Design, synthesis, and anti-cancer evaluation of the novel conjugate of gemcitabine's ProTide prodrug based on CD13.

NUC1031 is a gemcitabine ProTide prodrug which is currently undergoing phase III. CD13 inhibitor bestatin is utilized as an adjunct therapy in conjunction with chemotherapy for cancer treatment, which has limitations in cytotoxic efficacy. In this study, we designed and synthesized a novel series of bestatin-gemcitabine's ProTide prodrug conjugates aimed at enhancing the antitumor efficacy of NUC1031.

Long-term reconstructed vegetation index dataset in China from fused MODIS and Landsat data.

The vegetation index is a key satellite-based variable used to monitor global vegetation distribution and growth. However, existing vegetation index datasets face limitations in achieving both high spatial and temporal resolution, restricting their application potential. This study revised a machine learning spatiotemporal fusion model (InENVI) to produce a high-resolution NDVI dataset with 8-day temporal and 30 m spatial resolution, covering China from 2001 to 2020.

Targeting LncRNA is a Promising Therapeutic Strategy to Inhibit the Progression of Bladder Cancer.

Background: Bladder cancer (BC) is a malignant tumor that begins in the cells of the bladder, characterized by poor cell differentiation and strong invasion capacity, with a high incidence rate. Identifying key molecules that enhance BC cells' cisplatin sensitivity can help improve the clinical efficacy of BC treatment. Hence, this study aimed to determine the expression level of long non-coding RNA (lncRNA) ADAM Metallopeptidase with Thrombospondin Type 1 Motif 9 Antisense RNA 1 () in BC and explore its related mechanism underlying the amplification of cisplatin sensitivity.

Linkages between stem vulnerability curves and tree demography and their implications for plant physiological modeling.

Vulnerability curves (VCs) have been measured extensively to describe the differences in plant vulnerability to cavitation. Although the roles of hydraulic conductivity (Ks,max) and hydraulic safety (P50, embolism resistance), both of which are parameters of VCs ('sigmoidal' type), in tree demography have been evaluated across different forests, the direct linkages between VCs and tree demography are rarely explored. In this study, we combined measured VCs and plot data of 16 tree species in Panamanian seasonal tropical forests to investigate the connections between VCs and tree mortality, recruitment and growth.

Identification of diagnostic biomarkers correlate with immune infiltration in extra-pulmonary tuberculosis by integrating bioinformatics and machine learning.

The diagnosis of tuberculosis depends on detecting Mycobacterium tuberculosis (Mtb). Unfortunately, recognizing patients with extrapulmonary tuberculosis (EPTB) remains challenging due to the insidious clinical presentation and poor performance of diagnostic tests. To identify biomarkers for EPTB, the GSE83456 dataset was screened for differentially expressed genes (DEGs), followed by a gene enrichment analysis.

Long-term warming increased carbon sequestration capacity in a humid subtropical forest.

Tropical and subtropical forests play a crucial role in global carbon (C) pools, and their responses to warming can significantly impact C-climate feedback and predictions of future global warming. Despite earth system models projecting reductions in land C storage with warming, the magnitude of this response varies greatly between models, particularly in tropical and subtropical regions. Here, we conducted a field ecosystem-level warming experiment in a subtropical forest in southern China, by translocating mesocosms (ecosystem composed of soils and plants) across 600 m elevation gradients with temperature gradients of 2.

Mixed plantations do not necessarily provide higher ecosystem multifunctionality than monoculture plantations.

Forest stand transformation is a crucial strategy for enhancing the productivity and stability of planted forest ecosystems and maximizing their ecosystem functions. However, understanding forest ecosystem multifunctionality responses to various stand transformation methods remains limited. In this study, we assessed ecosystem multifunctionality, encompassing nutrient cycling, carbon stocks, water regulation, decomposition, wood production, and symbiosis, under different stand transformation methods (Chinese fir monoculture, mixed conifer and broad-leaf, broad-leaf mixed, and secondary forests).

IL-17 Imbalance Promotes the Pyroptosis in Immune-Mediated Liver Injury Through STAT3-IFI16 Axis.

Autoimmune hepatitis (AIH) affects all age group and occurs mainly in women. Pyroptosis is a novel programmed cell death featured with cell bursting and release of proinflammatory cytokines. A deeper understanding of AIH pathogenesis will contribute to novel therapy for AIH patients.

Predicting diagnostic gene biomarkers in patients with diabetic kidney disease based on weighted gene co expression network analysis and machine learning algorithms.

The present study was designed to identify potential diagnostic markers for diabetic kidney disease (DKD). Two publicly available gene expression profiles (GSE142153 and GSE30528 datasets) from human DKD and control samples were downloaded from the GEO database. Differentially expressed genes (DEGs) were screened between 23 DKD and 10 control samples using the gene data from GSE142153.

PRMT7 Inhibits the Proliferation and Migration of Gastric Cancer Cells by Suppressing the PI3K/AKT Pathway via PTEN.

Protein arginine methyltransferase 7 (PRMT7) plays a crucial role in tumor occurrence and development; however, its expression pattern, biological function, and specific mechanism in gastric cancer (GC) remain poorly defined. The present study aimed to investigate the role of PRMT7 during GC carcinogenesis and its underlying mechanism. We found that PRMT7 is expressed at low levels in GC tissues, and this low expression is associated with tumor size, differentiation degree, lymph node metastasis, and TNM stage.

Carbon sequestration and storage capacity of Chinese fir at different stand ages.

In southern China, Chinese fir Cunninghamia lanceolata is one of the most important native conifer trees, widely used in afforestation programs. This area has the largest forestland atmospheric carbon sink, and a relatively young stand age characterizes these forests. However, how C.

Discovery of a Novel Ubenimex Derivative as a First-in-Class Dual CD13/Proteasome Inhibitor for the Treatment of Cancer.

The CD13 inhibitor ubenimex is used as an adjuvant drug with chemotherapy for the treatment of cancer due to its function as an immunoenhancer, but it has limitations in its cytotoxic efficacy. The proteasome inhibitor ixazomib is a landmark drug in the treatment of multiple myeloma with a high anti-cancer activity. Herein, we conjugated the pharmacophore of ubenimex and the boric acid of ixazomib to obtain a dual CD13 and proteasome inhibitor ().

Impact of having surplus blastocysts cryopreserved on the ongoing pregnancy rate following a fresh transfer.

Purpose: This study aimed to investigate whether a surplus of vitrified blastocysts correlated with ongoing pregnancy by analyzing the clinical outcomes of fresh transfer cycles with/without a surplus of vitrified blastocysts.

Methods: This was a retrospective analysis carried out in the Reproductive Medicine Center of Guizhou Medical University Affiliated Hospital between January 2020 and December 2021. Overall, 2482 fresh embryo transfer cycles were included in this study, including 1731 cycles with a surplus of vitrified blastocysts (group A) and 751 cycles with no surplus of vitrified blastocysts (group B).

A Rare Strain Was First Isolated from the Bronchoalveolar Lavage Fluid of a Patient with Pneumonia.

Background: was first isolated in 2012 in Gelibolu, Canakkale, Turkey, and has not been reported to be isolated from humans until now. We have isolated it from the bronchoalveolar lavage fluid (BLF) of a patient with pneumonia and found its drug resistance. It is the first time that has been isolated from humans since its discovery and naming.

Design, Synthesis, and Anti-Cancer Evaluation of Novel Cyclic Phosphate Prodrug of Gemcitabine.

ProTide and cyclic phosphate ester are two successful prodrug technologies to overcome the limitations of nucleoside drugs, among which the cyclic phosphate ester strategy has not been widely used in the optimization of gemcitabine. Herein, we designed a series of novel ProTide and cyclic phosphate ester prodrugs of gemcitabine. Cyclic phosphate ester derivative exhibits much higher anti-proliferative activity than positive control NUC-1031 with ICs of 3.

Statistical traps lurk in the research of soil carbon dynamics.

Soil organic carbon (SOC) plays an essential role in sequestrating anthropogenic CO emissions and mitigating climate change. Hence, accurate knowledge of the SOC dynamics and its controlling factors is a key part of the soil carbon cycling. Slessarev et al.

Immunometabolism in the tumor microenvironment and its related research progress.

The tumor immune microenvironment has been a research hot spot in recent years. The cytokines and metabolites in the microenvironment can promote the occurrence and development of tumor in various ways and help tumor cells get rid of the surveillance of the immune system and complete immune escape. Many studies have shown that the existence of tumor microenvironment is an important reason for the failure of immunotherapy.

Metabolome and transcriptome integration reveals metabolic profile of hepatocellular carcinoma.

Background And Aim: Accumulated evidence highlights the role of metabolites in cancer diagnosis. However, the diagnosis of hepatocellular carcinoma (HCC), especially its early diagnosis, is still very difficult. The main purposes of the study are to explore the comprehensive characteristic metabolites of HCC through an integrated nontargeted metabolomics and transcriptomics approach and evaluate the diagnostic value of some metabolic changes in HCC.

Higher plant photosynthetic capability in autumn responding to low atmospheric vapor pressure deficit.

It has been long established that the terrestrial vegetation in spring has stronger photosynthetic capability than in autumn. However, this study challenges this consensus by comparing photosynthetic capability of terrestrial vegetation between the spring and autumn seasons based on measurements of 100 eddy covariance towers over global extratropical ecosystems. At the majority of these sites, photosynthetic capability, indicated by light use efficiency (LUE) and apparent quantum efficiency, is significantly higher in autumn than in spring, due to lower atmosphere vapor pressure deficit (VPD) at the same air temperature.

The long non-coding RNA NNT-AS1 promotes clear cell renal cell carcinoma progression via regulation of the miR-137/ Y-box binding protein 1 axis.

Long noncoding RNAs (lncRNAs) have been implicated in the progression of malignant tumors, including in clear cell renal cell carcinoma (ccRCC). However, the function and the specific mechanism of lncRNA nicotinamide nucleotide transhydrogenase antisense RNA 1 (NNT-AS1) in ccRCC remains unknown. Thus, this study explored the role of NNT-AS1 in ccRCC.

Design, synthesis and biological evaluation of hybrid of ubenimex-fluorouracil for hepatocellular carcinoma therapy.

In our previous study, we discovered a ubenimex-fluorouracil (5FU) conjugates BC-02, which displays significant in vivo anti-tumor activity, however, the instability of BC-02 in plasma limits its further development as a drug candidate. Herein, we designed and synthesized four novel ubenimex-5FU conjugates by optimizing the linkers between ubenimex and 5FU based on BC-02. Representative compound 20 is more stable than BC-02 in human plasma and displays about 100 times higher CD13 inhibitory activity than the positive control ubenimex.

Expression of microRNA-155 in circulating T cells is an indicator of immune activation levels in HIV-1 infected patients.

MicroRNA-155 (miR-155) regulates activation of T cells. However, its relationship with T-cell immune activation level in human immunodeficiency virus (HIV) patients remains unclear. We recruited 103 HIV-1 infected patients with combination antiretroviral therapy (cART) and 79 cART naïve patients.

Identification of a Potential PPAR-Related Multigene Signature Predicting Prognosis of Patients with Hepatocellular Carcinoma.

Peroxisome proliferator-activated receptors (PPARs) and part of their target genes have been reported to be related to the progression of hepatocellular carcinoma (HCC). The prognosis of HCC is not optimistic, and more accurate prognostic markers are needed. This study focused on discovering potential prognostic markers from the PPAR-related gene set.