New Insights into the Genetic Basis of Lysine Accumulation in Rice Revealed by Multi-Model GWAS.

Lysine is an essential amino acid that cannot be synthesized in humans. Rice is a global staple food for humans but has a rather low lysine content. Identification of the quantitative trait nucleotides (QTNs) and genes underlying lysine content is crucial to increase lysine accumulation. In this study, five grain and three leaf lysine content datasets and 4,630,367 single nucleotide polymorphisms (SNPs) of 387 rice accessions were used to perform a genome-wide association study (GWAS) by ten statistical models. A total of 248 and 71 common QTNs associated with grain/leaf lysine content were identified. The accuracy of genomic selection/prediction RR-BLUP models was up to 0.85, and the significant correlation between the number of favorable alleles per accession and lysine content was up to 0.71, which validated the reliability and additive effects of these QTNs. Several key genes were uncovered for fine-tuning lysine accumulation. Additionally, 20 and 30 QTN-by-environment interactions (QEIs) were detected in grains/leaves. The QEI-sf0111954416 candidate gene LOC_Os01g21380 putatively accounted for gene-by-environment interaction was identified in grains. These findings suggested the application of multi-model GWAS facilitates a better understanding of lysine accumulation in rice. The identified QTNs and genes hold the potential for lysine-rich rice with a normal phenotype.

Renal protective effect and clinical analysis of vitamin B6 in patients with sepsis.

OBJECTIVE: To investigate the protective effect and possible mechanisms of vitamin B6 against renal injury in patients with sepsis. METHODS: A total of 128 patients with sepsis who met the entry criteria in multiple centres were randomly divided into experimental (intravenous vitamin B6 therapy) and control (intravenous 0.9% sodium chloride therapy) groups based on usual care. Clinical data, the inflammatory response indicators interleukin 6 (IL-6), interleukin 8 (IL-8), tumour necrosis factor (TNF-α) and endothelin-1 (ET-1), the oxidative stress response indicators superoxide dismutase, glutathione and malondialdehyde, and renal function (assessed by blood urea nitrogen [BUN], serum creatinine [SCr] and renal resistance index [RRI] monitored by ultrasound) were compared between the two groups. RESULTS: After 7 d of treatment, the IL-6, IL-8, TNF-α and ET-1 levels in the experimental group were significantly lower than those in the control group, the oxidative stress response indicators were significantly improved in the experimental group and the BUN, SCr and RRI values in the experimental group were significantly lower than those in the control group (p < 0.05). There was no statistical difference between the two groups in the rate of renal replacement therapy and 28 d mortality (p > 0.05). However, the ICU length of stay and the total hospitalisation expenses in the experimental group were significantly lower than those in the control group (p < 0.05). CONCLUSION: The administration of vitamin B6 in the treatment of patients with sepsis attenuates renal injury, and the mechanism may be related to pyridoxine decreasing the levels of inflammatory mediators and their regulation by redox stress.Clinical trial registration: ClinicalTrials.gov Identifier: NCT06008223.

Prediction of rear-seat belt use: Application of extended theory of planned behavior.

OBJECTIVES: Rear-seat belts have been shown to significantly reduce the severity of road vehicle collisions and fatalities. However, their use by rear-seat passengers is significantly less than that by front-seat passengers. Thus, the psychological factors underlying individuals' decision to wear a seat belt in the rear seat require further investigation. METHODS: An extended theory of planned behavior (eTPB) was used to examine individuals' behavior of wearing a rear-seat belt. An online survey was conducted and a total of 515 valid questionnaires were collected in China. RESULTS: While attitude, descriptive norms, and law enforcement all have a significant effect on individuals' intention to wear a seat belt in the rear, subjective norms and perceived behavioral control do not. Individuals' attitudes toward wearing a seat belt in the rear seat are significantly influenced by law enforcement and behavioral intention, but not by perceived behavioral control. The mediation effect analysis reveals that law enforcement has the greatest overall effect on behavior, followed by attitude and descriptive norms. CONCLUSIONS: The results of this paper contribute to more effective recommendations to improve the use of rear seat belts and to safeguard rear seat passengers.

Heterozygous Eif4nif1 Stop Gain Mice Replicate the Primary Ovarian Insufficiency Phenotype in Women.

We created the c.1286C>G stop-gain mutation found in a family with primary ovarian insufficiency (POI) at age 30 years. The Eif4enif1 C57/Bl6 transgenic mouse model contained a floxed exon 10-19 cassette with a conditional knock-in cassette containing the c.1286C>G stop-gain mutation in exon 10. The hybrid offspring of CMV- Cre mice with Eif4enif1 WT/flx mice were designated Eif4enif1 WT/ Δ for simplicity. A subset of female heterozygotes ( Eif4enif1 WT/ Δ ) had no litters. In those with litters, the final litter was earlier (5.4±2.6 vs. 10.5±0.7 months; p=0.02). Heterozygous breeding pair ( Eif4enif1 WT/ Δ x Eif4enif1 WT/ Δ ) litter size was 60% of WT litter size (3.9±2.0 vs. 6.5±3.0 pups/litter; p <0.001). The genotypes were 35% Eif4enif1 WT/flx and 65% Eif4enif1 WT/ Δ , with no homozygotes. Homozygote embryos did not develop beyond the 4-8 cell stage. The number of follicles in ovaries from Eif4enif1 WT/ Δ mice was lower starting at the primordial (499±290 vs. 1445±381) and primary follicle stage (1069±346 vs. 1450±193) on day 10 (p<0.05). The preantral follicle number was lower starting on day 21 (213±86 vs. 522±227; p<0.01). Examination of ribosome protected mRNAs (RPR) demonstrated altered mRNA expression. The Eif4enif1 stop-gain mice replicate the POI phenotype in women. The unique mouse model provides a platform to study regulation of protein translation across oocyte and embryo development in mammals.

Heavy metal induced shifts in microbial community composition and interactions with dissolved organic matter in coastal sediments.

Heavy metals can impact the structure and function of coastal sediment. The dissolved organic matter (DOM) pool plays an important role in determining both the heavy metal toxicity and microbial community composition in coastal sediments. However, how heavy metals affect the interactions between microbial communities and DOM remains unclear. Here, we investigated the influence of heavy metals on the microbial community structure (including bacteria and archaea) and DOM composition in surface sediments of Beibu Gulf, China. Our results revealed firstly that chromium, zinc, cadmium, and lead were the heavy metals contributing to pollution in our studied area. Furthermore, the DOM chemical composition was distinctly different in the contaminated area from the uncontaminated area, characterized by a higher average O/C ratio and increased prevalence of carboxyl-rich alicyclic molecules (CRAM) and highly unsaturated compounds (HUC). This indicates that DOM in the contaminated area was more recalcitrant compared to the uncontaminated area. Except for differences in archaeal diversity between the two areas, there were no significant variations observed in the structure of archaea and bacteria, as well as the diversity of bacteria, across the two areas. Nevertheless, our co-occurrence network analysis revealed that the B2M28 and Euryarchaeota, dominating bacterial and archaeal groups in the contaminated area were strongly related to CRAM. The network analysis also unveiled correlations between active bacteria and elevated proportions of nitrogen-containing DOM molecules. In contrast, the archaea-DOM network exhibited strong associations with nitrogen- and sulfur-containing molecules. Collectively, these findings suggest that heavy metals indeed influence the interaction between microbial communities and DOM, potentially affecting the accumulation of recalcitrant compounds in coastal sediments.

Phosphorus starvation response genes and function coupling: A mechanism to regulate phosphorus availability in a subtropical estuary.

Phosphorus (P) plays an important role in regulating primary production in estuarine environments. However, knowledge of the P-functional gene composition of microbial communities and the mechanisms of microbial adaptation to changes in available P in estuaries remain limited. This study coupling 16 s rDNA and metagenomics sequencing was conducted to reveal the relationship between P cycling functional genes, microbial interactions, and P availability in the Jiulong River Estuary. The results showed that the relative abundance of P cycling functions genes was highest in winter, and lowest in summer. Spatially, the total relative abundance of P cycling functions genes was higher in the riverward than that in the seaward. P cycling functional microbial interactions and P cycling gene coupling were strongest in summer and in the seaward. Changes in both temperature and salinity had significant direct and indirect effects on P cycling function, and the influence of salinity on P cycling function was greater than that on the microbial community in the estuary. Salinity had significant direct negative effects on inorganic P-solubilization (IP), organic P-mineralization (OP), and P uptake and transport functions (PT). Whereas, salinity had a significant positive effect on P-starvation response regulation (PR) function. Thus, salinity and microbial communities regulate the soluble reactive phosphate concentrations in estuarine environments by strengthening internal coupling among P cycling functions, promoting PR function, and facilitating PT gene expression. PR is the most important predictors, PR, PT, and PR-PT together explained 38.56 % of the overall soluble reactive phosphorus (SRP) variation. Over 66 % of the explained SRP variations can be predicted by the PR, PT, and PR-PT functional genes. This finding improves the knowledge base of the microbial processes for P cycling and provides a foundation for eutrophication management strategies in the estuary.

Prevalence and predictors of prenatal depression during the COVID-19 pandemic: A multistage observational study in Beijing, China.

OBJECTIVE: While growing psychological health issues among pregnant women during the COVID-19 pandemic have been clearly validated, most research was conducted in countries with relatively lax quarantine measures. This study aimed to compare the prevalence of prenatal depression among pre-, peak-, and post-COVID-19 in Beijing, the region with a stringent response policy in China. We also explore predictors of prenatal depression throughout the outbreak. METHODS: We investigated prenatal depression among 742 pregnant women who received antenatal checkups in Beijing from March 28, 2019 to May 07, 2021 using the Edinburgh Postnatal Depression Scale and associative demographic, pregnancy-related, and psychosocial characteristics were measured. The phase was divided into pre-, peak-, and post-COVID-19 in light of the trajectory of COVID-19. Pearson's Chi-square test was used after the examination of confounders homogeneity. The bivariable and multivariable logistic regression was conducted to explore predictors. RESULTS: The pooled prevalence of prenatal depression was 11.9% throughout the COVID-19 pandemic. Rates at different phases were 10.6%, 15.2%, and 11.1% respectively and no significant difference was observed. Multivariable logistic regression revealed that history of mental illness, number of boy-preference from both pregnant women and husband's family, social support, occupation, and living space were independent predictors of prenatal depression in Beijing. CONCLUSION: Our data suggested that the impact of this pandemic on prenatal depression in Beijing appears to be not significant, which will strengthen confidence in adhering to current policy for decision-makers and provide important guidance for the development of major outbreak control and management policies in the future. Our findings may also provide a more efficient measure to identify high-risk pregnant women for professionals and help raise gender equity awareness of pregnant women and their husbands' families. Future studies should focus on the value of targeted care and family relations on the mental health of pregnant women.

A qualitative internet-based study of parental experiences of adolescents suffering from affective disorders with non-suicidal self-injury during the COVID-19 pandemic.

Objective: Non-suicidal self-injury (NSSI) behaviors of adolescents with affective disorders can directly deteriorate parents' internal experiences, and negative parental experiences can exacerbate or even worsen NSSI behaviors. This study investigates the impact of NSSI behaviors exhibited by adolescents with affective disorders on the internal experiences of parents. Specifically, our research focuses on the inner experiences of parents when their children engage in NSSI behaviors during social isolation of the COVID-19, offering insights for addressing parental mental health issues related to NSSI and developing positive parental behavioral models to optimize adolescent behavior during major public health events. Methods: Semi-structured interviews were conducted with 21 parents of adolescents with affective disorders displaying NSSI behaviors during the COVID-19 pandemic. The Colaizzi 7-step analysis was employed to refine and categorize emerging themes. Results: Our study revealed that parents of adolescents facing NSSI during the COVID-19 pandemic underwent different internal experiences, which could be classified into four themes: negative experience, high caregiving burden, lack of caregiving capacity, and resilience. Conclusion: This Internet-based research is the first to explore the internal experiences of parents of adolescents with affective disorders experiencing NSSI during the COVID-19 pandemic. It sheds light on how parents, in response to their children's NSSI behaviors, undergo resilience following negative experiences, explore more open and supportive family model. Despite these positive outcomes, parents express a need for increased knowledge about NSSI illness care and a desire for professional assistance.

Effect of different conditions on the germination of coix seed and its characteristics analysis.

Coix seed (CS) has high nutritional value, but the deep processing of CS is relatively limited. Sprouting can significantly improve nutritional value, laying the foundation for efficient consumption or further processing. The optimal conditions for the germination of CS are a soaking temperature of 36 °C for 10 h and a germination temperature of 29 °C for 24 h. Under these conditions, the final germination rate of CS reached 90%. Additionally, the content of γ-aminobutyric acid was 21.205 mg/100 g; soluble protein, free amino acids, γ-aminobutyric acid, and other essential substances increased in CS. Especially after germination, the γ-aminobutyric acid (GABA) content increased by 7.8 times compared with the GABA content of ungerminated CS. Therefore, the nutritional value and flavor of germinated CS are better than those of ungerminated ones, which establishs a solid foundation for its application in developing various products such as compound health drinks, coix yogurt, and others.

Foot pain in children and adolescents: a problem-based approach in musculoskeletal ultrasonography.

Various etiologies and risk factors contribute to foot pain in children and adolescents, including conditions such as Kohler's disease, Sever's disease, Iselin's disease, rigid flat foot, accessory navicular, Freiberg's disease, sesamoiditis, os trigonum syndrome, and more. High-frequency musculoskeletal ultrasonography can show both the bone surface and the surrounding soft tissue clearly from various angles in real-time, thereby providing a higher level of detail that is helpful for identifying the etiology of foot pain and monitoring disease progression compared with other imaging modalities. This review provides an overview of the epidemiology, pathophysiology, clinical manifestations and characteristic ultrasonographic findings of select foot pain conditions in children and adolescents.

COVID-19 vaccination affects short-term anti-coagulation levels in warfarin treatment.

Vaccines against SARS-CoV-2 have been recommended across the world, yet no study has investigated whether COVID-19 vaccination influences short-term warfarin anti-coagulation levels. Patients on stable warfarin treatment who received anti-SARS-CoV-2 vaccination were prospectively enrolled and followed up for three months. INR values less than 10 days before vaccination (baseline), 3-5 days (short-term) and 6-14 days (medium-term) after vaccination were recorded as INR0, INR1, and INR2, respectively. The variations of INR values within individuals were compared, and the linear mixed effect model was used to evaluate the variations of INR values at different time points. Logistic regression analysis was performed to determine covariates related to INR variations after COVID-19 vaccination. Vaccination safety was also monitored. There was a significant difference in INR values between INR0 and INR1 (2.15 vs. 2.26, p = 0.003), yet no marked difference was found between INR0 and INR2. The linear mixed effect model also demonstrated that INR variation was significant in short-term but not in medium-term or long-term period after vaccination. Logistic regression analysis showed that no investigated covariates, including age, vaccine dose, genetic polymorphisms of VKORC1 and CYP2C9 etc., were associated with short-term INR variations. Two patients (2.11%) reported gingival hemorrhage in the short-term due to increased INR values. The overall safety of COVID-19 vaccines for patients on warfarin was satisfying. COVID-19 vaccines may significantly influence warfarin anticoagulation levels 3-5 days after vaccination. We recommend patients on warfarin to perform at least one INR monitoring within the first week after COVID-19 vaccination.

Epigenetic modification: A novel insight into diabetic wound healing.

Wound healing is an intricate and fine regulatory process. In diabetic patients, advanced glycation end products (AGEs), excessive reactive oxygen species (ROS), biofilm formation, persistent inflammation, and angiogenesis regression contribute to delayed wound healing. Epigenetics, the fast-moving science in the 21st century, has been up to date and associated with diabetic wound repair. In this review, we go over the functions of epigenetics in diabetic wound repair in retrospect, covering transcriptional and posttranscriptional regulation. Among these, we found that histone modification is widely involved in inflammation and angiogenesis by affecting macrophages and endothelial cells. DNA methylation is involved in factors regulation in wound repair but also affects the differentiation phenotype of cells in hyperglycemia. In addition, noncodingRNA regulation and RNA modification in diabetic wound repair were also generalized. The future prospects for epigenetic applications are discussed in the end. In conclusion, the study suggests that epigenetics is an integral regulatory mechanism in diabetic wound healing.

Characterization of Thyroid Cancer among Hispanics in California, USA, from 2010 to 2020.

BACKGROUND: Previous studies on Hispanic thyroid cancer cases show sex disparities and an increased prevalence of large tumor sizes and nodal involvement. Here, we characterized Hispanic thyroid cancer cases in California. METHODS: We identified thyroid cancer cases from 2010 to 2020 using the California Cancer Registry by sex, race/ethnicity, histology, TNM stage, tumor size, lymph node involvement, and Charlson comorbidity score. The age-adjusted incidence rate (AAIR) and age-adjusted mortality rate (AAMR) for all causes of death were calculated. A Cox proportional hazards regression analysis was performed to evaluate the mortality risk from all causes of death by race. RESULTS: Overall, 56,838 thyroid cancer cases were identified, including 29.75% in Hispanics. Hispanics had the highest female-to-male incidence rate ratio (IRR 3.54) and the highest prevalence of T3/T4 tumor size (28.71%), the highest N1 nodal status (32.69%), and the highest AAMR (0.79 per 100,000 people). After adjusting for demographic and tumor covariates, compared to non-Hispanic White people, Hispanic ethnicity, with an HR of 1.22 (95% CI 1.18-1.25, p < 0.0001), remained a significant independent contributor to mortality risk. CONCLUSIONS: Hispanics had the greatest female-to-male IRR ratio, a greater prevalence of advanced disease features at diagnosis, along with the highest AAMR and increased mortality risk despite adjustments for demographic and tumor covariates. Further investigation into other risk factors is needed.

circNOX4 activates an inflammatory fibroblast niche to promote tumor growth and metastasis in NSCLC via FAP/IL-6 axis.

BACKGROUND: Cancer-associated fibroblasts (CAFs) orchestrate a supportive niche that fuels cancer metastatic development in non-small cell lung cancer (NSCLC). Due to the heterogeneity and plasticity of CAFs, manipulating the activated phenotype of fibroblasts is a promising strategy for cancer therapy. However, the underlying mechanisms of fibroblast activation and phenotype switching that drive metastasis remain elusive. METHODS: The clinical implications of fibroblast activation protein (FAP)-positive CAFs (FAP+CAFs) were evaluated based on tumor specimens from NSCLC patients and bioinformatic analysis of online databases. CAF-specific circular RNAs (circRNAs) were screened by circRNA microarrays of primary human CAFs and matched normal fibroblasts (NFs). Survival analyses were performed to assess the prognostic value of circNOX4 in NSCLC clinical samples. The biological effects of circNOX4 were investigated by gain- and loss-of-function experiments in vitro and in vivo. Fluorescence in situ hybridization, luciferase reporter assays, RNA immunoprecipitation, and miRNA rescue experiments were conducted to elucidate the underlying mechanisms of fibroblast activation. Cytokine antibody array, transwell coculture system, and enzyme-linked immunosorbent assay (ELISA) were performed to investigate the downstream effectors that promote cancer metastasis. RESULTS: FAP+CAFs were significantly enriched in metastatic cancer samples, and their higher abundance was correlated with the worse overall survival in NSCLC patients. A novel CAF-specific circRNA, circNOX4 (hsa_circ_0023988), evoked the phenotypic transition from NFs into CAFs and promoted the migration and invasion of NSCLC in vitro and in vivo. Clinically, circNOX4 correlated with the poor prognosis of advanced NSCLC patients. Mechanistically, circNOX4 upregulated FAP by sponging miR-329-5p, which led to fibroblast activation. Furthermore, the circNOX4/miR-329-5p/FAP axis activated an inflammatory fibroblast niche by preferentially inducing interleukin-6 (IL-6) and eventually promoting NSCLC progression. Disruption of the intercellular circNOX4/IL-6 axis significantly suppressed tumor growth and metastatic colonization in vivo. CONCLUSIONS: Our study reveals a role of the circRNA-induced fibroblast niche in tumor metastasis and highlights that targeting the circNOX4/FAP/IL-6 axis is a promising strategy for the intervention of NSCLC metastasis.

Assessing racial/ethnic and nativity disparities in US cancer mortality using a new integrated platform.

BACKGROUND: Foreign-born (FB) populations in the US have significantly increased, yet cancer trends remain unexplored. Survey-based Population-Adjusted Rate Calculator (SPARC) is a new tool for evaluating nativity differences in cancer mortality. METHODS: Using SPARC, we calculated 3-year (2016-2018) age-adjusted mortality rates (AAMRs) and rate ratios (RRs) for common cancers by sex, age group, race/ethnicity, and nativity. Trends by nativity were examined for the first time for 2006-2018. Traditional cancer statistics draw populations from decennial censuses. However, nativity-stratified populations are from the American Community Surveys, thus involve sampling errors. To rectify this, SPARC employed bias-corrected estimators. Death counts came from the National Vital Statistics System. RESULTS: AAMRs were higher among US-born (UB) populations across nearly all cancer types, with the largest UB- FB difference observed in lung cancer among Black females (RR = 3.67, 95%CI = 3.37-4.00). The well-documented White-Black differences in breast cancer mortality existed mainly among UB women. For all cancers combined, descending trends were more accelerated for the UB compared to the FB in all race/ethnicity groups with changes ranging from -2.6% per year in UB Black males to stable (non-significant) among FB Black females. Pancreas and liver cancers were exceptions with increasing, stable, or decreasing trends depending on nativity and race/ethnicity. Notably, FB Black males and FB Hispanic males did not show a favorable decline in colorectal cancer mortality. CONCLUSIONS: While all groups show beneficial cancer mortality trends, those with higher rates in 2006 have experienced sharper declines. Persistent disparities between the UB and the FB, especially among Black people, necessitate further investigation.

NEAT1_1 confers gefitinib resistance in lung adenocarcinoma through promoting AKR1C1-mediated ferroptosis defence.

Gefitinib is one of the most extensively utilized epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) for treating advanced lung adenocarcinoma (LUAD) patients harboring EGFR mutation. However, the emergence of drug resistance significantly compromised the clinical efficacy of EGFR-TKIs. Gaining further insights into the molecular mechanisms underlying gefitinib resistance holds promise for developing novel strategies to overcome the resistance and improve the prognosis in LUAD patients. Here, we identified that the inhibitory efficacy of gefitinib on EGFR-mutated LUAD cells was partially dependent on the induction of ferroptosis, and ferroptosis protection resulted in gefitinib resistance. Among the ferroptosis suppressors, aldo-keto reductase family 1 member C1 (AKR1C1) exhibited significant upregulation in gefitinib-resistant strains of LUAD cells and predicted poor progression-free survival (PFS) and overall survival (OS) of LUAD patients who received first-generation EGFR-TKI treatment. Knockdown of AKR1C1 partially reversed drug resistance by re-sensitizing the LUAD cells to gefitinib-mediated ferroptosis. The decreased expression of miR-338-3p contributed to the aberrant upregulation of AKR1C1 in gefitinib-resistant LUAD cells. Furthermore, upregulated long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1_1 (NEAT1_1) sponged miR-338-3p to neutralize its suppression on AKR1C1. Dual-luciferase reporter assay and miRNA rescue experiment confirmed the NEAT1_1/miR-338-3p/AKR1C1 axis in EGFR-mutated LUAD cells. Gain- and loss-of-function assays demonstrated that the NEAT1_1/miR-338-3p/AKR1C1 axis promoted gefitinib resistance, proliferation, migration, and invasion in LUAD cells. This study reveals the effects of NEAT1_1/miR-338-3p/AKR1C1 axis-mediated ferroptosis defence in gefitinib resistance in LUAD. Thus, targeting NEAT1_1/miR-338-3p/AKR1C1 axis might be a novel strategy for overcoming gefitinib resistance in LUAD harboring EGFR mutation.

Directed Evolution of Escherichia coli Nissle 1917 to Utilize Allulose as Sole Carbon Source.

Sugar substitutes are popular due to their akin taste and low calories. However, excessive use of aspartame and erythritol can have varying effects. While D-allulose is presently deemed a secure alternative to sugar, its excessive consumption is not devoid of cellular stress implications. In this study, the evolution of Escherichia coli Nissle 1917 (EcN) is directed to utilize allulose as sole carbon source through a combination of adaptive laboratory evolution (ALE) and fluorescence-activated droplet sorting (FADS) techniques. Employing whole genome sequencing (WGS) and clustered regularly interspaced short palindromic repeats interference (CRISPRi) in conjunction with compensatory expression displayed those genetic mutations in sugar and amino acid metabolic pathways, including glnP, glpF, gmpA, nagE, pgmB, ybaN, etc., increased allulose assimilation. Enzyme-substrate dynamics simulations and deep learning predict enhanced substrate specificity and catalytic efficiency in nagE A247E and pgmB G12R mutants. The findings evince that these mutations hold considerable promise in enhancing allulose uptake and facilitating its conversion into glycolysis, thus signifying the emergence of a novel metabolic pathway for allulose utilization. These revelations bear immense potential for the sustainable utilization of D-allulose in promoting health and well-being.

Unraveling the role of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer by multi-omics analyses.

The role of the serine/glycine metabolic pathway (SGP) has recently been demonstrated in tumors; however, the pathological relevance of the SGP in thyroid cancer remains unexplored. Here, we perform metabolomic profiling of 17 tumor-normal pairs; bulk transcriptomics of 263 normal thyroid, 348 papillary, and 21 undifferentiated thyroid cancer samples; and single-cell transcriptomes from 15 cases, showing the impact of mitochondrial one-carbon metabolism in thyroid tumors. High expression of serine hydroxymethyltransferase-2 (SHMT2) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is associated with low thyroid differentiation scores and poor clinical features. A subpopulation of tumor cells with high mitochondrial one-carbon pathway activity is observed in the single-cell dataset. SHMT2 inhibition significantly compromises mitochondrial respiration and decreases cell proliferation and tumor size in vitro and in vivo. Collectively, our results highlight the importance of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer and suggest that SHMT2 is a potent therapeutic target.

The relationship between adverse childhood experiences and depressive symptoms in rural left-behind adolescents: A cross-sectional survey.

Objective: We assessed the current status of depressive symptoms and the associated factors in rural left-behind adolescents. Moreover, we investigated the relationship between adverse childhood experiences and depressive symptoms. Methods: Students from two rural junior high schools in Huaihua City were enrolled from July to September 2022. Before distributing the questionnaires, guardians of the students were contacted, and consent was obtained from the students themselves. The questionnaires were filled out anonymously and collected on-site. Results: The prevalence of depressive symptoms among the 325 left-behind teenagers was 23.40%; the rate of emotional abuse in adverse childhood experiences was 17.50%, physical abuse was 15.70%, sexual abuse was 9.50%, emotional neglect was 24.60%, while physical neglect was 27.70%. The five dimensions of adverse childhood experiences were associated with depressive symptoms (r = 0.597, 0.395, 0.410, 0.498, 0.741, p < 0.01). Conclusions: Depressive symptoms were common among rural left-behind adolescents. Adverse childhood experiences were associated with depressive symptoms in rural left-behind adolescents. Occurrence of adverse childhood experiences should be reduced to improve on depressive symptoms.

A wheel-shaped Zr-substituted phosphotungstate [{Zr(C2O4)2}3 (PO4)(P6W39O150)]39- with tunable proton conduction properties.

A wheel-shaped Zr-substituted phosphotungstate, [N(CH3)4]2K16Na10.5H10.5[{Zr(C2O4)2}3(PO4)(P6W39O150)]·45H2O (1), was synthesised from a hexavacant Dawson-type precursor [H2P2W12O48]12-via a conventional solution method. Compound 1 features a wheel-shaped polyanion comprising an annular [P6W39O150]36- cluster supported by a turbine-shaped [{Zr(C2O4)2}3(PO4)]3- fragment, with three oxalate groups covalently anchored to W atoms. Compound 1 was systematically characterized by IR, UV, PXRD, TGA and 31P NMR spectra. The 31P NMR spectra over time were monitored to verify the stability of 1 in aqueous solution. This compound possesses remarkable proton conductive behavior with a high conductivity of 1.18 × 10-2 S cm-1 at 368 K.