Amino-modified IONPs potentiates ferroptotic cell death due to the release of Fe ion in the lysosome.

Iron oxide nanoparticles (IONPs) have wide applications in the biomedical field due to their outstanding physical and chemical properties. However, the potential adverse effects and related mechanisms of IONPs in human organs, especially the lung, are still largely ignored. In this study, we found that group-modified IONPs (carboxylated, aminated and silica coated) induce slight lung cell damage (in terms of the cell cycle, reactive oxygen species (ROS) production, cell membrane integrity and DNA damage) at a sublethal dosage. However, aminated IONPs could release more iron ions in the lysosome than the other two types of IONPs, but the abnormally elevated iron ion concentration did not induce ferroptosis. Intriguingly, amino-modified IONPs aggravated the accumulation of intracellular peroxides induced by the ferroptosis activator RSL3 and thus caused ferroptosis in vitro, and the coadministration of amino-modified IONPs and RSL3 induced more severe lung injury in vivo. Therefore, our data revealed that the surface functionalization of IONPs plays an important role in determining their potential pulmonary toxicity, as surface modification influences their degradation behavior. These results provide guidance for the design of future IONPs and the corresponding safety evaluations and predictions.

Promoting nitrogen-doped porous phosphorus spheres for high-rate lithium storage.

Phosphorus anode has shown great potential for the high-rate and high-energy-density lithium-ion batteries. Nevertheless, it still suffers from possible electrode cracking, ion-transport restrictions, and active-particle decomposition resulting from repeated alloying/de-alloying. To address the aforementioned issues, a nitrogen-doped flower-like porous phosphorus (f-P) sphere has been developed. The abundant micro-mesopores facilitate ion diffusion and enhance the internal bonding strength of the electrode. Concurrently, the doped nitrogen promotes the generation of a favorable solid electrolyte interphase constructed by fast-ion-conductors. As a result, the f-P exhibits a high-rate capacity of 735mAh g-1 at 20 A g-1 and maintains high Coulombic efficiencies over 900 cycles at 10 A g-1. Furthermore, coin full-cells comprising the f-P anode and lithium cobalt oxide cathode demonstrate stable operation at a high current density of 6 mA cm-2. The combination of a porous structure and doping strategy represents a viable approach for strengthening the durability of electrodes and optimizing the ion transport kinetics of advanced alloy anode materials.

The Impact of Medication Regimen Adjustment Ratio on Adherence and Glycemic Control in Patients with Type 2 Diabetes and Mild Cognitive Impairment.

BACKGROUND: An antidiabetic medication regimen is crucial for maintaining glycemic control. Type 2 diabetes mellitus (T2DM) and cognitive dysfunction have a bidirectional relationship. This study aims to explore the impact that adjusting antidiabetic medication regimens has on medication adherence, glycemic control, and cognitive function in patients with T2DM and mild cognitive impairment (MCI). METHODS: This is an observational cross-sectional analysis that includes 364 consecutive inpatients with T2DM. Clinical data were collected, medication adherence was assessed using the Medication Adherence Report Scale (MARS-5), and cognitive status was evaluated using the Chinese version of the Montreal Cognitive Assessment (MoCA) and Mini-mental State Examination (MMSE). These data were obtained both during hospitalization and at a three-month follow-up. Multivariable logistic regression analysis was applied to determine the association between changes in medication regimens and medication adherence, glycemic control, and cognitive function. RESULTS: Baseline medication adherence was high across all three different cognitive status groups, with no significant difference in MARS-5 scores. At the 3-month follow-up, the group with a high adjustment ratio of antidiabetic medication regimens showed an increase in their hemoglobin A1c (HbA1c) level compared to the baseline, while the group with a low adjustment ratio showed a decrease in this level. In addition, the MoCA, MMSE, and MARS-5 scores of the high-adjustment group were significantly lower than those of the low-adjustment group. CONCLUSIONS: A high ratio of medication adjustment was significantly associated with worse medication adherence and glycemic control in T2DM patients with MCI. Patients with a low ratio of medication adjustment had good adherence and better glycemic control. Clinicians should take cognitive status into account when adjusting antidiabetic regimens for T2DM patients and may need to provide additional guidance to patients with cognitive impairment to improve adherence and glycemic outcomes.

Rapid, sensitive and multiplexed detection of SARS-CoV-2 viral nucleic acids enabled by phase-based surface plasmon resonance of metallic gratings.

A rapid, sensitive and easy-to-implement approach is proposed for the detection of pathogenic nucleic acids based on phase-based plasmonic spectroscopy of metallic gratings. The plasmonic sensors were fabricated using interference lithography and functionalized with single-stranded DNA probes to specific target SARS-CoV-2. The biosensor achieved the detection of 40 fM viral nucleic acids within 5 min; furthermore, a detection capability of 1 aM (0.6 copies/µL) was acquired when combining with the recombinase polymerase amplification. Additionally, the multiplexed sensing system was demonstrated to simultaneously detect three genomic sequences on a single sensor chip, thereby enhancing diagnostic accuracy and enabling high-throughput detection.

Sortilin-mediated translocation of mitochondrial ACSL1 impairs adipocyte thermogenesis and energy expenditure in male mice.

Beige fat activation involves a fuel switch to fatty acid oxidation following chronic cold adaptation. Mitochondrial acyl-CoA synthetase long-chain family member 1 (ACSL1) localizes in the mitochondria and plays a key role in fatty acid oxidation; however, the regulatory mechanism of the subcellular localization remains poorly understood. Here, we identify an endosomal trafficking component sortilin (encoded by Sort1) in adipose tissues that shows dynamic expression during beige fat activation and facilitates the translocation of ACSL1 from the mitochondria to the endolysosomal pathway for degradation. Depletion of sortilin in adipocytes results in an increase of mitochondrial ACSL1 and the activation of AMPK/PGC1α signaling, thereby activating beige fat and preventing high-fat diet (HFD)-induced obesity and insulin resistance. Collectively, our findings indicate that sortilin controls adipose tissue fatty acid oxidation by substrate fuel selection during beige fat activation and provides a potential targeted approach for the treatment of metabolic diseases.

Adsorptive Shield Derived Cathode Electrolyte Interphase Formation with Impregnation on LiNi0.8Mn0.1Co0.1O2 Cathode: A Mechanism-Guiding-Experiment Study.

Lithium difluoro(oxalate) borate (LiDFOB) contributes actively to cathode-electrolyte interface (CEI) formation, particularly safeguarding high-voltage cathode materials. However, LiNixCozMnyO2-based batteries benefit from the LiDFOB and its derived CEI only with appropriate electrolyte design while a comprehensive understanding of the underlying interfacial mechanisms remains limited, which makes the rational design challenging. By performing ab initio calculations, the CEI evolution on the LiNi0.8Co0.1Mn0.1O2 has been investigated. The findings demonstrate that LiDFOB readily adheres to the cathode via semidissociative configuration, which elevates the Li deintercalation voltage and remains stable in solvent. Electrochemical processes are responsible for the subsequent cleavage of B-F and B-O bonds, while the B-F bond cleavage leading to LiF formation is dominant in the presence of adequate Li+ with a substantial Li intercalation energy. Thus, impregnation is established as an effective method to regulate the conversion channel for efficient CEI formation, which not only safeguards the cathode's structure but also counters electrolyte decomposition. Consequently, in comparison to utilizing LiDFOB as an electrolyte additive, employing LiDFOB impregnation in the NCM811/Li cell yields significantly improved cycling stability for over 2000 h.

Irisin alleviates chronic constriction injury-induced hyperalgesia and affective disorders in mice through NF-κB and Nrf2 signaling pathways.

This research is to explore the impacts of irisin on hyperalgesia and behavioral deficits caused by chronic constriction injury (CCI) and the underlying mechanisms. The CCI mice model was used in this study. The experimental mice were assigned into sham, sham + irisin (3 µg/kg), CCI, CCI + irisin (0.1, 1, and 3 µg/kg), and CCI + irisin (3 µg/kg) + ML385 (30 mg/kg) groups. The results showed that after CCI injury, the mice exhibited hyperalgesia, depression, and anxiety. In addition, the levels of inflammatory cytokines NF-κB, IL-1ß, IL-6, TNF-α, and iNOS increased in the mice hippocampus, frontal cortex, and spinal cord. Moreover, oxidative stress relevant factor MDA increased, while GSH and SOD decreased in the mice hippocampus, frontal cortex, and spinal cord. However, irisin treatment ameliorated CCI-induced mechanical allodynia, thermal hyperalgesia, depressive, and anxiety behaviors, and reversed the abnormal expressions of inflammatory and oxidative stress relevant cytokines. Interestingly, these therapeutic effects of irisin were partly abolished by ML385, a specific Nrf2 antagonist. Taken together, irisin may be an effective therapeutic agent for CCI-induced neuralgia and the affective disorders, and the mechanisms may be associated with the anti-neuroinflammation mediated by NF-κB and the anti- oxidative stress function regulated by Nrf2.

Sodium-glucose cotransporter 2 inhibition through henagliflozin ameliorates cognitive impairment in patients with type 2 diabetes.

AIMS/INTRODUCTION: To assess whether the sodium-glucose cotransporter 2 inhibitor, henagliflozin, improves cognitive impairment in patients with type 2 diabetes. MATERIALS AND METHODS: We carried out a prospective study on 290 patients with type 2 diabetes and cognitive impairment. Montreal Cognitive Assessment scores and plasma phosphorylated tau181 levels were used to assess cognition. The association between henagliflozin use and changes in cognition was examined using multivariable logistic regression analysis. RESULTS: Montreal Cognitive Assessment scores at enrollment and after 6 months were 21 (interquartile range [IQR]19-23) versus 22 (IQR 20-25; P < 0.0001) in all patients, 21 (IQR 19-23) versus 24 (IQR 22-26; P < 0.0001) in the henagliflozin group and 21 (IQR 19-22) versus 21 (IQR 19-23; P > 0.05) in the non-sodium-glucose cotransporter 2 inhibitor group. Logistic regression analysis showed that henagliflozin treatment was associated with Montreal Cognitive Assessment score improvement independent of potential confounders (odds ratio [OR] 3.670, 95% confidence interval [CI] 2.224-6.056, P < 0.0001). Additionally, plasma phosphorylated tau181 levels significantly decreased at 6-month follow up in all patients (OR 11.5, 95% CI 9.9-13.7 vs OR 10.1, 95% CI 7.8-12.9, P < 0.0001) and in the henagliflozin group (OR 11.5, 95% CI 10.3-13.0 vs OR 9.2, 95% CI 7.1-10.7, P < 0.0001), but not in the non-sodium-glucose cotransporter 2 inhibitor group. Henagliflozin treatment was independently associated with decreased phosphorylated tau181 levels (OR 3.670, 95% CI 1.598-4.213, P < 0.0001). CONCLUSIONS: Henagliflozin treatment was independently associated with improvements in Montreal Cognitive Assessment scores and plasma phosphorylated tau181 levels, indicating significant beneficial effects on cognitive impairment in patients with type 2 diabetes.

Gender Disparities in the Association Between Educational Attainment and Cardiovascular-Kidney-Metabolic Syndrome: Cross-Sectional Study.

Background: Cardiovascular-kidney-metabolic (CKM) health is affected by social determinants of health, especially education. CKM syndrome has not been evaluated in Chinese population, and the association of education with CKM syndrome in different sexes and its intertwined relation with lifestyles have not been explored. Objective: We aimed to explore the association between educational attainment and the prevalence of CKM syndrome stages in middle-aged and older Chinese men and women as well as the potential role of health behavior based on Life's Essential 8 construct. Methods: This study used data from the nationwide, community-based REACTION (Risk Evaluation of Cancers in Chinese diabetic individuals: a longitudinal study). A total of 132,085 participants with complete information to determine CKM syndrome stage and education level were included. Educational attainment was assessed by the self-reported highest educational level achieved by the participants and recategorized as low (elementary school or no formal education) or high (middle school, high school, technical school/college, or above). CKM syndrome was ascertained and classified into 5 stages according to the American Heart Association presidential advisory released in 2023. Results: Among 132,085 participants (mean age 56.95, SD 9.19 years; n=86,675, 65.62% women) included, most had moderate-risk CKM syndrome (stages 1 and 2), and a lower proportion were at higher risk of CKM (stages 3 and 4). Along the CKM continuum, low education was associated with 34% increased odds of moderate-risk CKM syndrome for women (odds ratio 1.36, 95% CI 1.23-1.49) with a significant sex disparity, but was positively correlated with high-risk CKM for both sexes. The association between low education and high-risk CKM was more evident in women with poor health behavior but not in men, which was also interactive with and partly mediated by behavior. Conclusions: Low education was associated with adverse CKM health for both sexes but was especially detrimental to women. Such sex-specific educational disparity was closely correlated with health behavior but could not be completely attenuated by behavior modification. These findings highlight the disadvantage faced by women in CKM health ascribed to low education, underscoring the need for public health support to address this inequality.

Inhibition of ANGPTL8 protects against diabetes-associated cognitive dysfunction by reducing synaptic loss via the PirB signaling pathway.

BACKGROUND: Type 2 diabetes mellitus (T2D) is associated with an increased risk of cognitive dysfunction. Angiopoietin-like protein 8 (ANGPTL8) is an important regulator in T2D, but the role of ANGPTL8 in diabetes-associated cognitive dysfunction remains unknown. Here, we explored the role of ANGPTL8 in diabetes-associated cognitive dysfunction through its interaction with paired immunoglobulin-like receptor B (PirB) in the central nervous system. METHODS: The levels of ANGPTL8 in type 2 diabetic patients with cognitive dysfunction and control individuals were measured. Mouse models of diabetes-associated cognitive dysfunction were constructed to investigate the role of ANGPTL8 in cognitive function. The cognitive function of the mice was assessed by the Barnes Maze test and the novel object recognition test, and levels of ANGPTL8, synaptic and axonal markers, and pro-inflammatory cytokines were measured. Primary neurons and microglia were treated with recombinant ANGPTL8 protein (rA8), and subsequent changes were examined. In addition, the changes induced by ANGPTL8 were validated after blocking PirB and its downstream pathways. Finally, mice with central nervous system-specific knockout of Angptl8 and PirB-/- mice were generated, and relevant in vivo experiments were performed. RESULTS: Here, we demonstrated that in the diabetic brain, ANGPTL8 was secreted by neurons into the hippocampus, resulting in neuroinflammation and impairment of synaptic plasticity. Moreover, neuron-specific Angptl8 knockout prevented diabetes-associated cognitive dysfunction and neuroinflammation. Mechanistically, ANGPTL8 acted in parallel to neurons and microglia via its receptor PirB, manifesting as downregulation of synaptic and axonal markers in neurons and upregulation of proinflammatory cytokine expression in microglia. In vivo, PirB-/- mice exhibited resistance to ANGPTL8-induced neuroinflammation and synaptic damage. CONCLUSION: Taken together, our findings reveal the role of ANGPTL8 in the pathogenesis of diabetes-associated cognitive dysfunction and identify the ANGPTL8-PirB signaling pathway as a potential target for the management of this condition.

Epicardial adipose tissue volume highly correlates with left ventricular diastolic dysfunction in endogenous Cushing's syndrome.

BACKGROUND: Cushing's syndrome (CS) is associated with increased risk for heart failure, which often initially manifests as left ventricular diastolic dysfunction (LVDD). In this study, we aimed to explore the potential risk factors of LVDD in CS by incorporating body composition parameters. METHODS: A retrospective study was conducted on patients diagnosed with endogenous CS no less than 18 years old. The control group consisted of healthy individuals who were matched to CS patients in terms of gender, age, and BMI. LIFEx software (version 7.3) was applied to measure epicardial adipose tissue volume (EATV) on non-contrast chest CT, as well as abdominal adipose tissue and skeletal muscle mass at the first lumbar vertebral level. Echocardiography was used to evaluate left ventricular (LV) diastolic function. Body compositions and clinical data were examined in relation to early LVDD. RESULTS: A total of 86 CS patients and 86 healthy controls were enrolled. EATV was significantly higher in CS patients compared to control subjects (150.33 cm3 [125.67, 189.41] vs 90.55 cm3 [66.80, 119.84], p < 0.001). CS patients had noticeably increased visceral fat but decreased skeletal muscle in comparison to their healthy counterparts. Higher prevalence of LVDD was found in CS patients based on LV diastolic function evaluated by E/A ratio (p < 0.001). EATV was proved to be an independent risk factor for LVDD in CS patients (OR = 1.015, 95%CI 1.003-1.026, p = 0.011). If the cut-point of EATV was set as 139.252 cm3 in CS patients, the diagnostic sensitivity and specificity of LVDD were 84.00% and 55.60%, respectively. CONCLUSION: CS was associated with marked accumulation of EAT and visceral fat, reduced skeletal muscle mass, and increased prevalence of LVDD. EATV was an independent risk factor for LVDD, suggesting the potential role of EAT in the development of LVDD in CS.

This study explored the potential risk factors of LVDD in endogenous CS by incorporating body composition parameters. EATV was identified as an independent risk factor for LVDD. Targeted therapeutic interventions to reduce excessive cortisol-induced EAT accumulation may be promising to mitigate the risk of LVDD development in patients with CS.

Prevalence and Risk Factors of Chronic Kidney Disease in Patients With Type 2 Diabetes in China: Cross-Sectional Study.

BACKGROUND: Chronic kidney disease (CKD) is a significant long-term complication of diabetes and is a primary contributor to end-stage kidney disease. OBJECTIVE: This study aimed to report comprehensive nationwide data on the prevalence, screening, and awareness rates of CKD in Chinese patients with type 2 diabetes, along with associated risk factors. METHODS: Baseline data analysis of the ongoing prospective, observational IMPROVE study was conducted. The study cohort comprised patients who had been diagnosed with type 2 diabetes more than 12 months prior, received at least 1 hypoglycemic medication, and were aged ≥18 years. The participants completed questionnaires and underwent laboratory assessments, including blood and urine samples. The data encompassed patient demographics, medical history, concurrent medications, and comorbidities. Comprehensive evaluations involved physical examinations, urinary albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), glycated hemoglobin (HbA1c), fasting blood glucose, 2-hour postprandial blood glucose, fasting blood lipid profile, and urinalysis. Descriptive statistics were applied for data interpretation, and logistic regression analyses were used to identify the CKD-associated risk factors in patients with type 2 diabetes. RESULTS: A national study from December 2021 to September 2022 enlisted 9672 participants with type 2 diabetes from 45 hospitals that had endocrinology departments. The enrollees were from diverse regions in China, as follows: central (n=1221), east (n=3269), south (n=1474), north (n=2219), and west (n=1489). The prevalence, screening, and awareness rates of CKD among patients with type 2 diabetes were 31% (2997/9672), 27% (810/2997), and 54.8% (5295/9672), respectively. Multivariate binary regression analysis revealed that the CKD risk factors were screening, awareness, smoking, age, diabetes duration, concurrent antihypertensive and microcirculation medications, diabetic complications (foot, retinopathy, and neuropathy), hypertension, elevated low-density lipoprotein (LDL) cholesterol, and suboptimal glycemic control. Subgroup analysis highlighted an increased CKD prevalence among older individuals, those with prolonged diabetes durations, and residents of fourth-tier cities. Residents of urban areas that had robust educational and economic development exhibited relatively high awareness and screening rates. Notably, 24.2% (1717/7107) of patients with an eGFR ≥90 mL/min/1.73 m2 had proteinuria, whereas 3.4% (234/6909) who had a UACR <30 mg/g presented with an eGFR <60 mL/min/1.73 m2. Compared with patients who were cognizant of CKD, those who were unaware of CKD had increased rates of HbA1c ≥7%, total cholesterol >5.18 µmol/L, LDL cholesterol >3.37 µmol/L, BMI ≥30 kg/m2, and hypertension. CONCLUSIONS: In a Chinese population of adults with type 2 diabetes, the CKD prevalence was notable, at 31%, coupled with low screening and awareness rates. Multiple risk factors for CKD have been identified. TRIAL REGISTRATION: ClinicalTrials.gov NCT05047471; https://clinicaltrials.gov/study/NCT05047471.

Long-Term Stable Dispersion of Multiwalled Carbon Nanotubes by Peroxydisulfate upon Ultrasonication Activation.

Poor dispersibility of carbon nanotubes greatly hinders their practical applications. Herein, a long-term stable dispersion of multiwalled carbon nanotubes (MWCNTs) in peroxydisulfate (PDS) is achieved. MWCNTs at 40 mg L-1 are completely dispersed by PDS upon ultrasonication (US/PDS) within 64 min and a stable dispersion is maintained at least 20 days. Mechanistically, US created defects on the nanomaterial and PDS-origin free radicals attacked these defects to introduce O-containing moieties (─OH and ─COOH). Interestingly, dispersion efficiency of MWCNTs by US/PDS initially at pH 7 and 3.8 is comparable, but lower than that initially at pH 12. Both •OH and SO4 •- are produced under alkaline condition, while SO4 •- is the dominant free radicals initially at pH 7 and 3.8 during the whole dispersion period. Stronger dispersion of MWCNTs initially at pH 12 resulted from greater amounts of O-containing moieties mainly in ─OH (46.32%) rather than ─COOH (24.19%) form. This differential more strongly promotes MWCNTs-water interaction via hydrogen bonding, thereby enhancing the dispersion. Notably, no significant mass loss of MWCNTs occurred during dispersion. Overall, the developed method achieves long-term stable dispersion of MWCNTs in a manner that can significantly extend their applications.

Estimating the short-term effect of PM2.5 on the mortality of cardiovascular diseases based on instrumental variables.

BACKGROUND: PM2.5 can induce and aggravate the occurrence and development of cardiovascular diseases (CVDs). The objective of our study is to estimate the causal effect of PM2.5 on mortality rates associated with CVDs using the instrumental variables (IVs) method. METHODS: We extracted daily meteorological, PM2.5 and CVDs death data from 2016 to 2020 in Binzhou. Subsequently, we employed the general additive model (GAM), two-stage predictor substitution (2SPS), and control function (CFN) to analyze the association between PM2.5 and daily CVDs mortality. RESULTS: The 2SPS estimated the association between PM2.5 and daily CVDs mortality as 1.14% (95% CI: 1.04%, 1.14%) for every 10 µg/m3 increase in PM2.5. Meanwhile, the CFN estimated this association to be 1.05% (95% CI: 1.02%, 1.10%). The GAM estimated it as 0.85% (95% CI: 0.77%, 1.05%). PM2.5 also exhibited a statistically significant effect on the mortality rate of patients with ischaemic heart disease, myocardial infarction, or cerebrovascular accidents (P < 0.05). However, no significant association was observed between PM2.5 and hypertension. CONCLUSION: PM2.5 was significantly associated with daily CVDs deaths (excluding hypertension). The estimates from the IVs method were slightly higher than those from the GAM. Previous studies based on GAM may have underestimated the impact of PM2.5 on CVDs.

Association of social determinants, lifestyle, and metabolic factors with mortality in Chinese adults: A nationwide 10-year prospective cohort study.

Nationwide estimates of the impact of common modifiable risk factors on mortality remain crucial. We aim to assess the influence of social determinants, lifestyle, and metabolic factors on mortality in 174,004 adults aged ≥40 years from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. We reveal that 17 modifiable factors are independently associated with mortality, accounting for 64.8% of all-cause mortality, 77.4% of cardiovascular mortality, and 44.8% of cancer mortality. Low education emerges as the leading factor for both all-cause and cancer mortality, while hypertension is predominant for cardiovascular mortality. Moreover, low gross domestic product per capita and high ambient particulate matter with a diameter of <2.5 µm (PM2.5) air pollution account for 7.8% and 4.3% for all-cause mortality, respectively, using a different method. Gender-specific analyses reveal distinct patterns, with women's mortality primarily associated with social determinants and men exhibiting stronger associations with lifestyle factors. Targeted health interventions are essential to mitigate mortality risks effectively in China.

Modular Fabrication of Microfluidic Graphene FET for Nucleic Acids Biosensing.

Graphene field-effect transistors (GFETs) are widely used in biosensing due to their excellent properties in biomolecular signal amplification, exhibiting great potential for high-sensitivity and point-of-care testing in clinical diagnosis. However, difficulties in complicated fabrication steps are the main limitations for the further studies and applications of GFETs. In this study, a modular fabrication technique is introduced to construct microfluidic GFET biosensors within 3 independent steps. The low-melting metal electrodes and intricate flow channels are incorporated to maintain the structural integrity of graphene and facilitate subsequent sensing operations. The as-fabricated GFET biosensor demonstrates excellent long-term stability, and performs effectively in various ion environments. It also exhibits high sensitivity and selectivity for detecting single-stranded nucleic acids at a 10 fm concentration. Furthermore, when combined with the CRISPR/Cas12a system, it facilitates amplification-free and rapid detection of nucleic acids at a concentration of 1 fm. Thus, it is believed that this modular-fabricated microfluidic GFET may shed light on further development of FET-based biosensors in various applications.

Effect of Bioactive Black Phosphorus Nanomaterials on Cancer-Associated Fibroblast Heterogeneity in Pancreatic Cancer.

Tumor-stromal interactions and stromal heterogeneity in the tumor microenvironment are critical factors that influence the progression, metastasis, and chemoresistance of pancreatic ductal adenocarcinoma (PDAC). Here, we used spatial transcriptome technology to profile the gene expression landscape of primary PDAC and liver metastatic PDAC after bioactive black phosphorus nanomaterial (bioactive BP) treatment using a murine model of PDAC (LSL-KrasG12D/+; LSL-Trp53R172H/+; and Pdx-1-Cre mice). Bioinformatic and biochemical analyses showed that bioactive BP contributes to the tumor-stromal interplay by suppressing cancer-associated fibroblast (CAF) activation. Our results showed that bioactive BP contributes to CAF heterogeneity by decreasing the amount of inflammatory CAFs and myofibroblastic CAFs, two CAF subpopulations. Our study demonstrates the influence of bioactive BP on tumor-stromal interactions and CAF heterogeneity and suggests bioactive BP as a potential PDAC treatment.

Serum Medium-Chain Fatty Acids and the Risk of Incident Diabetes: Findings from the 4C Study.

CONTEXT: Emerging studies have revealed associations between dietary medium-chain fatty acids (MCFAs) and glucose homeostasis. However, the relationship between serum MCFAs and the incidence of diabetes, and potential interactions with genetic predisposition, remains unclear in prospective cohort studies. OBJECTIVE: To investigate associations and genetic susceptibility between serum MCFAs and diabetes risk. METHODS: We investigated baseline serum MCFAs (n=5) in a nested case-control study comprising incident diabetes cases (n=1,707) and matched normoglycemic control subjects (n=1,707) from the China Cardiometabolic Disease and Cancer Cohort Study. Associations between MCFAs and type 2 diabetes mellitus (T2DM) were examined, both overall and stratified by diabetes genetic susceptibility. Genetic risk scores (GRS) were calculated based on 86 T2DM-associated genetic variants. RESULTS: In the fully adjusted conditional logistic regression model, serum octanoic acid and nonanoic acid exhibited inverse dose-response relationships with diabetes risk, showing odds ratios (95% confidence intervals) of 0.90 (0.82-0.98) and 0.84 (0.74-0.95), respectively. Subgroup analysis demonstrated that inverse associations between MCFAs and incident diabetes were more pronounced among individuals with physical inactivity (Pinteraction = 0.042, 0.034, and 0.037, for octanoic, nonanoic and decanoic acid, respectively). Moreover, inverse associations of octanoic acid with diabetes risk were notably enhanced among individuals with high genetic risk compared to those with low genetic risk. Significant interactions were observed between octanoic acid and GRS on T2DM risk (Pinteraction = 0.003). CONCLUSIONS: These findings provide evidence supporting inverse associations between serum MCFAs and T2DM risk, and reveal potential interplay between genetic susceptibility and circulating octanoic acid in modulating diabetes risk.

A black phosphorus nanosheet-based RNA delivery system for prostate cancer therapy by increasing the expression level of tumor suppressor gene PTEN via CeRNA mechanism.

BACKGROUND: Prostate cancer (PCa) has a high incidence in men worldwide, and almost all PCa patients progress to the androgen-independent stage which lacks effective treatment measures. PTENP1, a long non-coding RNA, has been shown to suppress tumor growth through the rescuing of PTEN expression via a competitive endogenous RNA (ceRNA) mechanism. However, PTENP1 was limited to be applied in the treatment of PCa for the reason of rapid enzymatic degradation, poor intracellular uptake, and excessively long base sequence to be synthesized. Considering the unique advantages of artificial nanomaterials in drug loading and transport, black phosphorus (BP) nanosheet was employed as a gene-drug carrier in this study. RESULTS: The sequence of PTENP1 was adopted as a template which was randomly divided into four segments with a length of about 1000 nucleotide bases to synthesize four different RNA fragments as gene drugs, and loaded onto polyethyleneimine (PEI)-modified BP nanosheets to construct BP-PEI@RNA delivery platforms. The RNAs could be effectively delivered into PC3 cells by BP-PEI nanosheets and elevating PTEN expression by competitive binding microRNAs (miRNAs) which target PTEN mRNA, ultimately exerting anti-tumor effects. CONCLUSIONS: Therefore, this study demonstrated that BP-PEI@RNAs is a promising gene therapeutic platform for PCa treatment.