marker of lipid peroxidation) and nitrotyrosine (a marker for peroxynitrite) were determined by Western blot and immunohistochemical staining, respectively. DOCA-salt increased SBP and LV weight similarly in both strains and decreased EF in WT but not in iNOS-/-. Cardiac contractile and relaxation responses to isoproterenol were greater, 4-HNE and nitrotyrosine levels were lower, and eNOS expression tended to be higher in iNOS-/-. We conclude that lack of iNOS leads to better preservation of cardiac function, which may be mediated by reduced oxidative stress and increased eNOS; however, it does not seem to play a significant role in preventing DOCA-salt-induced hypertension and hypertrophy.

PDGF-D contributes to neointimal hyperplasia in rat model of vessel injury.

In this study, we determined the role of PDGF-D, a new member of the PDGF family, in a rat model of balloon injured artery made with a 2F catheter in Sprague-Dawley male rats. PDGF-D expression was studied in the injured and control segments of abdominal aorta. The function of PDGF-D was evaluated in rat vascular smooth muscle cells stably transfected with PDGF-D gene. We found that in normal abdominal aorta, PDGF-D was highly expressed in adventia, moderate in endothelia, and unidentified in media. Stable transfection of PDGF-D gene into vascular smooth muscle cells increased the cell migration by 2.2-fold, and the proliferation by 2.3-fold, respectively, and MMP-2 production and activity as well. These results support the fact that PDGF-D is involved in the formation of neointimal hyperplasia induced by balloon catheter injury and may serve as a target in preventing vascular restenosis after coronary angioplasty.

Clinical and electrophysiological characterization of a novel mutation R863X in HERG C-terminus associated with long QT syndrome.

We have found a novel nonsense mutation in the C-terminus of HERG in a four-generation Chinese family with long QT syndrome and investigated the molecular mechanism of this mutation in vitro. Six family members, including the proband, were clinically affected. Syncope and ventricular tachycardia of torsades de pointes were triggered by startling or emotional stress, and beta-adrenergic blockade treatment was ineffective. Haplotype analysis showed that only LQT2 markers cosegregated with the disease, and sequence analysis revealed a substitution of T with C at nucleotide position 2770 of the HERG gene (U04270), which creates a stop codon at amino acid position 863 (R863X) of the HERG protein, leading to a deletion of 296 amino acids. Whole cell patch clamp studies showed that the R863X HERG could not induce time-dependent current. Coexpression of R863X with wild-type HERG showed reduced current densities and accelerated voltage-dependent inactivation of HERG channels. Subcellular localization of R863X-EGFP revealed that the mutant did not traffic to the cell surface. These data suggest that R863X failed to form functional HERG channels, contributing to a prolongation of the QT interval and long QT syndrome with a dominant phenotype. These findings provide new insights into the structure-function relationships of the HERG C-terminus.

Characterization of a novel Long QT syndrome mutation G52R-KCNE1 in a Chinese family.

OBJECTIVES: To identify the underlying genetic basis of a Chinese pedigree with Long QT syndrome, the causally related genes were screened in a family and the functional consequence of the identified gene mutation was evaluated in vitro. METHODS: Mutations in the five defined Long QT syndrome related genes were screened with polymerase chain reaction and single-strand conformation polymorphism methods and direct sequencing. The electrophysiological properties of the identified mutation were characterized in the Xenopus oocyte heterologous expression system. RESULTS: A novel missense mutation, G to A at position 154 in the KCNE1 gene was identified in a Chinese Long QT syndrome family, which leads to an amino acid substitution of arginine (R) for glycine (G) at position 52 (G52R-KCNE1). Of 26 family members (one DNA was not available), seven were mutation carriers and two of them with normal electrocardiogram. Compared with wild-type KCNE1/KCNQ1 channels, coexpression of G52R-KCNE1 with KCNQ1 in Xenopus oocytes did not amplify the KCNQ1 current amplitudes and slightly changed the activation kinetics of the KCNQ1 channels. Coexpression of KCNQ1 together with wild type KCNE1 and G52R-KCNE1 reduced the wild-type I(ks) current amplitude by 50%, whereas other biophysical properties of the I(ks) were not altered. CONCLUSIONS: Our findings indicate that glycine52 in the transmembrane domain is critical for KCNE1 function. The mutant G52R-KCNE1 has a dominant negative effect on I(ks) current, which reduces the I(ks) current amplitude and leads to a prolongation of the cardiac action potential. This could underlie the molecular mechanism of ventricular arrhythmias and sudden death in those patients.

Novel gene hKCNE4 slows the activation of the KCNQ1 channel.

The KCNE genes encode small, single transmembrane domain peptides that associate with pore-forming potassium channel subunits to form mixed complexes with unique characteristics. We have identified a novel member of the human KCNE gene family, hKCNE4. The hKCNE4 gene encodes 170 amino acid protein and is localized to chromosome 2q35-36. The protein sequence shows 90% homology to mouse KCNE4 and 38% identity to human KCNE1. Northern blot analysis revealed that hKCNE4 is expressed strongly in heart, skeletal muscle, and kidney, less in placenta, lung, and liver, and weakly in brain and blood cells. Electrophysiological study showed that hKCNE4 modulates the activation of the KCNQ1 channel.