Sirtuin 3-mediated deacetylation of superoxide dismutase 2 ameliorates sodium fluoride-induced mitochondrial dysfunction in porcine oocytes.

Fluoride exerts detrimental effects on germ cells and increases the infertility rate in women. Nevertheless, the precise mechanisms behind the developmental abnormalities caused by fluoride in oocytes remain poorly comprehended. The current study, we established mitochondrial damage model in oocytes via 50 µg/mL sodium fluoride (NaF) supplementation. We then examined the effects of honokiol in preventing mitochondrial deficits caused by NaF and investigated the mechanisms through which honokiol protects oocytes. The findings investigated that NaF increased levels of mitochondrial reactive oxygen species (mtROS) and hindered mitochondrial function, as evidenced by the dissipation of mitochondrial membrane potential, abnormal expression of mitochondrial DNA copy numbers, and mtDNA harm in oocytes. mtROS scavenging using Mito-TEMPO alleviated oxidative damage in mitochondria and restored the oocyte developmental competence. Superoxide dismutase 2 (SOD2) acetylation was significantly increased, whereas sirtuin 3 (SIRT3) expression was decreased in NaF-treated oocytes. The addition of honokiol helped in the deacetylation of SOD2 at K122 through SIRT3, resulting in the removal of excessive mtROS and the recovery of mitochondrial function. Therefore, SIRT3/SOD2 pathway aids honokiol in mitigating fluoride-induced mitochondrial dysfunction. Overall, honokiol improved the mitochondrial harm caused by NaF by controlling mtROS and mitochondrial function, with the SIRT3/SOD2 pathway having an important function. These findings suggest honokiol as a potential therapeutic strategy for NaF-induced oocyte development and mitochondrial deficits.

Case report: A novel homozygous variant in ZP3 is associated with human empty follicle syndrome.

Empty follicle syndrome (EFS) is a rare condition in female infertility. It is characterized by the inability to retrieve oocytes from visibly large, normally developing follicles in the ovaries, despite ovarian stimulation. The genetic factors contributing to this syndrome remain unclear. This study focused on patients who underwent three consecutive ovarian stimulation procedures for oocyte retrieval but experienced unsuccessful outcomes, despite the presence of observable large follicles. Ultrasound examinations were conducted to assess follicular development during each procedure. In order to investigate potential genetic causes, we performed whole exome sequencing on peripheral blood samples from the patient. Interestingly, we identified that this patient carries a homozygous mutation in the ZP3 genes. Within the ZP3 gene, we identified a homozygous variant [NM_001110354.2, c.176T>A (p.L59H)] specifically located in the zona pellucida (ZP) domain. Further analysis, including bioinformatics methods and protein structure modeling, was carried out to investigate the conservation of the ZP3L59H variant across different species. This homozygous variant exhibited a high degree of conservation across various species. Importantly, the homozygous ZP3L59H variant was associated with the occurrence of empty follicle syndrome in affected female patients. The homozygous ZP3L59H variant represents a newly discovered genetic locus implicated in the development of human empty follicle syndrome. Our findings contribute to a deeper understanding of the role of zona pellucida-related genes in infertility and provide valuable insights for the genetic diagnosis of female infertility.

Study on mechanism of Zhenwu Decoction in treatment of heart failure based on network pharmacology: A review.

To explore the mechanism of Zhenwu Decoction (ZWD) in the treatment of heart failure (HF) by network pharmacology analysis, so as to provide a basis for the innovation and application of drugs. The effective components and targets of 5 Chinese herbal medicines in ZWD were retrieved by TCM Pharmacology Database and Analysis Platform (TCMSP).Gene card, OMIM and TTD databases were used to obtain the disease targets of HF, and the intersection with the targets of ZWD was obtained. We used Cytoscape3.9.1 software to construct a drug-active component-disease-target interaction network for ZWD treatment of HF, and performed protein-protein interaction (PPI) network and topology analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were performed. Fifty-nine effective components and 229 targets of ZWD were screened. Among them, ZWD for HF has 27 active components and 38 common targets, and the core targets of PPI are IL-6, ATK1 and TNF. Pathway enrichment analysis included lipid and atherosclerotic and TNF signaling pathways. This study preliminarily clarified the main active components, targets and related pathways of ZWD in the treatment of HF, and laid a foundation for further study of the pharmacological effects of ZWD.

NUSAP1 regulates mouse oocyte meiotic maturation.

The correct assembly of the spindle apparatus directly regulates the precise separation of chromosomes in mouse oocytes, which is crucial for obtaining high-quality oocytes capable of successful fertilization. The localization, assembly, migration, and disassembly of the spindle are regulated by a series of spindle-associated proteins, which exhibit unique expression level variations and specific localization in oocytes. Proteomic analysis revealed that among many representative spindle-associated proteins, the expression level of nucleolar and spindle-associated protein 1 (NUSAP1) significantly increased after meiotic resumption, with a magnitude of change higher than that of other proteins. However, the role of NUSAP1 during oocyte meiosis maturation has not been reported. Here, we report that NUSAP1 is distributed within the cell nucleus during the germinal vesicle (GV) oocytes with non-surrounded nucleolus stage and is not enriched in the nucleus during the GV-surrounded nucleolus stage. Interestingly, NUSAP1 forms distinct granular aggregates near the spindle poles during the prophase of the first meiotic division (Pro-MI), metaphase I, and anaphase I/telophase I stages. Nusap1 depletion leads to chromosome misalignment, increased aneuploidy, and abnormal spindle assembly, particularly a decrease in spindle pole width. Correspondingly, RNA-seq analysis revealed significant suppression of the "establishment of spindle orientation" signaling pathway. Additionally, the attenuation of F-actin in NUSAP1-deficient oocytes may affect the asymmetric division process. Gene ontology analysis of NUSAP1 interactomes, identified through mass spectrometry here, revealed significant enrichment for RNA binding. As an RNA-binding protein, NUSAP1 is likely involved in the regulation of messenger RNA homeostasis by influencing the dynamics of processing (P)-body components. Overall, our results demonstrate the critical importance of precise regulation of NUSAP1 expression levels and protein localization for maintaining mouse oocyte meiosis.

Causal association of epigenetic aging and osteoporosis: a bidirectional Mendelian randomization study.

BACKGROUND: The relationship between aging and osteoporosis is well established. However, the relationship between the body's physiological age, i.e. epigenetic age, and osteoporosis is not known. Our goal is to analyze the bidirectional causal relationship between epigenetic clocks and osteoporosis using a bidirectional Mendelian randomization study. METHODS: We used SNPs closely associated with GrimAge, Hannum, PhenoAge, and HorvathAge in epigenetic age and SNPs closely associated with femoral neck bone mineral density, lumbar spine bone mineral density, and forearm bone mineral density as instrumental variables, respectively, using the inverse variance weighting method and several other MR methods to assess the bidirectional causal relationship between epigenetic age and osteoporosis. RESULT: There was no evidence of a clear causal relationship of epigenetic age (GrimAge, Hannum, PhenoAge, and HorvathAge) on femoral neck bone mineral density, lumbar spine bone mineral density, and forearm bone mineral density. In reverse Mendelian randomization analysis showed a significant causal effect of lumbar spine bone mineral density on GrimAge: odds ratio (OR) = 0.692, 95% confidence interval (CI) = (0.538-0.890), p = 0.004. The results suggest that a decrease in lumbar spine bone mineral density promotes an acceleration of GrimAge. CONCLUSION: There was no significant bidirectional causal relationship between epigenetic age and osteoporosis A decrease in lumbar spine bone density may lead to an acceleration of the epigenetic clock "GrimAge". Our study provides partial evidence for a bidirectional causal effect between epigenetic age and Osteoporosis.

Identifying a Panel of Nine Genes as Novel Specific Model in Endometriosis Noninvasive Diagnosis.

OBJECTIVE: To study biomarkers to develop a novel diagnosis model for endometriosis and validate it using clinical samples. DESIGN: We utilized publicly available datasets and weighted gene co-expression network analysis to identify differentially expressed genes. Ten machine learning algorithms were used for developing an integrative model for predicting endometriosis. The accuracy and robustness of the model were validated using datasets and clinical samples. SETTING: Department of Obstetrics and Gynecology, Tangdu Hospital, Air Force Medical University, Xi'an, Shaanxi, China SUBJECT(S): The study included clinical patients between the ages of 20 and 40 years who required laparoscopic surgery and who had not undergone hormone therapy within the previous three months. All the healthy subjects had given birth to a child at least once in their lives. Patients with inflammatory conditions, malignant diseases, immune diseases, myoma, or adenomyosis were excluded. Paraffin blocks of the samples were collected (case, n = 5; control, n = 5). Blood samples of 58 individuals were collected (case, n = 28; control, n = 30). INTERVENTION(S): None MAIN OUTCOME MEASURE(S): The areas under the receiver operator characteristic curve of our diagnostic model were measured for datasets and clinical samples. Multiplex immunohistochemical staining and quantitative real-time polymerase chain reaction assays were utilized for the validation of the model from tissue slides and peripheral blood samples. RESULT(S): A nine-gene panel endometriosis mRNA score (EMScore), was constructed to distinguish the patients with endometriosis from healthy individuals using algorithms. The EMScore accurately predicted endometriosis, and the areas under the receiver operator characteristic curve of our diagnostic model were 0.920, and 0.942 for tissue and blood samples, respectively. Moreover, the EMScore outperformed other acknowledged signature for predicting endometriosis across seven clinical cohorts. Overall, the EMScore constitutes a sensitive and specific noninvasive diagnostic method for endometriosis. CONCLUSION(S): We developed the EMScore, a novel model that can aid in the diagnosis of endometriosis using peripheral blood samples. This study will contribute to the development of improved clinical noninvasive and sensitive diagnostic tools for endometriosis. These nine genes might be potential target molecules for treating endometriosis.

Determination of suitable reference genes for RT-qPCR normalisation in Bombyx mori (Lepidoptera: Bombycidae) infected by the parasitoid Exorista sorbillans (Diptera, Tachinidae).

The silkworm Bombyx mori (Lepidoptera: Bombycidae) is a lepidopteran model insect of great economic importance. The parasitoid Exorista sorbillans (Diptera, Tachinidae) is the major pest of B. mori and also a promising candidate for biological control. However, the molecular interactions between hosts and dipteran parasitoids have only partially been studied. Gene expression analysis by reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR) is indispensable to characterise their interactions. Accurate normalisation of RT-qPCR-based gene expression requires the use of reference genes that are constantly expressed irrespective of experimental conditions. In this study, the expression stability of 13 traditionally used reference genes was estimated by five statistical algorithms (ΔCt, geNorm, Normfinder, BestKeeper, and RefFinder) to determine the best reference genes for gene expression studies in different tissues of B. mori under E. sorbillans parasitism. Specifically, TATA-box-binding protein was the best reference gene in epidermis and testis, while elongation factor 1α was the most stable gene in prothoracic gland and midgut. Elongation factor 1γ, ribosomal protein L3, actin A1, ribosomal protein L40, glyceraldehyde-3-phosphate dehydrogenase and eukaryotic translation initiation factor 4A were the most suitable genes in head, silk gland, fat body, haemolymph, Malpighian tubule and ovary, respectively. Our study offers a set of suitable reference genes for gene expression normalisation in B. mori under the parasitic stress of E. sorbillans, which will benefit the in-depth exploration of host-dipteran parasitoid interactions, and also provide insights for further improvements of B. mori resistance against parasitoids and biocontrol efficacy of dipteran parasitoids.

Therapeutic role of EGFR - Tyrosine kinase inhibitors in non-small cell lung cancer with leptomeningeal metastasis.

Leptomeningeal metastasis (LM) is a significant complication that advances fast and has a poor prognosis for patients with advanced non-small cell lung cancer (NSCLC) who have epidermal growth factor receptor (EGFR) mutations. Current therapies for LM are inconsistent and ineffective, and established techniques such as radiation, chemotherapy, and surgery continue to fall short of potential outcomes. Nonetheless, EGFR tyrosine kinase inhibitors (TKIs) exhibit potent anti-tumor activity and hold considerable promise for NSCLC patients with EGFR mutations. Thus, assessing EGFR-TKIs effectiveness in treating these central nervous system (CNS) problems is crucial. This review integrates current literature on the intracranial efficacy of EGFR-TKIs to explore the varying impacts of approved EGFR-TKIs in LM patients and the therapeutic possibilities presented by other EGFR-TKIs in development. To delineate the optimal clinical treatment strategy, further exploration is needed regarding the optimal sequencing of EGFR-TKIs and the selection of alternative therapy options following initial treatment failure with EGFR-TKIs.

Causal effects of genetically predicted testosterone on Alzheimer's disease: a two-sample mendelian randomization study.

OBJECTIVE: Although several studies have reported that testosterone may protect against Alzheimer's disease, no evidence of a causal relationship has been demonstrated. METHODS: A Mendelian randomization (MR) study was performed to determine the causal role of testosterone in Alzheimer's disease. The study utilized public databases obtained from separately published genome-wide associationstudies (GWAS). Single-nucleotide polymorphisms (SNPs) for testosterone were extracted from the most recent and largest published GWAS meta-analysis (178,782 participants), and SNPs for Alzheimer's disease were extracted from UK Biobank (954 AD cases and 487,331 controls). The odds ratio (OR) of the inverse variance weighting (IVW) approach was the primary outcome, and the weighted median and MR Egger regression were used for sensitivity analysis. RESULTS: Through IVW, we observed a causal association between genetically predicted testosterone and the risk of Alzheimer's disease, with an OR of 0.99 (95% confidence interval [CI] = 0.998-0.999, p = 0.047). In the sensitivity analyses, the weighted median regression showed directionally similar estimates (OR = 0.99, 95% CI = 0.998-0.999, p = 0.048). The MR Egger regression showed similar estimates (OR = 0.99, 95% CI = 0.998-1.00, p = 0.35), but with lower precision. Funnel plots, MR Egger intercepts, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) analysis indicated the absence of directional pleiotropy effects. CONCLUSION: In conclusion, our MR study provides evidence of a causal relationship between testosterone levels and Alzheimer's disease; however, this relationship must be validated in future studies with larger sample sizes. Early testosterone monitoring may enable the prevention of Alzheimer's and related diseases.

Association between area under the C-peptide curve during an oral glucose tolerance test and diabetic retinopathy in type 2 diabetes patients.

AIMS/INTRODUCTION: To evaluate the relative contributions of the area under the C-peptide curve (AUCC ) in diabetic retinopathy (DR) during an oral glucose tolerance test and C-peptide release test in patients with type 2 diabetes. MATERIALS AND METHODS: We retrospectively analyzed the data of 969 patients. Their general characteristics were retrieved. A series of parameters for assessing pancreatic ß-cells function, such as the AUCC for six time periods: 0-60 min (AUCC0-60 ), 0-120 min (AUCC0-120 ), 0-180 min (AUCC0-180 ), 60-120 min (AUCC60-120 ), 60-180 min (AUCC60-180 ) and 120-180 min (AUCC120-180 ); the area under the glucose-time curve for six time periods: 0-60 min (AUCG0-60 ), 0-120 min (AUCG0-120 ), 0-180 min (AUCG0-180 ), 60-120 min (AUCG60-120 ), 60-180 min (AUCG60-180 ) and 120-180 min (AUCG120-180 ) and their related indexes, were calculated through 0-180 min oral glucose tolerance test and C-peptide release test. We used univariate analysis to examine the potential factors affecting DR. Spearman's correlation was used to analyze the correlation between AUCC -related indexes and DR. The logistic regression model was used to investigate AUCC and its related indexes' contribution to incidence DR. A smooth curve fitting model was used to determine the correlation, non-linear relationship, and threshold effect between AUCC and DR. RESULTS: Of the 969 patients with type 2 diabetes, 469 (48.40%) and 500 (51.60%) were classified as the DR group and non-DR group. Compared with the non-DR group, the DR patients had lower AUCC and AUCC /AUCG . Spearman's correlation analysis showed that AUCC -related indexes were all negatively correlated with DR. The logistic regression analysis determined that there were associations between AUCC and DR in the adjusted models. The odds ratio values of AUCC0-60 , AUCC0-120 , AUCC0-180 , AUCC0-60 /AUCG0-60 , AUCC0-120 /AUCG0-120 , AUCC0-180 /AUCG0-180 , AUCC60-120 , AUCC60-180 , AUCC120-180 , AUCC60-120 /AUCG60-120 , AUCC60-180 /AUCG60-180 and AUCC120-180 /AUCG120-180 were 0.817 (0.750, 0.890), 0.925 (0.895, 0.955), 0.951 (0.932, 0.970), 0.143 (0.060, 0.340), 0.194 (0.093, 0.406), 0.223 (0.116, 0.427), 0.886 (0.842, 0.933), 0.939 (0.915, 0.963), 0.887 (0.846, 0.930), 0.253 (0.133, 0.479), 0.282 (0.160, 0.497) and 0.355 (0.220, 0.573), respectively. AUCC showed a non-linear relationship with DR, with an inflection point. The inflection points of AUCC180 /AUCG180 , AUCC60-120 , AUCC60-180 , AUCC120-180 , AUCC60-120 /AUCG60-120 , AUCC60-180 /AUCG60-180 , AUCC120-180 /AUCG120-180 and DR were 17.51, 0.542, 6.6, 15.7, 8.23, 0.534, 0.593 and 0.808 (P < 0.0001). When the indexes related to the AUCC were less than the inflection point value, they were significantly negatively associated with DR. CONCLUSIONS: The indexes related to the AUCC for six time periods during an oral glucose tolerance test and C-peptide release test was closely associated with the incidence to DR in patients with type 2 diabetes. AUCC has the added advantage of being a cheap and convenient risk assessment over traditional ophthalmic screening.

Comparison of perioperative outcomes of selective arterial clipping guided by near-infrared fluorescence imaging using indocyanine green versus undergoing standard robotic-assisted partial nephrectomy: a systematic review and meta-analysis.

BACKGROUND: This study employs a meta-analytic approach to investigate the impact of robotic-assisted partial nephrectomy, with and without near-infrared fluorescence imaging (NIRF-RAPN vs S-RAPN), on patients' perioperative outcomes and postoperative changes in renal function. MATERIALS AND METHODS: We conducted a comprehensive and rigorous systematic review and cumulative meta-analysis of primary outcomes following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), AMSTAR (Assessing the Methodological Quality of Systematic Reviews) Guidelines, and Risk-of-Bias Tool (RoB2). To ensure a thorough search, we systematically searched five major databases, including Medline, PubMed, Cochrane Library, Scopus, and Web of Science, from databases' inception to April 2023. RESULTS: No significant differences were found between the two groups in terms of age (P=0.19), right side (P=0.54), BMI (P=0.39), complexity score (P=0.89), tumor size (P = 0.88), operating time (P = 0.39), estimated blood loss (P = 0.47), length of stay (P = 0.87), complications (P = 0.20), transfusion (P = 0.36), and positive margins (P = 0.38). However, it is noteworthy that the NIRF-RAPN group exhibited significant reductions in warm ischemia time (P=0.001), the percentage change in estimated glomerular filtration rate at discharge (P=0.01) compared to the S-RAPN group. CONCLUSION: This meta-analysis provides evidence that the group undergoing NIRF-RAPN showed a statistically significant protective effect on the estimated glomerular filtration rate (eGFR).

GGC expansions in NOTCH2NLC contribute to Parkinson disease and dopaminergic neuron degeneration.

BACKGROUND AND PURPOSE: The role of GGC repeat expansions within NOTCH2NLC in Parkinson's disease (PD) and the substantia nigra (SN) dopaminergic neuron remains unclear. Here, we profile the NOTCH2NLC GGC repeat expansions in a large cohort of patients with PD. We also investigate the role of GGC repeat expansions within NOTCH2NLC in the dopaminergic neurodegeneration of SN. METHODS: A total of 2,522 patients diagnosed with PD and 1,085 health controls were analyzed for the repeat expansions of NOTCH2NLC by repeat-primed PCR and GC-rich PCR assay. Furthermore, the effects of GGC repeat expansions in NOTCH2NLC on dopaminergic neurons were investigated by using recombinant adeno-associated virus (AAV)-mediated overexpression of NOTCH2NLC with 98 GGC repeats in the SN of mice by stereotactic injection. RESULTS: Four PD pedigrees (4/333, 1.2%) and three sporadic PD patients (3/2189, 0.14%) were identified with pathogenic GGC repeat expansions (larger than 60 GGC repeats) in the NOTCH2NLC gene, while eight PD patients and one healthy control were identified with intermediate GGC repeat expansions ranging from 41 to 60 repeats. No significant difference was observed in the distribution of intermediate NOTCH2NLC GGC repeat expansions between PD cases and controls (Fisher's exact test p-value = 0.29). Skin biopsy showed P62-positive intranuclear NOTCH2NLC-polyGlycine (polyG) inclusions in the skin nerve fibers of patient. Expanded GGC repeats in NOTCH2NLC produced widespread intranuclear and perinuclear polyG inclusions, which led to a severe loss of dopaminergic neurons in the SN. Consistently, polyG inclusions were presented in the SN of EIIa-NOTCH2NLC-(GGC)98 transgenic mice and also led to dopaminergic neuron loss in the SN. CONCLUSIONS: Overall, our findings provide strong evidence that GGC repeat expansions within NOTCH2NLC contribute to the pathogenesis of PD and cause degeneration of nigral dopaminergic neurons.

Analyzing the dynamics of social media texts using coherency network analysis: a case study of the tweets with the co-hashtags of #BlackLivesMatter and #StopAsianHate.

Introduction: This study examines the associations between time series, termed "coherency," using spectral analysis. Coherence squared, analogous to the squared correlation coefficient, serves as a metric to quantify the degree of interdependence and co-evolution of individual nodes. Methods: We utilized spectral analysis to compute coherence squared, unveiling relationships and co-evolution patterns among individual nodes. The resultant matrix of these relationships was subjected to network analysis. Results: By conducting a case study analyzing tweets associated with the co-hashtags #StopAsianHate and #BlackLivesMatter, we present a novel approach utilizing coherency network analysis to investigate the dynamics of social media text. Frequency domain analysis aided in calculating coherence squared, effectively illustrating the relationships and co-evolution of individual nodes. Furthermore, an analysis of the phase spectrum's slope facilitated the determination of time lag and potential causality direction between highly co-evolved node pairs. Discussion: Our findings underline the potential of coherency network analysis in comprehending the intricate dynamics of social media text. This approach offers valuable insights into how topics, sentiments, or movements manifest and evolve within the digital realm. Future research should explore diverse datasets and domains to broaden our understanding of this novel analytical technique.

Discriminant Analysis of Aroma Differences between Cow Milk Powder and Special Milk Powder (Donkey, Camel, and Horse Milk Powder) in Xinjiang Based on GC-IMS and Multivariate Statistical Methods.

In order to explore the aromatic differences between Xinjiang cow milk powder and specialty milk powder (donkey, camel, and horse milk powder), Gas Chromatography-Ion Mobility Spectrometry (GC-IMS) analysis was employed to investigate the volatile compounds in these four types of milk powders. A total of 61 volatile substances were detected, with ketones, aldehydes, and alcohols being the primary flavor components in the milk powders. While the aromatic components of the different milk powders showed similarities in terms of types, there were significant differences in their concentrations, exhibiting distinct characteristics for each type. The Partial Least Squares Discriminant Analysis (PLS-DA) showed that there were 15, 14, and 23 volatile compounds that could be used for discrimination of cow milk powder against specialty milk powders, respectively. And it was validated by Receiver Operating Characteristic (ROC) analysis, and finally, 8, 6, and 19 volatile compounds were identified as valid differential marker substances. To facilitate visual discrimination between the different milk powders, we established GC-IMS fingerprint spectra based on the final discriminant markers. These studies provide theoretical guidance for the application of volatile compounds to discriminate adulteration of milk powder marketed in Xinjiang.

Halomonas ventosae JPT10 promotes salt tolerance in foxtail millet (Setaria italica) by affecting the levels of multiple antioxidants and phytohormones.

Plant growth-promoting bacterias (PGPBs) can increase crop output under normal and abiotic conditions. However, the mechanisms underlying the plant salt tolerance-promoting role of PGPBs still remain largely unknown. In this study, we demonstrated that Halomonas ventosae JPT10 promoted the salt tolerance of both dicots and monocots. Physiological analysis revealed that JPT10 reduced reactive oxygen species accumulation by improving the antioxidant capability of foxtail millet seedlings. The metabolomic analysis of JPT10-inoculated foxtail millet seedlings led to the identification of 438 diversely accumulated metabolites, including flavonoids, phenolic acids, lignans, coumarins, sugar, alkaloids, organic acids, and lipids, under salt stress. Exogenous apigenin and chlorogenic acid increased the salt tolerance of foxtail millet seedlings. Simultaneously, JPT10 led to greater amounts of abscisic acid (ABA), indole-3-acetic acid (IAA), salicylic acid (SA), and their derivatives but lower levels of 12-oxo-phytodienoic acid (OPDA), jasmonate (JA), and JA-isoleucine (JA-Ile) under salt stress. Exogenous JA, methyl-JA, and OPDA intensified, whereas ibuprofen or phenitone, two inhibitors of JA and OPDA biosynthesis, partially reversed, the growth inhibition of foxtail millet seedlings caused by salt stress. Our results shed light on the response of foxtail millet seedlings to H. ventosae under salt stress and provide potential compounds to increase salt tolerance in foxtail millet and other crops.

The role of APOBEC3C in modulating the tumor microenvironment and stemness properties of glioma: evidence from pancancer analysis.

Background: It is now understood that APOBEC3 family proteins (A3s) are essential in tumor progression, yet their involvement in tumor immunity and stemness across diverse cancer types remains poorly understood. Methods: In the present study, comprehensive genome-wide statistical and bioinformatic analyses were conducted to elucidate A3 family expression patterns, establishing clinically relevant correlations with prognosis, the tumor microenvironment(TME), immune infiltration, checkpoint blockade, and stemness across cancers. Different experimental techniques were applied, including RT-qPCR, immunohistochemistry, sphere formation assays, Transwell migration assays, and wound-healing assays, to investigate the impact of A3C on low-grade glioma (LGG) and glioblastoma multiforme (GBM), as well as its function in glioma stem cells(GSCs). Results: Dysregulated expression of A3s was observed in various human cancer tissues. The prognostic value of A3 expression differed across cancer types, with a link to particularly unfavorable outcomes in gliomas. A3s are associated with the the TME and stemness in multiple cancers. Additionally, we developed an independent prognostic model based on A3s expression, which may be an independent prognostic factor for OS in patients with glioma. Subsequent validation underscored a strong association between elevated A3C expression and adverse prognostic outcomes, higher tumor grades, and unfavorable histology in glioma. A potential connection between A3C and glioma progression was established. Notably, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses implicated A3C in immune system-related diseases, with heightened A3C levels contributing to an immunosuppressive tumor microenvironment (TME) in glioma. Furthermore, in vitro experiments substantiated the role of A3C in sustaining and renewing glioma stem cells, as A3C deletion led to diminished proliferation, invasion, and migration of glioma cells. Conclusion: The A3 family exhibits heterogeneous expression across various cancer types, with its expression profile serving as a predictive marker for overall survival in glioma patients. A3C emerges as a regulator of glioma progression, exerting its influence through modulation of the tumor microenvironment and regulation of stemness.

Interpretable modeling of time-resolved single-cell gene-protein expression with CrossmodalNet.

Cell-surface proteins play a critical role in cell function and are primary targets for therapeutics. CITE-seq is a single-cell technique that enables simultaneous measurement of gene and surface protein expression. It is powerful but costly and technically challenging. Computational methods have been developed to predict surface protein expression using gene expression information such as from single-cell RNA sequencing (scRNA-seq) data. Existing methods however are computationally demanding and lack the interpretability to reveal underlying biological processes. We propose CrossmodalNet, an interpretable machine learning model, to predict surface protein expression from scRNA-seq data. Our model with a customized adaptive loss accurately predicts surface protein abundances. When samples from multiple time points are given, our model encodes temporal information into an easy-to-interpret time embedding to make prediction in a time-point-specific manner, and is able to uncover noise-free causal gene-protein relationships. Using three publicly available time-resolved CITE-seq data sets, we validate the performance of our model by comparing it with benchmarking methods and evaluate its interpretability. Together, we show that our method accurately and interpretably profiles surface protein expression using scRNA-seq data, thereby expanding the capacity of CITE-seq experiments for investigating molecular mechanisms involving surface proteins.

Development and validation of a risk prediction model for osteoporosis in elderly patients with type 2 diabetes mellitus: a retrospective and multicenter study.

BACKGROUND: This study aimed to construct a risk prediction model to estimate the odds of osteoporosis (OP) in elderly patients with type 2 diabetes mellitus (T2DM) and evaluate its prediction efficiency. METHODS: This study included 21,070 elderly patients with T2DM who were hospitalized at six tertiary hospitals in Southwest China between 2012 and 2022. Univariate logistic regression analysis was used to screen for potential influencing factors of OP and least absolute shrinkage. Further, selection operator regression (LASSO) and multivariate logistic regression analyses were performed to select variables for developing a novel predictive model. The area under the receiver operating characteristic curve (AUROC), calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) were used to evaluate the performance and clinical utility of the model. RESULTS: The incidence of OP in elderly patients with T2DM was 7.01% (1,476/21,070). Age, sex, hypertension, coronary heart disease, cerebral infarction, hyperlipidemia, and surgical history were the influencing factors. The seven-variable model displayed an AUROC of 0.713 (95% confidence interval [CI]:0.697-0.730) in the training set, 0.716 (95% CI: 0.691-0.740) in the internal validation set, and 0.694 (95% CI: 0.653-0.735) in the external validation set. The optimal decision probability cut-off value was 0.075. The calibration curve (bootstrap = 1,000) showed good calibration. In addition, the DCA and CIC demonstrated good clinical practicality. An operating interface on a webpage ( https://juntaotan.shinyapps.io/osteoporosis/ ) was developed to provide convenient access for users. CONCLUSIONS: This study constructed a highly accurate model to predict OP in elderly patients with T2DM. This model incorporates demographic characteristics and clinical risk factors and may be easily used to facilitate individualized prediction.

On-Surface Synthesis of Novel Kagome Lattices Coordinated via Four-Fold N-Ag Bonding.

The Kagome lattice structures based on metal-organic coordination have garnered widespread interest because of their topologically Dirac/flat bands and other exotic electronic structures. However, the experimental fabrication of large-area two-dimensional (2D) Kagome lattice structures of metal-organic frameworks (MOFs) via on-surface synthesis remains limited. Herein, we successfully construct two kinds of large-scale 2D Kagome-type lattices stabilized by 4-fold N-Ag coordination on the Ag(111) surface. With the aid of scanning tunneling microscopy (STM) and synchrotron radiation photoemission spectroscopy (SRPES), we clearly elucidate the reaction pathway and mechanism of fabrication of the two Kagome lattices. This work provides a novel platform for investigating related intriguing physical properties.