Sex-dependent phenological responses to climate vary across species' ranges.

Anthropogenic climate change has significantly altered the flowering times (i.e., phenology) of plants worldwide, affecting their reproduction, survival, and interactions. Recent studies utilizing herbarium specimens have uncovered significant intra- and inter-specific variation in flowering phenology and its response to changes in climate but have mostly been limited to animal-pollinated species. Thus, despite their economic and ecological importance, variation in phenological responses to climate remain largely unexplored among and within wind-pollinated dioecious species and across their sexes. Using both herbarium specimens and volunteer observations of cottonwood (Populus) species, we examined how phenological sensitivity to climate varies across species, their ranges, sexes, and phenophases. The timing of flowering varied significantly across and within species, as did their sensitivity to spring temperature. In particular, male flowering generally happened earlier in the season and was more sensitive to warming than female flowering. Further, the onset of flowering was more sensitive to changes in temperature than leaf out. Increased temporal gaps between male and female flowering time and between the first open flower date and leaf out date were predicted for the future under two climate change scenarios. These shifts will impact the efficacy of sexual reproduction and gene flow among species. Our study demonstrates significant inter- and intra-specific variation in phenology and its responses to environmental cues, across species' ranges, phenophases, and sex, in wind-pollinated species. These variations need to be considered to predict accurately the effects of climate change and assess their ecological and evolutionary consequences.

Voxel-based texture similarity networks reveal individual variability and correlate with biological ontologies.

The human brain is organized as a complex, hierarchical network. However, the structural covariance patterns among brain regions and the underlying biological substrates of such covariance networks remain to be clarified. The present study proposed a novel individualized structural covariance network termed voxel-based texture similarity networks (vTSNs) based on 76 refined voxel-based textural features derived from structural magnetic resonance images. Validated in three independent longitudinal healthy cohorts (40, 23, and 60 healthy participants, respectively) with two common brain atlases, we found that the vTSN could robustly resolve inter-subject variability with high test-retest reliability. In contrast to the regional-based texture similarity networks (rTSNs) that calculate radiomic features based on region-of-interest information, vTSNs had higher inter- and intra-subject variability ratios and test-retest reliability in connectivity strength and network topological properties. Moreover, the Spearman correlation indicated a stronger association of the gene expression similarity network (GESN) with vTSNs than with rTSNs (vTSN: r = 0.600, rTSN: r = 0.433, z = 39.784, P < 0.001). Hierarchical clustering identified 3 vTSN subnets with differential association patterns with 13 coexpression modules, 16 neurotransmitters, 7 electrophysiology, 4 metabolism, and 2 large-scale structural and 4 functional organization maps. Moreover, these subnets had unique biological hierarchical organization from the subcortex-limbic system to the ventral neocortex and then to the dorsal neocortex. Based on 424 unrelated, qualified healthy subjects from the Human Connectome Project, we found that vTSNs could sensitively represent sex differences, especially for connections in the subcortex-limbic system and between the subcortex-limbic system and the ventral neocortex. Moreover, a multivariate variance component model revealed that vTSNs could explain a significant proportion of inter-subject behavioral variance in cognition (80.0 %) and motor functions (63.4 %). Finally, using 494 healthy adults (aged 19-80 years old) from the Southwest University Adult Lifespan Dataset, the Spearman correlation identified a significant association between aging and vTSN strength, especially within the subcortex-limbic system and between the subcortex-limbic system and the dorsal neocortex. In summary, our proposed vTSN is robust in uncovering individual variability and neurobiological brain processes, which can serve as biologically plausible measures for linking biological processes and human behavior.

Simultaneous assessment of stress hyperglycemia ratio and glycemic variability to predict mortality in patients with coronary artery disease: a retrospective cohort study from the MIMIC-IV database.

BACKGROUND: Stress hyperglycemia and glycemic variability (GV) can reflect dramatic increases and acute fluctuations in blood glucose, which are associated with adverse cardiovascular events. This study aimed to explore whether the combined assessment of the stress hyperglycemia ratio (SHR) and GV provides additional information for prognostic prediction in patients with coronary artery disease (CAD) hospitalized in the intensive care unit (ICU). METHODS: Patients diagnosed with CAD from the Medical Information Mart for Intensive Care-IV database (version 2.2) between 2008 and 2019 were retrospectively included in the analysis. The primary endpoint was 1-year mortality, and the secondary endpoint was in-hospital mortality. Levels of SHR and GV were stratified into tertiles, with the highest tertile classified as high and the lower two tertiles classified as low. The associations of SHR, GV, and their combination with mortality were determined by logistic and Cox regression analyses. RESULTS: A total of 2789 patients were included, with a mean age of 69.6 years, and 30.1% were female. Overall, 138 (4.9%) patients died in the hospital, and 404 (14.5%) patients died at 1 year. The combination of SHR and GV was superior to SHR (in-hospital mortality: 0.710 vs. 0.689, p = 0.012; 1-year mortality: 0.644 vs. 0.615, p = 0.007) and GV (in-hospital mortality: 0.710 vs. 0.632, p = 0.004; 1-year mortality: 0.644 vs. 0.603, p < 0.001) alone for predicting mortality in the receiver operating characteristic analysis. In addition, nondiabetic patients with high SHR levels and high GV were associated with the greatest risk of both in-hospital mortality (odds ratio [OR] = 10.831, 95% confidence interval [CI] 4.494-26.105) and 1-year mortality (hazard ratio [HR] = 5.830, 95% CI 3.175-10.702). However, in the diabetic population, the highest risk of in-hospital mortality (OR = 4.221, 95% CI 1.542-11.558) and 1-year mortality (HR = 2.013, 95% CI 1.224-3.311) was observed in patients with high SHR levels but low GV. CONCLUSIONS: The simultaneous evaluation of SHR and GV provides more information for risk stratification and prognostic prediction than SHR and GV alone, contributing to developing individualized strategies for glucose management in patients with CAD admitted to the ICU.

Non-insulin-based insulin resistance indexes in predicting atrial fibrillation recurrence following ablation: a retrospective study.

BACKGROUND: Insulin resistance (IR) is involved in the pathophysiological processes of arrhythmias. Increasing evidence suggests triglyceride and glucose (TyG) index, metabolic score for insulin resistance (METS-IR), triglyceride glucose-body mass index (TyG-BMI), and triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio are simple and reliable surrogates for IR. Although they have been associated with atrial fibrillation (AF), evidence supporting this is limited. Here, this is the first study to investigate the association between TyG-BMI index and AF recurrence following radiofrequency catheter ablation (RFCA). The performance of the four non-insulin-based IR indexes in predicting AF recurrence after ablation was explored. METHODS: A total of 2242 AF patients who underwent a de novo RFCA between June 2018 to January 2022 at two hospitals in China were included in this retrospective study. The predictive values of IR indexes for AF recurrence after ablation were assessed. RESULTS: During 1-year follow-up, 31.7% of patients experienced AF recurrence. The multivariable analysis revealed that TyG index, METS-IR, and TyG-BMI index were independent risk factors for AF recurrence. Restricted cubic spline analysis revealed a connection between METS-IR, TyG-BMI index, and AF recurrence (P < 0.001). Furthermore, incorporating the METS-IR or TyG-BMI index to the basic risk model with fully adjusted factors considerably enhanced the forecast of AF recurrence, as demonstrated by the C-statistic, continuous net reclassification improvement, and integrated discrimination improvement. CONCLUSIONS: TyG index, METS-IR, and TyG-BMI index were independently associated with AF recurrence following ablation. Among the four non-insulin-based IR indexes, TyG-BMI had the highest predictive value, followed by METS-IR.

The additive effect of the triglyceride-glucose index and estimated glucose disposal rate on long-term mortality among individuals with and without diabetes: a population-based study.

BACKGROUND: The triglyceride-glucose (TyG) index and estimated glucose disposal rate (eGDR), which are calculated using different parameters, are widely used as markers of insulin resistance and are associated with cardiovascular diseases and prognosis. However, whether they have an additive effect on the risk of mortality remains unclear. This study aimed to explore whether the combined assessment of the TyG index and eGDR improved the prediction of long-term mortality in individuals with and without diabetes. METHODS: In this cross-sectional and cohort study, data were derived from the National Health and Nutrition Examination Survey (NHANES) 2001-2018, and death record information was obtained from the National Death Index. The associations of the TyG index and eGDR with all-cause and cardiovascular mortality were determined by multivariate Cox regression analysis and restricted cubic splines. RESULTS: Among the 17,787 individuals included in the analysis, there were 1946 (10.9%) all-cause deaths and 649 (3.6%) cardiovascular deaths during a median follow-up of 8.92 years. In individuals with diabetes, the restricted cubic spline curves for the associations of the TyG index and eGDR with mortality followed a J-shape and an L-shape, respectively. The risk of mortality significantly increased after the TyG index was > 9.04 (all-cause mortality) or > 9.30 (cardiovascular mortality), and after eGDR was < 4 mg/kg/min (both all-cause and cardiovascular mortality). In individuals without diabetes, the association between eGDR and mortality followed a negative linear relationship. However, there was no association between the TyG index and mortality. Compared with individuals in the low TyG and high eGDR group, those in the high TyG and low eGDR group (TyG > 9.04 and eGDR < 4) showed the highest risk for all-cause mortality (hazard ratio [HR] = 1.592, 95% confidence interval [CI] 1.284-1.975) and cardiovascular mortality (HR = 1.683, 95% CI 1.179-2.400) in the overall population. Similar results were observed in individuals with and without diabetes. CONCLUSIONS: There was a potential additive effect of the TyG index and eGDR on the risk of long-term mortality in individuals with and without diabetes, which provided additional information for prognostic prediction and contributed to improving risk stratification.

Key Role of Vegetation Cover in Alleviating Microplastic-Enhanced Carbon Emissions.

Microplastics (MPs) are considered to influence fundamental biogeochemical processes, but the effects of plant residue-MP interactions on soil carbon turnover in urban greenspaces are virtually unknown. Here, an 84-day incubation experiment was constructed using four types of single-vegetation-covered soils (6 years), showing that polystyrene MP (PSMP) pollution caused an unexpectedly large increase in soil CO2 emissions. The additional CO2 originating from highly bioavailable active dissolved organic matter molecules (<380 °C, predominantly polysaccharides) was converted from persistent carbon (380-650 °C, predominantly aromatic compounds) rather than PSMP derivatives. However, the priming effect of PSMP derivatives was weakened in plant-driven soils (resistivity: shrub > tree > grass). This can be explained from two perspectives: (1) Plant residue-driven humification processes reduced the percentage of bioavailable active dissolved organic matter derived from the priming effects of PSMPs. (2) Plant residues accelerated bacterial community succession (dominated by plant residue types) but slowed fungal community demise (retained carbon turnover-related functional taxa), enabling specific enrichment of glycolysis, the citric acid cycle and the pentose phosphate pathway. These results provide a necessary theoretical basis to understand the role of plant residues in reducing PSMP harm at the ecological level and refresh knowledge about the importance of biodiversity for ecosystem stability.

The global burden, trends and cross-country inequalities of female breast and gynaecologic cancers: A population based study.

OBJECTIVE: To analyse the global burden, trends and cross-country inequalities of female breast and gynaecologic cancers (FeBGCs). DESIGN: Population-Based Study. SETTING: Data sourced from the Global Burden of Disease Study 2019. POPULATION: Individuals diagnosed with FeBGCs. METHODS: Age-standardised mortality rates (ASMRs), age-standardised Disability-Adjusted Life Years (DALYs) rates (ASDRs) and their 95% uncertainty interval (UI) described the burden. Estimated annual percentage changes (EAPCs) and their confidence interval (CI) of age-standardised rates (ASRs) illustrated trends. Social inequalities were quantified using the Slope Index of Inequality (SII) and Concentration Index. MAIN OUTCOME MEASURES: The main outcome measures were the burden of FeBGCs and the trends in its inequalities over time. RESULTS: In 2019, the ASDRs per 100 000 females were as follows: breast cancer: 473.83 (95% UI: 437.30-510.51), cervical cancer: 210.64 (95% UI: 177.67-234.85), ovarian cancer: 124.68 (95% UI: 109.13-138.67) and uterine cancer: 210.64 (95% UI: 177.67-234.85). The trends per year from 1990 to 2019 were expressed as EAPCs of ASDRs and these: for Breast cancer: -0.51 (95% CI: -0.57 to -0.45); Cervical cancer: -0.95 (95% CI: -0.99 to -0.89); Ovarian cancer: -0.08 (95% CI: -0.12 to -0.04); and Uterine cancer: -0.84 (95% CI: -0.93 to -0.75). In the Social Inequalities Analysis (1990-2019) the SII changed from 689.26 to 607.08 for Breast, from -226.66 to -239.92 for cervical, from 222.45 to 228.83 for ovarian and from 74.61 to 103.58 for uterine cancer. The concentration index values ranged from 0.2 to 0.4. CONCLUSIONS: The burden of FeBGCs worldwide showed a downward trend from 1990 to 2019. Countries or regions with higher Socio-demographic Index (SDI) bear a higher DALYs burden of breast, ovarian and uterine cancers, while those with lower SDI bear a heavier burden of cervical cancer. These inequalities increased over time.

Exploring the correlation between childhood trauma experiences, inflammation, and brain activity in first-episode, drug-naive major depressive disorder.

BACKGROUND: Childhood trauma experiences and inflammation are pivotal factors in the onset and perpetuation of major depressive disorder (MDD). However, research on brain mechanisms linking childhood trauma experiences and inflammation to depression remains insufficient and inconclusive. METHODS: Resting-state fMRI scans were performed on fifty-six first-episode, drug-naive MDD patients and sixty healthy controls (HCs). A whole-brain functional network was constructed by thresholding 246 brain regions, and connectivity and network properties were calculated. Plasma interleukin-6 (IL-6) levels were assessed using enzyme-linked immunosorbent assays in MDD patients, and childhood trauma experiences were evaluated through the Childhood Trauma Questionnaire (CTQ). RESULTS: Negative correlations were observed between CTQ total (r = -0.28, p = 0.047), emotional neglect (r = -0.286, p = 0.042) scores, as well as plasma IL-6 levels (r = -0.294, p = 0.036), with mean decreased functional connectivity (FC) in MDD patients. Additionally, physical abuse exhibited a positive correlation with the nodal clustering coefficient of the left thalamus in patients (r = 0.306, p = 0.029). Exploratory analysis indicated negative correlations between CTQ total and emotional neglect scores and mean decreased FC in MDD patients with lower plasma IL-6 levels (n = 28), while these correlations were nonsignificant in MDD patients with higher plasma IL-6 levels (n = 28). CONCLUSIONS: This finding enhances our understanding of the correlation between childhood trauma experiences, inflammation, and brain activity in MDD, suggesting potential variations in their underlying pathophysiological mechanisms.

A Real-World Study on Adverse Reactions of Belimumab Based on the FDA Adverse Event Reporting System Database.

BACKGROUND AND OBJECTIVES: This investigation leverages data derived from the United States Food and Drug Administration Adverse Event Reporting (FAERS) to real-world adverse reactions associated with Belimumab, with the intention of providing guidance for safe clinical pharmacotherapy. METHODS: Data encompassing adverse drug event (ADE) reports relating to Belimumab from Q1 2011 to Q4 2023 within the FAERS were extracted and analyzed using methodologies such as the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). RESULTS: The study identified a total of 19 825 ADE reports where Belimumab was the primary suspect medication, with the United States constituting the majority of reporting countries (16 312 cases, or 82.28%). Patients aged 18 to 64.9 years accounted for the largest demographic (36.29%), while the proportion of female patients (77.91%) significantly surpassed that of male patients (5.03%). The analysis uncovered 184 unique Preferred Terms (PTs) across 21 System Organ Classes (SOCs). Following selection through ROR, the SOC signal strength was prioritized as follows: Systemic disorders and administration site conditions, infections and infestations, a variety of musculoskeletal and connective tissue disorders, and conditions related to pregnancy, puerperium, and the perinatal period. The top five PTs for ADE reports not included in the product's labeling were hypersensitivity reactions, immunosuppression, non-vascular diseases, herpes virus infections, and Sjögren's syndrome. The top five PTs for ADE signal strength not included in the labeling were disseminated cutaneous herpes zoster, herpes zoster meningitis, onycholysis, cyclothymic disorder, and mixed connective tissue disease. DISCUSSION: Based on pharmacovigilance research utilizing the FAERS database, it is recommended that clinical monitoring of Bevacizumab should be intensified to support effective pharmaceutical care and ensure rational clinical medication use.

Structural covariances of prefrontal subregions selectively associate with dopamine-related gene coexpression and schizophrenia.

Evidence highlights that dopamine (DA) system dysregulation and prefrontal cortex (PFC) dysfunction may underlie the pathophysiology of schizophrenia. However, the associations among DA genes, PFC morphometry, and schizophrenia have not yet been fully clarified. Based on the brain gene expression dataset from Allen Human Brain Atlas and structural magnetic resonance imaging data (NDIS = 1727, NREP = 408), we first identified 10 out of 22 PFC subregions whose gray matter volume (GMV) covariance profiles were reliably associated with their DA genes coexpression profiles, then four out of the identified 10 PFC subregions demonstrated abnormally increased GMV covariance with the hippocampus, insula, and medial frontal areas in schizophrenia patients (NCASE = 100; NCONTROL = 102). Moreover, based on a schizophrenia postmortem expression dataset, we found that the DA genes coexpression of schizophrenia was significantly reduced between the middle frontal gyrus and hippocampus, in which 21 DA genes showed significantly unsynchronized expression changes, and the 21 genes' brain expression were enriched in brain activity invoked by working memory, reward, speech production, and episodic memory. Our findings indicate the DA genes selectively regulate the structural covariance of PFC subregions by their coexpression profiles, which may underlie the disrupted GMV covariance and impaired cognitive functions in schizophrenia.

Mapping cerebral atrophic trajectory from amnestic mild cognitive impairment to Alzheimer's disease.

Alzheimer's disease (AD) patients suffer progressive cerebral atrophy before dementia onset. However, the region-specific atrophic processes and the influences of age and apolipoprotein E (APOE) on atrophic trajectory are still unclear. By mapping the region-specific nonlinear atrophic trajectory of whole cerebrum from amnestic mild cognitive impairment (aMCI) to AD based on longitudinal structural magnetic resonance imaging data from Alzheimer's disease Neuroimaging Initiative (ADNI) database, we unraveled a quadratic accelerated atrophic trajectory of 68 cerebral regions from aMCI to AD, especially in the superior temporal pole, caudate, and hippocampus. Besides, interaction analyses demonstrated that APOE ε4 carriers had faster atrophic rates than noncarriers in 8 regions, including the caudate, hippocampus, insula, etc.; younger patients progressed faster than older patients in 32 regions, especially for the superior temporal pole, hippocampus, and superior temporal gyrus; and 15 regions demonstrated complex interaction among age, APOE, and disease progression, including the caudate, hippocampus, etc. (P < 0.05/68, Bonferroni correction). Finally, Cox proportional hazards regression model based on the identified region-specific biomarkers could effectively predict the time to AD conversion within 10 years. In summary, cerebral atrophic trajectory mapping could help a comprehensive understanding of AD development and offer potential biomarkers for predicting AD conversion.

Cheese consumption on atherosclerosis, atherosclerotic cardiovascular diseases and its complications: A two-sample Mendelian randomization study.

BACKGROUND AND AIM: Evidence from prospective cohort studies has revealed an inverse association between cheese consumption and the development of atherosclerosis (AS), atherosclerotic cardiovascular diseases (ASCVD), and their complications. However, it remains unclear whether this observed association is influenced by potential confounding factors that may arise during the long-term development process of AS, ASCVD, and its complications. Therefore, to further clarify the causal relationship between cheese consumption and AS, ASCVD, and its complications, we conducted a two-sample Mendelian randomization (MR) analysis to explore the causal association between cheese intake and the aforementioned health outcomes. METHODS AND RESULTS: We employed a two-sample MR analysis based on publicly available genome-wide association studies (GWAS) to infer the causal relationship, with no overlap between their participating populations. The effect estimates were calculated using the random-effects inverse-variance-weighted method. Sensitivity analyses were conducted using Cochran's Q statistic, funnel plot, leave-one-out analysis, and MR-Egger intercept tests. The genetically predicted cheese intake was found to be associated with lower risks of coronary AS (odds ratio [OR] = 0.72, 95 % confidence interval [CI] 0.59-0.88, P = 0.001), peripheral vascular AS (OR = 0.56, 95 % CI 0.37-0.84, P = 0.006), other vascular AS (OR = 0.66, 95 % CI 0.44-0.99, P = 0.043), coronary artery disease (OR = 0.64, 95 % CI 0.56-0.74, P = 1.57e-09), angina pectoris (OR = 0.70, 95 % CI 0.58-0.84, P = 4.92e-05), myocardial infarction (OR = 0.63, 95 % CI 0.52-0.77, P = 3.56e-06), heart failure (OR = 0.62, 0.49-0.79, P = 1.20e-04), total ischemic stroke (OR = 0.76, 95 % CI 0.63-0.91, P = 0.003), peripheral artery disease (OR = 0.64, 95 % CI 0.43-0.95, P = 0.028), and cognitive impairment (OR = 0.65, 95 % CI 0.56-0.74, P = 3.40e-10). However, no associations were observed for cerebrovascular AS, arrhythmia, cardiac death, ischemic stroke (large artery AS), ischemic stroke (small vessel), ischemic stroke (cardioembolic), and transient ischemic attack. CONCLUSION: This two-sample MR analysis reveals a causally inverse association between cheese intake and multi-vascular AS (including coronary AS, peripheral vascular AS, and other vascular AS), as well as multiple types of ASCVD and its complications (such as coronary artery disease, angina pectoris, myocardial infarction, heart failure, total ischemic stroke, and peripheral artery disease). The findings from this study may lay a stronger theoretical foundation and present new opportunities for the dietary management of future atherosclerotic cardiovascular diseases.

The global burden and risk factors of cardiovascular diseases in adolescent and young adults, 1990-2019.

BACKGROUND: To provide details of the burden and the trend of the cardiovascular disease (CVD) and its risk factors in adolescent and young adults. METHODS: Age-standardized rates (ASRs) of incidence, mortality and Disability-Adjusted Life Years (DALYs) were used to describe the burden of CVD in adolescents and young adults. Estimated Annual Percentage Changes (EAPCs) of ASRs were used to describe the trend from 1990 to 2019. Risk factors were calculated by Population Attributable Fractions (PAFs). RESULTS: In 2019, the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR) and age-standardized DALYs rate (ASDR) of CVD were 129.85 per 100 000 (95% Confidence interval (CI): 102.60, 160.31), 15.12 per 100 000 (95% CI: 13.89, 16.48) and 990.64 per 100 000 (95% CI: 911.06, 1076.46). The highest ASRs were seen in low sociodemographic index (SDI) and low-middle SDI regions. The burden was heavier in male and individuals aged 35-39. From 1990 to 2019, 72 (35.29%) countries showed an increasing trend of ASIR and more than 80% countries showed a downward trend in ASMR and ASDR. Rheumatic heart disease had the highest ASIR and Ischemic Heart Disease was the highest in both ASMR and ASDR. The main attributable risk factor for death and DALYs were high systolic blood pressure, high body-mass index and high LDL cholesterol. CONCLUSIONS: The burden of CVD in adolescent and young adults is a significant global health challenge. It is crucial to take into account the disparities in SDI levels among countries, gender and age characteristics of the population, primary types of CVD, and the attributable risk factors when formulating and implementing prevention strategies.

MiR-2110 induced by chemically synthesized cinobufagin functions as a tumor-metastatic suppressor via targeting FGFR1 to reduce PTEN ubiquitination degradation in nasopharyngeal carcinoma.

Tumor cell metastasis is the key cause of death in patients with nasopharyngeal carcinoma (NPC). MiR-2110 was cloned and identified in Epstein-Barr virus (EBV)-positive NPC, but its role is unclear in NPC. In this study, we investigated the effect of miR-2110 on NPC metastasis and its related molecular basis. In addition, we also explored whether miR-2110 can be regulated by cinobufotalin (CB) and participate in the inhibition of CB on NPC metastasis. Bioinformatics, RT-PCR, and in situ hybridization were used to observe the expression of miR-2110 in NPC tissues and cells. Scratch, Boyden, and tail vein metastasis model of nude mouse were used to detect the effect of miR-2110 on NPC metastasis. Western blot, Co-IP, luciferase activity, colocalization of micro confocal and ubiquitination assays were used to identify the molecular mechanism of miR-2110 affecting NPC metastasis. Finally, miR-2110 induced by CB participates in CB-stimulated inhibition of NPC metastasis was explored. The data showed that increased miR-2110 significantly suppresses NPC cell migration, invasion, and metastasis. Suppressing miR-2110 markedly restored NPC cell migration and invasion. Mechanistically, miR-2110 directly targeted FGFR1 and reduced its protein expression. Decreased FGFR1 attenuated its recruitment of NEDD4, which downregulated NEDD4-induced phosphatase and tensin homolog (PTEN) ubiquitination and degradation and further increased PTEN protein stability, thereby inactivating PI3K/AKT-stimulated epithelial-mesenchymal transition signaling and ultimately suppressing NPC metastasis. Interestingly, CB, a potential new inhibitory drug for NPC metastasis, significantly induced miR-2110 expression by suppressing PI3K/AKT/c-Jun-mediated transcription inhibition. Suppression of miR-2110 significantly restored cell migration and invasion in CB-treated NPC cells. Finally, a clinical sample assay indicated that reduced miR-2110 was negatively correlated with NPC lymph node metastasis and positively related to NPC patient survival prognosis. In summary, miR-2110 is a metastatic suppressor involving in CB-induced suppression of NPC metastasis.

P2-Type Moisture-Stable and High-Voltage-Tolerable Cathodes for High-Energy and Long-Life Sodium-Ion Batteries.

P2-Na0.67Ni0.33Mn0.67O2 represents a promising cathode for Na-ion batteries, but it suffers from severe structural degradation upon storing in a humid atmosphere and cycling at a high cutoff voltage. Here we propose an in situ construction to achieve simultaneous material synthesis and Mg/Sn cosubstitution of Na0.67Ni0.33Mn0.67O2 via one-pot solid-state sintering. The materials exhibit superior structural reversibility and moisture insensitivity. In-operando XRD reveals an essential correlation between cycling stability and phase reversibility, whereas Mg substitution suppressed the P2-O2 phase transition by forming a new Z phase, and Mg/Sn cosubstitution enhanced the P2-Z transition reversibility benefiting from strong Sn-O bonds. DFT calculations disclosed high chemical tolerance to moisture, as the adsorption energy to H2O was lower than that of the pure Na0.67Ni0.33Mn0.67O2. A representative Na0.67Ni0.23Mg0.1Mn0.65Sn0.02O2 cathode exhibits high reversible capacities of 123 mAh g-1 (10 mA g-1), 110 mAh g-1 (200 mA g-1), and 100 mAh g-1 (500 mA g-1) and a high capacity retention of 80% (500 mA g-1, 500 cycles).

Treatment of landfill leachate by black soldier fly (Hermetia illucens L.) larvae and the changes of intestinal microbial community.

Black soldier fly larvae (BSFL) (Hermetia illucens) are commonly used to treat organic waste. This work aims to evaluate the transformation effect, heavy metal migration, and alterations in the gut microbiota of BSFL in addition to treating landfill leachate (LL) with BSFL. We found that BSFL may grow in various landfill leachate concentrations without obvious toxicity and growth inhibition. In addition, the results indicated a significant increase in the content of ammonia nitrogen and the activity of urease and ß-glucosidase (ß-GC) in LL, increased from 2570.17 mg/L to 5853.67 mg/L, 1859.17 mg/(g·d) to 517,177.98 mg/(g·d), 313.73 µg/(g·h) to 441.91 µg/(g·h) respectively. Conversely, the content of total nitrogen (TN) and total organic carbon (TOC) decreased in LL, decreasing by 31.24% and 29.45% respectively. Heavy metals are accumulated in the leachate by the BSFL to differing degrees, the descending sequence of accumulation is Cd > As > Cu > Cr. As dropped by 26.0%, Cd increased by 22.6%, Cu reduced by 5.23%, and Cr increased by 317.1% in the remaining matrix. The concentration of heavy metals satisfies the organic fertilizers' limit index (NY/T1978). The diversity of intestinal microorganisms in BSFL decreased, from 2819 OTUs to 2338 OTUs, with Providencia and Morganella emerging as the core flora. The gene abundance of nitrogen metabolism in the microbiota increased significantly. The TOC, ß-GC, and Copper (Cu) content in BSFL correlated significantly with the gut microbiota. In Summary, this study revealed the treatment effect of BSFL on LL, the migration of heavy metals, and changes in the intestinal microorganisms of BSFL. The content of heavy metals in BSFL was found to be much lower than the upper limit of feed protein raw materials, demonstrating that BSFL is a sustainable method to treat LL.

MRAß: A multimodal MRI-derived amyloid-ß biomarker for Alzheimer's disease.

Florbetapir 18 F (AV45), a highly sensitive and specific positron emission tomographic (PET) molecular biomarker binding to the amyloid-ß of Alzheimer's disease (AD), is constrained by radiation and cost. We sought to combat it by combining multimodal magnetic resonance imaging (MRI) images and a collaborative generative adversarial networks model (CollaGAN) to develop a multimodal MRI-derived Amyloid-ß (MRAß) biomarker. We collected multimodal MRI and PET AV45 data of 380 qualified participants from the ADNI dataset and 64 subjects from OASIS3 dataset. A five-fold cross-validation CollaGAN were applied to generate MRAß. In the ADNI dataset, we found MRAß could characterize the subject-level AV45 spatial variations in both AD and mild cognitive impairment (MCI). Voxel-wise two-sample t-tests demonstrated amyloid-ß depositions identified by MRAß in AD and MCI were significantly higher than healthy controls (HCs) in widespread cortices (p < .05, corrected) and were much similar to those by AV45 (r > .92, p < .001). Moreover, a 3D ResNet classifier demonstrated that MRAß was comparable to AV45 in discriminating AD from HC in both the ADNI and OASIS3 datasets, and in discriminate MCI from HC in ADNI. Finally, we found MRAß could mimic cortical hyper-AV45 in HCs who later converted to MCI (r = .79, p < .001) and was comparable to AV45 in discriminating them from stable HC (p > .05). In summary, our work illustrates that MRAß synthesized by multimodal MRI could mimic the cerebral amyloid-ß depositions like AV45 and lends credence to the feasibility of advancing MRI toward molecular-explainable biomarkers.

Unraveling schizophrenia replicable functional connectivity disruption patterns across sites.

Functional connectivity (FC) disruption is a remarkable characteristic of schizophrenia. However, heterogeneous patterns reported across sites severely hindered its clinical generalization. Based on qualified nodal-based FC of 340 schizophrenia patients (SZ) and 348 normal controls (NC) acquired from seven different scanners, this study compared four commonly used site-effect correction methods in removing the site-related heterogeneities, and then tried to cluster the abnormal FCs into several replicable and independent disrupted subnets across sites, related them to clinical symptoms, and evaluated their potentials in schizophrenia classification. Among the four site-related heterogeneity correction methods, ComBat harmonization (F1 score: 0.806 ± 0.145) achieved the overall best balance between sensitivity and false discovery rate in unraveling the aberrant FCs of schizophrenia in the local and public data sets. Hierarchical clustering analysis identified three replicable FC disruption subnets across the local and public data sets: hypo-connectivity within sensory areas (Net1), hypo-connectivity within thalamus, striatum, and ventral attention network (Net2), and hyper-connectivity between thalamus and sensory processing system (Net3). Notably, the derived composite FC within Net1 was negatively correlated with hostility and disorientation in the public validation set (p < .05). Finally, the three subnet-specific composite FCs (Best area under the receiver operating characteristic curve [AUC] = 0.728) can robustly and meaningfully discriminate the SZ from NC with comparable performance with the full identified FCs features (best AUC = 0.765) in the out-of-sample public data set (Z = -1.583, p = .114). In conclusion, ComBat harmonization was most robust in detecting aberrant connectivity for schizophrenia. Besides, the three subnet-specific composite FC measures might be replicable neuroimaging markers for schizophrenia.

Complex climate-mediated effects of urbanization on plant reproductive phenology and frost risk.

Urbanization can affect the timing of plant reproduction (i.e. flowering and fruiting) and associated ecosystem processes. However, our knowledge of how plant phenology responds to urbanization and its associated environmental changes is limited. Herbaria represent an important, but underutilized source of data for investigating this question. We harnessed phenological data from herbarium specimens representing 200 plant species collected across 120 yr from the eastern US to investigate the spatiotemporal effects of urbanization on flowering and fruiting phenology and frost risk (i.e. time between the last frost date and flowering). Effects of urbanization on plant reproductive phenology varied significantly in direction and magnitude across species ranges. Increased urbanization led to earlier flowering in colder and wetter regions and delayed fruiting in regions with wetter spring conditions. Frost risk was elevated with increased urbanization in regions with colder and wetter spring conditions. Our study demonstrates that predictions of phenological change and its associated impacts must account for both climatic and human effects, which are context dependent and do not necessarily coincide. We must move beyond phenological models that only incorporate temperature variables and consider multiple environmental factors and their interactions when estimating plant phenology, especially at larger spatial and taxonomic scales.

Microplastics Reshape the Fate of Aqueous Carbon by Inducing Dynamic Changes in Biodiversity and Chemodiversity.

The interactions among dissolved organic matter (DOM), microplastics (MPs) and microbes influence the fate of aqueous carbon and greenhouse gas emissions. However, the related processes and mechanisms remain unclear. Here, we found that MPs determined the fate of aqueous carbon by influencing biodiversity and chemodiversity. MPs release chemical additives such as diethylhexyl phthalate (DEHP) and bisphenol A (BPA) into the aqueous phase. The microbial community, especially autotrophic bacteria such as Cyanobacteria, showed a negative correlation with the additives released from MPs. The inhibition of autotrophs promoted CO2 emissions. Meanwhile, MPs stimulated microbial metabolic pathways such as the tricarboxylic acid (TCA) cycle to accelerate the DOM biodegradation process, and then the transformed DOM presented low bioavailability, high stability, and aromaticity. Our findings highlight an urgent need for chemodiversity and biodiversity surveys to assess ecological risks from MP pollution and the impact of MPs on the carbon cycle.