Novel interacting proteins identified by tandem affinity purification and mass spectrometry associated with IFITM3 protein during PDCoV infection.

Interferon-induced transmembrane 3 (IFITM3) is a membrane-associated protein that exhibits antiviral activities against a wide range of viruses through interactions with other cellular and viral proteins. However, knowledge of the mechanisms of IFITM3 in Porcine deltacoronavirus (PDCoV) infection has been lacking. In this study, we demonstrate that IFN-α treatment induces the upregulation of IFITM3 activity and thus attenuates PDCoV infection. PDCoV replication is inhibited in a dose-dependent manner by IFITM3 overexpression. To clarify the novel roles of IFITM3 during PDCoV infection, proteins that interact with IFITM3 were screened by TAP/MS in an ST cell line stably expressing IFITM3 via a lentivirus. We identified known and novel candidate IFITM3-binding proteins and analyzed the protein complexes using GO annotation, KEGG pathway analysis, and protein interaction network analysis. A total of 362 cellular proteins associate with IFITM3 during the first 24 h post-infection. Of these proteins, the relationship between IFITM3 and Rab9a was evaluated by immunofluorescence colocalization analysis using confocal microscopy. IFITM3 partially colocalized with Rab9a and Rab9a exhibited enhanced colocalization following PDCoV infection. We also demonstrated that IFITM3 interacts specifically with Rab9a. Our results considerably expand the protein networks of IFITM3, suggesting that IFITM3 participates in multiple cellular processes during PDCoV infection.

[A new cucurbitane glycoside from Picrorhiza scrophulariiflora].

Chemical constituents from the ethanol extract of Picrorhiza scrophulariiflora were isolated and purified by column chromatography. Their structures were identified by HR-MS, 1D and 2D-NMR, and their cytotoxicity was assessed by CCK-8 assay. Four compounds were isolated and identified as follows: 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosterol-5,25-diene-22-one(1), 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,24-diene-22-one(2), 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5-ene-22-one(3) and 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,23-(E)-diene-22-one(4). Compound 1 represents a new cucurbitane glycoside. The half inhibitory concentrations of the 4 compounds exceeded 100 µmol·L~(-1) against four tumor cell lines, indicating no significant cytotoxicity.

Association of the retinol to all-trans retinoic acid pathway with autism spectrum disorder.

BACKGROUND: Autism spectrum disorder (ASD) is a complex group of neurodevelopmental disorders. Research has highlighted a close association between the retinoic acid (RA) signaling pathway and ASD. This study investigates alterations in the vitamin A (VA, retinol) to RA metabolic pathway in children with ASD and speculates on the underlying reasons for these changes. We propose a subtype characterized by downregulated RA signaling in ASD, laying the groundwork for precise diagnosis and treatment research. METHODS: We included 489 children with ASD and 280 typically developing (TD) children. Those with ASD underwent evaluations of core symptoms and neuro-developmental levels, which were conducted by professional developmental behavior physicians using assessment scales. Serum VA and all-trans RA (atRA) levels were determined by high-performance liquid chromatography and ultra-high-performance liquid chromatography-tandem mass spectrometry. The expression levels and concentrations of enzyme molecules such as retinol dehydrogenase 10 were assessed using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: Children with ASD exhibited reduced serum atRA, accompanied by a downregulation of atRA synthesis enzymes. The reduction in serum atRA levels was linked not only to VA levels but also to the aberrant expression of metabolic enzymes responsible for atRA. Furthermore, the serum atRA levels in children with ASD were more strongly correlated with core symptoms and neurodevelopmental levels than VA levels. CONCLUSION: Children with ASD exhibited a dual regulation of reduced serum atRA levels, influenced by both VA levels and abnormal expression of atRA metabolic enzymes.

Impact factors and obstetric outcomes of preeclampsia in twin pregnancies by prepregnancy body mass index: a six-year retrospective cohort study.

OBJECTIVES: Among many risk factors for preeclampsia (PE), prepregnancy body mass index (BMI) is one of few controllable factors. However, there is a lack of stratified analysis based on the prepregnancy BMI. This study aimed to determine the influencing factors for PE and assess the impact of PE on obstetric outcomes in twin pregnancies by prepregnancy BMI. METHODS: This was a retrospective cohort study between January 1, 2017, and December 31, 2022, in Southwest China. Impact factors and associations between PE and obstetric outcomes were analyzed separately for twin pregnancies with prepregnancy BMI < 24kg/m2 (non-overweight group) and BMI ≥ 24kg/m2 (overweight group). RESULTS: In total, 3602 twin pregnancies were included, of which, 672 women were allocated into the overweight group and 11.8% of them reported with PE; 2930 women were allocated into the non-overweight group, with a PE incidence of 5.6%. PE had a negative effect on birthweight and increased the incidence of neonatal intensive care unit admission in both the overweight and non-overweight groups (43.0% vs. 28.0%, p = .008; 45.7% vs. 29.1%, p < .001). Among overweight women, PE increased the proportion of postpartum hemorrhage (15.2% vs. 4.4%, p < .001). After adjustments, multivariate regression analysis showed that excessive gestational weight gain (aOR = 1.103, 95% CI: 1.056-1.152; aOR = 1.094, 95% CI: 1.064-1.126) and hypoproteinemia (aOR = 2.828, 95% CI: 1.501-5.330; aOR = 6.932, 95% CI: 4.819-9.971) were the shared risk factors for PE in both overweight and non-overweight groups. In overweight group, in vitro fertilization was the other risk factor (aOR = 2.713, 95% CI: 1.183-6.878), whereas dichorionic fertilization (aOR = 0.435, 95% CI: 0.193-0.976) and aspirin use during pregnancy (aOR = 0.456, 95% CI: 0.246-0.844) were protective factors. Additionally, anemia during pregnancy (aOR = 1.542, 95% CI: 1.090-2.180) and growth discordance in twins (aOR = 2.451, 95% CI: 1.215-4.205) were connected with an increased risk of PE only in non-overweight twin pregnancies. CONCLUSIONS: Both discrepancy and similarity of impact factors on developing PE were found between overweight and non-overweight twin pregnancies in this study. However, the dosage and initiation time of aspirin, as well as twin chorionicity on the occurrence of PE in two subgroups, are still debated.

[Serum folate and vitamin B12 levels and their association with neurodevelopmental features in preschool children with autism spectrum disorder]. / å­¦é¾„å‰å­¤ç‹¬ç—‡è°±ç³»éšœç¢å„¿ç«¥è¡€æ¸ å¶é ¸ã€ç»´ç”Ÿç´ B12æ°´å¹³åŠå ¶ä¸Žç¥žç»å‘è‚²ç‰¹å¾çš„å ³è”.

OBJECTIVES: To investigate the levels of serum folate and vitamin B12 (VB12) and their association with the level of neurodevelopment in preschool children with autism spectrum disorder (ASD). METHODS: A total of 324 ASD children aged 2-6 years and 318 healthy children aged 2-6 years were recruited. Serum levels of folate and VB12 were measured using chemiluminescent immunoassay. The Social Responsiveness Scale and the Childhood Autism Rating Scale were used to assess the core symptoms of ASD children, and the Gesell Developmental Schedule was employed to evaluate the level of neurodevelopment. RESULTS: The levels of serum folate and VB12 in ASD children were significantly lower than those in healthy children (P<0.05). Serum folate levels in ASD children were positively correlated with gross and fine motor developmental quotients (P<0.05), and serum VB12 levels were positively correlated with adaptive behavior, fine motor, and language developmental quotients (P<0.05). In ASD children aged 2 to <4 years, serum folate levels were positively correlated with developmental quotients in all domains (P<0.05), and serum VB12 levels were positively correlated with language developmental quotient (P<0.05). In male ASD children, serum VB12 levels were positively correlated with language and personal-social developmental quotients (P<0.05). CONCLUSIONS: Serum folate and VB12 levels in preschool ASD children are lower than those in healthy children and are associated with neurodevelopmental levels, especially in ASD children under 4 years of age. Therefore, maintaining normal serum folate and VB12 levels may be beneficial for the neurodevelopment of ASD children, especially in ASD children under 4 years of age.

Mitochondrial calcium uniporter promotes mitophagy by regulating the PINK1/Parkin pathway in caerulein­treated pancreatic ductal epithelial cells in vitro.

The mitochondrial calcium uniporter (MCU) is a major protein for the uptake of mitochondrial calcium to regulate intracellular energy metabolism, including processes such as mitophagy. The present study investigated the effect of the MCU on mitophagy in pancreatic ductal epithelial cells (PDECs) in acute pancreatitis (AP) in vitro. The normal human PDECs (HPDE6-C7) were treated with caerulein (CAE) to induce AP-like changes, with or without ruthenium red to inhibit the MCU. The mitochondrial membrane potentials (MMPs) and mitochondrial Ca2+ levels were analyzed by fluorescence. The expression levels of MCU, LC3, p62, and translocase of the outer mitochondrial membrane complex subunit 20 (TOMM20), putative kinase 1 (PINK1), and Parkin were measured by western blotting and immunofluorescence. Mitophagy was observed by confocal fluorescence microscopy and transmission electron microscopy. The results showed that CAE increased the MCU protein expression, mitochondrial Ca2+ levels, MMP depolarization and the protein expression of mitophagy markers including the LC3II/I ratio, PINK1, and Parkin. CAE decreased the protein expression of p62 and TOMM20, and promoted the formation of mitophagosomes in HPDE6-C7 cells. Notably, changes in these markers were reversed by inhibiting the MCU. In conclusion, an activated MCU may promote mitophagy by regulating the PINK1/Parkin pathway in PDECs in AP.

Object detection: A novel AI technology for the diagnosis of hepatocyte ballooning.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has reached epidemic proportions worldwide and is the most frequent cause of chronic liver disease in developed countries. Within the spectrum of liver disease in MAFLD, steatohepatitis is a progressive form of liver disease and hepatocyte ballooning (HB) is a cardinal pathological feature of steatohepatitis. The accurate and reproducible diagnosis of HB is therefore critical for the early detection and treatment of steatohepatitis. Currently, a diagnosis of HB relies on pathological examination by expert pathologists, which may be a time-consuming and subjective process. Hence, there has been interest in developing automated methods for diagnosing HB. This narrative review briefly discusses the development of artificial intelligence (AI) technology for diagnosing fatty liver disease pathology over the last 30 years and provides an overview of the current research status of AI algorithms for the identification of HB, including published articles on traditional machine learning algorithms and deep learning algorithms. This narrative review also provides a summary of object detection algorithms, including the principles, historical developments, and applications in the medical image analysis. The potential benefits of object detection algorithms for HB diagnosis (specifically those combined with a transformer architecture) are discussed, along with the future directions of object detection algorithms in HB diagnosis and the potential applications of generative AI on transformer architecture in this field. In conclusion, object detection algorithms have huge potential for the identification of HB and could make the diagnosis of MAFLD more accurate and efficient in the near future.

Programmable DNA Hydrogel Assisting Microcrystal Formulations for Sustained Locoregional Drug Delivery in Surgical Residual Tumor Lesions and Lymph Node Metastasis.

Surgical residual tumor lesions (R1 resection of surgical procedures (e.g., liver cancer infiltrating the diaphragm, surgical residual breast cancer, postoperative residual ovarian cancer) or boundary residual after ablation) and lymph node metastasis that cannot be surgically resected (retroperitoneal lymph nodes) significantly affect postoperative survival of tumor patients. This clinical conundrum poses three challenges for local drug delivery systems: stable and continuous delivery, good biocompatibility, and the ability to package new targeted drugs that can synergize with other treatments. Here, a drug-laden hydrogel generated from pure DNA strands and highly programmable in adjusting its mesh size is reported. Meanwhile, the DNA hydrogel can assist the microcrystallization of novel radiosensitizing drugs, ataxia telangiectasia and rad3-related protein (ATR) inhibitor (Elimusertib), further facilitating its long-term release. When applied to the tumor site, the hydrogel system demonstrates significant antitumor activity, minimized systemic toxicity, and has a modulatory effect on the tumor-immune cell interface. This drug-loaded DNA-hydrogel platform represents a novel modality for adjuvant therapy in patients with surgical residual tumor lesions and lymph node metastasis.

Single-cell morphological and topological atlas reveals the ecosystem diversity of human breast cancer.

Digital pathology allows computerized analysis of tumor ecosystem using whole slide images (WSIs). Here, we present single-cell morphological and topological profiling (sc-MTOP) to characterize tumor ecosystem by extracting the features of nuclear morphology and intercellular spatial relationship for individual cells. We construct a single-cell atlas comprising 410 million cells from 637 breast cancer WSIs and dissect the phenotypic diversity within tumor, inflammatory and stroma cells respectively. Spatially-resolved analysis identifies recurrent micro-ecological modules representing locoregional multicellular structures and reveals four breast cancer ecotypes correlating with distinct molecular features and patient prognosis. Further analysis with multiomics data uncovers clinically relevant ecosystem features. High abundance of locally-aggregated inflammatory cells indicates immune-activated tumor microenvironment and favorable immunotherapy response in triple-negative breast cancers. Morphological intratumor heterogeneity of tumor nuclei correlates with cell cycle pathway activation and CDK inhibitors responsiveness in hormone receptor-positive cases. sc-MTOP enables using WSIs to characterize tumor ecosystems at the single-cell level.

Mechanism and application of modified bioelectrochemical system anodes made of carbon nanomaterial for the removal of heavy metals from soil.

Bioelectrochemical techniques are quick, efficient, and sustainable alternatives for treating heavy metal soils. The use of carbon nanomaterials in combination with electroactive microorganisms can create a conductive network that mediates long-distance electron transfer in an electrode system, thereby resolving the issue of low electron transfer efficiency in soil remediation. As a multifunctional soil heavy metal remediation technology, its application in organic remediation has matured, and numerous studies have demonstrated its potential for soil heavy metal remediation. This is a ground-breaking method for remediating soils polluted with high concentrations of heavy metals using soil microbial electrochemistry. This review summarizes the use of bioelectrochemical systems with modified anode materials for the remediation of soils with high heavy metal concentrations by discussing the mass-transfer mechanism of electrochemically active microorganisms in bioelectrochemical systems, focusing on the suitability of carbon nanomaterials and acidophilic bacteria. Finally, we discuss the emerging limitations of bioelectrochemical systems, and future research efforts to improve their performance and facilitate practical applications. The mass-transfer mechanism of electrochemically active microorganisms in bioelectrochemical systems emphasizes the suitability of carbon nanomaterials and acidophilic bacteria for remediating soils polluted with high concentrations of heavy metals. We conclude by discussing present and future research initiatives for bioelectrochemical systems to enhance their performance and facilitate practical applications. As a result, this study can close any gaps in the development of bioelectrochemical systems and guide their practical application in remediating heavy-metal-contaminated soils.

Comparison of two echocardiography-based methods for evaluating pediatric left ventricular diastolic dysfunction.

Objectives: To investigate the consistency between the 2016 America Society of Echocardiography (ASE)/European Association of Cardiovascular Imaging (EACVI) guideline-based recommendations and the body surface area (BSA)-transformed Z value-based cut-off for the assessment of left ventricular diastolic function (LVDF) in children. Methods: Clinical data of children with heart failure (HF) and those with a high risk of HF and a low risk of HF were collected from the Children's Hospital of Chongqing Medical University between March 2021 and October 2022. The mitral annular e' velocity, lateral E/e' ratio, left atrial volume index, and peak tricuspid regurgitation velocity were detected by Echocardiography. The cut-off values recommended by the 2016 ASE/EACVI guidelines and the cut-off value based on the BSA-transformed Z value were used to evaluate LVDF. The consistencies and differences of the two criteria were compared. Results: A total of 132 children with HF, 189 with a high risk of HF, and 231 with a low risk of HF, were enrolled. The consistency of the two criteria in evaluating LVDF in children with HF and with high risk of HF was moderate, with weighted kappa coefficients of 0.566 and 0.468, respectively (P < 0.001). The positivity rate of left ventricular diastolic dysfunction (LVDD) with Z value-based criteria (HF group, 23.5%; high-risk group, 8.5%) was higher than that with guideline-based criteria (HF group, 15.6%; high-risk group, 3.2%). In children with a low risk of HF, no case with LVDD was found. The consistency between the two criteria for grading the degree of LVDD was moderate, with a kappa coefficient of 0.522 (P = 0.001). The degree of LVDD according to the Z value-based criteria was higher than that of the guideline-based criteria (P = 0.004). Conclusions: The Z value-based criteria used to evaluate LVDD in children with HF and high risk of HF may be more conducive to the early identification of LVDD, thereby permitting the possibility of early treatment intervention.

Analysis on the current situation of twin breastfeeding and its influencing factors.

Studies have found that exclusive breastfeeding can not only promote the growth and development of infants, but also increase the emotional communication between mothers and infants, and reduce the incidence of maternal breast diseases. To analysis the current situation and influencing factors of breastfeeding twins. A total of 420 twin mothers delivered in our hospital from January 2019 to December 2022 were selected to investigate the situation of breastfeeding within 6 months after delivery. An electronic questionnaire was conducted, and clinical information were collected. Univariate analysis and multivariate logistic regression analysis were applied to analyze the factors influencing exclusive breastfeeding. The rate of exclusive breastfeeding was 21.90%; in the exclusive breastfeeding group, the age <35 years old, bachelor degree or above, rural areas, no nipple depression or flat, no breast distension, no postpartum depression, adequate breast milk, participation in health education during pregnancy, husband support for breastfeeding, no infant feeding difficulties, infant diarrhea, lactose intolerance and return to milk were 96.74%, 53.26%, 65.22%, 80.43%, 76.09%, 80.43%, 73.91%, 63.04%, 69.57%, 71.74%, 65.22%, 70.65%, and 66.30%, respectively. It was significantly higher than that in the non-exclusive breastfeeding group (P < .05). The score of Edinburgh Postpartum Depression Scale (EPDS) was (8.08 ± 1.03) in the exclusive breastfeeding group, which was significantly lower than that in the non-exclusive breastfeeding group (P < .001), while the score of Perceived Social Support Scale (PSSS) was (67.32 ± 9.92), which was significantly higher than that in the non-exclusive breastfeeding one(P < .001). Logistic regression analysis showed that age, education level, nipple depression or flat, breast tenderness, postpartum depression, breast milk volume, health education training during pregnancy, husband support for breastfeeding, PSSS score, infant diarrhea, lactose intolerance, and delectation were the influencing factors of exclusive breastfeeding (P < .001). Our findings suggest that various factors were associated with a low rate of exclusive breastfeeding in twin births, such as age, educational level, and social support. Corresponding measures should be formulated for intervention to promote exclusive breastfeeding.

Research Note: A recombinant duck-derived H6N2 subtype avian influenza virus can replicate and shed in young chickens and cause disease.

The H6N2 subtype avian influenza virus (AIV) is commonly detected in the migratory waterfowl reservoirs. Previously, H6N2 AIV was believed to be nonpathogenic to young chickens and could not infect or shed in their respiratory tract under experimental conditions. However, in present study, a highly recombinant strain of duck-derived H6N2 AIV was discovered and isolated for pathogenicity tests. The results revealed that H6N2 could induce seroconversion in chickens and high morbidity of over 86.7%, along with evident upper respiratory tract hemorrhage. Moreover, 5 substitutions were detected in the upper respiratory tract shedding reisolated virus, with a high viral load in the target organs of infected chickens. In contrast, ducks failed to exhibit any symptoms, pathological lesions, or viral shedding, while demonstrated seroconversion and high viral load in the livers. These findings indicate that H6N2 AIV could also show pathogenicity to chickens under experimental conditions, thereby effectively replicating and shedding in chickens. Therefore, the study provides further elucidations on the pathogenicity of H6N2 AIV.

Irritable bowel syndrome: Epidemiology, overlap disorders, pathophysiology and treatment.

Irritable bowel syndrome (IBS) is a common chronic gastrointestinal disease with a significant impact on patients' quality of life and a high socioeconomic burden. And the understanding of IBS has changed since the release of the Rome IV diagnosis in 2016. With the upcoming Rome V revision, it is necessary to review the results of IBS research in recent years. In this review of IBS, we can highlight future concerns by reviewing the results of IBS research on epidemiology, overlap disorders, pathophysiology, and treatment over the past decade and summarizing the latest research.

Enhancement of phytoextraction efficiency coupling Pteris vittata with low-dose biochar in arsenic-contaminated soil.

Phytoremediation of arsenic (As) by Pteris vittata (P. vittata) is a cost-effective and environmentally friendly method for restoring As-contaminated sites. However, the phytoextraction efficiency is low in some cases, such as clay soil, thus biochar was applied to enhance the efficiency of As extraction. The paper investigated the effect of biochar on soil characteristic, As mobility, and As uptake in P. vittata with a 90-day greenhouse experiment. Biochar derived from rice straw was added at rates of 0.5, 1.5, and 4% (w/w). The results showed that, under biochar amendment, soil pH raised from 5.24 to 6.03 and 4.91 to 5.85, soil dissolved organic carbon (DOC) increased 11.1-46.1% and 2.8-11.2%, respectively, in rhizosphere and bulk soils. Biochar also increased soil catalase (CAT) activity significantly, especially for the rhizosphere soil. Besides, biochar increased the labile As in the soils and transfer coefficient from roots to aboveground, thereby enhancing As accumulation by P. vittata tissues. The accumulation of As in fronds of P. vittata was up to 350 mg kg-1 in 1.5% biochar, which was more than twice the control and far beyond other biochar treatments. The results indicate that biochar addition is favorable to improve phytoremediation of P. vittata in As-contaminated soil and 1.5% (w/w) biochar may be a reasonable application ratio, thus providing an effective solution to enhance the efficiency of As phytoextraction.

Biochar increased soil catalase activity in the rhizosphere of P. vittata.Biochar increased the labile concentration of arsenic in soil and arsenic accumulation in P. vittata significantly.Combining biochar and P. vittata reduced arsenic in soil.Biochar amendment was favorable for phytoremediation of P. vittata in arsenic-contaminated soil.

Clinical, Morphological, and Molecular Study on Grade 2 and 3 Pleomorphic Xanthoastrocytoma.

PURPOSE: Pleomorphic xanthoastrocytoma (PXA) is an uncommon astrocytoma that tends to occur in children and young adults and has a relatively favorable prognosis. The 2021 WHO classification of tumors of the central nervous system (CNS WHO), 5th edition, rates PXAs as grade 2 and grade 3. The histological grading was based on mitotic activity (≥2.5 mitoses/mm2). This study specifically evaluates the clinical, morphological, and, especially, the molecular characteristics of grade 2 and 3 PXAs. METHODS: Between 2003 and 2021, we characterized 53 tumors with histologically defined grade 2 PXA (n = 36, 68%) and grade 3 PXA (n = 17, 32%). RESULTS: Compared with grade 2 PXA, grade 3 PXA has a deeper location and no superiority in the temporal lobe and is more likely to be accompanied by peritumoral edema. In histomorphology, epithelioid cells and necrosis were more likely to occur in grade 3 PXA. Molecular analysis found that the TERT promoter mutation was more prevalent in grade 3 PXA than in grade 2 PXA (35% vs. 3%; p = 0.0005) and all mutation sites were C228T. The cases without BRAF V600E mutation or with necrosis in grade 3 PXA had a poor prognosis (p = 0.01). CONCLUSION: These data define PXA as a heterogeneous astrocytoma. Grade 2 and grade 3 PXAs have different clinical and histological characteristics as well as distinct molecular profiles. TERT promoter mutations may be a significant genetic event associated with anaplastic progression. Necrosis and BRAF V600E mutation play an important role in the prognosis of grade 3 PXA.

Small noncoding vault RNA2-1 disrupts gut epithelial barrier function via interaction with HuR.

Vault RNAs (vtRNAs) are small noncoding RNAs and highly expressed in many eukaryotes. Here, we identified vtRNA2-1 as a novel regulator of the intestinal barrier via interaction with RNA-binding protein HuR. Intestinal mucosal tissues from patients with inflammatory bowel diseases and from mice with colitis or sepsis express increased levels of vtRNAs relative to controls. Ectopically expressed vtRNA2-1 decreases the levels of intercellular junction (IJ) proteins claudin 1, occludin, and E-cadherin and causes intestinal epithelial barrier dysfunction in vitro, whereas vtRNA2-1 silencing promotes barrier function. Increased vtRNA2-1 also decreases IJs in intestinal organoid, inhibits epithelial renewal, and causes Paneth cell defects ex vivo. Elevating the levels of tissue vtRNA2-1 in the intestinal mucosa increases the vulnerability of the gut barrier to septic stress in mice. vtRNA2-1 interacts with HuR and prevents HuR binding to claudin 1 and occludin mRNAs, thus decreasing their translation. These results indicate that vtRNA2-1 impairs intestinal barrier function by repressing HuR-facilitated translation of claudin 1 and occludin.

The conserved L1089 in the S2 subunit of avian infectious bronchitis virus determines viral kidney tropism by disrupting virus-cell fusion.

The virulence of avian gamma-coronavirus infectious bronchitis viruses (IBV) for the kidney has led to high mortality in dominant-genotype isolations, but the key sites of viral protein that determine kidney tropism are still not fully clear. In this study, the amino acid sequences of the S2 subunit of IBVs with opposing adaptivity to chicken embryonic kidney cells (CEKs) were aligned to identify putative sites associated with differences in viral adaptability. The S2 gene and the putative sites of the non-adapted CN strain were introduced into the CEKs-adapted SczyC30 strain to rescue seven mutants. Analysis of growth characteristics showed that the replacement of the entire S2 subunit and the L1089I substitution in the S2 subunit entirely abolished the proliferation of recombinant IBV in CEKs as well as in primary chicken oviduct epithelial cells. Pathogenicity assays also support the decisive role of this L1089 for viral nephrotropism, and this non-nephrotropic L1089I substitution significantly attenuates pathogenicity. Analysis of the putative cause of proliferation inhibition in CEKs suggests that the L1089I substitution affects neither virus attachment nor endocytosis, but instead fails to form double-membrane vesicles to initiate the viral replication and translation. Position 1089 of the IBV S2 subunit is conservative and predicted to lie in heptad repeat 2 domains. It is therefore reasonable to conclude that the L1089I substitution alters the nephrotropism of parent strain by affecting virus-cell fusion. These findings provide crucial insights into the adaptive mechanisms of IBV and have applications in the development of vaccines and drugs against IB.

A nomogram to predict preterm birth in twin pregnancies.

PURPOSE: To investigate risk factors for preterm birth in twin pregnancies, and to establish a nomogram model for predicting preterm birth and verify its application value. METHODS: Data from 266 twin pregnancies between January 2015 and December 2020 were analyzed in this retrospective study. According to the gestational weeks of delivery, the included subjects were divided into a preterm birth group (gestational age < 37 weeks) and a full-term group (gestational age ≥ 37 weeks). The general situation and pregnancy complications of the two groups were analyzed by univariate analysis, and the factors with statistical significance were entered into multivariate logistic regression analysis. Furthermore, the nomogram model for predicting the risk of preterm birth was established by using R. The predictive effect of the model was evaluated by the area under the ROC curve, C-index, and decision curve analysis. RESULTS: Demographic characteristics and their associations with preterm birth and full-term birth in twin pregnancies were summarized and analyzed. After validation, we identified the following significant predictors of preterm birth: chorionic status, inconsistent development of twins, premature rupture of membranes, fetal distress, scar uterus, and preeclampsia. Overall, we constructed preterm risk nomogram model with C-index of 0.783. A nomogram using a 0-100 scale illustrated our final model for predicting preterm birth in twin pregnancies. CONCLUSIONS: We developed and validated a clinical nomogram to predict preterm birth in twin pregnancy. Chorionic status, inconsistent development of twins, premature rupture of membranes, fetal distress, scar uterus, and preeclampsia were independent risk predictors for preterm birth in twin pregnancy.

In Situ S-Doping Strategy of Promoting Iron Coordinated by Nitrogen-Doped Carbon Nanosheets for Efficient Oxygen Reduction Reaction.

Improving transition metal-nitrogen-carbon (M-N-C) as a noble-metal-free catalyst for the oxygen reduction reaction (ORR) is critical to achieve low-cost electrochemical energy conversion. Herein, an in situ S doping strategy of enhancing Fe-N-C activity for ORR was developed by newly designed Fe(II) ion coordinated S-containing bis(imino)-pyridine-based polymers as precursors, which were synthesized through copolymerizing three monomers of 2, 6-diacetylpyridine (DAP), triamterene (TIT), and 2,5-dithiobiurea (DTB) as both N and S sources. All samples derived from various molar ratios of the three monomers possess a self-supporting structure of nanosheets. Additionally, incorporating DTB into the copolymer can not only strongly affect the derived coordinative species of N dopants to Fe atom but also effectively induce the synergistic effect between S dopants and FeNx moieties, resulting a significant improvement for ORR. The S-doped Fe-N-C nansheets with Fe coordinated by 4 pyrrolic N dopants exhibit the highest ORR activity and stability in alkaline media with a higher power output of Zn-air battery than that of the same loading of Pt/C. Theoretical calculation identifies that the thiophenic S dopant adjacent to Fe-pyrrolic N moiety can decrease the d band center of Fe atom, greatly weakening the energy profiles of oxygenated intermediates and thus enhancing ORR. In addition, because of the designability of transition metal coordinated S-containing bis(imino)-pyridine based polymers in the work, therefore, it is believable that this strategy would open a wide space to explore the structural relationship between precursors and MNx active sites with S dopants for the purpose of achieving highly efficient and robust M-N-C catalysts for energy-related electrocatalysis.