FOXO3 Activates MFN2 Expression to Maintain the Autophagy Response in Cancer Cells Under Amino Acid Deprivation.

The lack of amino acids triggers the autophagic response. Some studies have shown such starvation conditions also induce mitochondrial fusion, revealing a close correlation between the two processes. Although Mitofusin-2 (MFN2) has been demonstrated to play a role in fusion regulation, its role in the autophagic response and the variables that activate MFN2 under stress remain unknown. In this investigation, we screened and confirmed that forkhead box protein O3 (FOXO3) participates in MFN2's expression during short periods of starvation. Luciferase reporter test proved that FOXO3 facilitates MFN2's transcription by binding to its promoter region, and FOXO3 downregulation directly depresses MFN2's expression. Consequently, inhibiting the FOXO3-MFN2 axis results in the loss of mitochondrial fusion, disrupting the normal morphology of mitochondria, impairing the degradation of substrates, and reducing autophagosome accumulation, ultimately leading to the blockage of the autophagy. In conclusion, our work demonstrates that the FOXO3-MFN2 pathway is essential for adaptive changes in mitochondrial morphology and cellular autophagy response under nutritional constraints.

Avermectin induced vascular damage in zebrafish larvae: association with mitochondria-mediated apoptosis and VEGF/Notch signaling pathway.

Avermectin is a highly effective insecticide that has been widely used in agriculture since the 1990s. In recent years, the safety of avermectin for non-target organisms has received much attention. The vasculature is important organs in the body and participate in the composition of other organs. However, studies on the vascular safety of avermectin are lacking. The vasculature of zebrafish larvae is characterized by ease of observation and it is a commonly used model for vascular studies. Therefore, zebrafish larvae were used to explore the potential risk of avermectin on the vasculature. The results showed that avermectin induced vascular damage throughout the body of zebrafish larvae, including the head, eyes, intestine, somite, tail and other vasculature. The main forms of damage are reduction in vascular diameter, vascular area and vascular abundance. Meanwhile, avermectin induced a decrease in the number of endothelial cells and apoptosis within the vasculature. In addition, vascular damage may be related to impairment of mitochondrial function and mitochondria-mediated apoptosis. Finally, exploration of the molecular mechanisms revealed abnormal alterations in the expression of genes related to the VEGF/Notch signaling pathway. Therefore, the VEGF/Notch signaling pathway may be an important mechanism for avermectin-induced vascular damage in zebrafish larvae. This study demonstrates the vascular toxicity of avermectin in zebrafish larvae and reveals the possible molecular mechanism, which would hopefully draw more attention to the safety of avermectin in non-target organisms.

Breast phyllodes tumour with epithelioid feature predisposes to malignant transformation.

AIMS: Phyllodes tumours (PTs) are relatively common fibroepithelial tumours comprising epithelial and stromal component. Usually, PTs show a spindle cell morphology with a fibroblast phenotype, while some tumour cells exhibit epithelioid morphological features and sarcomatoid transformation. However, the molecular characteristics of this morphology subset remain unclear. This study aimed to summarise the clinicopathological, morphological and molecular characteristics of seven cases of PT with epithelioid features. METHODS: Morphological and clinicopathological characteristics were observed and retrieved. Immunohistochemistry, immunofluorescence and electron microscope were performed on seven cases of epithelioid PT to explore immunophenotypic and ultrastructural characteristics. Transcriptomic and proteomic analyses were conducted to compare differentially expressed genes and proteins between epithelioid PT and classical PT. RESULTS: Patients with epithelioid PT exhibit a high recurrence rate (42.8%). Morphologically, in addition to having epithelioid cytological features, neoplastic stromal cells exhibit moderate to marked atypia and often exhibit sarcomatoid transformation, similar to the characteristics of borderline PT. Transcriptomic and proteomic analyses demonstrated that epithelioid PTs are distinct from classical PTs in gene expression and protein abundance levels. Immunohistochemical analysis showed that among all differentially expressed proteins, epithelioid PT showed abnormal p16/retinoblastoma expression patterns, similar to those of malignant PT. CONCLUSIONS: Epithelioid PT has unique morphological characteristics, biological behaviour and protein expression profile, which meets the diagnostic criteria of borderline PT and is prone to sarcomatoid transformation. It may be a special morphological subgroup of borderline PT and has partial characteristics of malignant PT, which should be taken seriously in pathological diagnosis and clinical management.

Advancements in understanding substantia nigra hyperechogenicity via transcranial sonography in Parkinson's disease and its clinical implications.

Amidst rising Parkinson's disease (PD) incidence in an aging global population, the need for non-invasive and reliable diagnostic methods is increasingly critical. This review evaluates the strategic role of transcranial sonography (TCS) in the early detection and monitoring of PD. TCS's ability to detect substantia nigra hyperechogenicity offers profound insights into its correlation with essential neuropathological alterations-namely, iron accumulation, neuromelanin depletion, and glial proliferation-fundamental to PD's pathophysiology. Our analysis highlights TCS's advantages, including its non-invasiveness, cost-effectiveness, and ease of use, positioning it as an invaluable tool for early diagnosis and continual disease progression monitoring. Moreover, TCS assists in identifying potential risk and protective factors, facilitating tailored therapeutic strategies to enhance clinical outcomes. This review advocates expanding TCS utilization and further research to maximize its diagnostic and prognostic potential in PD management, contributing to a more nuanced understanding of the disease.

Novel Susceptibility Genes and Biomarkers for Obstructive Sleep Apnea: Insights from Genetic and Inflammatory Proteins.

STUDY OBJECTIVES: Numerous observational studies link obstructive sleep apnea (OSA) to inflammatory proteins, yet the directionality of these associations remains ambiguous. Therefore, we aimed to clarify the potential associations of gene-predicted inflammatory proteins with OSA. METHODS: Based on genome-wide association study data, we applied Mendelian randomization (MR) to explore potential connections between circulating inflammatory proteins and OSA, primarily using the inverse variance weighting method for robustness. Cochran's Q test, MR‒Egger intercept test, MR-PRESSO, and leave-one-out method were used to perform sensitivity tests for pleiotropy and heterogeneity. Replication analyses and meta-analyses were performed using other independent data. Steiger tests and multivariate MR assessed the independent effects of exposure factors, and the functional mapping and annotation (FUMA) platform was used to identify key genes to enhance the understanding of genetics. RESULTS: Our investigation revealed 21 circulating inflammatory proteins significantly associated with OSA-related phenotypes. Notably, IL-10RA, IL-18R1, TNFSF14, CCL23, ADA, and SLAMF1 had significant effects on multiple phenotypes. After FDR correction, IL-18R1, SLAMF1, IL-10RA, and IL-17C were identified as important candidates for OSA, and multivariate MR analysis strengthened the independent heritability of 20 inflammatory factors. The FUMA platform revealed seven overlapping genes: ROBO1, PRIM1, NACA, SHBG, HSD17B6, RBMS2, and WWOX. All reverse MR analyses and sensitivity analyses confirmed the robustness of these associations. CONCLUSIONS: Our results underscore crucial associations between inflammatory proteins and OSA pathogenesis, revealing new correlates and susceptibility genes. These findings advance biomarker identification for OSA risk and highlight the importance of genetic and inflammatory profiles in OSA management.

[Analysis of genetic variants and molecular pathogenesis in a Chinese pedigree affected with Multiple epiphyseal dysplasia].

OBJECTIVE: To analyze the genetic variant and molecular pathogenesis in a Chinese pedigree affected with Multiple epiphyseal dysplasia (MED). METHODS: A MED pedigree which had presented at the Beijing Jishuitan Hospital Affiliated to Capital Medical University on September 13, 2020 was selected as the study subject. Clinical data of the pedigree were collected. Peripheral blood samples were drawn from pedigree members for the extraction of genomic DNA. Whole exome sequencing (WES) was carried out for the pedigree. Candidate variant was verified by Sanger sequencing. Wild type and mutant SLC26A2 expression plasmids were constructed and transfected into human primary chondrocytes. The effect of the variants on the protein localization and cell proliferation was determined by immunofluorescence and CCK8 assays. RESULTS: WES and Sanger sequencing revealed that the proband has harbored compound heterozygous variants of the SLC26A2 gene, including a paternally derived c.484G>T (p.Val162Leu) missense variant and a maternally derived c.485_486delTG (p.Val162Glyfs*12) frameshifting variant. The SLC26A2WT and its mutant SLC26A2Val162Leu and SLC26A2Val162Glyfs*12 expression plasmids were distributed in the nuclei and cytoplasm of human primary chondrocytes. Compared with SLC26A2WT, the expressions of SLC26A2Val162Leu and SLC26A2Val162Glyfs*12 were decreased, along with reduced proliferation of human primary chondrocytes. CONCLUSION: The c.484G>T and c.485_486delTG compound heterozygous variants of the SLC26A2 gene may affect the proliferation of human primary chondrocytes and underlay the pathogenesis of MED in this pedigree.

Predicting MET exon 14 skipping mutation in pulmonary sarcomatoid carcinoma by whole-tumour texture analysis combined with clinical and conventional contrast-enhanced computed tomography features.

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare, highly malignant type of non-small cell lung cancer (NSCLC) with a poor prognosis. Targeted drugs for MET exon 14 (METex14) skipping mutation can have considerable clinical benefits. This study aimed to predict METex14 skipping mutation in PSC patients by whole-tumour texture analysis combined with clinical and conventional contrast-enhanced computed tomography (CECT) features. Methods: This retrospective study included 56 patients with PSC diagnosed by pathology. All patients underwent CECT before surgery or other treatment, and both targeted DNA- and RNA-based next-generation sequencing (NGS) were used to detect METex14 skipping mutation status. The patients were divided into two groups: METex14 skipping mutation and nonmutation groups. Overall, 1,316 texture features of the whole tumour were extracted. We also collected 12 clinical and 20 conventional CECT features. After dimensionality reduction and selection, predictive models were established by multivariate logistic regression analysis. Models were evaluated using the area under the curve (AUC), and the clinical utility of the model was assessed by decision curve analysis. Results: METex14 skipping mutation was detected in 17.9% of PSCs. Mutations were found more frequently in those (I) who had smaller long- or short-axis diameters (P=0.02, P=0.01); (II) who had lower T stages (I, II) (P=0.02); and (III) with pseudocapsular or annular enhancement (P=0.03). The combined model based on the conventional and texture models yielded the best performance in predicting METex14 skipping mutation with the highest AUC (0.89). The conventional and texture models also had good performance (AUC =0.83 conventional; =0.88 texture). Conclusions: Whole-tumour texture analysis combined with clinical and conventional CECT features may serve as a noninvasive tool to predict the METex14 skipping mutation status in PSC.

Basic study on cryopreservation of rat calvarial osteoblasts with different cryoprotectants.

Cryopreservation is a method adopted for storage of autologous skulls. Herein, this current research sought to explore the effects of different cryoprotectants on the biological characteristics of rat calvarial osteoblasts after cryopreservation. Neonatal Sprague-Dawley rats were selected and their skull tissues were isolated. The skull tissues were allocated into the refrigerating-3M, refrigerating-6M, M199-3M, M199-6M, povidone iodine-3M, and povidone iodine-6M groups according to the usage of cryoprotectants and treatment time (month) and the fresh group. Osteoblasts were isolated from skull tissues in each group through digestion. The histomorphology of the skull was evaluated by H&E staining and cell morphology was observed by microscopy. The viability, proliferation, apoptosis, and osteogenic activity of osteoblasts were assessed by trypan blue staining, MTT, flow cytometry, and alkaline phosphatase (ALP) staining. The skull histomorphology and osteoblast morphology were similar between the fresh and refrigerating groups. Osteoblast viability was weakened after cryopreservation. The longer the refrigeration time, the lower the number of living cells and the higher the apoptosis rate. However, cryopreservation using different cryoprotectants did not evidently affect osteoblast proliferation and ALP activity. Different cryoprotectants show no apparent effect on the osteogenic activity of rat calvarial osteoblasts after cryopreservation.

Research trends in functionalized Fe3O4 composites based on affinity recognition systems for targeted extraction of natural products.

In recent years, target-specific affinity recognition systems based on Fe3O4-based composites have proven to be an effective method for screening natural products. Herbal medicines contain a wide range of natural products and are considered to be a major source for the development of novel drugs. However, the process of isolating and obtaining these bioactive components for the production of novel drugs is complex. Meanwhile, the complexity and diversity of herbal constituents have posed a great challenge to the screening studies of herbal active ingredients. Currently, traditional extraction and screening studies of active ingredients in herbal medicine include extraction and chromatographic separation technology development, serum medicinal chemistry, metabolomics and computerized virtual screening. In order to achieve integrated targeting of Fe3O4 for extraction and separation of natural products from herbs, various Fe3O4-based composites need to be synthesized so that the composites can be further functionalized and modified. Composites such as Fe3O4@SiO2, Fe3O4-based magnetic graphene oxide and Fe3O4-based magnetic carbon nanotubes were used to achieve targeted extraction and isolation of natural products from herbal medicines. The main extraction techniques involved based on these Fe3O4-based composites are molecularly imprinted techniques, immobilized ligand fishing techniques, and cell membrane-coated bionanotechnology methods. This article will present recent advances in the synthesis and modification of Fe3O4 composites and their applications for the extraction of natural products in conjunction with molecular imprinting, immobilization-targeted fishing, and cell-membrane-coated biomimetic techniques, as well as the future goals and challenges of functionalized modification of Fe3O4 composites for the targeted extraction of natural products, like protein overexpression modification, doping of fluorescent substances and genetic engineering development. A deeper understanding of the multi-level, multidisciplinary, and applied studies in materials science and phytochemistry will be provided by this article.

A Prognostic Model Based on Nutritional Indexes for Patients With Pan-Cancer: A Real-World Cohort Study.

BACKGROUND: The aim was to identify the nutritional indexes, construct a prognostic model, and develop a nomogram for predicting individual survival probability in pan-cancers. METHODS: Nutritional indicators, clinicopathological characteristics, and previous major treatment details of the patients were collected. The enrolled patients were randomly divided into training and validation cohorts. Least absolute shrinkage and selection operator (Lasso) regression cross-validation was used to determine the variables to include in the cox regression model. The training cohort was used to build the prediction model, and the validation cohort was used to further verify the discrimination, calibration, and clinical effectiveness of the model. RESULTS: A total of 2020 patients were included. The median OS was 56.50 months (95% CI, 50.36-62.65 months). In the training cohort of 1425 patients, through Lasso regression cross-validation, 13 characteristics were included in the model. Cox proportional hazards model was developed and visualized as a nomogram. The C-indexes of the model for predicting 1-, 3-, 5-, and 10-year OS were 0.848, 0.826, 0.814, and 0.799 in the training cohort and 0.851, 0.819, 0.814, and 0.801 in the validation cohort. The model showed great calibration in the two cohorts. Patients with a score of less than 274.29 had a better prognosis (training cohort: HR, 6.932; 95% CI, 5.723-8.397; log-rank p < 0.001; validation cohort: HR, 8.429; 95% CI, 6.180-11.497; log-rank p < 0.001). CONCLUSION: The prognostic model based on the nutritional indexes of pan-cancer can divide patients into different survival risk groups and performed well in the validation cohort.

Biallelic variants in SLC26A2 cause multiple epiphyseal dysplasia-4 by disturbing chondrocyte homeostasis.

BACKGROUND: Multiple epiphyseal dysplasia-4 (MED-4, MIM 226900) is a rare autosomal recessive disease characterized by disproportionate height and early onset osteoarthritis of the lower limbs. MED-4 is caused by homozygous or compound heterozygous pathogenic variants in the SLC26A2 gene. However, the underlying pathogenic mechanisms in chondrocytes remains unknown. This study aimed to identify the pathogenic variants within a MED-4 family and explore the molecular etiology of this condition in human primary chondrocyte cells. METHODS: Clinical data were recorded and peripheral blood samples were collected for analysis. Whole exome sequencing (WES) and bioinformatic analyses were performed to determine causative variants. Wild-type SLC26A2 and corresponding mutant expression plasmids were constructed and transfected into human primary chondrocytes. The expression and subcellular distribution of SLC26A2 protein in chondrocytes were detected by immunoblotting and immunofluorescence. Effects of these variants on chondrocytes viability and apoptosis were measured by Cell Counting Kit-8 (CCK-8) assay. Expression of genes related to cartilage homeostasis was subsequently analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: We identified two compound heterozygous variants c.1020_1022delTGT(p.Val341del) and c.1262 T > C(p.Ile421Thr) in the SLC26A2 gene in the patients. Mutant SLC26A2Val341del and SLC26A2Ile421Thr proteins were distributed in relatively few cells and were observed only within the nucleus. The viability of chondrocytes with the SLC26A2 variant group was similar to the wild-type (WT) group. However, the protein expressions of SLC26A2Val341del and SLC26A2Ile421Thr were decreased compared with SLC26A2WT. Expression levels of matrix metallopeptidase 13 (MMP13), α-1 chain of type X collagen (COL10A1), and Runt-related transcription factor 2 (RUNX2) were significantly decreased in the variant group. However, aggrecan (ACAN) expression was higher in the variant group than the WT group. CONCLUSIONS: Overall, our data demonstrate that the variants p.Val341del and p.Ile421Thr in SLC26A2 cause MED-4 and that these two variants promote chondrocyte proliferation while inhibiting chondrocyte differentiation.

MicroRNAs in opisthorchiids and their definitive hosts: Current Status and Perspectives.

Opisthorchis felineus, Opisthorchis viverrini, and Clonorchis sinensis (family Opisthorchiidae) are parasitic flatworms that pose serious threats to humans in certain countries and cause opisthorchiasis/clonorchiasis. Opisthorchiid flukes parasitize the biliary tract of the host, causing cholangitis, cholecystitis, cholelithiasis and cholangiocarcinoma. In this review, we primarily focus on recent microRNAs (miRNAs) studies of opisthorchiid flukes and their definitive hosts. Many miRNAs are conserved and expressed in a developmentally stage specific manner in the three opisthorchiid flukes, which play important roles in the growth and development of Opisthorchiidae spp., as well as host-pathogen interactions. Some miRNAs might be potential biomarkers related to carcinogenesis of cholangiocarcinoma. Therefore, this review provides the basis for further investigating the roles of miRNAs in opisthorchiid flukes and their definitive hosts, as well as promoting the development of novel approaches to prevent and treat opisthorchiasis/clonorchiasis.

A genome-wide association study reveals novel loci and candidate genes associated with plant height variation in Medicago sativa.

BACKGROUND: Plant height (PH) is an important agronomic trait influenced by a complex genetic network. However, the genetic basis for the variation in PH in Medicago sativa remains largely unknown. In this study, a comprehensive genome-wide association analysis was performed to identify genomic regions associated with PH using a diverse panel of 220 accessions of M. sativa worldwide. RESULTS: Our study identified eight novel single nucleotide polymorphisms (SNPs) significantly associated with PH evaluated in five environments, explaining 8.59-12.27% of the phenotypic variance. Among these SNPs, the favorable genotype of chr6__31716285 had a low frequency of 16.4%. Msa0882400, located proximal to this SNP, was annotated as phosphate transporter 3;1, and its role in regulating alfalfa PH was supported by transcriptome and candidate gene association analysis. In addition, 21 candidate genes were annotated within the associated regions that are involved in various biological processes related to plant growth and development. CONCLUSIONS: Our findings provide new molecular markers for marker-assisted selection in M. sativa breeding programs. Furthermore, this study enhances our understanding of the underlying genetic and molecular mechanisms governing PH variations in M. sativa.

[Multi Scenario Carbon Peak Prediction and Emission Reduction Path Analysis of Xi'an Hi-tech Zone].

The fifth session of the 13th National People's Congress proposed to be committed to promoting carbon peaking and carbon neutrality, promoting the comprehensive green and low-carbon transformation of the economy and society and achieving high-quality development. As an important scientific and technological innovation and industrial cluster in Shaanxi Province, the economic development of the Xi'an Hi-tech Zone largely relies on energy consumption, making the task of carbon reduction particularly challenging. Firstly, taking the Xi'an Hi-tech Zone as the research object, through systematic accounting of carbon emissions within the park, we analyzed the current carbon emission status of enterprises in different energy types and industries. Then, using the Kaya model, multiple independent carbon peak scenarios were set up to predict the total carbon emissions and peak time under different scenarios. Finally, based on the development characteristics of the Xi'an Hi-tech Zone, we scientifically selected corresponding carbon emission reduction paths and provided reasonable emission reduction suggestions. The results showed that the proportion of carbon emissions consumed by electricity was currently the highest, and the share was increasing yearly. Industrial carbon emissions had always been dominant, and the development of the tertiary industry was becoming increasingly prosperous. In the scenario prediction, the carbon emission factor scenario, energy intensity scenario, and economic level scenario could reach the carbon peak by 2030. Among them, the economic development level had the greatest impact on the peak and time of the future carbon peak in the Xi'an Hi-tech Zone, whereas the industrial structure scenario, energy source structure scenario, and population size scenario had no peak before 2030. The future emission reduction path mainly started from decarbonization of the power sector, stable and high-quality economic development, green upgrading of energy and industrial structure, and building a green transportation system. This can reserve more preparation time for achieving carbon neutrality and provide decision-making reference for the low-carbon development of industrial parks in China.

IDD10-NAC079 transcription factor complex regulates sheath blight resistance by inhibiting ethylene signaling in rice.

INTRODUCTION: Rhizoctonia solani Kühn is a pathogen causing rice sheath blight (ShB). Ammonium transporter 1 (AMT1) promotes resistance of rice to ShB by activating ethylene signaling. However, how AMT1 activates ethylene signaling remains unclear. OBJECTIVE: In this study, the indeterminate domain 10 (IDD10)-NAC079 interaction model was used to investigate whether ethylene signaling is modulated downstream of ammonium signaling and modulates ammonium-mediated ShB resistance. METHODS: RT-qPCR assay was used to identify the relative expression levels of nitrogen and ethylene related genes. Yeast two-hybrid assays, Bimolecular fluorescence complementation (BiFC) and Co-immunoprecipitation (Co-IP) assay were conducted to verify the IDD10-NAC079-calcineurin B-like interacting protein kinase 31 (CIPK31) transcriptional complex. Yeast one-hybrid assay, Chromatin immunoprecipitation (ChIP) assay, and Electrophoretic mobility shift assay (EMSA) were used to verify whether ETR2 was activated by IDD10 and NAC079. Ethylene quantification assay was used to verify ethylene content in IDD10 transgenic plants. Genetic analysis is used to detect the response of IDD10, NAC079 and CIPK31 to ShB infestation. RESULTS: IDD10-NAC079 forms a transcription complex that activates ETR2 to inhibit the ethylene signaling pathway to negatively regulating ShB resistance. CIPK31 interacts and phosphorylates NAC079 to enhance its transcriptional activation activity. In addition, AMT1-mediated ammonium absorption and subsequent N assimilation inhibit the expression of IDD10 and CIPK31 to activate the ethylene signaling pathway, which positively regulates ShB resistance. CONCLUSION: The study identified the link between ammonium and ethylene signaling and improved the understanding of the rice resistance mechanism.

Targeted Modulation of Redox and Immune Homeostasis in Acute Lung Injury Using a Thioether-Functionalized Dendrimer.

Acute lung injury (ALI) is the pathophysiological precursor of acute respiratory distress syndrome. It is characterized by increased oxidative stress and exaggerated inflammatory response that disrupts redox reactions and immune homeostasis in the lungs, thereby posing significant clinical challenges. In this study, an internally functionalized thioether-enriched dendrimer Sr-G4-PEG is developed, to scavenge both proinflammatory cytokines and reactive oxygen species (ROS) and restore homeostasis during ALI treatment. The dendrimers are synthesized using an efficient and orthogonal thiol-ene "click" chemistry approach that involves incorporating thioether moieties within the dendritic architectures to neutralize the ROS. The ROS scavenging of Sr-G4-PEG manifests in its capacity to sequester proinflammatory cytokines. The synergistic effects of scavenging ROS and sequestering inflammatory cytokines by Sr-G4-PEG contribute to redox remodeling and immune homeostasis, along with the modulation of the NLRP3-pyroptosis pathway. Treatment with Sr-G4-PEG enhances the therapeutic efficacy of ALIs by alleviating alveolar bleeding, reducing inflammatory cell infiltration, and suppressing the release of inflammatory cytokines. These results suggest that Sr-G4-PEG is a potent nanotechnological candidate for remodeling redox and immune homeostasis in the treatment of ALIs, demonstrating the great potential of dendrimer-based nanomedicine for the treatment of respiratory pathologies.

Associations between Intake of Dietary Sugars and Diet Quality: A Systematic Review of Recent Literature.

Understanding the relationship between the intake of sugars and diet quality can inform public health recommendations. This systematic review synthesized recent literature on associations between sugar intake and diet quality in generally healthy populations aged 2 years or older. We searched databases from 2010 to 2022 for studies of any design examining associations between quantified sugar intake in the daily diet and dietary indexes (DIs) or micronutrient intakes. Different sugar types and diet quality measures were analyzed separately. We converted DI results to Pearson's r correlations and grouped indexes with or without a free or added sugar component to facilitate cross-study comparisons. Meta-analysis was deemed inappropriate. From 13,869 screened records, we included 27 cross-sectional studies. NUQUEST risk of bias ratings were neutral (n = 18 studies) or poor (n = 9), and strength of evidence by the GRADE approach was very low due to study design. Most studies reported negative associations for added and free sugars with diet quality indexes (r ranging from -0.13 to -0.42) and nutrients of public health concern (fiber, vitamin D, calcium, potassium), while associations with total sugars were mixed. Due to cross-sectional study designs, the clinical relevance of these findings is unclear. Prospective studies are needed to minimize confounding and inform causal relationships.

Efficacy and safety of bevacizumab and platinum­based chemotherapy as neoadjuvant regimen for stage­IIIA non­squamous non­small cell lung cancer: A retrospective study.

Bevacizumab plus platinum-based chemotherapy provides modest benefits in non-squamous non-small cell lung cancer (NSCLC), while its application as a neoadjuvant regimen has yet to be validated. The present study aimed to assess the efficacy of neoadjuvant bevacizumab plus platinum-based chemotherapy in patients with stage-IIIA non-squamous NSCLC. Data from 110 patients with stage-IIIA non-squamous NSCLC with negative driver genes, who received neoadjuvant bevacizumab plus platinum-based chemotherapy (n=50) or neoadjuvant platinum-based chemotherapy alone (n=60), and tumor resection, were retrospectively reviewed in the current study. In addition, the data on pathological response, disease-free survival (DFS), overall survival (OS) and adverse events were obtained. The results demonstrated that neoadjuvant bevacizumab plus chemotherapy did not significantly increase the pathological complete response (pCR) rate in comparison with neoadjuvant chemotherapy alone (18.0 vs. 8.3%; P=0.130). However, neoadjuvant bevacizumab plus chemotherapy significantly increased the rates of DFS (P=0.007) and OS (P=0.049) compared with neoadjuvant chemotherapy alone. Adjustments were then performed using multivariate logistic or Cox regression analyses, which demonstrated that neoadjuvant bevacizumab plus chemotherapy in comparison with neoadjuvant chemotherapy alone only significantly independently prolonged DFS [hazard ratio (HR)=0.251; P=0.042], but did not significantly affect pCR (odds ratio=2.897; P=0.117) or OS (HR=0.297; P=0.158). Furthermore, no significant differences were demonstrated between the number of adverse events in patients receiving neoadjuvant bevacizumab plus chemotherapy in comparison with those receiving neoadjuvant chemotherapy alone (all P>0.05). In conclusion, neoadjuvant bevacizumab plus platinum-based chemotherapy was only associated with a significant improvement in the rate of DFS, but showed limited efficacy in improving pCR and OS rates in comparison with neoadjuvant chemotherapy alone in patients with stage-IIIA non-squamous NSCLC. Therefore, a larger sample size and randomized controlled studies are needed for further validation of the findings of the present study.

Isolation, identification, and degradation mechanism by multi-omics of mesotrione-degrading Amycolatopsis nivea La24.

Mesotrione is a herbicide used in agricultural production; however, its stability and long-term residues pose ecological risks to soil health and subsequent crops. In this research, the strain Amycolatopsis nivea La24 was identified as capable of completely degrading 50 mg∙L-1 mesotrione within 48 h. It exhibited a broad adaptability to various environment and could degrade three sulfonylurea herbicides (nicosulfuron, chlorimuron-methyl, and cinosulfuron). Non-target metabonomic and mass spectrometry demonstrated that La24 strain broke down the mesotrione parent molecule by targeting the ß-diketone bond and nitro group, resulting in the production of five possible degradation products. The differentially expressed genes were significantly enriched in fatty acid degradation, amino acid metabolism, and other pathways, and the differentially metabolites in glutathione metabolism, arginine/proline metabolism, cysteine/methionine metabolism, and other pathways. Additionally, it was confirmed by heterologous expression that nitroreductase was directly involved in the mesotrione degradation, and NDMA-dependent methanol dehydrogenase would increase the resistance to mesotrione. Finally, the intracellular response of La24 during mesotrione degradation was proposed. This work provides insight for a comprehensive understanding of the mesotrione biodegradation mechanism, significantly expands the resources for pollutant degradation, and offers the potential for a more sustainable solution to address herbicide pollution in soil.

Natural pyrethrins induce cytotoxicity in SH-SY5Y cells and neurotoxicity in zebrafish embryos (Danio rerio).

Natural pyrethrins are widely used in agriculture because of their good insecticidal activity. Meanwhile, natural pyrethrins play an important role in the safety evaluation of pyrethroids as precursors for structural development of pyrethroid insecticides. However, there are fewer studies evaluating the neurological safety of natural pyrethrins on non-target organisms. In this study, we used SH-SY5Y cells and zebrafish embryos to explore the neurotoxicity of natural pyrethrins. Natural pyrethrins were able to induce SH-SY5Y cells damage, as evidenced by decreased viability, cycle block, apoptosis and DNA damage. The apoptotic pathway may be related to the involvement of mitochondria and the results showed that natural pyrethrins induced a rise in Capase-3 viability, Ca2+ overload, a decrease in adenosine triphosphate (ATP) and a collapse of mitochondrial membrane potential in SH-SY5Y cells. Natural pyrethrins may mediate DNA damage in SH-SY5Y cells through oxidative stress. The results showed that natural pyrethrins induced an increase in reactive oxygen species (ROS) levels, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content and catalase (CAT) activity, and induced a decrease in glutathione peroxidase (GPx) activity in SH-SY5Y cells. In vivo, natural pyrethrins induced developmental malformations in zebrafish embryos, which were mainly characterized by pericardial edema and yolk sac edema. Meanwhile, the results showed that natural pyrethrins induced damage to the Huc-GFP axis and disturbed lipid metabolism in the head of zebrafish embryos. Further results showed elevated ROS levels and apoptosis in the head of zebrafish embryos, which corroborated with the results of the cell model. Finally, the results of mRNA expression assay of neurodevelopment-related genes indicated that natural pyrethrins exposure interfered with their expression and led to neurodevelopmental damage in zebrafish embryos. Our study may raise concerns about the neurological safety of natural pyrethrins on non-target organisms.