Research on evaluation indicators of healthspan for veterans: A single-center exploratory study.

Objective: To explore a definition of healthspan that based on actual situation of veterans is of significance for improving their health status and life quality. Methods: This was a retrospective study. Based on the medical data of veterans from the Chinese PLA General Hospital. Total of 1,421 subjects were enrolled to this study, among which 441 deceased cases were further analyzed. The indicators of healthspan of the subjects was calculated from four dimensions (the status of chronic diseases, physical function, social function and psychological function). The risk factors for death were analyzed in a population cohort from 2008 to 2021 (including 763 subjects, among which 372 were deceased). Results: The average lifespan and adjusted healthspan of the subjects were 93.3 years and 75.1 years, respectively. The four dimensions of healthspan were: adjusted healthspan without chronic diseases was 76.3 years, social function-related healthspan was 88.8 years, physical function-related healthspan was 91.5 years, and psychological function-related healthspan was 92.7 years. By analyzing the cohort in 2008, it was inferred that the main risk factors for the death of veterans were poor nutritional status, renal function injury, high blood pressure, high blood sugar, and aging. Conclusions: This study proposed four dimensions related to "healthspan" for Chinese veterans (adjusted healthspan without chronic diseases, physical function-related healthspan, social function-related healthspan, and psychological function-related healthspan). Besides, poor nutritional status, renal function injury, and high blood pressure were the most important risk factors affecting the death of veterans.

Sustainable Plastics with High Performance and Convenient Processibility.

Designing and making sustainable plastics is especially urgent to reduce their ecological and environmental impacts. However, it remains challenging to construct plastics with simultaneous high sustainability and outstanding comprehensive performance. Here, a composite strategy of in situ polymerizing a petroleum-based monomer with the presence of an industrialized bio-derived polymer in a quasi-solvent-free system is introduced, affording the plastic with excellent mechanical robustness, impressive thermal and solvent stability, as well as low energy, consumes during production, processing, and recycling. Particularly, the plastic can be easily processed into diverse shapes through 3D printing, injection molding, etc. during polymerization and further reprocessed into other complex structures via eco-friendly hydrosetting. In addition, the plastic is mechanically robust with Young's modulus of up to 3.7 GPa and tensile breaking strength of up to 150.2 MPa, superior to many commercially available plastics and other sustainable plastics. It is revealed that hierarchical hydrogen bonds in plastic predominate the well-balanced sustainability and performance. This work provides a new path for fabricating high-performance sustainable plastic toward practical applications, contributing to the circular economy.

[Analysis of Delphain lymph node detection rate, metastasis rate and risk factors for metastasis in papillary thyroid adenocarcinoma patients].

Objective:To investigate the detection rate and metastasis rate of delphain lymph node （DLN）in thyroid papillary adenocarcinoma（PTC） and to analyze the risk factors for DLN metastasis. Methods:The clinicopathological data of 200 PTC patients admitted to the from January 2018 to June 2020 were retrospectively analyzed, and the detection of DLN was clearly recorded in the pathological reports of all patients. The number of DLN detected, the number of metastasis, the detection rate and the metastasis rate were counted. The clinicopathological factors that might affect DLN metastasis were analyzed by univariate analysis and multivariate Logistic regression analysis, including gender, age, tumor size and tumor location. Results:DLN was detected in 121 of 200 PTC patients, with a detection rate of 60.50% （121/200）. DLN metastasis was found in 46 of the 121 patients with a metastasis rate of 38.02% （46/121）.Univariate analysis showed that tumor diameter, multiple foci, capsular invasion, extradandular invasion, lymphatic vascular invasion, lymph node metastasis in central region （excluding DLN）, and lateral cervical lymph node metastasis were the risk factors for DLN metastasis of PTC （P<0.05）. Gender, age, tumor location, bilateral tumors, Hashimoto's thyroiditis and BRAFV600E mutation were not significantly correlated with DLN metastasis of PTC（P>0.05）. The 7 variables with statistically significant differences in univariate analysis were incorporated into Logistic regression model for multivariate analysis, and the results showed that, Tumor diameter ≥1.0 cm, capsule invasion, lymphatic vascular invasion, lymph node metastasis in central region （excluding DLN）, and lateral cervical lymph node metastasis were independent risk factors for DLN metastasis of PTC （OR= 3.386-9.186, P<0.05）. The sensitivity and specificity of DLN metastasis in predicting central lymph node （excluding DLN） metastasis in PTC patients were 36.79% and 92.55%, respectively, while the sensitivity and specificity of DLN metastasis in predicting lateral cervical lymph node metastasis were 41.03% and 81.37%, respectively.The incidence of central lymph node metastasis （excluding DLN） in DLN-positive patients were was 4.94 times higher than that in DLN-negative patients, and the incidence of lateral neck lymph node metastasis in DLN-positive patients were 2.20 times higher than that in DLN-negative patients. Conclusion:The detection rate and metastasis rate of DLN in PTC patients were higher, DLN metastasis predicts more extensive lymph node metastasis, and DLN metastasis was related to multiple factors,among which tumor diameter ≥ 1.0 cm, capsule invasion, lymphatic vascular infiltration, lymph node metastasis in the central region （excluding DLN）, and lateral cervical lymph node metastasis were independent risk factors for DLN metastasis of PTC. Therefore, PTC patients with the above characteristics should actively explore DLN and formulate appropriate surgical strategies.

Combinatorial Bionic Hierarchical Flexible Strain Sensor for Sign Language Recognition with Machine Learning.

Flexible strain sensors have been widely researched in fields such as smart wearables, human health monitoring, and biomedical applications. However, achieving a wide sensing range and high sensitivity of flexible strain sensors simultaneously remains a challenge, limiting their further applications. To address these issues, a cross-scale combinatorial bionic hierarchical design featuring microscale morphology combined with a macroscale base to balance the sensing range and sensitivity is presented. Inspired by the combination of serpentine and butterfly wing structures, this study employs three-dimensional printing, prestretching, and mold transfer processes to construct a combinatorial bionic hierarchical flexible strain sensor (CBH-sensor) with serpentine-shaped inverted-V-groove/wrinkling-cracking structures. The CBH-sensor has a high wide sensing range of 150% and high sensitivity with a gauge factor of up to 2416.67. In addition, it demonstrates the application of the CBH-sensor array in sign language gesture recognition, successfully identifying nine different sign language gestures with an impressive accuracy of 100% with the assistance of machine learning. The CBH-sensor exhibits considerable promise for use in enabling unobstructed communication between individuals who use sign language and those who do not. Furthermore, it has wide-ranging possibilities for use in the field of gesture-driven interactions in human-computer interfaces.

Intermittent hypoxic pretreatment exacerbates house dust mite-induced asthma airway inflammation.

BACKGROUND: Asthma is widely recognized as an inflammatory disorder. In the context of this inflammatory microenvironment, the involvement of hypoxia and its impact on related pathways have drawn considerable attention. However, the exact role of hypoxia, a prevalent environmental factor, in the development and progression of asthma remains poorly understood. METHODS: Mice were treated with house dust mite (HDM) extracts for 23 days to induce asthma. Mice were divided into room air (RA) group and intermittent hypoxic (IH) group by exposing to different conditions and IH preconditioning (IHP) were underwent to the above groups before the hypoxic regimen. Airway inflammation in mice was evaluated by airway hyperresponsiveness, excessive mucus secretion, and recruitment of inflammatory cells. Immunohistochemistry was employed to quantify the expression levels of NF-κB. Subsequently, the dose of allergen was modified to investigate whether the impact of hypoxia on asthma is affected by different doses of allergens. RESULT: Compared to the RA and IH groups, HDM-treated mice in the IHP group exhibited aggravated inflammatory cell infiltration and airway hyperresponsiveness (p＜.05). Moreover, there was an increased release of inflammatory mediators and higher expression levels of NF-κB (p＜.05). Importantly, the impact ia on asthma was found to be influenced by high dose of allergen (p＜.05). CONCLUSION: IHP treatment potentially exacerbates HDM-induced airway inflammation in asthma, with the involvement of NF-κB, particularly under high-dose allergen stimulation.

Hypoxia-inducible PRMT2 addiction in glioblastomas.

Hypoxia-inducible transcription factors (HIFs) are key transcription factors for cellular response to low oxygen levels. However, the specific mediators responsible for activating downstream transcription are not well characterized. We previously identified Protein Arginine methyltransferase 2 (PRMT2), a highly expressed methyltransferase in glioblastoma multiforme, as a transcription co-activator. And we established a connection between PRMT2-mediated histone H3R8 asymmetric methylation (H3R8me2a) and transcription activation. Here we find that PRMT2 is activated by HIF1α under hypoxic conditions. And we demonstrate that PRMT2 and its H3R8me2a activity are required for the transcription activation of a significant subset of hypoxia-induced genes. Consequently, the inactivation of PRMT2 suppresses hypoxia-induced glioblastoma cell migration, attenuates tumor progression, and enhances chemotherapeutic sensitivity in mouse xenograft models. In addition, our analysis of clinical glioma specimens reveals a correlation between PRMT2 protein levels, HIF1α abundance, and an unfavorable prognosis. Our study establishes HIF1α-induced PRMT2 as a critical modulator in the activation of hypoxia-related transcriptional programs, ultimately driving malignant progression.

Female Protection Against Diabetic Kidney Disease Is Regulated by Kidney-Specific AMPK Activity.

Reduced kidney AMPK activity is associated with nutrient stress-induced chronic kidney disease (CKD) in male mice. In contrast, female mice resist nutrient stress-induced CKD. The role of kidney AMPK in sex-related organ protection against nutrient stress and metabolite changes was evaluated in diabetic kidney tubule-specific AMPKγ2KO (KTAMPKγ2ΚΟ) male and female mice. In wild-type (WT) males, diabetes increased albuminuria, urinary kidney injury molecule-1, hypertension, kidney p70S6K phosphorylation, and kidney matrix accumulation; these features were not exacerbated with KTAMPKγ2ΚΟ. Whereas WT females had protection against diabetes-induced kidney injury, KTAMPKγ2ΚΟ led to loss of female protection against kidney disease. The hormone 17ß-estradiol ameliorated high glucose-induced AMPK inactivation, p70S6K phosphorylation, and matrix protein accumulation in kidney tubule cells. The mechanism for female protection against diabetes-induced kidney injury is likely via an estrogen-AMPK pathway, as inhibition of AMPK led to loss of estrogen protection to glucose-induced mTORC1 activation and matrix production. RNA sequencing and metabolomic analysis identified a decrease in the degradation pathway of phenylalanine and tyrosine resulting in increased urinary phenylalanine and tyrosine levels in females. The metabolite levels correlated with loss of female protection. The findings provide new insights to explain evolutionary advantages to females during states of nutrient challenges.

Association between insulin resistance and vascular damage in an adult population in China: a cross-sectional study.

There is a relative scarcity of large-scale population studies investigating the relationship between the insulin resistance index of homeostasis model assessment (HOMA-IR) and vascular damage. Therefore, we assessed the association between HOMA-IR and vascular damage in adults aged 18 years and older in China. A total of 17,985 research subjects were included. Vascular damage markers and relevant laboratory tests were measured. HOMA-IR was calculated as (fasting insulin * fasting blood glucose)/22.5. Vascular damage included arteriosclerosis (ba-PWV > 1800 cm/s), peripheral artery disease (ABI < 0.9), and microalbuminuria (UACR > 30 mg/g). The relationship between HOMA-IR and vascular damage was analyzed using the RCS. The restricted cubic spline (RCS) analysis suggested that HOMA-IR was nonlinearly associated with arteriosclerosis (P for no-liner < 0.01), peripheral artery disease (P for no-liner < 0.01), and microalbuminuria (P for no-liner < 0.01). Further segmented regression analyses revealed that in study subjects with HOMA-IR < 5, we found that HOMA-IR was associated with an increased OR for arteriosclerosis (OR: 1.36, 95% CI (1.28, 1.45), P < 0.01), peripheral artery disease (OR: 1.33, 95% CI (1.10, 1.60), P < 0.01) and microalbuminuria (OR: 1.59, 95% CI (1.49, 1.70), P < 0.01). HOMA-IR is an independent risk factor for vascular damage, both macrovascular and microvascular. The phenomenon of saturation of HOMA-IR with vascular damage needs further investigation.

Ketogenic diet induces p53-dependent cellular senescence in multiple organs.

A ketogenic diet (KD) is a high-fat, low-carbohydrate diet that leads to the generation of ketones. While KDs improve certain health conditions and are popular for weight loss, detrimental effects have also been reported. Here, we show mice on two different KDs and, at different ages, induce cellular senescence in multiple organs, including the heart and kidney. This effect is mediated through adenosine monophosphate-activated protein kinase (AMPK) and inactivation of mouse double minute 2 (MDM2) by caspase-2, leading to p53 accumulation and p21 induction. This was established using p53 and caspase-2 knockout mice and inhibitors to AMPK, p21, and caspase-2. In addition, senescence-associated secretory phenotype biomarkers were elevated in serum from mice on a KD and in plasma samples from patients on a KD clinical trial. Cellular senescence was eliminated by a senolytic and prevented by an intermittent KD. These results have important clinical implications, suggesting that the effects of a KD are contextual and likely require individual optimization.

Mitochondrial ACSS1-K635 acetylation knock-in mice exhibit altered metabolism, cell senescence, and nonalcoholic fatty liver disease.

Acetyl-CoA synthetase short-chain family member 1 (ACSS1) uses acetate to generate mitochondrial acetyl-CoA and is regulated by deacetylation by sirtuin 3. We generated an ACSS1-acetylation (Ac) mimic mouse, where lysine-635 was mutated to glutamine (K635Q). Male Acss1K635Q/K635Q mice were smaller with higher metabolic rate and blood acetate and decreased liver/serum ATP and lactate levels. After a 48-hour fast, Acss1K635Q/K635Q mice presented hypothermia and liver aberrations, including enlargement, discoloration, lipid droplet accumulation, and microsteatosis, consistent with nonalcoholic fatty liver disease (NAFLD). RNA sequencing analysis suggested dysregulation of fatty acid metabolism, cellular senescence, and hepatic steatosis networks, consistent with NAFLD. Fasted Acss1K635Q/K635Q mouse livers showed increased fatty acid synthase (FASN) and stearoyl-CoA desaturase 1 (SCD1), both associated with NAFLD, and increased carbohydrate response element-binding protein binding to Fasn and Scd1 enhancer regions. Last, liver lipidomics showed elevated ceramide, lysophosphatidylethanolamine, and lysophosphatidylcholine, all associated with NAFLD. Thus, we propose that ACSS1-K635-Ac dysregulation leads to aberrant lipid metabolism, cellular senescence, and NAFLD.