Silencing TRIM8 alleviates allergic asthma and suppressing Th2 differentiation through inhibiting NF-κB/NLRP3 signaling pathway.

BACKGROUND AND AIM: Allergic asthma is a primary type of asthma and characterized by T helper 2 (Th2) cells -mediated inflammation. Tripartite motif containing 8 (TRIM8) protein is involved in immunoreaction and inflammatory response in many diseases. However, its role in allergic asthma remains unclear. Medical databank showed that TRIM8 was increased in lung of ovalbumin (OVA)-challenged mice. This study aimed to elucidate the effects of TRIM8 on allergic asthma and Th2 development. METHODS: Asthma were induced by OVA challenge in mice, and the adenovirus vector loaded with TRIM8 knockdown sequence was delivered into asthma mice by nasal inhalation. The percentage of Th2 cells in lung was assessed by flow cytometric analysis, and the contents of Th2 cytokines (interleukin (IL)-4, IL-5 and IL-13) in bronchoalveolar lavage fluid (BALF) were assessed with ELISA. In vitro Th2 induction was performed in CD4+ cells from mouse spleen, the expression of Th2 molecules (IL-4, IL-5 and GATA binding protein 3 (GATA3)) were measured by real-time PCR. In addition, the nuclear factor-kappa B (NF-κB)/nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 3 (NLRP3) signaling was determined. RESULTS: TRIM8 was highly expressed in the lung tissues of asthmatic mice and Th2-induced CD4+ cells. OVA challenge-induced Th2 development and Th2 cytokine secretion were restrained by silencing of TRIM8 in vivo. Similarly, the Th2 differentiation in vitro was also suppressed by TRIM8 knockdown. TRIM8 inhibited the NF-κB/NLRP3 activity by blocking transforming growth factor-beta-activated kinase 1 (TAK1), and the effects of TRIM8 were abrogated by overexpression of NLRP3. CONCLUSIONS: Silencing TRIM8 relieved the asthmatic injury in mice and excessive Th2 development via inhibiting the NF-κB/NLRP3 pathway. It is indicated that TRIM8 may contribute to the airway inflammation in allergic asthma via activating the NF-κB/NLRP3 signaling pathway. The current study provided a novel potential target for allergic asthma treatment.

The potential of a nomogram risk assessment model for the diagnosis of abdominal aortic aneurysm: a multicenter retrospective study.

The incidence of abdominal aortic aneurysm (AAA) is very high, but there is no risk assessment model for early identification of AAA in clinic. The aim of this study was to develop a nomogram risk assessment model for predicting AAA. The data of 280 patients diagnosed as AAA and 385 controls in The Affiliated Suzhou Hospital of Nanjing Medical University were retrospectively reviewed. The LASSO regression method was applied to filter variables, and multivariate logistic regression was used to construct a nomogram. The discriminatory ability of the model was determined by calculating the area under the curve (AUC). The calibration capability of the model is evaluated by using bootstrap (resampling = 1000) internal validation and Hosmer-Lemeshow test. The clinical utility and clinical application value were evaluated by decision curve analysis (DCA) and clinical impact curve (CIC). In addition, a retrospective review of 133 AAA patients and 262 controls from The First Affiliated Hospital of Soochow University was performed as an external validation cohort. Eight variables are selected to construct the nomogram of AAA risk assessment model. The nomogram predicted AAA with AUC values of 0.928 (95%CI, 0.907-0.950) in the training cohort, and 0.902 (95%CI, 0.865-0.940) in the external validation cohort, the risk prediction model has excellent discriminative ability. The calibration curve and Hosmer-Lemeshow test proved that the nomogram predicted outcomes were close to the ideal curve, the predicted outcomes were consistent with the real outcomes, the DCA curve and CIC curve showed that patients could benefit. This finding was also confirmed in the external validation cohort. In this study, a nomogram was constructed that incorporated eight demographic and clinical characteristics of AAA patients, which can be used as a practical approach for the personalized early screening and auxiliary diagnosis of the potential risk factors.

Diagnostic Nomogram Model for ACR TI-RADS 4 Nodules Based on Clinical, Biochemical Data and Sonographic Patterns.

OBJECTIVES: The objective of this study was to develop and validate a nomogram model integrating clinical, biochemical and ultrasound features to predict the malignancy rates of Thyroid Imaging Reporting and Data System 4 (TR4) thyroid nodules. METHODS: A total of 1557 cases with confirmed pathological diagnoses via fine-needle aspiration (FNA) were retrospectively included. Univariate and multivariate logistic regression analyses were conducted to identify independent predictors of malignancy. These predictors were incorporated into the nomogram model, and its predictive performance was evaluated using receiver-operating characteristic curve (AUC), calibration plots, net reclassification improvement (NRI), integrated discrimination improvement (IDI) and decision curve analysis (DCA). RESULTS: Eight out of 22 variables-age, margin, extrathyroidal extension, halo, calcification, suspicious lymph node metastasis, aspect ratio and thyroid peroxidase antibody-were identified as independent predictors of malignancy. The calibration curve demonstrated excellent performance, and DCA indicated favourable clinical utility. Additionally, our nomogram exhibited superior predictive ability compared to the current American College of Radiology (ACR) score model, as indicated by higher AUC, NRI, IDI, negative likelihood ratio (NLR) and positive likelihood ratio (PLR) values. CONCLUSIONS: The developed nomogram model effectively predicts the malignancy rate of TR4 thyroid nodules, demonstrating promising clinical applicability.

Recent advances in fluorescent probes for fatty liver imaging by detecting lipid droplets.

Fatty liver, a major health problem worldwide, is closely associated with aberrant accumulation and alteration of energy storage organelles, lipid droplets (LDs), in the disease process. Fluorescent probes with excellent optical performance, high sensitivity/selectivity and real-time monitoring have emerged as an attractive tool for the detection of LDs used in the diagnosis of fatty liver. In this review, we summarize various probes based on different response mechanisms to image LDs in the fatty liver process using different excitation imaging modes and emission wavelengths, including the visible to the near-infrared, two/three-photon, and the second near-infrared region. The perspectives and barriers associated with the reported lipid droplet (LD) probes for future development are also discussed.

Balancing Maillard reaction products formation and antioxidant activities for improved sensory quality and health benefit properties of pan baked buns.

This study investigated the impact of processing temperatures (190 °C, 210 °C, and 230 °C) and durations (7 min, 10 min, and 14 min) on the formation of Maillard reaction products (MRPs) and antioxidant activities in pan baked buns. Key Maillard reaction indicators, including glyoxal (GO), methylglyoxal (MGO), 5-hydroxymethylfurfural (5-HMF), melanoidins, and fluorescent advanced glycation end products (AGEs) were quantified. The results demonstrated significant increases in GO, MGO, 5-HMF contents (p < 0.05), and antioxidant activities (p < 0.05) when the buns were baked at 210 °C for 14 min, 230 °C for 10 min and 14 min. However, the interior MRPs of baked buns were minimally affected by the baking temperature and duration. Prolonged heating temperatures and durations exacerbated MRPs production (43.8 %-1038 %) in the bottom crust. Nonetheless, this process promoted the release of bound phenolic compounds and enhanced the antioxidant activity. Heating induces the thermal degradation of macromolecules in food, such as proteins and polysaccharides, which releases bound phenolic compounds by disrupting their chemical bonds within the food matrix. Appropriate selections of baking parameters can effectively reduce the formation of MRPs while simultaneously improve sensory quality and health benefit of the pan baked buns. Considering the balance between higher antioxidant properties and lower MRPs, the optimal thermal parameters for pan baked buns were 210 °C for 10 min. Furthermore, a normalized analysis revealed a consistent trend for GO, MGO, 5-HMF, fluorescent AGEs, and melanoidins. Moreover, MRPs were positively correlated with total contents of phenolic compounds, ferric-reducing antioxidant power (FRAP), and color, but negatively correlated with moisture contents and reducing sugars. Additionally, the interaction between baking conditions and Maillard reactions probably contributed to enhanced primary flavors in the final product. This study highlights the importance of optimizing baking parameters to achieve desirable MRPs levels, higher antioxidant activity, and optimal sensory attributes in baked buns.

Unraveling how hydrogen-bonding networks affect the capture of amphetamine-type stimulants by polymerized deep eutectic solvent modified magnetic biochar: Coupling quantum chemical calculations with experiment.

The abuse of amphetamine-type stimulants (ATSs) has caused irreversible harm to public safety and ecosystems. A novel polymerized deep eutectic solvent modified magnetic pomelo peel biochar (PMBC) was prepared, and the differences in adsorption of four abused amphetamine-type stimulants (ATSs: AMP, MAMP, MDA and MDMA) were due to varying hydrogen bonds quantities and strengths. PMBC showed excellent chemical reactivity to MDMA, with a maximum adsorption capacity of 926.13 µg g-1, which was 3.25, 2.52 and 1.15 times higher than that of AMP, MAMP and MDA, respectively. Modern spectral analysis showed that there were a series of active centers (-COOH, -NH2 and -OH) on the PMBC, which could form hydrogen bond networks with the nitrogen and oxygen functional groups of ATSs. In various chemical environments: pH level (4-11), inorganic ion and organic matter (humic acid), PMBC maintained high activity towards four ATSs. Additionally, the quantum chemical calculations revealed that the methylenedioxy bridge of ATSs can increase the active sites, and the -NH- and -NH2 groups had different hydrogen bond formation capabilities, which together resulted in the adsorption order of PMBC on the four ATSs: MDMA > MDA > MAMP > AMP. Moreover, the hydrogen-bonding binding energies of several common hydrogen-bonding types were compared, including O-H····O, N-H····O/O-H····N and N-H···N. This study laid an empirical and theoretical foundation for the efficient capture of ATSs in water and contributed to the innovative design of materials.

Variations in the alveolar bone morphology in maxillary molar area: a retrospective CBCT study.

BACKGROUND: This study quantitatively analyzed the anatomic structure of the alveolar bone in the maxillary molar region at three potential locations for Temporary Anchorage Device (TAD) placement. Additionally, the study compared the variability in this region across different age groups, sagittal skeletal patterns, vertical facial types, and sexes. METHODS: In this retrospective cone-beam computed tomography study, the buccal alveolar bone was analyzed in the posterior molar area of 200 patients, the measurement items include buccal alveolar bone height, alveolar bone thickness, interradicular distance, and maxillary retromolar space. RESULTS: Buccal alveolar height was greatest in the U56 region. The interradicular space was largest in the U56 region and increased from the alveolar crest to the sinus floor. Buccal alveolar bone thickness was highest in the U67 region and generally increased from the alveolar crest to the sinus floor. The maxillary retromolar space gradually increased from the alveolar crest to the root apex. CONCLUSIONS: TADs are safest when placed in the buccal area between the maxillary second premolar and the first molar, particularly at the 9 mm plane. The U67 region is the optimal safe zone for TAD placement for maxillary dentition distalization. TADs placement in adolescents can be challenging. Maxillary third molar extraction can be considered for maxillary dentition distalization.

Utilization of Germinated Seeds as Functional Food Ingredients: Optimization of Nutrient Composition and Antioxidant Activity Evolution Based on the Germination Characteristics of Chinese Chestnut (Castanea mollissima).

The current study investigated the impact of germination duration on the functional components (vitamin C, γ-aminobutyric acid (GABA), polyphenols, flavonoids) and antioxidant activity of germs and cotyledons of the germinated Chinese chestnut (Castanea mollissima). We utilized seeds of the "Zaofeng" Chinese chestnut to germinate, and sowed the seeds in wet sand at 22 °C and 85% relative humidity. The germination rate, length, diameter, and fresh weight of the sprouts were investigated at 0, 2, 4, 6, 8, and 10 days after sowing, and the kinetic changes of amylose, amylopectin, sugar components, soluble protein, vitamin C, GABA, total phenols, flavonoids, and the DPPH and ABTS free radical scavenging activity in the germs and cotyledons were monitored, respectively. The findings revealed that the germination rate and germ biomass increased continuously during germination. The germination rate reached 90% on the 8th day after sowing. Germination reduced amylose in cotyledons from 42.3% to 34.2%, amylopectin from 42.9% to 25.8%, total sugar from 12.6% to 11.4%, and vitamin C from 1.45 mg/g to 0.77 mg/g. Meanwhile, soluble protein in the embryos rose from 0.31% to 0.60%, vitamin C from 21.1 to 29.4 mg/g, GABA from 0.49 to 1.68 mg/g, total flavonoids from 53.6 to 129.7 mg/g, and ABTS antioxidant activity from 1.52 to 3.27 µmol TE/g. The average contents of D-fructose, inositol, vitamin C, GABA, polyphenols, and flavonoids and the DPPH and ABTS antioxidant activity in germs were as high as 22.5, 6, 35, 7.5, 10, 20, and 10 and 20-fold those of cotyledons, respectively. Especially, the average content of glucose in germ was as high as 80-fold that of cotyledon. D-xylulose, D-galacturonic acid, and D-ribose were only found in germs, but not in cotyledons. Considering the germ biomass and functional components content, germs of Chinese chestnuts germinated at 22 °C for 8 days are considered the most suitable raw material for functional food products. In conclusion, controlled germination not only enhances the physicochemical and functional properties of Chinese chestnut germs but also reduces the caloric content and improves the nutritional composition of the cotyledons appropriately. Moreover, the comprehensive evaluation of compositional changes and functionality in the embryo and cotyledon of Chinese chestnuts will provide a solid foundation for subsequent functional food processing utilizing germinated Chinese chestnuts.

Adult Outpatients with Long COVID Infected with SARS-CoV-2 Omicron Variant. Part 1: Oral Microbiota Alterations.

BACKGROUND: Many individuals experience long COVID after SARS-CoV-2 infection. As microbiota can influence health, it may change with COVID-19. This study investigated differences in oral microbiota between COVID-19 patients with and without long COVID. METHODS: Based on a prospective follow-up investigation, this nested case-control study evaluated the differences in oral microbiota in individuals with and without long COVID (Symptomatic and Asymptomatic groups), which were assessed by 16S rRNA sequencing on tongue coating samples. A predictive model was established using machine learning based on specific differential microbial communities. RESULTS: One-hundred-and-eight patients were included (n=54 Symptomatic group). The Symptomatic group had higher Alpha diversity indices (observed_otus, Chao1, Shannon, and Simpson indices), differences in microbial composition (Beta diversity), and microbial dysbiosis with increased diversity and relative abundance of pathogenic bacteria. Marker bacteria (c__Campylobacterota, o__Coriobacteriales, o__Pseudomonadales, and o__Campylobacterales) were associated with long COVID by linear discriminant analysis effect size and receiver operating characteristic curves (AUC 0.821). CONCLUSION: There were distinct variations in oral microbiota between COVID-19 patients with and without long COVID. Changes in oral microbiota may indicate long COVID.

Comprehensive Understanding on the Aging Process and Mechanism of Microplastics in the Sediment-Water Interface: Untangling the Role of Photoaging and Biodegradation.

Microplastics (MPs) in coastal wetlands have been of great concern, but information on the aging behavior of MPs in the sediment-water interface is still lacking. In this study, the contribution of a typical abiotic (photoaging) and biotic (biodegradation) process and the underlying aging pathway of MPs with different degradabilities (including polypropylene, polyethylene terephthalate, and polylactic acid) were studied. With a quantified relative importance of photoaging (>55%) vs biodegradation, the crucial contribution of photoaging on MP aging was highlighted. This was likely attributed to more generation of reactive oxygen species (ROS) under sunlight irradiation conditions, containing O2•- and H2O2. By raising higher the level of malondialdehyde (0.5-3.5 times as high as that in the dark condition), these photochemically formed ROS caused oxidative stress and inhibited the selective attachment of plastic-degrading microbes on the MP surface, thereby weakening the effect of biodegradation. On this basis, the aging characteristics and potential pathway of different MPs were revealed. The functional group of nondegradable polypropylene tends to be broken by ROS first, while biodegradation (Arthrobacter oryzae and Bacillus sp.) played a relatively dominant role in biodegradable polylactic acid. This study provides a new sight for the understanding on the aging behaviors of MPs in the sediment-water interface.

The impact of evidence-based nursing leadership in healthcare settings: a mixed methods systematic review.

BACKGROUND: The central component in impactful healthcare decisions is evidence. Understanding how nurse leaders use evidence in their own managerial decision making is still limited. This mixed methods systematic review aimed to examine how evidence is used to solve leadership problems and to describe the measured and perceived effects of evidence-based leadership on nurse leaders and their performance, organizational, and clinical outcomes. METHODS: We included articles using any type of research design. We referred nurses, nurse managers or other nursing staff working in a healthcare context when they attempt to influence the behavior of individuals or a group in an organization using an evidence-based approach. Seven databases were searched until 11 November 2021. JBI Critical Appraisal Checklist for Quasi-experimental studies, JBI Critical Appraisal Checklist for Case Series, Mixed Methods Appraisal Tool were used to evaluate the Risk of bias in quasi-experimental studies, case series, mixed methods studies, respectively. The JBI approach to mixed methods systematic reviews was followed, and a parallel-results convergent approach to synthesis and integration was adopted. RESULTS: Thirty-one publications were eligible for the analysis: case series (n = 27), mixed methods studies (n = 3) and quasi-experimental studies (n = 1). All studies were included regardless of methodological quality. Leadership problems were related to the implementation of knowledge into practice, the quality of nursing care and the resource availability. Organizational data was used in 27 studies to understand leadership problems, scientific evidence from literature was sought in 26 studies, and stakeholders' views were explored in 24 studies. Perceived and measured effects of evidence-based leadership focused on nurses' performance, organizational outcomes, and clinical outcomes. Economic data were not available. CONCLUSIONS: This is the first systematic review to examine how evidence is used to solve leadership problems and to describe its measured and perceived effects from different sites. Although a variety of perceptions and effects were identified on nurses' performance as well as on organizational and clinical outcomes, available knowledge concerning evidence-based leadership is currently insufficient. Therefore, more high-quality research and clinical trial designs are still needed. TRAIL REGISTRATION: The study was registered (PROSPERO CRD42021259624).

ER-GUARD: an evolutionarily conserved antioxidant defense system at ER membranes.

Oxidative protein folding in the endoplasmic reticulum (ER) is essential for all eukaryotic cells yet generates hydrogen peroxide (H2O2), a reactive oxygen species (ROS). The ER-transmembrane protein that provides reducing equivalents to ER and guards the cytosol for antioxidant defense remains unidentified. Here we combine AlphaFold2-based and functional reporter screens in C. elegans to identify a previously uncharacterized and evolutionarily conserved protein ERGU-1 that fulfills these roles. Deleting C. elegans ERGU-1 causes excessive H2O2 and transcriptional gene up-regulation through SKN-1, homolog of mammalian antioxidant master regulator NRF2. ERGU-1 deficiency also impairs organismal reproduction and behaviors. Both C. elegans and human ERGU-1 proteins localize to ER membranes and form network reticulum structures. We name this system ER-GUARD, Endoplasmic Reticulum Guardian Aegis of Redox Defense. Human and Drosophila homologs of ERGU-1 can rescue C. elegans mutant phenotypes, demonstrating evolutionarily ancient and conserved functions. Together, our results reveal an ER-membrane-specific protein machinery and defense-net system ER-GUARD for peroxide detoxification and suggest a previously unknown but conserved pathway for antioxidant defense in animal cells.

Erratum to 'B4GALNT1 promotes hepatocellular carcinoma stemness and progression via integrin α2ß1-mediated FAK and AKT activation' (JHEP Reports 5 [2023] 100903).

[This corrects the article DOI: 10.1016/j.jhepr.2023.100903.].

Enhanced anaerobic digestion of waste-activated sludge by thermal-alkali pretreatment: a pilot-scale study.

The composition of waste-activated sludge (WAS) is complex, containing a large amount of harmful substances, which pose a threat to the environment and human health. The reduction and resource utilization of sludge has become a development demand in sludge treatment and disposal. Based on the technical bottlenecks in the practical application of direct anaerobic digestion technology, this study adopted two different thermal and thermal-alkali hydrolysis technologies to pretreat sludge. A pilot-scale experiment was conducted to investigate the experimental conditions, parameters, and effects of two hydrolysis technologies. This study showed that the optimal hydrolysis temperature was 70 °C, the hydrolysis effect and pH can reach equilibrium with the hydrolysis retention time was 4-8 h, and the optimal alkali concentration range was 0.0125-0.015 kg NaOH/kg dry-sludge. Thermal-alkali combination treatment greatly improved the performance of methane production, the addition of NaOH increased methane yield by 31.2% than that of 70 °C thermal hydrolysis. The average energy consumption is 75 kWh/m3 80% water-content sludge during the experiment. This study provides a better pretreatment strategy for exploring efficient anaerobic digestion treatment technologies suitable for southern characteristic sewage sludge.

Advances in the Differentiation of hiPSCs into Cerebellar Neuronal Cells.

The cerebellum has historically been primarily associated with the regulation of precise motor functions. However, recent findings suggest that it also plays a pivotal role in the development of advanced cognitive functions, including learning, memory, and emotion regulation. Pathological changes in the cerebellum, whether congenital hereditary or acquired degenerative, can result in a diverse spectrum of disorders, ranging from genetic spinocerebellar ataxias to psychiatric conditions such as autism, and schizophrenia. While studies in animal models have significantly contributed to our understanding of the genetic networks governing cerebellar development, it is important to note that the human cerebellum follows a protracted developmental timeline compared to the neocortex. Consequently, employing animal models to uncover human-specific molecular events in cerebellar development presents significant challenges. The emergence of human induced pluripotent stem cells (hiPSCs) has provided an invaluable tool for creating human-based culture systems, enabling the modeling and analysis of cerebellar physiology and pathology. hiPSCs and their differentiated progenies can be derived from patients with specific disorders or carrying distinct genetic variants. Importantly, they preserve the unique genetic signatures of the individuals from whom they originate, allowing for the elucidation of human-specific molecular and cellular processes involved in cerebellar development and related disorders. This review focuses on the technical advancements in the utilization of hiPSCs for the generation of both 2D cerebellar neuronal cells and 3D cerebellar organoids.

Development and evaluation of a family-child reading picture book on reducing autism spectrum disorder caregivers' psychological stress: a mixed method study.

Introduction: The rapid increasing prevalence of ASD has become a significant global health issue. Caregivers of children with ASD are experiencing higher level of psychological stress and mental disorders. However, interventions to improve the psychological health of caregivers of children with ASD have largely been neglected. Methods: Based on the ADDIE (Analysis, Design, Development, Implementation, and Evaluation) model, we initially did in-depth interviews with 8 caregivers, and conducted field observation in two rehabilitation centers to analyze the daily lives, the empowered components, the emotional moments of the children with autism and their caregivers. Then we designed the outline of the picture book, and developed it by a multi-disciplinary team by 4 rounds. After that, this picture book was sent out to 54 caregivers of children with ASD for family-child reading in one month. A quantitative questionnaire was administered before and after their reading to evaluate the efficacy of reducing their stress and affiliate stigma, and improving self-efficacy, resilience, empowerment capacity; and exit interviews were conducted after their initial reading to assess the acceptability, content appropriateness, perceived benefits and generalizability of this picture book. Quantitative data were analyzed by descriptive analysis and paired t-tests using IBM SPSS 26.0. Qualitative data were analyzed using template analysis. Results: In total, 54 caregivers read the picture book with their child, with the total of 149 (an average of 2.76 per family) times reading in one month. Among them, 39 caregivers returned the following-up questionnaires. Although most of the outcome measures did not showed significant changes except the stress level decreased statistically significant (13.38 ± 3.864 to 11.79 ± 3.238, P=0.001), caregivers reported that the picture book echoed their daily lives and gave them a sense of warmth, inspiration, and hope, as well as some insight on family relationships and attitudes towards the disorder. They also expressed a willingness to disseminate the book to other families with children suffering ASD and the public. Conclusion: This specially designed picture book has been proven to be an acceptable, content-appropriate, and effective family-centered psychological intervention, which could be easily scaled up.

Genetic analysis of congenital unilateral renal agenesis in children based on next-generation sequencing.

BACKGROUND: Congenital unilateral renal agenesis (URA) is a kind of rare birth defect during fetal development with varies clinical phenotypes. The pathogenesis and the relationship between gene and phenotype are still unclear. METHODS: Ten URA fetuses were followed up after birth using postnatal renal ultrasound examination to confirm the diagnosis with nine children were URA and one was Renal Ectopy (RE). Trio- WES, CNV- seq were performed with the 10 children and their close relatives. RESULTS: There were 3 heterozygous variants of CHD7, PROKR2 and NRIP1 genes were identified in 3 children, respectively. CHD7 (c.2663T>C, p.M888T) is classified as likely pathogenic (LP), PROKR2 (c.685G>C, p.G229R) and NRIP1 (c.2705T>G, p.F902C) are classified as variants of uncertain significance (VUS). CHD7 (c.2663T>C, p.M888T) and PROKR2 (c.685G>C, p.G229R) as URA-related genes may be associated with idiopathic hypogonadotropic hypogonadism (IHH) or CHARGE syndrome (CS), and 3D-protein structure prediction revealed that the two variants may affect the stability in the CHD7 protein or PROKR2 protein, separately. The RE-related gene NRIP1 (c.2705T>G, p.F902C) may be causative of congenital anomalies of the kidneys and urinary tract (CAKUT). CONCLUSIONS: Identification of these variants can in exploring the etiology of URA or RE and improve the level of genetic counseling. IMPACTS: We performed trio-whole-exome sequencing (trio- WES) and copy number variation sequencing (CNV- seq) in 10 children, including 9 children with Unilateral Renal Agenesis and 1 with Renal Ectopy after birth. The possible pathogenic genes of URA can be screened using prenatal and postnatal diagnosis of URA fetuses and gene detection after birth. Future studies evaluating this association may lead to a better understanding of URA and elucidate exploring the etiology of URA or RE and improve the level of genetic counseling.

Prognostic prediction of patients having classical papillary thyroid carcinoma with a 4 mRNA-based risk model.

The dysregulation of protein-coding genes involved in various biological functions is closely associated with the progression of thyroid cancer. This study aimed to investigate the effects of dysregulated gene expressions on the prognosis of classical papillary thyroid carcinoma (cPTC). Using expression profiling datasets from the Cancer Genome Atlas (TCGA) database, we performed differential expression analysis to identify differentially expressed genes (DEGs). Cox regression and Kaplan-Meier analysis were used to identify DEGs, which were used to construct a risk model to predict the prognosis of cPTC patients. Functional enrichment analysis unveiled the potential significance of co-expressed protein-encoding genes in tumors. We identified 4 DEGs (SALL3, PPBP, MYH1, and SYNDIG1), which were used to construct a risk model to predict the prognosis of cPTC patients. These 4 genes were independent of clinical parameters and could be functional in cPTC carcinogenesis. Furthermore, PPBP exhibited a strong correlation with poorer overall survival (OS) in the advanced stage of the disease. This study suggests that the 4-gene signature could be an independent prognostic biomarker to improve prognosis prediction in cPTC patients older than 46.

Metal-Free Cascade Formation of C-C and C-N Bond for the Construction of 3-Cyano-2-Pyridones with Insecticidal Properties.

A straightforward and efficient methodology has been developed for the synthesis of 3-cyano-2-pyridones via the C-C and C-N bond formation processes. A total of 51 diverse 3-cyano-2-pyridone derivatives were obtained in moderate to excellent yields. This reaction featured advantages such as a metal-free process, wide functional group tolerance, simple operation, and mild conditions. A plausible mechanism for the reaction was proposed. 3-cyano-2-pyridones as ricinine analogues for insecticidal properties were evaluated, and the compound 3ci (LC50 = 2.206 mg/mL) showed the best insecticidal property.

Maize Autophagy-Related Protein ZmATG3 Confers Tolerance to Multiple Abiotic Stresses.

Abiotic stresses pose a major increasing problem for the cultivation of maize. Autophagy plays a vital role in recycling and re-utilizing nutrients and adapting to stress. However, the role of autophagy in the response to abiotic stress in maize has not yet been investigated. Here, ZmATG3, which is essential for ATG8-PE conjugation, was isolated from the maize inbred line B73. The ATG3 sequence was conserved, including the C-terminal domains with HPC and FLKF motifs and the catalytic domain in different species. The promoter of the ZmATG3 gene contained a number of elements involved in responses to environmental stresses or hormones. Heterologous expression of ZmATG3 in yeast promoted the growth of strain under salt, mannitol, and low-nitrogen stress. The expression of ZmATG3 could be altered by various types of abiotic stress (200 mM NaCl, 200 mM mannitol, low N) and exogenous hormones (500 µM ABA). GUS staining analysis of ZmATG3-GUS transgenic Arabidopsis revealed that GUS gene activity increased after abiotic treatment. ZmATG3-overexpressing Arabidopsis plants had higher osmotic and salinity stress tolerance than wild-type plants. Overexpression of ZmATG3 up-regulated the expression of other AtATGs (AtATG3, AtATG5, and AtATG8b) under NaCl, mannitol and LN stress. These findings demonstrate that overexpression of ZmATG3 can improve tolerance to multiple abiotic stresses.