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.

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.

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.

Downregulation of miR-181c-5p in Alzheimer's disease weakens the response of microglia to Aß phagocytosis.

Alzheimer's disease (AD) is an age-associated neurodegenerative disease. Recently, studies have demonstrated the potential involvement of microRNA-181c-5p (miR-181c-5p) in AD. However, the mechanism through which miR-181c-5p is responsible for the onset and progression of this disease remains unclear, and our study aimed to explore this problem. Differential expression analysis of the AD dataset was performed to identify dysregulated genes. Based on hypergeometric analysis, AD differential the upstream regulation genes miR-181c-5p was found. We constructed a model where SH-SY5Y and BV2 cells were exposed to Aß1-42 to simulate AD. Levels of tumor necrosis factor-alpha, interleukin-6, and IL-1ß were determined using enzyme-linked immunosorbent assay or reverse transcription quantitative polymerase chain reaction. Phosphorylation levels of p-P38 and P38 were detected by Western blot. The level of apoptosis in BV2 cells under Aß1-42 stress was exacerbated by miR-181c-5p mimic. Downregulated miR-181c-5p impaired the phagocytosis and degradation of Aß by BV2 cells. The release of proinflammatory cytokines in BV2 cells with Aß1-42 stress was alleviated by miR-181c-5p upregulation. Additionally, miR-181c-5p downregulation alleviated the phosphorylation of P38 in Aß1-42-induced SH-SY5Y cells. In conclusion, miR-181c-5p improves the phagocytosis of Aß by microglial cells in AD patients, thereby reducing neuroinflammation.

Understanding, diagnosing, and treating pancreatic cancer from the perspective of telomeres and telomerase.

Telomerase is associated with cellular aging, and its presence limits cellular lifespan. Telomerase by preventing telomere shortening can extend the number of cell divisions for cancer cells. In adult pancreatic cells, telomeres gradually shorten, while in precancerous lesions of cancer, telomeres in cells are usually significantly shortened. At this time, telomerase is still in an inactive state, and it is not until before and after the onset of cancer that telomerase is reactivated, causing cancer cells to proliferate. Methylation of the telomerase reverse transcriptase (TERT) promoter and regulation of telomerase by lactate dehydrogenase B (LDHB) is the mechanism of telomerase reactivation in pancreatic cancer. Understanding the role of telomeres and telomerase in pancreatic cancer will help to diagnose and initiate targeted therapy as early as possible. This article reviews the role of telomeres and telomerase as biomarkers in the development of pancreatic cancer and the progress of research on telomeres and telomerase as targets for therapeutic intervention.

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.

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.

Iron-Based Catalysts with Oxygen Vacancies Obtained by Facile Pyrolysis for Selective Hydrogenation of Nitrobenzene.

The development of preparation strategies for iron-based catalysts with prominent catalytic activity, stability, and cost effectiveness is greatly significant for the field of catalytic hydrogenation but still remains challenging. Herein, a method for the preparation of iron-based catalysts by the simple pyrolysis of organometallic coordination polymers is described. The catalyst Fe@C-2 with sufficient oxygen vacancies obtained in specific coordination environment exhibited superior nitro hydrogenation performance, acid resistance, and reaction stability. Through solvent effect experiments, toxicity experiments, TPSR, and DFT calculations, it was determined that the superior activity of the catalyst was derived from the contribution of sufficient oxygen vacancies to hydrogen activation and the good adsorption ability of FeO on substrate molecules.

Zexieyin formula alleviates atherosclerosis with cognitive impairment: A novel role in the treatment of comorbidities and its underlying mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCY: Zexieyin formula (ZXYF) has been identified to have therapeutic actions of atherosclerosis (AS). It's unknown that whether ZXYF has therapeutic potential of atherosclerosis (AS) with cognitive impairment (CI) and its underlying mechanisms. AIM OF THE STUDY: To elucidate therapeutic effect of ZXYF for AS with CI as well as its underlying mechanisms in AS with CI mice model. METHODS AND MATERIALS: To establish AS with CI model, we fed ApoE-/- mice with high-fat diet (HFD) for 8 weeks. Oil red O staining (ORO) and Hematoxylin-eosin staining (HE) were used to detect aortic plaque area. Morris water maze (MWM) and Y-maze were used to measure cognitive function and cognitive improvement after administration of ZXYF and atorvastatin (ATO). Network pharmacology was used to screen for potential mechanisms for improving cognitive function. Western blot was used to detect expressions of MAPK, Aß and synaptic proteins in hippocampus. RESULTS: HFD caused and accelerated the AS in ApoE-/- mice, while it was easier able to produce CI than normal mice. Administration of ZXYF or ATO for 8 weeks significantly reduced aortic plaque area in ORO and HE tests, and improved cognitive abilities in MWM and Y-maze tests. Network pharmacology results showed that MAPK or synaptic proteins were highly associated with CI. HFD contributed to abnormal expressions of MAPK (pERK, pP38, pJNK), NF-kB, synaptic proteins (PSD95, synapsin1) and ß-amyloid (Aß) in hippocampus, which were all reversed by ZXYF. However, ERK and PSD95 expressions were not reversed by ATO in hippocampus. CONCLUSIONS: ZXYF mitigated AS, further alleviating CI by modulating MAPK signaling, relating to synaptic proteins enhancing and Aß protein decreasing in the hippocampus. This study firstly lit up the new clinical application of ZXYF, which might promote the use of ZXYF in AS and CI patients.

Cooperative Armoring of CAR and TCR T Cells by T Cell-Restricted IL15 and IL21 Universally Enhances Solid Tumor Efficacy.

PURPOSE: Chimeric antigen receptor (CAR) and T-cell receptor (TCR) T-cell therapies are effective in a subset of patients with solid tumors, but new approaches are needed to universally improve patient outcomes. Here, we developed a technology to leverage the cooperative effects of IL15 and IL21, two common cytokine-receptor gamma chain family members with distinct, pleiotropic effects on T cells and other lymphocytes, to enhance the efficacy of adoptive T cells. EXPERIMENTAL DESIGN: We designed vectors that induce the constitutive expression of either membrane-tethered IL15, IL21, or IL15/IL21. We used clinically relevant preclinical models of transgenic CARs and TCRs against pediatric and adult solid tumors to determine the effect of the membrane-tethered cytokines on engineered T cells for human administration. RESULTS: We found that self-delivery of these cytokines by CAR or TCR T cells prevents functional exhaustion by repeated stimulation and limits the emergence of dysfunctional natural killer (NK)-like T cells. Across different preclinical murine solid tumor models, we observed enhanced regression with each individual cytokine but the greatest antitumor efficacy when T cells were armored with both. CONCLUSIONS: The coexpression of membrane-tethered IL15 and IL21 represents a technology to enhance the resilience and function of engineered T cells against solid tumors and could be applicable to multiple therapy platforms and diseases. See related commentary by Ruffin et al., p. 1431.

A pharmacovigilance study of etoposide in the FDA adverse event reporting system (FAERS) database, what does the real world say?

Introduction: Etoposide is a broad-spectrum antitumor drug that has been extensively studied in clinical trials. However, limited information is available regarding its real-world adverse reactions. Therefore, this study aimed to assess and evaluate etoposide-related adverse events in a real-world setting by using data mining method on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: Through the analysis of 16,134,686 reports in the FAERS database, a total of 9,892 reports of etoposide-related adverse drug events (ADEs) were identified. To determine the significance of these ADEs, various disproportionality analysis algorithms were applied, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms. Results: As a result, 478 significant disproportionality preferred terms (PTs) that were identified by all four algorithms were retained. These PTs included commonly reported adverse events such as thrombocytopenia, leukopenia, anemia, stomatitis, and pneumonitis, which align with those documented in the drug's instructions and previous clinical trials. However, our analysis also uncovered unexpected and significant ADEs, including thrombotic microangiopathy, ototoxicity, second primary malignancy, nephropathy toxic, and ovarian failure. Furthermore, we examined the time-to-onset (TTO) of these ADEs using the Weibull distribution test and found that the median TTO for etoposide-associated ADEs was 10 days (interquartile range [IQR] 2-32 days). The majority of cases occurred within the first month (73.8%) after etoposide administration. Additionally, our analysis revealed specific high-risk signals for males, such as pneumonia and cardiac infarction, while females showed signals for drug resistance and ototoxicity. Discussion: These findings provide valuable insight into the occurrence of ADEs following etoposide initiation, which can potentially support clinical monitoring and risk identification efforts.

Potential chemoprotective effects of active ingredients in Salvia miltiorrhiza on doxorubicin-induced cardiotoxicity: a systematic review of in vitro and in vivo studies.

Background: Recently, attention has been paid to the protective properties of active ingredients in Salvia miltiorrhiza (AISM) against organ toxicity induced by chemotherapy drugs. Purpose of the present systematic review is to evaluate the chemoprotective effects and mechanisms of AISM on in vitro and in vivo models of doxorubicin-induced cardiotoxicity (DIC). Methods: According to the PRISMA guideline, the current systematic review was conducted in the Web of Science, PubMed, Embase, and the Cochrane Library to collect all relevant in vitro and in vivo studies on "the role of AISM on DIC" published up until May 2023. The SYRCLE's tool was used to identify potential risk of bias. Results: Twenty-two eligible articles were included in this systematic review. Eleven types of active ingredients in Salvia miltiorrhiza were used for DIC, which have the following effects: improvement of physical signs and biochemical indicators, reduction of cardiac function damage caused by DIC, protection of heart tissue structure, enhancement of myocardial cell viability, prevention of cardiomyocyte apoptosis, increase of the chemosensitivity of cancer cells to Doxorubicin, etc. The cardioprotective mechanism of AISM involves inhibiting apoptosis, attenuating oxidative stress, suppressing endoplasmic reticulum (ER) stress, decreasing inflammation, improving mitochondrial structure and function, affecting cellular autophagy and calcium homeostasis. The quality scores of included studies ranged from 4 to 7 points (a total of 10 points), according to SYRCLE's risk of bias tool. Conclusion: This systematic review demonstrated that AISM have chemoprotective effects on DIC in vivo and in vitro models through several main mechanisms such as anti-apoptosis, antioxidant effects, anti-ER stress, and anti-inflammatory.

SDC1 and ITGA2 as novel prognostic biomarkers for PDAC related to IPMN.

The existing biomarkers are insufficient for predicting the prognosis of pancreatic ductal adenocarcinoma (PDAC). Intraductal papillary mucinous neoplasm (IPMN) is a precursor to PDAC; therefore, identifying biomarkers from differentially expressed genes (DEGs) of PDAC and IPMN is a new and reliable strategy for predicting the prognosis of PDAC. In this study, four datasets were downloaded from the Gene Expression Omnibus database and standardized using the R package 'limma.' A total of 51 IPMN and 81 PDAC samples were analyzed, and 341 DEGs in PDAC and IPMN were identified; DEGs were involved in the extracellular matrix and tumor microenvironment. An acceptable survival prognosis was demonstrated by SDC1 and ITGA2, which were highly expressed during in vitro PDAC cell proliferation, apoptosis, and migration. SDC1high was enriched in interferon alpha (IFN-α) response and ITGA2high was primarily detected in epithelial-mesenchymal transition (EMT), which was verified using western blotting. We concluded that SDC1 and ITGA2 are potential prognostic biomarkers for PDAC associated with IPMN. Downregulation of SDC1 and ITGA2 expression in PDAC occurs via a mechanism involving possible regulation of IFN-α response, EMT, and immunity, which may act as new targets for PDAC therapy.

MYCN driven oncogenesis involves cooperation with WDR5 to activate canonical MYC targets and G9a to repress differentiation genes.

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 is needed to facilitate 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.

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.

Pan-cancer analysis and experimental validation identify ndc1 as a potential immunological, prognostic and therapeutic biomarker in pancreatic cancer.

NDC1 is a transmembrane nucleoporin that participates in cell mitosis. In the field of oncology, NDC1 has shown its potential as a prognostic marker for multiple tumors. However, pan-cancer analysis of NDC1 to fully explore its role in tumors has not been performed and little is reported on its role in pancreatic cancers. In the present study, a pan-cancer analysis of NDC1 was performed using a bioinformatic approach. Survival analysis was performed by univariate Cox regression analysis and Kaplan-Meier survival analysis. Subsequently, the relationship between NDC1 and immune cell infiltration, TMB/MSI and drug sensitivity was analyzed. Moreover, the mechanism of NDC1 in pancreatic cancer were further analyzed by GSEA, GSVA. Finally, we conducted in vitro experiments including MTT, scratch, EdU, and apoptosis assays to explore the function of NDC1 in pancreatic cancer cells. High expression of NDC1 was demonstrated in 28 cancer types. Univariate Cox regression analysis revealed that NDC1 expression was closely associated with the survival outcome of 15 cancer types, and further Kaplan-Meier survival analysis showed negative associations with the progression-free survival in 14 cancers. In addition, a significant association between the NDC1 expression and immune cell infiltration in tumor microenvironment, immune-related genes, common tumor-regulatory and drug sensitivity was observed. Furthermore, NDC1 is abnormally expressed in pancreatic cancer, and is closely related to the prognosis of pancreatic cancer patients and chemosensitivity. The study reveals that NDC1 could be used as a potential immunological, prognostic and therapeutic target for pancreatic cancer.

Conservation planning for the endemic and endangered medicinal plants under the climate change and human disturbance: a case study of Gentiana manshurica in China.

Human activities and climate change have significantly impacted the quantity and sustainable utilization of medicinal plants. Gentiana manshurica Kitagawa, a high-quality original species of Gentianae Radix et Rhizoma, has significant medicinal value. However, wild resources have experienced a sharp decline due to human excavation, habitat destruction, and other factors. Consequently, it has been classified as an Endangered (EN) species on the IUCN Red List and is considered a third-level national key-protected medicinal material in China. The effects of climate change on G. manshurica are not yet known in the context of the severe negative impacts of climate change on most species. In this study, an optimized MaxEnt model was used to predict the current and future potential distribution of G. manshurica. In addition, land use data in 1980, 2000, and 2020 were used to calculate habitat quality by InVEST model and landscape fragmentation by the Fragstats model. Finally, using the above-calculated results, the priority protection areas and wild tending areas of G. manshurica were planned in ZONATION software. The results show that the suitable area is mainly distributed in the central part of the Songnen Plain. Bio15, bio03, bio01, and clay content are the environmental variables affecting the distribution. In general, the future potential distribution is expected to show an increasing trend. However, the species is expected to become threatened as carbon emission scenarios and years increase gradually. At worst, the high suitability area is expected to disappear completely under SSP585-2090s. Combined with the t-test, this could be due to pressure from bio01. The migration trends of climate niche centroid are inconsistent and do not all move to higher latitudes under different carbon emission scenarios. Over the past 40 years, habitat quality in the current potential distribution has declined yearly, and natural habitat has gradually fragmented. Existing reserves protect only 9.52% of G. manshurica's priority conservation area. To avoid extinction risk and increase the practicality of the results, we clarified the hotspot counties of priority protection area gaps and wild tending areas. These results can provide an essential reference and decision basis for effectively protecting G. manshurica under climate change.

Experimental Study on Lap-Spliced Performance of High-Strength Stainless Steel Wire Mesh in Engineering Cementitious Composites.

To investigate the mechanical properties of high-strength stainless steel wire mesh (HSSSWM) in Engineering Cementitious Composites (ECCs) and determine a reasonable lap length, a total of 39 specimens in 13 sets were designed and fabricated by considering the diameter of the steel strand, spacing of the transverse steel strand, and lap length. The lap-spliced performance of the specimens was tested through a pull-out test. The results revealed two failure modes in the lap connection of steel wire mesh in ECCs: pull-out failure and rupture failure. The spacing of the transverse steel strand had little effect on the ultimate pull-out force, but it restricted the slip of the longitudinal steel strand. A positive correlation was found between the spacing of the transverse steel strand and the slip amount of the longitudinal steel strand. With an increase in lap length, the slip amount and 'lap stiffness' to peak load increased, while the ultimate bond strength decreased. Based on the experimental analysis, a calculation formula for lap strength considering the correction coefficient ß was established.