Development and validation of a prognostic prediction model for cervical cancer patients treated with radical radiotherapy: a study based on TCGA database.

Background: Radiotherapy or concurrent chemoradiotherapy is the standard treatment for patients with locally advanced or inoperable cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). However, treatment failure for CESC patients treated with radical radiotherapy still occurs due to local recurrence and distant metastasis. The previous prediction models were focused on all CESC patients, neglecting the prognostic differences under different treatment modalities. Therefore, there is a pressing demand to explore novel biomarkers for the prognosis and sensitivity of radiotherapy in CESC patients treated with radical radiotherapy. As a single biomarker has limited effect in stratifying these patients, our objective was to identify radioresponse-related mRNAs to ameliorate forecast of the prognosis for CESC patients treated with radical radiotherapy. Methods: Sample data on CESC patients treated with radical radiotherapy were obtained from The Cancer Genome Atlas (TCGA) database. We randomly separated these patients into a training and test cohorts using a 1:1 ratio. Differential expression analysis was carried out to identify radioresponse-related mRNA sets that were significantly dysregulated between complete response (CR) and radiographic progressive disease (RPD) groups, and univariate Cox regression analyses, least absolute shrinkage and selection operator (LASSO) method and multivariate Cox regression were performed to identify the radioresponse-related signature in the training cohort. we adopted survival analysis to measure the predictive value of the radioresponse-related signature both in the test and entire cohorts. Moreover, we developed a novel nomogram to predict the overall survival (OS) of CESC patients treated with radical radiotherapy. In addition, immune infiltration analysis and Gene Set Enrichment Analysis (GSEA) were conducted to preliminarily explore possible mechanisms. Results: This study included a total of 92 CESC patients subjected to radical radiotherapy. We developed and verified a risk score model based on radioresponse-related mRNA. The radioresponse-related mRNA signature and International Federation of Gynecology and Obstetrics (FIGO) stage were served as independent prognostic factors for CESC patients treated with radical radiotherapy. Moreover, a nomogram integrating radioresponse-related mRNA signature with FIGO stage was established to perform better for predicting 1-, 3-, and 5-year survival rates. Mechanically, the low-risk group under the risk score of this model had a better survival status, and the distribution of CD4 T cells was potentially involved in the regulation of radiotherapy response in CESC, leading to a better survival outcome in the low-risk group. Conclusions: This study presents a new radioresponse-related mRNA signature that shows promising clinical efficacy in predicting the prognosis of CESC patients treated with radical radiotherapy.

Pan-cancer prognostic model and immune microenvironment analysis of natural killer cell-related genes.

Background: Natural killer (NK) cells play a significant role in antitumor immunity and are closely related to tumor prognosis and recurrence. NK cell-based tumor immunotherapy, including immune checkpoint inhibition and CAR-engineered NK cells, is a promising area of research. However, there is a need for better NK cell-related models and associated biomarkers. Methods: The sequences of NK cell-related genes were obtained from the published NK cell CRISPR/Cas9 library data, and the common genes were selected as NK cell-related genes. The RNA sequencing (RNA-seq) and clinical data of 32 solid tumors from The Cancer Genome Atlas (TCGA) were downloaded from the UCSC Xena database, and the RNA-seq data of normal samples were downloaded from the Genotype-Tissue Expression (GTEx) database. The differentially expressed NK cell-related genes (DENKGs) between the tumor and normal samples were analyzed. The DENKGs related to the prognosis of solid tumors were selected via univariate Cox analysis, and 32 kinds of solid tumor prognostic models were constructed using least absolute shrinkage and selection operator (LASSO) and multivariate Cox analysis. Survival, receiver operating characteristic (ROC), and independent prognostic analyses were employed to test the effectiveness of the model, along with a nomogram model and prediction curve. Differences in the immune pathways and microenvironment cells were analyzed between the high- and low-risk groups identified by the model. Results: We constructed a pan-cancer prognostic model with 63 NK cell-related genes and further identified DEPDC1 and ASPM as potentially offering new directions in tumor research by literature screening. Conclusions: In this study, 63 prognostic solid tumor markers were investigated using NK cell-related genes, and for the first time, a pan-cancer prognostic model was constructed to analyze their role in the immune microenvironment, which may contribute new insights into tumor research.

First report of large-berry coffee (Coffea liberica) anthracnose caused by Colletotrichum kahawae in China.

Large-berry coffee (Coffea liberica) is one of the three cultivated coffee species and a precious breeding germplasm in China (Yan et al, 2019). Anthracnose is a damaging epidemic disease on coffee worldwide (Mohammed et al. 2015). Between June and September 2022, anthracnose was observed on coffee plants in Puer area, Yunnan, China and disease incidence (% plants diseased) of 8.5%-28.2% was recorded in the field. The disease symptoms were observed at all growth stages. Lesions on leaves were circular or oval, with a white to gray central zone outlined by a brown margin and surrounded by a chlorotic halo, Φ5.1-18.5 mm; some lesions extended and coalesced later to form large, blighted areas, leading to complete leaf senescence, defoliation and bare blighted branches on heavily infected trees. The spots on coffee berries were oval or fusiform, sunken and brown-black; diseased berries became gray-black and dried-out but remained on the tree. Leaves with typical anthracnose lesions were collected from fields in Simao ( 22.07°E,100.98°N) to isolate the pathogen. Leaf pieces (5×5mm) from the lesion margin were cut, surface-sterilized with 75% ethanol and 2% NaClO, and cultured on PDA at 25°C. Three isolates with the same colony morphology were obtained by hyphal tip purification. Detached and intact leaves of 6-month coffee seedlings were inoculated with Φ5mm mycelial discs of the isolates. Anthracnose lesions developed on the inoculated leaves, with all 3 isolates, 7d after incubation in a growth chamber (25°C, > 90% RH and lighting 8 h/d at 11000 lux). Pathogens with the same colony morphology as those of the original isolates were re-isolated from the infected tissues of inoculated leaves, thus fulfilling Koch's Postulates. The ITS sequence (PP550861) for the isolate was PCR-amplified and Blast-n analyses showed 100 % (554/554bp) identity to Colletotrichum kahawae LWTJ01; so they were the same population and coded as KFTJ02. The actin (ACT), calmodulin(CAL), glyceraldehydes-3-phosphate dehydrogenase (GAPHD) and histone 3 (HIS3) genes (Qiu et al. 2020) were amplified from one of KFTJ02 isolates, sequenced and deposited in NCBI GenBank (OR842543, OR842544, OR842545 & OR842546). A phylogenetic tree was generated based on the concatenated sequences of the four genes and those of related Colletotrichum spp. using MEGA 6.0 and KFTJ02 clustered in the same clade with C. kahawae IMI319418 on the tree (Bootstrap sup.=88%). When cultured at 25°C on PDA for 7 days, its colonies were near round or ovoid, gray-white, contoured, Φ73.2-80.1 (76.2±2.3)mm or growth rate 10.2-11.1(8.1) mm/d (n=10). The hyphae were hyaline, septated, branching at near right angles. Conidial masses formed 14 days after incubation. The conidia were elliptical, hyaline, monocellular, 10.2-15.5 (12.7±1.06)×3.8-5.2 (4.3±0.52) µm (n=50). The appressoria were black-brown, oval or irregular, 7.8-9.3 (8.5±0.81)µm (n= 50). These morphological characteristics were consistent with those of C. kahawae (Bridge et al, 2008). Therefore, KFTJ02 was identified as C. kahawae, which has been found to infect Camellia oleifera, Areca catechu and Ficus microcarpa (Wei et al, 2023; Zhang et al, 2020; Lin 2023). The coffee berry disease pathogen (C. kahawae) is a quarantine species which has not been recorded and so it is first reported on coffee crops in China. Results of the present study provide important references for further studies on this disease.

The impact of poverty alleviation policy on the industrial structure: Evidence from the Qinba Mountain contiguous poverty-stricken areas.

In 2015, the Chinese government issued the Decision on Poverty Alleviation(DPA), requiring poverty-stricken areas to develop local characteristic industries based on their resource endowments, to promote industrial structure diversification and industrial structure upgrading through industry-driven poverty alleviation. However, existing research lacks empirical analysis to evaluate it. Therefore, this paper takes poor counties in the Qinba Mountain contiguous poverty-stricken areas(QMCPA) as an example, using the difference in difference model and boundary effect model to evaluate whether DPA has promoted industrial structure upgrading and industrial structure diversification in poor counties. The results show that the DPA has promoted industrial structure upgrading and improved industrial structure diversification in the QMCPA. However, the effectiveness of it is not sufficient. Poor counties have failed to maintain the policy requirement of developing characteristic industries based on local natural resource endowments, leading to a decline in the degree of industrial structure diversification in the later period of the policy. This study indicates that local governments should strive to develop advantageous industries and form a division of labor and cooperation with neighboring areas, strengthen inter-regional cooperation and contact, and enhance anti-risk capabilities to avoid homogenized competition. Studying the changes in industrial structure in the QMCPA has important significance for the long-term stable development and poverty elimination of various poor areas.

Genetic- and fiber-diet-mediated changes in virulence factors in pig colon contents and feces and their driving factors.

Virulence factors (VFs) are key factors for microorganisms to establish defense mechanisms in the host and enhance their pathogenic potential. However, the spectrum of virulence factors in pig colon and feces, as well as the influence of dietary and genetic factors on them, remains unreported. In this study, we firstly revealed the diversity, abundance and distribution characteristics of VFs in the colonic contents of different breeds of pigs (Taoyuan, Xiangcun and Duroc pig) fed with different fiber levels by using a metagenomic analysis. The analysis resulted in the identification of 1,236 virulence factors, which could be grouped into 16 virulence features. Among these, Taoyuan pigs exhibited significantly higher levels of virulence factors compared to Duroc pigs. The high-fiber diet significantly reduced the abundance of certain virulence factor categories, including iron uptake systems (FbpABC, HitABC) and Ig protease categories in the colon, along with a noteworthy decrease in the relative abundance of plasmid categories in mobile genetic elements (MGEs). Further we examined VFs in feces using absolute quantification. The results showed that high-fiber diets reduce fecal excretion of VFs and that this effect is strongly influenced by MGEs and short-chain fatty acids (SCFAs). In vitro fermentation experiments confirmed that acetic acid (AA) led to a decrease in the relative abundance of VFs (p < 0.1). In conclusion, our findings reveal for the first time how fiber diet and genetic factors affect the distribution of VFs in pig colon contents and feces and their driving factors. This information provides valuable reference data to further improve food safety and animal health.

Proteomics study the potential targets for Rifampicin-resistant spinal tuberculosis.

Introduction: The escalating global surge in Rifampicin-resistant strains poses a formidable challenge to the worldwide campaign against tuberculosis (TB), particularly in developing countries. The frequent reports of suboptimal treatment outcomes, complications, and the absence of definitive treatment guidelines for Rifampicin-resistant spinal TB (DSTB) contribute significantly to the obstacles in its effective management. Consequently, there is an urgent need for innovative and efficacious drugs to address Rifampicin-resistant spinal tuberculosis, minimizing the duration of therapy sessions. This study aims to investigate potential targets for DSTB through comprehensive proteomic and pharmaco-transcriptomic analyses. Methods: Mass spectrometry-based proteomics analysis was employed to validate potential DSTB-related targets. PPI analysis confirmed by Immunohistochemistry (IHC) and Western blot analysis. Results: The proteomics analysis revealed 373 differentially expressed proteins (DEPs), with 137 upregulated and 236 downregulated proteins. Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses delved into the DSTB-related pathways associated with these DEPs. In the context of network pharmacology analysis, five key targets-human leukocyte antigen A chain (HLAA), human leukocyte antigen C chain (HLA-C), HLA Class II Histocompatibility Antigen, DRB1 Beta Chain (HLA-DRB1), metalloproteinase 9 (MMP9), and Phospholipase C-like 1 (PLCL1)-were identified as pivotal players in pathways such as "Antigen processing and presentation" and "Phagosome," which are crucially enriched in DSTB. Moreover, pharmaco-transcriptomic analysis can confirm that 58 drug compounds can regulate the expression of the key targets. Discussion: This research confirms the presence of protein alterations during the Rifampicin-resistant process in DSTB patients, offering novel insights into the molecular mechanisms underpinning DSTB. The findings suggest a promising avenue for the development of targeted drugs to enhance the management of Rifampicin-resistant spinal tuberculosis.

Non-invasive prediction of preeclampsia using the maternal plasma cell-free DNA profile and clinical risk factors.

Background: Preeclampsia (PE) is a pregnancy complication defined by new onset hypertension and proteinuria or other maternal organ damage after 20 weeks of gestation. Although non-invasive prenatal testing (NIPT) has been widely used to detect fetal chromosomal abnormalities during pregnancy, its performance in combination with maternal risk factors to screen for PE has not been extensively validated. Our aim was to develop and validate classifiers that predict early- or late-onset PE using the maternal plasma cell-free DNA (cfDNA) profile and clinical risk factors. Methods: We retrospectively collected and analyzed NIPT data of 2,727 pregnant women aged 24-45 years from four hospitals in China, which had previously been used to screen for fetal aneuploidy at 12 + 0 ~ 22 + 6 weeks of gestation. According to the diagnostic criteria for PE and the time of diagnosis (34 weeks of gestation), a total of 143 early-, 580 late-onset PE samples and 2,004 healthy controls were included. The wilcoxon rank sum test was used to identify the cfDNA profile for PE prediction. The Fisher's exact test and Mann-Whitney U-test were used to compare categorical and continuous variables of clinical risk factors between PE samples and healthy controls, respectively. Machine learning methods were performed to develop and validate PE classifiers based on the cfDNA profile and clinical risk factors. Results: By using NIPT data to analyze cfDNA coverages in promoter regions, we found the cfDNA profile, which was differential cfDNA coverages in gene promoter regions between PE and healthy controls, could be used to predict early- and late-onset PE. Maternal age, body mass index, parity, past medical histories and method of conception were significantly differential between PE and healthy pregnant women. With a false positive rate of 10%, the classifiers based on the combination of the cfDNA profile and clinical risk factors predicted early- and late-onset PE in four datasets with an average accuracy of 89 and 80% and an average sensitivity of 63 and 48%, respectively. Conclusion: Incorporating cfDNA profiles in classifiers might reduce performance variations in PE models based only on clinical risk factors, potentially expanding the application of NIPT in PE screening in the future.

Observation of Anisotropic Second Harmonic Generation in Two-Dimensional Niobium Diselenide.

The intrinsic anisotropy of NbSe2 provides a favorable prerequisite of second harmonic generation (SHG) and rich possibilities for tailoring its nonlinear optical (NLO) properties. Here we report the highly efficient SHG of mechanically exfoliated NbSe2 flakes. The nonlinear optical response changes with excitation wavelengths, layer thicknesses, and polarizations of the excitation laser. The anisotropic SHG response further exhibits the intrinsic non-centrosymmetric crystal structure and could effectively assign the crystalline orientation of NbSe2 flakes. Interestingly, although NbSe2 flakes with tens of nanometers thickness experience attenuations in SHG performance, more efficient SHG anisotropy ratios were obtained, which are around 4 times higher than that of the 5-layer counterpart. The determined second-order nonlinearities of NbSe2 flakes (monolayer: ∼1.0 × 103 pm/V; 3-layer: ∼73 pm/V) are comparable to those of the commonly reported two-dimensional materials (e.g., MoS2, WSe2, graphene) with the same number of layers and much higher than those of commercial nonlinear optical crystals.

The protective role of prebiotics and probiotics on diarrhea and gut damage in the rotavirus-infected piglets.

Rotavirus is one of the pathogenic causes that induce diarrhea in young animals, especially piglets, worldwide. However, nowadays, there is no specific drug available to treat the disease, and the related vaccines have no obvious efficiency in some countries. Via analyzing the pathogenesis of rotavirus, it inducing diarrhea is mainly due to disturb enteric nervous system, destroy gut mucosal integrity, induce intracellular electrolyte imbalance, and impair gut microbiota and immunity. Many studies have already proved that prebiotics and probiotics can mitigate the damage and diarrhea induced by rotavirus infection in hosts. Based on these, the current review summarizes and discusses the effects and mechanisms of prebiotics and probiotics on rotavirus-induced diarrhea in piglets. This information will highlight the basis for the swine production utilization of prebiotics and probiotics in the prevention or treatment of rotavirus infection in the future.

Enhanced anaerobic digestion performance and sludge filterability by membrane microaeration for anaerobic membrane bioreactor application.

Slow dissolution/hydrolysis of insoluble/macromolecular organics and poor sludge filterability restrict the application potential of anaerobic membrane bioreactor (AnMBR). Bubble-free membrane microaeration was firstly proposed to overcome these obstacles in this study. The batch anaerobic digestion tests feeding insoluble starch and soluble peptone with and without microaeration showed that microaeration led to a 65.7-144.8% increase in methane production and increased critical flux of microfiltration membrane via driving the formation of large sludge flocs and the resultant improvement of sludge settleability. The metagenomic and bioinformatic analyses showed that microaeration significantly enriched the functional genes and bacteria for polysaccharide and protein hydrolysis, microaeration showed little negative effects on the functional genes involved in anaerobic metabolisms, and substrate transfer from starch to peptone significantly affected the functional genes and microbial community. This study demonstrates the dual synergism of microaeration to enhance the dissolution/hydrolysis/acidification of insoluble/macromolecular organics and sludge filterability for AnMBR application.

A Reconfigurable Bipolar Image Sensor for High-Efficiency Dynamic Vision Recognition.

Dynamic vision perception and processing (DVPP) is in high demand by booming edge artificial intelligence. However, existing imaging systems suffer from low efficiency or low compatibility with advanced machine vision techniques. Here, we propose a reconfigurable bipolar image sensor (RBIS) for in-sensor DVPP based on a two-dimensional WSe2/GeSe heterostructure device. Owing to the gate-tunable and reversible built-in electric field, its photoresponse shows bipolarity as being positive or negative. High-efficiency DVPP incorporating front-end RBIS and back-end CNN is then demonstrated. It shows a high recognition accuracy of over 94.9% on the derived DVS128 data set and requires much fewer neural network parameters than that without RBIS. Moreover, we demonstrate an optimized device with a vertically stacked structure and a stable nonvolatile bipolarity, which enables more efficient DVPP hardware. Our work demonstrates the potential of fabricating DVPP devices with a simple structure, high efficiency, and outputs compatible with advanced algorithms.

SENP1 facilitates OM-MSC differentiation through activating OPTN-mediated mitophagy to mitigate the neurologic impairment following ICH.

Previous studies have indicated the neuroprotective effect of olfactory mucosa mesenchymal stem cells (OM-MSCs) on brain injury. Intracerebral hemorrhage (ICH) models were established in rats by injecting autologous blood. SENP1 expression was enhanced in neurons but decreased in astrocytes compared to that in OM-MSCs. Overexpression of SENP1 promoted the proliferation and neuronal differentiation, while inhibiting the astrocytic differentiation of OM-MSCs. Conversely, its knockdown had the opposite effect. Moreover, OM-MSCs reduced neurological dysfunction in rats after ICH, and the neuroprotective effect of OM-MSCs could be further enhanced by SENP1 overexpression. In addition, SENP1 promoted mitophagy, which might be related to SENP1-mediated OPTN deSUMOylation. Furthermore, SENP1 promoted neuronal differentiation of OM-MSCs through mitophagy mediated by OPTN. Similar to SENP1, OPTN transfection further enhanced the remission effect of OM-MSC on ICH rats. SENP1 promoted neuronal differentiation of OM-MSCs through OPTN-mediated mitophagy to improve neurological deficits in ICH rats.

GPR30 improved subarachnoid hemorrhage induced blood-brain barrier dysfunction by activating PI3K/Akt and Nrf2/HO-1 pathways.

The blood-brain barrier (BBB) plays a critical role in the development and outcome of subarachnoid hemorrhage (SAH). This study focuses on the potential mechanism by which GPR30 affects the BBB after SAH. A rat SAH model was established using an intravascular perforation approach. G1 (GPR30 agonist) was administered to investigate the mechanism of BBB damage after SAH. Brain water content, western blotting, Evans blue leakage, and immunofluorescence staining were performed. Brain microvascular endothelial cells were induced by hemin to establish SAH model in vitro. By adding LY294002 (a PI3K blocker) and ZnPP IX (an HO-1 antagonist), the mechanism of improving BBB integrity through the activation of GPR30 was studied. In vivo, GPR30 activation improved BBB disruption, as evidenced by decreased cerebral edema, downregulated Albumin expression, and reduced extravasation of Evans blue and lgG after G1 administration in SAH rats. Moreover, SAH downregulated the levels of tight junction (TJ) proteins, while treatment with G1 reversed the effect of SAH. The protective effect of G1 on BBB integrity in vitro was consistent with that in vivo, as evidenced by G1 reducing the impact of hemin on TEER value, dextran diffusivity, and TJ protein levels in brain microvascular endothelial cells. In addition, G1 activated the PI3K/AKT and Nrf2/HO-1 pathways both in vivo and in vitro. Furthermore, the administration of LY294002 and ZnPP IX partially reversed the protective effect of G1 on BBB integrity in hemin-stimulated cells. These findings provide valuable insights for potential treatments for SAH. NEW & NOTEWORTHY We demonstrated that the activation of GPR30, at least partly through the PI3K/AKT and Nrf2/HO-1 pathways, alleviated BBB damage both in vivo and in vitro. This study introduced a novel therapeutic approach for protecting the BBB after SAH.

Next-generation probiotic candidates targeting intestinal health in weaned piglets: Both live and heat-killed Akkermansia muciniphila prevent pathological changes induced by enterotoxigenic Escherichia coli in the gut.

The use of next-generation probiotics (NGP) in pigs for combating diseases has been subject to limited research. Here we explored the potential of a well-known NGP candidate Akkermansia muciniphila targeting pig gut health. In the first screening experiment, we found that the abundance of A. muciniphila peaked at 14 d old but decreased at weaning (21 d old; P < 0.05), suggesting the weaning period may be an effective window for A. muciniphila intervention. Following that, 48 crossbred weaned pigs at 28 d old were randomly assigned to five groups: control (CON), high/low live A. muciniphila (HA/LA), and high/low heat-killed A. muciniphila (HIA/LIA). From 1 to 28 d old, the CON group received gastric infusion of anaerobic sterile saline every other day; the HA and LA groups were gavaged every other day with 1 × 1010 CFU/5 mL and 5 × 108 CFU/5 mL live A. muciniphila, respectively; and the HIA and LIA groups were gavaged every other day with 1 × 1010 CFU/5 mL and 5 × 108 CFU/5 mL heat-killed A. muciniphila, respectively. At d 29, pigs in the CON group were randomly and equally divided into two groups, one of which was named the enterotoxigenic Escherichia coli (ETEC) group, and all groups except CON received a 5-d ETEC challenge. The supplementation of A. muciniphila numerically reduced the diarrhea rate of weaned pigs compared to the pigs that only received the ETEC challenge (P = 0.57), but the LIA group had a higher diarrhea rate than the CON group (P < 0.05). Consistent with this, the supplementation of A. muciniphila improved the small intestinal morphology and structure, proportion of CD4+ T lymphocytes in the blood, as well as the expression of genes related to intestinal barrier and antioxidant indices of pigs with ETEC challenge, especially for the LA group (P < 0.05). Meanwhile, A. muciniphila supplementation reduced the expression of ETEC virulence factor genes in the ileum and colon of pigs challenged by ETEC (P < 0.05). Therefore, A. muciniphila may protect the intestinal health of weaned piglets from damage caused by ETEC infection, but the effect may vary depending on the concentration and activity of A. muciniphila.

The genetics and clinical outcomes in 151 cases of fetal growth restriction: A Chinese single-center study.

OBJECTIVE: To determine the detection rate of chromosomal abnormalities and pregnancy outcomes in fetuses with intrauterine growth restriction. Study design A total of 151 fetal samples with intrauterine growth restriction were divided into the isolated fetal growth restriction (FGR) group, FGR group with structural malformation, and FGR group with non-structural malformation, according to ultrasound abnormalities. The enrolled patients were divided into an early onset FGR group (<32 weeks) and a late-onset FGR group (≥32 weeks). Chromosomal karyotype and microarray analyses were performed and pregnancy outcomes were monitored. Results The karyotypes of 122 patients were analyzed. Four patients exhibited abnormal chromosome numbers or structures. Variations in copy number were detected in 151 cases; 19 cases were found to have chromosomal abnormalities, with a positivity rate of 12.6 %. There was one trisomy in 18 cases, one trisomy in 21 cases, eight pathogenic copy number variations (CNVs), and nine CNVs of unknown clinical significance. The detection rate of FGR combined with structural malformation was significantly higher than that of isolated FGR group. The detection rate of FGR with structural malformations was significantly higher than that with non-structural malformations. The positive detection rate in the FGR group was similar to that in the FGR group with non-structural malformations, with no statistical significance. Chromosomal abnormalities were detected in 17 patients with early onset FGR, with a positivity rate of 13.8 %. Two cases of chromosomal abnormalities were detected in the late-onset FGR group, with a positive rate of 7.1 %, with no statistical significance. A total of 151 fetuses with FGR were followed up for pregnancy outcomes, resulting in 36 cases of pregnancy termination and 13 cases of loss to follow-up. Among the 102 delivered fetuses, six exhibited delayed growth and development, one presented with hypospadias, and another failed the hearing screening. The remaining 94 fetuses demonstrated normal growth and development. Conclusions This study confirms the value of CNV detection in fetuses and dynamic ultrasound monitoring for fetuses with intrauterine growth restriction.

Integrative transcriptomics and proteomics analysis reveal the protection of Astragaloside IV against myocardial fibrosis by regulating senescence.

Myocardial fibrosis (MF) is a pivotal pathological process implicated in various cardiovascular diseases, particularly heart failure. Astragaloside IV (AS-IV), a natural compound derived from Astragalus membranaceus, possesses potent cardioprotective properties. However, the precise molecular mechanisms underlying its anti-MF effects, particularly in relation to senescence, remain elusive. Thus, this study aimed to investigate the therapeutic potential and underlying molecular mechanisms of AS-IV in treating ISO-induced MF in mice, employing transcriptomics, proteomics, in vitro, and in vivo experiments. We assessed the positive effects of AS-IV on ISO-induced MF using HE staining, Masson staining, ELISA, immunohistochemical staining, transthoracic echocardiography, transmission electron microscopy, and DHE fluorescence staining. Additionally, we elucidated the regulatory role of AS-IV in MF through comprehensive transcriptomics and proteomics analyses, complemented by Western blotting and RT-qPCR validation of pertinent molecular pathways. Our findings demonstrated that AS-IV treatment markedly attenuated ISO-induced myocardial injury and oxidative stress, concomitantly inhibiting the release of SASPs. Furthermore, integrated transcriptomics and proteomics analyses revealed that the anti-MF mechanism of AS-IV was associated with regulating cellular senescence and the p53 signaling pathway. These results highlight AS-IV exerts its anti-MF effects not only by inhibiting oxidative stress but also by modulating senescence through the p53 signaling pathway.

Van der Waals Epitaxial Growth of Ultrathin Indium Antimonide on Arbitrary Substrates through Low-Thermal Budget.

III-V semiconductors possess high mobility, high frequency response, and detection sensitivity, making them potentially attractive for beyond-silicon electronics applications. However, the traditional heteroepitaxy of III-V semiconductors is impeded by a significant lattice mismatch and the necessity for extreme vacuum and high temperature conditions, thereby impeding their in situ compatibility with flexible substrates and silicon-based circuits. In this study, a novel approach is presented for fabricating ultrathin InSb single-crystal nanosheets on arbitrary substrates with a thickness as thin as 2.4 nm using low-thermal-budget van der Waals (vdW) epitaxy through chemical vapor deposition (CVD). In particular, in situ growth has been successfully achieved on both silicon-based substrates and flexible polyimide (PI) substrates. Notably, the growth temperature required for InSb nanosheets (240 °C) is significantly lower than that employed in back-end-of-line processes (400 °C). The field effect transistor devices based on fabricated ultrathin InSb nanosheets exhibit ultra-high on-off ratio exceeding 108 and demonstrate minimal gate leakage currents. Furthermore, these ultrathin InSb nanosheets display p-type characteristics with hole mobilities reaching up to 203 cm2 V-1 s-1 at room temperatures. This study paves the way for achieving heterogeneous integration of III-V semiconductors and facilitating their application in flexible electronics.

Distinguishing vulnerability and resilience to posttraumatic stress disorder evaluating traumatic experiences, genetic risk and electronic health records.

What distinguishes vulnerability and resilience to posttraumatic stress disorder (PTSD) remains unclear. Levering traumatic experiences reporting, genetic data, and electronic health records (EHR), we investigated and predicted the clinical comorbidities (co-phenome) of PTSD vulnerability and resilience in the UK Biobank (UKB) and All of Us Research Program (AoU), respectively. In 60,354 trauma-exposed UKB participants, we defined PTSD vulnerability and resilience considering PTSD symptoms, trauma burden, and polygenic risk scores. EHR-based phenome-wide association studies (PheWAS) were conducted to dissect the co-phenomes of PTSD vulnerability and resilience. Significant diagnostic endpoints were applied as weights, yielding a phenotypic risk score (PheRS) to conduct PheWAS of PTSD vulnerability and resilience PheRS in up to 95,761 AoU participants. EHR-based PheWAS revealed three significant phenotypes positively associated with PTSD vulnerability (top association "Sleep disorders") and five outcomes inversely associated with PTSD resilience (top association "Irritable Bowel Syndrome"). In the AoU cohort, PheRS analysis showed a partial inverse relationship between vulnerability and resilience with distinct comorbid associations. While PheRSvulnerability associations were linked to multiple phenotypes, PheRSresilience showed inverse relationships with eye conditions. Our study unveils phenotypic differences in PTSD vulnerability and resilience, highlighting that these concepts are not simply the absence and presence of PTSD.

Multivitamins co-intake can reduce the prevalence of kidney stones: a large-scale cross-sectional study.

BACKGROUND: This research aimed to explore the association between changes in the intake of common individual vitamins and combinations of vitamins and the prevalence of kidney calculi. METHODS: We used data from NHANES to investigate the association between nine common vitamins and kidney stone prevalence. Participants were clustered into several vitamin exposure patterns using an unsupervised K-means clustering method. We used logistic regression models and restrictive cubic spline curves to explore the influence of vitamins. RESULTS: The regression model exposed that compared to lower intake, high intake of vitamin B6 [Q4: OR (95% CI) = 0.76 (0.62, 0.93)], vitamin C [Q4: OR (95% CI) = 0.73 (0.59, 0.90)] and vitamin D [Q4: OR (95% CI) = 0.77 (0.64, 0.94)] individually exerted protective effects against the prevalence of kidney stones. Furthermore, the restrictive cubic spline analysis showed that the protective effect against the prevalence of kidney stones is enhanced as the take of vitamin B6 and vitamin D increased. Moreover, with the increase in vitamin C intake, its protective effect may turn into a risk factor. Regarding mixed exposure, Cluster 4 exhibited a significant protective effect against kidney stones compared with Cluster 1 [Model 3: OR (95% CI) = 0.79 (0.64, 0.98)]. CONCLUSIONS: Our research revealed that high levels of vitamin B6 and vitamin D intake were linked to a lower prevalence of kidney stone. With the gradual increase intake of vitamin C, the prevalence of kidney calculi decreased first and then increased. In addition, the co-exposure of nine vitamins is a protective factor for kidney stone disease.