Tumour vasculature at single-cell resolution.

Tumours can obtain nutrients and oxygen required to progress and metastasize through the blood supply1. Inducing angiogenesis involves the sprouting of established vessel beds and their maturation into an organized network2,3. Here we generate a comprehensive atlas of tumour vasculature at single-cell resolution, encompassing approximately 200,000 cells from 372 donors representing 31 cancer types. Trajectory inference suggested that tumour angiogenesis was initiated from venous endothelial cells and extended towards arterial endothelial cells. As neovascularization elongates (through angiogenic stages SI, SII and SIII), APLN+ tip cells at the SI stage (APLN+ TipSI) advanced to TipSIII cells with increased Notch signalling. Meanwhile, stalk cells, following tip cells, transitioned from high chemokine expression to elevated TEK (also known as Tie2) expression. Moreover, APLN+ TipSI cells not only were associated with disease progression and poor prognosis but also hold promise for predicting response to anti-VEGF therapy. Lymphatic endothelial cells demonstrated two distinct differentiation lineages: one responsible for lymphangiogenesis and the other involved in antigen presentation. In pericytes, endoplasmic reticulum stress was associated with the proangiogenic BASP1+ matrix-producing pericytes. Furthermore, intercellular communication analysis showed that neovascular endothelial cells could shape an immunosuppressive microenvironment conducive to angiogenesis. This study depicts the complexity of tumour vasculature and has potential clinical significance for anti-angiogenic therapy.

MYCN drives oncogenesis by cooperating with the histone methyltransferase G9a and the WDR5 adaptor to orchestrate global gene transcription.

MYCN activates canonical MYC targets involved in ribosome biogenesis, protein synthesis, and represses neuronal differentiation genes to drive oncogenesis in neuroblastoma (NB). How MYCN orchestrates global gene expression remains incompletely understood. Our study finds that MYCN binds promoters to up-regulate canonical MYC targets but binds to both enhancers and promoters to repress differentiation genes. MYCN binding also increases H3K4me3 and H3K27ac on canonical MYC target promoters and decreases H3K27ac on neuronal differentiation gene enhancers and promoters. WDR5 facilitates MYCN promoter binding to activate canonical MYC target genes, whereas MYCN recruits G9a to enhancers to repress neuronal differentiation genes. Targeting both MYCN's active and repressive transcriptional activities using both WDR5 and G9a inhibitors synergistically suppresses NB growth. We demonstrate that MYCN cooperates with WDR5 and G9a to orchestrate global gene transcription. The targeting of both these cofactors is a novel therapeutic strategy to indirectly target the oncogenic activity of MYCN.

Heteroatom-Doped Ag25 Nanoclusters Encapsulated in Metal-Organic Frameworks for Photocatalytic Hydrogen Production.

Atomically precise metal nanoclusters (NCs) with unique optical properties and abundant catalytic sites are promising in photocatalysis. However, their light-induced instability and the difficulty of utilizing the photogenerated carriers for photocatalysis pose significant challenges. Here, MAg24 (M=Ag, Pd, Pt, and Au) NCs doped with diverse single heteroatoms have been encapsulated in a metal-organic framework (MOF), UiO-66-NH2, affording MAg24@UiO-66-NH2. Strikingly, compared with Ag25@UiO-66-NH2, the MAg24@UiO-66-NH2 doped with heteroatom exhibits much enhanced activity in photocatalytic hydrogen production, among which AuAg24@UiO-66-NH2 presents the best activity up to 3.6 mmol g-1 h-1, far superior to all other counterparts. Moreover, they display excellent photocatalytic recyclability and stability. X-ray photoelectron spectroscopy and ultrafast transient absorption spectroscopy demonstrate that MAg24 NCs encapsulated into the MOF create a favorable charge transfer pathway, similar to a Z-scheme heterojunction, when exposed to visible light. This promotes charge separation, along with optimized Ag electronic state, which are responsible for the superior activity in photocatalytic hydrogen production.

Conductive Covalent Organic Frameworks of Polymetallophthalocyanines as a Tunable Platform for Electrocatalysis.

Developing an electrocatalyst platform that can control the interplay among activity, selectivity, and stability at atomic precision remains a grand challenge. Here, we have synthesized highly crystalline polymetallophthalocyanines (pMPcs, M = Fe, Co, Ni, and Cu) through the annulation of tetracyanobenzene in the presence of transition metals. The conjugated, conductive, and stable backbones with precisely installed metal sites render pMPcs a unique platform in electrochemical catalysis, where tunability emerges from long-range interactions. The construction of pCoNiPc with a Co and Ni dual-site integrates the advantageous features of pCoPc and pNiPc in electrocatalytic CO2 reduction through electronic communication of the dual-site with an unprecedented long atomic separation of ≥14 chemical bonds. This integration provides excellent activity (current density, j = -16.0 and -100 mA cm-2 in H-type and flow cell, respectively), selectivity (CO Faraday efficiency, FECO = 94%), and stability (>10 h), making it one of the best-performing reticular materials.

Association between a Calcium-to-Magnesium Ratio and Osteoporosis among Puerto Rican Adults.

BACKGROUND: The ratio of calcium-to-magnesium intake (Ca:Mg) may be important for bone due to their competitive absorption. The Ca:Mg ratio has been related to health outcomes, but few studies have related it to bone. OBJECTIVES: The purpose of this analysis was to examine associations between the Ca:Mg intake with bone mineral density (BMD) and osteoporosis among Puerto Rican adults. METHODS: Adults, aged 47-79 y, from the Boston Puerto Rican Osteoporosis Study, with complete BMD and dietary data (n = 955) were included. BMD was assessed with dual-energy X-ray absorptiometry and diet by a food frequency questionnaire. Calcium and magnesium intakes from food were energy adjusted, and the Ca:Mg was calculated. Adjusted linear and logistic regression models were utilized for testing associations between Ca:Mg and bone outcomes. RESULTS: Calcium intake was greater in the highest compared with lowest tertile, whereas magnesium intake was similar across tertiles. Mean BMD at hip sites was higher in the middle, compared with the lowest, tertile. Higher odds of osteoporosis were observed for the highest and lowest tertiles, compared with the middle tertile, after adjustment (T3 compared with T2 OR: 2.79; 95% CI: 1.47, 5.3; T1 compared with T2 OR: 2.01; 95% CI: 1.03, 3.92). Repeated analyses without supplement users (n = 432) led to stronger differences and ORs, but lost significance for some comparisons. CONCLUSIONS: Dietary calcium and magnesium are important for bone, perhaps not independently. The Ca:Mg intake ratio appeared most protective within a range of 2.2-3.2, suggesting that a balance of these nutrients may be considered in recommendations for osteoporosis..

PI3K/AKT/SERBP-1 pathway regulates Alisma orientalis beverage treatment of atherosclerosis in APOE-/- high-fat diet mice.

CONTEXT: Previously, we found Alisma orientalis beverage (AOB), a classic traditional Chinese medicine (TCM) formulation, had the potential effect of treating atherosclerosis (AS). The underlying mechanism was still unclear. OBJECTIVE: As an extention of our previous work, to investigate the underlying mechanism of action of AOB in the treatment for AS. MATERIALS AND METHODS: Network pharmacology was conducted using SwissTargetPrediction, GeneCards, DrugBank, Metascape, etc., to construct component-target-pathway networks. In vivo, AS models were induced by a high-fat diet (HFD) for 8 consecutive weeks in APOE-/- mice. After the administration of AOB (3.8 g/kg, i.g.) for 8 weeks, we assessed the aortic plaque, four indicators of blood lipids, and expression of the PI3K/AKT/SREBP-1 pathway in liver. RESULTS: Network pharmacology showed that PI3K/AKT/SREBP-1 played a role in AOB's treatment for AS (PI3K: degree = 18; AKT: degree = 17). Moreover, we found that the arterial plaque area and four indicators of blood lipids were all significantly reversed by AOB treatment in APOE-/- mice fed with HFD (plaque area reduced by about 37.75%). In addition, phosphorylated expression of PI3K/AKT and expression of SREBP-1 were obviously increased in APOE-/- mice fed with HFD, which were all improved by AOB (PI3K: 51.6%; AKT: 23.6%; SREBP-1: 40.0%). CONCLUSIONS: AOB had therapeutic effects for AS by improving blood lipids and inhibition of the PI3K/AKT/SERBP-1 pathway in the liver. This study provides new ideas for the treatment of AS, as well as new evidence for the clinical application of AOB.

Enaminone-Linked Covalent Organic Frameworks for Boosting Photocatalytic Hydrogen Production.

Covalent organic frameworks (COFs), possessing pre-designable structures and tailorable functionalities, are promising candidates for photocatalysis. Nevertheless, the most studied imine-linked COFs (Im-COFs) usually suffer from unsatisfactory stability and photocatalytic performance. To meet this challenge, a series of highly stable enaminone-linked COFs (En-COFs) have been synthesized and afford much improved visible-light-driven hydrogen production activities, ranging from 44 to 1078 times that of isoreticular Im-COFs, with the only difference being the linkages (enaminone vs. imine) in their structures. The enhanced light-harvesting ability, facilitated exciton dissociation and improved chemical stability account for the superior activity. Furthermore, quinoline-linked COFs (Qu-COFs) have been further obtained via the post-modification of Im-COFs. Compared with Im-COFs, the photocatalytic activities of Qu-COFs are significantly improved after modification, but still below those of the corresponding En-COFs (3-107 times). The facile synthesis, excellent activity, and high chemical stability demonstrate that En-COFs are a promising platform for photocatalysis.

Radiosynthesis of a novel antisense imaging probe targeting LncRNA HOTAIR in malignant glioma.

BACKGROUND: Long non-coding RNA (LncRNA) HOTAIR was amplified and overexpressed in many human carcinomas, which could serve as a useful target for cancer early detection and treatment. The 99mTc radiolabeled antisense oligonucleotides (ASON) could visualize the expression of HOTAIR and provide a diagnostic value for malignant tumors. The aim of this study was to evaluate whether liposome-coated antisense oligonucleotide probe 99mTc-HYNIC-ASON targeting HOTAIR can be used in in vivo imaging of HOTAIR in malignant glioma xenografts. METHODS: The ASON targeting LncRNA HOTAIR as well as mismatched ASON (ASONM) were designed and modified. The radiolabeling of 99mTc with two probes were via the conjugation of bifunctional chelator HYNIC. Then probes were purified by Sephadex G25 and tested for their radiolabeling efficiency and purity, as well as stability by ITLC (Instant thin-layer chromatography) and gel electrophoresis. Then the radiolabeled probes were transfected with lipofectamine 2000 for cellular uptake test and the next experimental use. Furthermore, biodistribution study and SPECT imaging were performed at different times after liposome-coated 99mTc-HYNIC-ASON/ASONM were intravenously injected in glioma tumor-bearing mice models. All data were analyzed by statistical software. RESULTS: The labeling efficiencies of 99mTc-HYNIC-ASON and 99mTc-HYNIC-ASONM measured by ITLC were (91 ± 1.5) % and (90 ± 0.6) %, respectively, and both radiochemical purities were more than 89%. Two probes showed good stability within 12 h. Gel electrophoresis confirmed that the oligomers were successfully radiolabeled no significant degradation were found. Biodistribution study demonstrated that liposome-coated antisense probes were excreted mainly through the kidney and bladder and has higher uptake in the tumor. Meanwhile, the tumor was clearly shown after injection of liposome coated 99mTc-HYNIC-ASON, and its T/M ratio was higher than that in the non-transfection group and mismatched group. No tumor was seen in mismatched and blocking group. CONCLUSION: The liposome encapsulated 99mTc-HYNIC-ASON probe can be used in the in vivo, real-time imaging of LncRNA HOTAIR expression in malignant glioma.

Dual-channel detection of viscosity and pH with a near-infrared fluorescent probe for cancer visualization.

Compared to ordinary cells, tumor cells have a unique microenvironment, characterized by high viscosity, low pH, high reactive oxygen species level and the overexpression of certain proteases. Therefore, viscosity and pH can be used as important parameters for visualizing cancer. We designed a spiro-oxazolidine compound (In-1) for the dual-channel detection of viscosity and pH, with the red channel for detecting viscosity and the blue channel for pH. Interestingly, In-1 can locate different organelles under different conditions. Under physiological conditions, In-1 efficiently targeted lysosomes and showed that the viscosity of lysosomes increases in cancer cells while the pH decreases, which can be used to distinguish and detect cancer cells and normal cells. When we treated HL-7702 cells with CCCP, the probe could effectively target the mitochondria, and the fluorescence intensity in the pH channel decreased. This indicates that In-1 can be used as a powerful tool to simultaneously monitor viscosity and pH in different organelles, and may have a guiding role in diseases caused by mitochondrial and lysosomal microenvironments.

Red meat consumption, incident CVD and the influence of dietary quality in the Jackson Heart Study.

OBJECTIVES: We investigated the prospective associations between meat consumption and CVD and whether these relationships differ by dietary quality among African American (AA) adults. DESIGN: Baseline diet was assessed with a regionally specific FFQ. Unprocessed red meat included beef and pork (120 g/serving); processed meat included sausage, luncheon meats and cured meat products (50 g/serving). Incident total CVD, CHD, stroke and heart failure were assessed annually over 9·8 years of follow-up. We characterised dietary quality using a modified Healthy Eating Index-2010 score (m-HEI), excluding meat contributions. SETTING: Jackson, MS, USA. PARTICIPANTS: AA adults (n 3242, aged 55 y, 66 % female). RESULTS: Mean total, unprocessed red and processed meat intakes were 5·7 ± 3·5, 2·3 ± 1·8 and 3·3 ± 2·7 servings/week, respectively. Mostly, null associations were observed between meat categories and CVD or subtypes. However, greater intake of unprocessed red meat (three servings/week) was associated with significantly elevated risk of stroke (hazard ratio = 1·43 (CI: 1·07,1·90)). With the exception of a more positive association between unprocessed meat consumption and stroke among individuals in m-HEI Tertile 2, the strength of associations between meat consumption categories and CVD outcomes did not differ by m-HEI tertile. In formal tests, m-HEI did not significantly modify meat-CVD associations. CONCLUSIONS: In this cohort of AA adults, total and processed meat were not associated with CVD outcomes, with the exception that unprocessed red meat was related to greater stroke risk. Dietary quality did not modfiy these associations. Research is needed in similar cohorts with longer follow-up and greater meat consumption to replicate these findings.

African Americans' discussions about living-donor kidney transplants with family or friends: Who, what, and why not?

BACKGROUND: Although discussions with family or friends can improve access to living-donor kidney transplantation (LDKT), they remain an understudied step in the LDKT process. METHODS: Among 300 African American transplant candidates, we examined how sociodemographic, clinical, LDKT-related, and psychosocial characteristics related to the occurrence of LDKT discussions with family or friends. We also analyzed the relation between discussion occurrence and donor activation on transplant candidates' behalves (at least one donor inquiry or completed donor evaluation in the medical record). We assessed associations of discussion characteristics (context, content, and perceptions) with donor activation among discussants, and we identified discussion barriers among non-discussants. RESULTS: Most candidates (90%) had discussed LDKT. Only family functioning was statistically significantly associated with discussion occurrence. Specifically, family dysfunction was associated with 62% lower odds of discussion than family function. Family functioning, discussion occurrence, and different discussion characteristics were statistically significantly related to donor activation. The most prevalent discussion barrier was never having thought about discussing LDKT. CONCLUSIONS: Family functioning affected the likelihood of discussing LDKT, and family functioning, discussion occurrence, and discussion characteristics were associated with donor activation. Advancing understanding of how family functioning and LDKT discussions affect progression to LDKT may benefit interventions to increase LDKT.

Diastereoselective Synthesis of Tetrabenzohydrofuran Spirooxindoles via Diethyl Phosphite-Mediated Coupling of Isatins with o-Quinone Methides.

Diethyl phosphite-initiated coupling of isatins with o-quinone methides (o-QMs) is reported. This reaction involves a cascade transformation initiated by base-promoted addition of phosphite to isatins, followed by [1,2]-phospha-Brook rearrangement. This generates α-phosphonyloxy enolates that are subsequently intercepted by o-QMs and finally intramolecular ring closure. This protocol was used to diastereoselectively synthesize a range of trans-tetrabenzohydrofuran spirooxindoles in moderate to good yields with moderate to excellent diastereoselectivities.

Prognostic Value of Pre-Autologous Stem Cell Transplantation PET/CT in Diffuse Large B-Cell Lymphoma: The Deauville Score Is Prognostically Superior to ΔSUVmax.

OBJECTIVE: The predictive value of pre-autologous stem cell transplantation (pre-ASCT) positron emission tomography/computed tomography (PET/CT) scans according to different criteria remains elusive in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 46 DLBCL patients treated with pre-ASCT were enrolled in the present study, and two methods, Deauville score and maximal standardized uptake value reduction (ΔSUVmax), were used to evaluate the PET/CT scans before transplantation. RESULTS: In patients with Deauville 1-3 and ≥4, the 2-year progression-free survival (PFS) rates were 82.8 and 11.8% (p < 0.001), respectively, while the 2-year overall survival (OS) rates were 89.7 and 41.2%, respectively (p < 0.001). When using the ΔSUVmax cut-off of 66% criterion, in patients with a ΔSUVmax of >66 and ≤66%, the 2-year PFS rates were 78.1 and 7.1%, respectively (p < 0.001), while the 2-year OS rates were 87.5 and 35.7%, respectively (p < 0.001). In the univariate analysis, the ΔSUVmax, Deauville score, NCCN-IPI and serum lactate dehydrogenase levels were significantly correlated with the 2-year PFS/OS. Furthermore, the multivariate analysis revealed that the Deauville score was an independent prognostic factor for 2-year PFS. CONCLUSION: The present results indicate that PET/CT scans at pre-ASCT can predict the survival of DLBCL patients, and the Deauville score is better than ΔSUVmax in prognostic prediction.

Dental Cleaning, Community Water Fluoridation and Preterm Birth, Massachusetts: 2009-2016.

Objectives Data on the potential effect of dental cleaning and community water fluoridation (CWF) on pregnancy outcomes are scarce. While numerous studies confirm the cost-effectiveness of fluoride in preventing dental caries, the benefit of CWF during pregnancy has not been well established. Methods This cross-sectional study used data from 2009 to 2016 Massachusetts Pregnancy Risk Assessment Monitoring System and restricted to singleton live births (n = 9234, weighted response rate = 64.3%). Our exposures were: (1) dental cleaning alone during pregnancy; (2) CWF alone; and (3) dental cleaning and CWF combined (DC-CWF). Women without dental cleaning during pregnancy and CWF comprised our reference group. The outcome was preterm birth, (birth < 37 weeks gestation). This study used multivariate logistic regression modeling, controlling for maternal sociodemographic characteristics, previous medical risk and behavioral factors, and calculated adjusted risk ratios (aRRs) and 95% confidence intervals (CIs). Results During 2009-2016, the prevalence of preterm birth among women with a singleton live birth was 8.5% in Massachusetts. Overall, 58.7% of women had dental cleaning during pregnancy, and 63.6% lived in CWF. After adjusting for potential confounders, the associations between dental cleaning alone and preterm birth (aRR = 0.74 [95% CI 0.55-0.98]), and DC-CWF and preterm birth (aRR = 0.74 [95% CI 0.57-0.95]) were significant, while the association between CWF alone and preterm birth was not significant (aRR = 0.81 [95% CI 0.63-1.05]), compared to women without dental cleaning and CWF. Conclusions for Practice This study shows that the prevalence of preterm birth was lower among women with DC only and DC-CWF.

Maternal intake of high n-6 polyunsaturated fatty acid diet during pregnancy causes transgenerational increase in mammary cancer risk in mice.

BACKGROUND: Maternal and paternal high-fat (HF) diet intake before and/or during pregnancy increases mammary cancer risk in several preclinical models. We studied if maternal consumption of a HF diet that began at a time when the fetal primordial germ cells travel to the genital ridge and start differentiating into germ cells would result in a transgenerational inheritance of increased mammary cancer risk. METHODS: Pregnant C57BL/6NTac mouse dams were fed either a control AIN93G or isocaloric HF diet composed of corn oil high in n-6 polyunsaturated fatty acids between gestational days 10 and 20. Offspring in subsequent F1-F3 generations were fed only the control diet. RESULTS: Mammary tumor incidence induced by 7,12-dimethylbenz[a]anthracene was significantly higher in F1 (p < 0.016) and F3 generation offspring of HF diet-fed dams (p < 0.040) than in the control offspring. Further, tumor latency was significantly shorter (p < 0.028) and burden higher (p < 0.027) in F1 generation HF offspring, and similar trends were seen in F3 generation HF offspring. RNA sequencing was done on normal mammary glands to identify signaling differences that may predispose to increased breast cancer risk by maternal HF intake. Analysis revealed 1587 and 4423 differentially expressed genes between HF and control offspring in F1 and F3 generations, respectively, of which 48 genes were similarly altered in both generations. Quantitative real-time polymerase chain reaction analysis validated 13 chosen up- and downregulated genes in F3 HF offspring, but only downregulated genes in F1 HF offspring. Ingenuity Pathway Analysis identified upregulation of Notch signaling as a key alteration in HF offspring. Further, knowledge-fused differential dependency network analysis identified ten node genes that in the HF offspring were uniquely connected to genes linked to increased cancer risk (ANKEF1, IGFBP6, SEMA5B), increased resistance to cancer treatments (SLC26A3), poor prognosis (ID4, JAM3, TBX2), and impaired anticancer immunity (EGR3, ZBP1). CONCLUSIONS: We conclude that maternal HF diet intake during pregnancy induces a transgenerational increase in offspring mammary cancer risk in mice. The mechanisms of inheritance in the F3 generation may be different from the F1 generation because significantly more changes were seen in the transcriptome.

Analyzing the involvement of diverse cell death-related genes in diffuse large B-cell lymphoma using bioinformatics techniques.

Diffuse large B-cell lymphoma (DLBCL) stands as the most prevalent subtype of non-Hodgkin's lymphoma and exhibits significant heterogeneity. Various forms of programmed cell death (PCD) have been established to have close associations with tumor onset and progression. To this end, this study has compiled 16 PCD-related genes. The investigation delved into genes linked with prognosis, constructing risk models through consecutive application of univariate Cox regression analysis and Lasso-Cox regression analysis. Furthermore, we employed RT-qPCR to validate the mRNA expression levels of certain diagnosis-related genes. Subsequently, the models underwent validation through KM survival curves and ROC curves, respectively. Additionally, nomogram models were formulated employing prognosis-related genes and risk scores. Lastly, disparities in immune cell infiltration abundance and the expression of immune checkpoint-associated genes between high- and low-risk groups, as classified by risk models, were explored. These findings contribute to a more comprehensive understanding of the role played by the 16 PCD-associated genes in DLBCL, shedding light on potential novel therapeutic strategies for the condition.

Adherence to Mediterranean, Dietary Approaches to Stop Hypertension and Healthy Eating Indices are associated with lower risk of disability among Puerto Rican adults from the longitudinal Boston Puerto Rican Health Study.

BACKGROUND: Emerging evidence suggests that poor dietary quality is an important risk factor for disability. However, few studies have compared adherence to dietary patterns with disability and none among Puerto Rican adults. OBJECTIVES: This study was designed to examine relationships between 3 dietary patterns-including Dietary Approaches to Stop Hypertension (DASH), Mediterranean dietary score (MeDS), and Healthy Eating Index (HEI)-2010-and ∼6-y incidence of activities of daily living (ADL) and instrumental activities of daily living (IADL) disability and to assess potential mediation by handgrip strength. METHODS: Data are from the Boston Puerto Rican Health Study, a longitudinal cohort of Puerto Rican adults aged 45-75 y (N = 1502). Adherence to dietary pattern variables were derived from food frequency questionnaire (FFQ) data averaged at baseline and ∼2 y. Handgrip strength was assessed at baseline. Cox proportional hazards models were used to assess longitudinal associations between DASH, MeDS, and HEI-2010 and incident ∼6-y ADL (and subscales) and IADL disability. Mediation by handgrip strength was also tested. RESULTS: Participants with higher adherence DASH had lower risk of ADL, ADL mobility, and ADL manual dexterity disabilities (hazards ratio [HR]: 0.96; 95% confidence interval [CI]: 0.91, 0.98; HR: 0.96; 95% CI: 0.92, 0.99; and HR: 0.95; 95% CI: 0.92, 0.98, respectively). Higher adherence to MeDS was associated with lower risk of ADL and ADL mobility disabilities (HR: 0.89; 95% CI: 0.81, 0.98; HR: 0.90; 95% CI: 0.82, 1.00), and higher adherence to HEI with lower risk of ADL manual dexterity (HR: 0.98; 95% CI: 0.97, 0.99) in fully adjusted models. Only DASH tended to be associated with IADL (HR: 0.97; 95% CI: 0.94, 1.00). Baseline handgrip strength was a mediator between HEI and ADL manual dexterity (23.7% of the indirect effect was explained through handgrip strength). CONCLUSIONS: Higher adherence to a healthy diet pattern may decrease risk of disability and may be an important prevention strategy for ADL and IADL disability associated with aging.

Distribution and protection of Thesium chinense Turcz. under climate and land use change.

Wild medicinal plants are prominent in the field of Traditional Chinese Medicine (TCM), but their availability is being impacted by human activities and ecological degradation in China. To ensure sustainable use of these resources, it is crucial to scientifically plan areas for wild plant cultivation. Thesium chinense, a known plant antibiotic, has been overharvested in recent years, resulting in a sharp reduction in its wild resources. In this study, we employed three atmospheric circulation models and four socio-economic approaches (SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5) to investigate the primary environmental factors influencing the distribution of T. chinense. We also examined changes in its suitable area using the Biomod2 package. Additionally, we utilized the PLUS model to project and analyze future land use changes in climate-stable regions for T. chinense. Our planning for wild tending areas of T. chinense was facilitated by the ZONATION software. Over the next century, the climate-stable regions for T. chinense in China is approximately 383.05 × 104 km2, while the natural habitat in this region will progressively decline. Under the current climate conditions, about 65.06% of the habitats in the high suitable areas of T. chinense are not affected by future land use changes in China. Through hotspot analysis, we identified 17 hotspot cities as ideal areas for the wild tending of T. chinense, including 6 core hotspot cities, 6 sub-hotspot cities, and 5 fringe hotspot cities. These findings contribute to a comprehensive research framework for the cultivation planning of T. chinense and other medicinal plants.

Developing Zn-2Cu-xLi (x < 0.1 wt %) alloys with suitable mechanical properties, degradation behaviors and cytocompatibility for vascular stents.

Biodegradable Zn alloys show great potential for vascular stents due to their moderate degradation rates and acceptable biocompatibility. However, the poor mechanical properties limit their applications. In this study, low alloyed Zn-2Cu-xLi (x = 0.004, 0.01, 0.07 wt %) alloys with favorable mechanical properties were developed. The microstructure consists of fine equiaxed η-Zn grains, micron, submicron-sized and coherent nano ε-CuZn4 phases. The introduced Li exists as a solute in the η-Zn matrix and ε-CuZn4 phase, and results in the increase of ε-CuZn4 volume fraction, the refinement of grains and more uniform distribution of grain sizes. As Li content increases, the strength of alloys is dramatically improved by grain boundary strengthening, precipitate strengthening of ε-CuZn4 and solid solution strengthening of Li. Zn-2Cu-0.07Li alloy has the optimal mechanical properties with a tensile yield strength of 321.8 MPa, ultimate tensile strength of 362.3 MPa and fracture elongation of 28.0 %, exceeding the benchmark of stents. It also has favorable mechanical property stability, weak tension compression yield asymmetry and strain rate sensitivity. It exhibits uniform degradation and a little improved degradation rate of 89.5 µm∙year-1, due to the improved electrochemical activity by increased ε-CuZn4 volume fraction, and generates Li2CO3 and LiOH. It shows favorable cytocompatibility without adverse influence on endothelial cell viability by trace Li+. The fabricated microtubes show favorable mechanical properties, and stents exhibit an average radial strength of 118 kPa. The present study indicates that Zn-2Cu-0.07Li alloy is a potential and promising candidate for vascular stent applications. STATEMENT OF SIGNIFICANCE: Zn alloys are promising candidates for biodegradable vascular stents. However, improving their mechanical properties is challenging. Combining the advantages of Cu and trace Li, Zn-2Cu-xLi (x < 0.1 wt %) alloys were developed for stents. As Li increases, the strength of alloys is dramatically improved by refined grains, increased volume fraction of ε-CuZn4 and solid solution of Li. Zn-2Cu-0.07Li alloy exhibits a TYS exceeding 320 MPa, UTS exceeding 360 MPa and fracture EL of nearly 30 %. It shows favorable mechanical stability, degradation behaviors and cytocompatibility. The alloy was fabricated into microtubes and stents for mechanical property tests to verify application feasibility for the first time. This indicates that Zn-2Cu-0.07Li alloy has great potential for vascular stent applications.