Rice OsPUB16 modulates the 'SAPK9-OsMADS23-OsAOC' pathway to reduce plant water-deficit tolerance by repressing ABA and JA biosynthesis.

Ubiquitin-mediated proteolysis plays crucial roles in plant responses to environmental stress. However, the mechanism by which E3 ubiquitin ligases modulate plant stress response still needs to be elucidated. In this study, we found that rice PLANT U-BOX PROTEIN 16 (OsPUB16), a U-box E3 ubiquitin ligase, negatively regulates rice drought response. Loss-of-function mutants of OsPUB16 generated through CRISPR/Cas9 system exhibited the markedly enhanced water-deficit tolerance, while OsPUB16 overexpression lines were hypersensitive to water deficit stress. Moreover, OsPUB16 negatively regulated ABA and JA response, and ospub16 mutants produced more endogenous ABA and JA than wild type when exposed to water deficit. Mechanistic investigations revealed that OsPUB16 mediated the ubiquitination and degradation of OsMADS23, which is the substrate of OSMOTIC STRESS/ABA-ACTIVATED PROTEIN KINASE 9 (SAPK9) and increases rice drought tolerance by promoting ABA biosynthesis. Further, the ChIP-qPCR analysis and transient transactivation activity assays demonstrated that OsMADS23 activated the expression of JA-biosynthetic gene OsAOC by binding to its promoter. Interestingly, SAPK9-mediated phosphorylation on OsMADS23 reduced its ubiquitination level by interfering with the OsPUB16-OsMADS23 interaction, which thus enhanced OsMADS23 stability and promoted OsAOC expression. Collectively, our findings establish that OsPUB16 reduces plant water-deficit tolerance by modulating the 'SAPK9-OsMADS23-OsAOC' pathway to repress ABA and JA biosynthesis.

The enhanced connectivity between the frontoparietal, somatomotor network and thalamus as the most significant network changes of chronic low back pain.

The prolonged duration of chronic low back pain (cLBP) inevitably leads to changes in the cognitive, attentional, sensory and emotional processing brain regions. Currently, it remains unclear how these alterations are manifested in the interplay between brain functional and structural networks. This study aimed to predict the Oswestry Disability Index (ODI) in cLBP patients using multimodal brain magnetic resonance imaging (MRI) data and identified the most significant features within the multimodal networks to aid in distinguishing patients from healthy controls (HCs). We constructed dynamic functional connectivity (dFC) and structural connectivity (SC) networks for all participants (n = 112) and employed the Connectome-based Predictive Modeling (CPM) approach to predict ODI scores, utilizing various feature selection thresholds to identify the most significant network change features in dFC and SC outcomes. Subsequently, we utilized these significant features for optimal classifier selection and the integration of multimodal features. The results revealed enhanced connectivity among the frontoparietal network (FPN), somatomotor network (SMN) and thalamus in cLBP patients compared to HCs. The thalamus transmits pain-related sensations and emotions to the cortical areas through the dorsolateral prefrontal cortex (dlPFC) and primary somatosensory cortex (SI), leading to alterations in whole-brain network functionality and structure. Regarding the model selection for the classifier, we found that Support Vector Machine (SVM) best fit these significant network features. The combined model based on dFC and SC features significantly improved classification performance between cLBP patients and HCs (AUC=0.9772). Finally, the results from an external validation set support our hypotheses and provide insights into the potential applicability of the model in real-world scenarios. Our discovery of enhanced connectivity between the thalamus and both the dlPFC (FPN) and SI (SMN) provides a valuable supplement to prior research on cLBP.

The dihydrofolate reductase 19-bp deletion modifies the beneficial effect of B-vitamin therapy in mild cognitive impairment: pooled study of two randomized placebo-controlled trials.

BACKGROUND: Higher serum homocysteine is associated with cognitive decline in older people. But homocysteine-lowering trials including folic acid (FA) show inconsistent results on cognitive decline. The reduction of FA to dihydrofolate by dihydrofolate reductase (DHFR) is slow in humans. OBJECTIVE: We examined the effects of the DHFR 19-bp deletion/insertion (del/ins) polymorphism on FA-containing treatment on cognitive decline and brain atrophy in older people with mild cognitive impairment (MCI). METHODS: This study used pooled data from two randomized B-vitamin trials on 545 MCI subjects who received either FA-containing B vitamins or placebo for 24 months. Subjects were typed for the DHFR genotype. Primary outcome was the Clinical Dementia Rating scale-global score (CDR-global). Secondary outcomes were CDR-sum of boxes score (CDR-SOB), memory and executive Z-scores and whole brain atrophy rate by serial MRI. RESULTS: The proportions of subjects with del/del, del/ins and ins/ins genotype were 29.5, 44.3 and 26.1%, respectively. DHFR genotypes modified the effects of B vitamins on CDR-global, CDR-SOB and executive function Z-score (Pinteraction = 0.017, 0.014 and 0.052, respectively), with significant benefits being observed only in those with ins/ins genotype (Beta = -1.367, -0.614 and 0.315, P = 0.004, 0.014 and 0.012, respectively). The interaction was not significant for memory Z-score and whole brain atrophy rate. Notably, the supplements only slowed brain atrophy in members of the 'ins/ins' group who were not using aspirin. CONCLUSIONS: Our data indicate that the beneficial effects of B vitamins including FA on cognitive function are only apparent in those with ins/ins genotype, i.e. relatively better preserved DHFR activity.

Label-Free Direct Identification of MicroRNAs Based on a Narrow Constant-Inner-Diameter Emitter Mass Spectrometry Analysis.

MicroRNAs (miRNAs) are a class of endogenous noncoding small RNAs that play important roles in various biological processes and diseases. Direct determination of miRNAs is a cost-efficient and accurate method for analysis. Herein, we established a novel method for the analysis of miRNAs based on a narrow constant-inner-diameter mass spectrometry emitter. We utilized the gravity-assisted sleeving etching method to prepare a constant-inner-diameter mass spectrometry emitter with a capillary inner diameter of 5.5 µm, coupled it with a high-voltage power supply and a high-resolution mass spectrometer, and used it for miRNA direct detection. The method showed high sensitivity and reproducibility for the analysis of four miRNAs, with a limit of detection of 100 nmol/L (170 amol) for the Hsa-miR-1290 analysis. Compared with commercial ion sources, our method achieved higher sensitivity for miRNA detection. In addition, we analyzed the total miRNAs in the A549 cells. The result indicated that both spiked and endogenous miRNAs could be quantified with high accuracy. As a result, this method offers a promising platform for highly sensitive and accurate miRNA analysis. Furthermore, this approach can be extended to the analysis of other small oligonucleotides and holds the potential for studying clinical samples and facilitating disease diagnosis.

High-Throughput Study of Amorphous Stability and Optical Properties of Superlattice-Like Ge-Sb-Te Thin Films.

A high-throughput ion beam sputtering system is used to synthesize compositional gradient superlattice-like (SLL) thin film libraries of Ge-Sb-Te alloys over the entire phase diagram. The optical properties and structural evolution of the Ge-Sb-Te combinatorial SLL thin film are investigated. A systematic screening over the annealing temperature, annealing time, and modulation period has elucidated the critical factors that affect the stability of the metastable phase and optical properties. It is found that amorphous stability and optical constant are highly dependent on the modulation period and chemical composition of the thin film. This data-driven approach offers new perspectives for accelerating the development of new materials with excellent optical and amorphous stability and for exploring their mechanisms, by greatly expanding the dataset of Ge-Sb-Te alloys with SLL structures through high-throughput experiments.

Synthesis of α-sulfenylated carbonyl compounds under metal-free conditions.

An efficient synthesis of α-sulfenylated carbonyl compounds from propargylic alcohols and aryl thiols under heating conditions is described. The method is characterized by mild conditions, simple operation, metal-free catalysis and good functional group tolerance. Mechanistic studies suggest that the reaction involves a radical pathway and an isomerization process.

miR-212/132 attenuates OVA-induced airway inflammation by inhibiting mast cells activation through MRGPRX2 and ASAP1.

Allergic asthma is a chronic inflammatory disease of airways involving complex mechanisms, including MAS-related GPR family member X2 (MRGPRX2) and its orthologue MRGPRB2 on mast cells (MCs). Although miRNAs have been previously shown to related to allergic asthma, the role of miR-212/132 in this process has not been studied. In this study, the predicted pairing of miRNAs and MRGPRX2 (MRGPRB2) mRNAs was carried out by online databases and the function was verify using in vivo and in vitro experiments. Database prediction showed that miR-212/132 interact with MRGPRX2 and MRGPRB2. miR-212/132 mimics alleviated MRGPRB2 mRNA expression as well as pathology changes in lungs and AHR of mice with airway inflammation in vivo. The expression level of MRGPRB2 in the mice lungs after inhaled OVA was also decreased by miR-212/132 mimics. Meanwhile, miR-212/132 inhibited MCs degranulation and cytokines release triggered by C48/80 in vitro. Further, ASAP1 (ARF GTPase-Activating Protein 1) was selected from the junction related pathways using RNAseq and KEGG enrichment. ASAP1 mRNA level was upregulated in airway inflammation and MCs activation and decreased by miR-212/132 mimics. miR-212/132 attenuated OVA-induced airway inflammation by inhibiting MCs activation through MRGPRX2 and ASAP1.

Dual regulation effect and mechanism of human myeloid-derived suppressor cells on anticolorectal cancer cells activity of Vγ9Vδ2 T cells.

Myeloid-derived suppressor cells (MDSC) are a group of immature inhibitory cells of bone marrow origin. Human γδ T cells (mainly Vγ9Vδ2 T cells) have emerged as dominant candidates for cancer immunotherapy because of their unique recognition pattern and broad killing activity against tumor cells. Intestinal mucosal intraepithelial lymphocytes are almost exclusively γδ T cells, so it plays an important role in inhibiting the development of colorectal cancer. In this study, we investigated the effects and molecular mechanism of human MDSC on anticolorectal cancer cells activity of Vγ9Vδ2 T cells. Our results suggested that MDSC can reduce the NKG2D expression of Vγ9Vδ2 T cells through direct cell-cell contact, which is associated with membrane-type transforming growth factor-ß. In contrast, MDSC can increase Vγ9Vδ2 T cells activation and production of IFN-γ, perforin, Granzyme B through direct cell-cell contact. This may be related to the upregulation of T-bet in Vγ9Vδ2 T cells by MDSC. However, MDSC had a dominant negative regulatory effect on the anticolorectal cancer cells activity of Vγ9Vδ2 T cells. Our study provides a theoretical basis for the immune regulatory function of human MDSC on γδ T cells. This will be conducive to the clinical development of a new antitumor therapy strategy.

Autophagy Proteins and clinical data reveal the prognosis of polycystic ovary syndrome.

OBJECTIVE: We aimed to investigate the significance of autophagy proteins and their association with clinical data on pregnancy loss in polycystic ovary syndrome (PCOS), while also constructing predictive models. METHODS: This study was a secondary analysis. we collected endometrial samples from 33 patients with polycystic ovary syndrome (PCOS) and 7 patients with successful pregnancy control women at the Reproductive Center of the Second Hospital of Lanzhou University between September 2019 and September 2020. Liquid chromatography tandem mass spectrometry was employed to identify expressed proteins in the endometrium of 40 patients. R was use to identify differential expression proteins(DEPs). Subsequently, Metascape was utilized for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Multivariate Cox analysis was performed to analyze autophagy proteins associated with reproductive outcomes, while logistic regression was used for analyzing clinical data. Linear correlation analysis was conducted to examine the relationship between autophagy proteins and clinical data. We established prognostic models and constructed the nomograms based on proteome data and clinical data respectively. The performance of the prognostic model was evaluated by the receiver operating characteristic curve (ROC) and decision curve analysis (DCA). RESULTS: A total of 5331 proteins were identified, with 450 proteins exhibiting significant differential expression between the PCOS and control groups. A prognostic model for autophagy protein was developed based on three autophagy proteins (ARSA, ITGB1, and GABARAPL2). Additionally, another prognostic model for clinical data was established using insulin, TSH, TPOAB, and VD3. Our findings revealed a significant positive correlation between insulin and ARSA (R = 0.49), as well as ITGB1 (R = 0.3). Conversely, TSH exhibited a negative correlation with both ARSA (-0.33) and ITGB1 (R = -0.26). CONCLUSION: Our research could effectively predict the occurrence of pregnancy loss in PCOS patients and provide a basis for subsequent research.

The degree of risk factor and accumulation effect for large niche in individuals after cesarean section.

BACKGROUND: The risk factors associated with niche on the cesarean scar have been reported, however, the degree of these factors associated with large niche and the accumulation effects of these risk factors on the development of large niche are unclear. METHODS: Large niche was evaluated by transvaginal sonography during mid-follicular phase. Logistic regression model was used to assess 32 risk factors by univariate analysis. Then, a scoring model based on the screened risk factors was generated. The performance of this model was evaluated by area under curve (AUC). Finally, the scoring model was applied in 123 women to assess the external validation. RESULT(S): In the training cohort study, 163 women were diagnosed with large niche. The final scoring model involves eight risk factors with the rating scores including age at delivery (30-34 years: 1 point; ≥ 35 years: 4.5 points), retroflexed uterus (8.5 points), meconium-stained amniotic fluid (4.5 points), twice CSs (4.0 points), postpartum endometritis (4.5 points), premature rupture of membranes (2.5 points), intrahepatic cholestasis of pregnancy (mild to moderate: 3 points; severe: 6.5 points), and cervical dilatation (1-3 cm: 2.0 points; 4-10 cm: 4.5 points). The accumulation effect with a cut-off value of 8.0 in the scoring was associated with the large niche after CS. CONCLUSION(S): This is the first scoring model to objectively quantify the risk of a large niche after CS. Optimal risk factors control by avoiding high score factors and multiple factors accumulation may eliminate the risk of large niche development.

Quantitative proteomics reveals pregnancy prognosis signature of polycystic ovary syndrome women based on machine learning.

OBJECTIVE: We aimed to screen and construct a predictive model for pregnancy loss in polycystic ovary syndrome (PCOS) patients through machine learning methods. METHODS: We obtained the endometrial samples from 33 PCOS patients and 7 healthy controls at the Reproductive Center of the Second Hospital of Lanzhou University from September 2019 to September 2020. Liquid chromatography tandem mass spectrometry (LCMS/MS) was conducted to identify the differentially expressed proteins (DEPs) of the two groups. Gene Ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to analyze the related pathways and functions of the DEPs. Then, we used machine learning methods to screen the feature proteins. Multivariate Cox regression analysis was also conducted to establish the prognostic models. The performance of the prognostic model was then evaluated by the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). In addition, the Bootstrap method was conducted to verify the generalization ability of the model. Finally, linear correlation analysis was performed to figure out the correlation between the feature proteins and clinical data. RESULTS: Four hundred and fifty DEPs in PCOS and controls were screened out, and we obtained some pathways and functions. A prognostic model for the pregnancy loss of PCOS was established, which has good discrimination and generalization ability based on two feature proteins (TIA1, COL5A1). Strong correlation between clinical data and proteins were identified to predict the reproductive outcome in PCOS. CONCLUSION: The model based on the TIA1 and COL5A1 protein could effectively predict the occurrence of pregnancy loss in PCOS patients and provide a good theoretical foundation for subsequent research.

Sigmoidal relationship between liver fat content and nonalcoholic fatty liver disease in Chinese adults.

PURPOSE: To explore the relationship between liver fat content (LFC) and nonalcoholic fatty liver disease (NAFLD) and determine the new threshold of LFC to diagnose NAFLD. METHODS: The data from questionnaire survey, general physical examination, laboratory examination, and image examination were collected. Multivariate regression analysis, receiver operating characteristic curve analysis, smooth curve fitting, and threshold effect analysis were performed using the R software to investigate the relationship between LFC and NAFLD and to identify the new threshold of LFC to diagnose NAFLD. RESULTS: The prevalence of NAFLD was 30.42%, with a significantly higher prevalence in men than in women. Regression analyses demonstrated that LFC odds ratio [95% confidence interval (CI)] was 1.28 (95% CI: 1.24-1.31) in fully-adjust model. Analysis of the LFC quartile, with Q1 as a reference, revealed that the odds ratios of NAFLD were 1.47 (95% CI: 1.08-1.99), 2.29 (95% CI: 1.72-3.06), and 10.02 (95% CI: 7.45-13.47) for Q2, Q3, and Q4 groups, respectively. Smooth curve fitting and threshold effect analysis displayed a nonlinear relationship between LFC and NAFLD, and the threshold was 4.5%. The receiver operating characteristic curve indicated that when LFC was 4.5%, the area under curve (95% CI) was 0.80 (0.79-0.82), and the sensitivity and specificity of LFC in diagnosing NAFLD were 0.64% and 0.82%, respectively. CONCLUSION: The relationship between LFC and NAFLD was sigmoidal, with an inflection point of 4.5%.

Xianling Lianxia formula enhances the inhibitory effects of trastuzumab on HER2-positive breast cancer.

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) is characterized by high invasiveness. Trastuzumab considerably improves the prognoses of HER2-positive BC, but some patients exhibit drug resistance. In this study, the effects of XLLXF combined with trastuzumab on the proliferation, apoptosis, invasion, and migration of HER2-positive BC cells are evaluated, and network pharmacology is performed. Then, we conduct an in vivo study using a xenograft mouse model of HER2-positive BC, and tumor growth is monitored. The expression levels of cytokines are measured by ELISA. Molecular docking is performed to observe the binding stability of IL2, JAK, STAT, and TNF with curcumenol, icariside-II, lobetyolin, and scutellarein. Finally, we observe changes in JAK1 and TNF-α in tumor tissues by immunohistochemistry. The results show that XLLXF enhances the inhibitory effects of trastuzumab on the proliferation, colony formation ability, migration, and invasion of HER2-positive BC cells and promotes apoptosis. Network pharmacology reveals that XLLXF may exert its effects on HER2-positive BC by modulating pathways such as the ErbB, JAK-STAT, and NF-κB pathways. Potential targets include cytokines closely related to immune function. In the in vivo study, XLLXF synergistically enhances the inhibitory effects of trastuzumab on tumor growth. ELISA reveals that XLLXF combined with trastuzumab increases the levels of IL-15, IL-2, TNF-α, and IFN-γ in tumor-bearing mice. Immunohistochemistry confirms that XLLXF can regulate the expressions of JAK1 and TNF-α. This study demonstrates that XLLXF can synergistically enhance the efficacy of trastuzumab in targeting HER2-positive BC. The mechanism may involve the modulation of inflammatory factors.

Integrated network pharmacology and experimental verification to explore the potential mechanism of San Ying decoction for treating triple-negative breast cancer.

Traditional Chinese medicine (TCM) has been used to treat triple-negative breast cancer (TNBC), a breast cancer subtype with poor prognosis. Clinical studies have verified that the Sanyingfang formula (SYF), a TCM prescription, has obvious effects on inhibiting breast cancer recurrence and metastasis, prolonging patient survival, and reducing clinical symptoms. However, its active ingredients and molecular mechanisms are still unclear. In this study, the active ingredients of each herbal medicine composing SYF and their target proteins are obtained from the Traditional Chinese Medicine Systems Pharmacology database. Breast cancer-related genes are obtained from the GeneCards database. Major targets and pathways related to SYF treatment in breast cancer are identified by analyzing the above data. By conducting molecular docking analysis, we find that the active ingredients quercetin and luteolin bind well to the key targets KDR1, PPARG, SOD1, and VCAM1. In vitro experiments verify that SYF can reduce the proliferation, migration, and invasion ability of TNBC cells. Using a TNBC xenograft mouse model, we show that SYF could delay tumor growth and effectively inhibit the occurrence of breast cancer lung metastasis in vivo. PPARG, SOD1, KDR1, and VCAM1 are all regulated by SYF and may play important roles in SYF-mediated inhibition of TNBC recurrence and metastasis.

Hoffmann's sign in cervical spondylotic myelopathy patients: pathological insights from neuroimaging.

OBJECTIVE: Hoffmann's sign testing is a commonly used physical examination in clinical practice for patients with cervical spondylotic myelopathy (CSM). However, the pathophysiological mechanisms underlying its occurrence and development have not been thoroughly investigated. Therefore, the present study aimed to explore whether a positive Hoffmann's sign (PHS) in CSM patients is associated with spinal cord and brain remodeling and to identify potential neuroimaging biomarkers with diagnostic value. METHODS: Seventy-six patients with CSM and 40 sex- and age-matched healthy controls (HCs) underwent multimodal MRI. Based on the results of the Hoffmann's sign examination, patients were divided into two groups: those with a PHS (n = 38) and those with a negative Hoffmann's sign (NHS; n = 38). Quantification of spinal cord and brain structural and functional parameters of the participants was performed using various methods, including functional connectivity analysis, voxel-based morphometry, and atlas-based analysis based on functional MRI and structural MRI data. Furthermore, this study conducted a correlation analysis between neuroimaging metrics and neurological function and utilized a support vector machine (SVM) algorithm for the classification of PHS and NHS. RESULTS: In comparison with the NHS and HC groups, PHS patients exhibited significant reductions in the cross-sectional area and fractional anisotropy (FA) of the lateral corticospinal tract (CST), reticulospinal tract (RST), and fasciculus cuneatus, concomitant with bilateral reductions in the volume of the lateral pallidum. The functional connectivity analysis indicated a reduction in functional connectivity between the left lateral pallidum and the right angular gyrus in the PHS group. The correlation analysis indicated a significant positive association between the CST and RST FA and the volume of the left lateral pallidum in PHS patients. Furthermore, all three variables exhibited a positive correlation with the patients' motor function. Finally, using multimodal neuroimaging metrics in conjunction with the SVM algorithm, PHS and NHS were classified with an accuracy rate of 85.53%. CONCLUSIONS: This research revealed a correlation between structural damage to the pallidum and RST and the presence of Hoffmann's sign as well as the motor function in patients with CSM. Features based on neuroimaging indicators have the potential to serve as biomarkers for assessing the extent of neuronal damage in CSM patients.

Partisan Bias in COVID-19 Conspiracy Theories: News Reliance and the Moderating Role of Trust in Health Authorities.

Neglecting the role of political bias in the public's perceptions of health authorities could be deceptive when studying potentially politicized COVID-19 conspiracy theories (CCTs); however, previous studies often treated health authorities as a single entity and did not distinguish between different types of CCTs. Drawing from motivated reasoning theory, we investigate the politically motivated nature of CCTs by examining their associations with individuals' media reliance, party identification, conspiratorial mentality, and importantly, trust in (politicized or independent) health authorities. In a national survey conducted in late 2020 (N = 2,239) in Turkey, a heavily polarized context, we found that not accounting for political identities shown in CCTs and health authorities could be misleading. While those with a strong conspiracy mentality were more likely to endorse all types of CCTs, party identification and trust in different types of health authorities led people to believe in certain CCTs aligning with their political attitudes. The influence of media reliance on CCTs depended on the level of trust in health authorities, again suggestive of the influence of political partialities.

Preconception or prenatal acceptance of SMN1 gene carrier screening and carrier rate of spinal muscular atrophy: a retrospective study in 18,818 reproductive age women in Wuhan area of China.

OBJECTIVE: Spinal muscular atrophy (SMA) is an autosomal recessive disorder mainly affecting the neuromuscular system, which seriously threatens the life and health of patients. But few studies have reported the acceptance rate of SMA gene screening and SMA carrier rate in China. The present study aimed to clarify the two issues in China through a retrospective analysis of 18,818 reproductive age women in Wuhan area of China. METHODS: The copy number (CN) of exons 7 and 8 in survival motor neuron 1 (SMN1) gene was detected by real-time quantitative PCR, and the results were verified by multiplex ligation-dependent probe amplification. RESULTS: Carrier screening was offered to 44,953 women of childbearing age in our medical center from March, 2018, to February, 2022, of whom 18,818 were enrolled in the program. A total of 336 women were identified as carriers (1.73%; 326/18,808; without fertility history of the children with SMA). Among 18,818 reproductive age women, 286 spouses (85.12%; 286/336) were successfully recalled for screening. The results showed 17 couples at high risk of having children with SMA, of whom prenatal diagnosis was implemented in 11, and 6 fetuses were identified with SMA. All the 5 pregnant women bearing the 6 SMA fetuses chose to terminate the pregnancy by artificial abortion. CONCLUSION: Reproductive age women and their spouses in Wuhan area showed a positive attitude toward general screening for SMA carriers. Given the high early mortality of children with SMA, screening for SMA carriers in women of reproductive age is necessary and feasible.

The chromosomal characteristics of spontaneous abortion and its potential associated copy number variants and genes.

PURPOSE: This study aimed to investigate the correlation between chromosomal abnormalities in spontaneous abortion with clinical features and seek copy number variations (CNVs) and genes that might be connected to spontaneous abortion. METHODS: Over 7 years, we used CNV-seq and STR analysis to study POCs, comparing chromosomal abnormalities with clinical features and identifying critical CNVs and genes associated with spontaneous abortion. RESULTS: Total chromosomal variants in the POCs were identified in 66.8% (2169/3247) of all cases, which included 45.2% (1467/3247) numerical abnormalities and 21.6% (702/3247) copy number variants (CNVs). Chromosome number abnormalities, especially aneuploidy abnormalities, were more pronounced in the group of mothers aged ≥ 35 years, the early miscarriage group, and the chorionic villi group. We further analyzed 212 pathogenic and likely pathogenic CNVs in 146 POCs as well as identified 8 statistically significant SORs through comparison with both a healthy population and a group of non-spontaneously aborted fetuses. Our analysis suggests that these CNVs may play a crucial role in spontaneous abortion. Furthermore, by utilizing the RVIS score and MGI database, we identified 86 genes associated with spontaneous abortion, with particular emphasis on PARP6, ISLR, ULK3, FGFRL1, TBC1D14, SCRIB, and PLEC. CONCLUSION: We found variability in chromosomal abnormalities across clinical features, identifying eight crucial copy number variations (CNVs) and multiple key genes that may be linked to spontaneous abortion. This research enhances the comprehension of genetic factors contributing to spontaneous abortion.

Diagnostic yield of copy number variation sequencing in fetuses with increased nuchal translucency: a retrospective study.

OBJECTIVE: To assess the efficacy of copy number variation sequencing (CNV-seq) and karyotyping for prenatal detection of chromosomal abnormalities in fetuses with increased nuchal translucency. METHODS: Amniotic fluid samples were extracted from 205 fetuses with increased nuchal translucency (NT ≥ 2.5 mm), diagnosed by ultrasound between gestational ages of 11 and 13 + 6 weeks. Karyotyping and CNV-seq were performed for detecting chromosomal abnormalities. RESULTS: There are 40 fetuses (19.51%) showing increased NT detected with chromosomal abnormalities in karyotyping, and trisomy 21 was found to be the most common abnormalities. There are 50 fetuses (24.39%) identified with chromosomal abnormalities by CNV-seq. The detection of the applied techniques indicated that CNV-seq revealed higher chromosomal aberrations. The risk of chromosomal abnormalities was significantly increased with NT thickening, from 13.64% in the NT group of 2.5-3.4 mm, 38.64% in the NT group of 3.5-4.4 mm, and to 51.72% in the NT group of over 4.5 mm (P < 0.05). The investigated cases with increased NT with presence of soft markers in ultrasound or high risk in non-invasive prenatal testing presented chromosomal abnormalities in higher rates, comparing with those with isolated NT or low risk (P < 0.05). CONCLUSION: The results indicated that the risk of chromosomal abnormalities was associated with the NT thickness, detected by karyotype or CNV-seq. The combination application of two analysis was efficient to reveal the possible genetic defects in prenatal diagnosis. The finding suggested that the detection should be considered with ultrasonographic soft markers, and the NT thickness of 2.5-3.4 mm could be a critical value for detecting chromosomal abnormalities to prevent the occurrence of missed diagnosis.

Identification and analysis of immunogenicity and immunotherapy efficacy by fatty acid genes: a novel prognostic features of lumbar disc herniation and Mendelian randomization analysis.

BACKGROUND: Sciatica is a phrase used to describe radiating leg discomfort. The most common cause is lumbar disc herniation (LDH), which is considered to start in the nucleus pulposus. Advancements in lipidomics and metabolomics have unveiled the complex role of fatty acid metabolism (FAM) in both healthy and pathological states. However, the specific roles of fatty acid metabolism-related genes (FAMGs) in shaping therapeutic approaches, especially in LDH, remain largely unexplored and are a subject of ongoing research. METHODS: The junction of the weighted correlation network analysis (WGCNA) test with 6 FAMGs enabled the finding of FAMGs. Gene set variation analysis (GSVA) was used to identify the possible biological activities and pathways of FAMGs. LASSO was used to determine diagnostic effectiveness of the four FAMGs in diagnosing LDH. GSE124272, GSE147383, GSE150408, and GSE153761 were utilized to confirm the levels of expression of four FAMGs. RESULTS: Four FAMGs were discovered [Acyl-CoA Thioesterase 4 (ACOT4), Cytochrome P450 Family 4 Subfamily A Member 11 (CYP4A11), Acyl-CoA Dehydrogenase Long Chain (ACADL), Enoyl-CoA Hydratase and 3-Hydroxyacyl CoA Dehydrogenase (EHHADH)] For biological function analysis, mhc class ib receptor activity, response to thyroxine, response to l phenylalanine derivative were emphasized. CONCLUSIONS: FAMGs can help with prognosis and immunology, and provide evidence for fatty acid metabolism-related targeted therapeutics. In LDH, FAMGs and their interactions with immune cells might be therapeutic targets.