Assessing the responses of ecosystem patterns, structures and functions to drought under climate change in the Yellow River Basin, China.

Understanding how ecosystems respond and adapt to drought has become an urgent issue as drought stress intensifies under climate change, yet this topic is not fully understood. Currently, conclusions on the response of ecosystems in different regions to drought disturbance are inconsistent. Based on long MODIS data and observed data, this study systematically explored the relationships between ecosystem patterns, structures and functions and drought, taking a typical climate change-sensitive area and an ecologically fragile area-the Yellow River Basin-as a case study. Drought assessment results revealed that the Yellow River Basin has experienced meteorological and hydrological drought during most of the last two decades, predominantly characterized by medium and slight droughts. The ecosystem patterns and structures changed dramatically as the grassland decreased and the landscape fragmentation index (F) increased with increasing wetness. The annual gross primary productivity (GPP) increased, the water use efficiency (WUE) declined and ecosystem service value (ESV) exhibited a W-shaped increase at the watershed scale, but there were significant regional differences. There were positive correlations between F, GPP, ESV and drought indices, while there was a negative correlation between WUE and drought indices at the watershed scale. Under drought stress, the ecosystem structure in the basin was disrupted, the GPP and ESV decreased, but the WUE increased. Notably, approximately 106 %, 20 %, and 1 % of the maximum reductions in F, GPP, and ESV, respectively, were caused by drought, while the maximum 4 % of WUE increased. Responses of some functions in the wetland and grassland to drought vary from those in other ecosystems. The mechanisms underlying ecosystem responses to drought were further investigated. This study enhances the understanding of these responses and will help stakeholders formulate drought mitigation policies and protect ecosystem health.

Novel insights into RB1 in prostate cancer lineage plasticity and drug resistance.

Prostate cancer is the second most common malignancy among men in the world, posing a serious threat to men's health and lives. RB1 is the first human tumor suppressor gene to be described, and it is closely associated with the development, progression, and suppression of a variety of tumors. It was found that the loss of RB1 is an early event in prostate cancer development and is closely related to prostate cancer development, progression and treatment resistance. This paper reviews the current status of research on the relationship between RB1 and prostate cancer from three aspects: RB1 and prostate cell lineage plasticity; biological behavior; and therapeutic resistance. Providing a novel perspective for developing new therapeutic strategies for RB1-loss prostate cancer.

The Sanbi Decoction alleviates intervertebral disc degeneration in rats through intestinal flora and serum metabolic homeostasis modulation.

BACKGROUND: Intervertebral disc degeneration (IVDD) is an essential cause of low back pain (LBP), the incidence of which has risen in recent years and is progressively younger, but treatment options are limited, placing a serious economic burden on society. Sanbi decoction (SBD) is an important classical formula for the treatment of IVDD, which can significantly improve patients' symptoms and is a promising alternative therapy. PURPOSE: The aim of this study is to investigate the safety and efficacy of SBD in the treatment of IVDD and to explore the underlying mechanisms by using an integrated analytical approach of microbiomics and serum metabolomics, as well as by using molecular biology. METHODS: A rat IVDD puncture model was established and treated by gavage with different concentrations of SBD, and clean faeces, serum, liver, kidney, and intervertebral disc (IVD) were collected after 4 weeks. We assessed the safety by liver and kidney weighing, functional tests and tissue staining, the expression of tumor necrosis factor-alpha (TNF-ɑ), interleukin 1ß (IL-1ß) and interleukin 6 (IL-6) inflammatory factors in serum was detected by ELISA kits, and X-ray test, magnetic resonance imaging (MRI) examination, immunohistochemistry (IHC), western blotting (WB), hematoxylin-eosin (HE) staining and safranin O-fast green (SO/FG) staining were used to assess the efficacy. Finally, we performed 16S rRNA sequencing analysis on the faeces of different groups and untargeted metabolomics on serum and analyzed the association between them. RESULTS: SBD can effectively reduce the inflammatory response, regulate the metabolic balance of extracellular matrix (ECM), improve symptoms, and restore IVD function. In addition, SBD can significantly improve the diversity of intestinal flora and maintain the balance. At the phylum level, SBD greatly increased the relative abundance of Patescibacteria and Actinobacteriota and decreased the relative abundance of Bacteroidota. At the genus level, SBD significantly increased the relative abundance of Clostridia_UCG-014, Enterorhabdus, and Adlercreutzia, and decreased the relative abundance of Ruminococcaceae_UCG-005 (p < 0.05). Untargeted metabolomics indicated that SBD significantly improved serum metabolites and altered serum expression of 4alpha-phorbol 12,13-didecanoate (4alphaPDD), euscaphic acid (EA), alpha-muricholic acid (α-MCA), 5-hydroxyindoleacetic acid (5-HIAA), and kynurenine (Kyn) (p < 0.05), and the metabolic pathways were mainly lipid metabolism and amino acid metabolism. CONCLUSIONS: This study demonstrated that SBD can extensively regulate intestinal flora and serum metabolic homeostasis to reduce inflammatory response, inhibit the degradation of ECM, restore IVD height and water content to achieve apparent therapeutic effect for IVDD.

Mechanical Factors Regulate Annulus Fibrosus (AF) Injury Repair and Remodeling: A Review.

Low back pain is a common chronic disease that can severely affect the patient's work and daily life. The breakdown of spinal mechanical homeostasis caused by intervertebral disc (IVD) degeneration is a leading cause of low back pain. Annulus fibrosus (AF), as the outer layer structure of the IVD, is often the first affected part. AF injury caused by consistent stress overload will further accelerate IVD degeneration. Therefore, regulating AF injury repair and remodeling should be the primary goal of the IVD repair strategy. Mechanical stimulation has been shown to promote AF regeneration and repair, but most studies only focus on the effect of single stress on AF, and lack realistic models and methods that can mimic the actual mechanical environment of AF. In this article, we review the effects of different types of stress stimulation on AF injury repair and remodeling, suggest possible beneficial load combinations, and explore the underlying molecular mechanisms. It will provide the theoretical basis for designing better tissue engineering therapy using mechanical factors to regulate AF injury repair and remodeling in the future.

Tet methylcytosine dioxygenase 2 (TET2) deficiency elicits EGFR-TKI (tyrosine kinase inhibitors) resistance in non-small cell lung cancer.

Despite epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) have shown remarkable efficacy in patients with EGFR-mutant non-small cell lung cancer (NSCLC), acquired resistance inevitably develops, limiting clinical efficacy. We found that TET2 was poly-ubiquitinated by E3 ligase CUL7FBXW11 and degraded in EGFR-TKI resistant NSCLC cells. Genetic perturbation of TET2 rendered parental cells more tolerant to TKI treatment. TET2 was stabilized by MEK1 phosphorylation at Ser 1107, while MEK1 inactivation promoted its proteasome degradation by enhancing the recruitment of CUL7FBXW11. Loss of TET2 resulted in the upregulation of TNF/NF-κB signaling that confers the EGFR-TKI resistance. Genetic or pharmacological inhibition of NF-κB attenuate the TKI resistance both in vitro and in vivo. Our findings exemplified how a cell growth controlling kinase MEK1 leveraged the epigenetic homeostasis by regulating TET2, and demonstrated an alternative path of non-mutational acquired EGFR-TKI resistance modulated by TET2 deficiency. Therefore, combined strategy exploiting EGFR-TKI and inhibitors of TET2/NF-κB axis holds therapeutic potential for treating NSCLC patients who suffered from this resistance.

Multicellular ecotypes shape progression of lung adenocarcinoma from ground-glass opacity toward advanced stages.

Lung adenocarcinoma is a type of cancer that exhibits a wide range of clinical radiological manifestations, from ground-glass opacity (GGO) to pure solid nodules, which vary greatly in terms of their biological characteristics. Our current understanding of this heterogeneity is limited. To address this gap, we analyze 58 lung adenocarcinoma patients via machine learning, single-cell RNA sequencing (scRNA-seq), and whole-exome sequencing, and we identify six lung multicellular ecotypes (LMEs) correlating with distinct radiological patterns and cancer cell states. Notably, GGO-associated neoantigens in early-stage cancers are recognized by CD8+ T cells, indicating an immune-active environment, while solid nodules feature an immune-suppressive LME with exhausted CD8+ T cells, driven by specific stromal cells such as CTHCR1+ fibroblasts. This study also highlights EGFR(L858R) neoantigens in GGO samples, suggesting potential CD8+ T cell activation. Our findings offer valuable insights into lung adenocarcinoma heterogeneity, suggesting avenues for targeted therapies in early-stage disease.

A bibliometric and visualization study of global research trends in sacral Tarlov cyst from 2000 to 2022.

Background: Symptomatic sacral Tarlov cyst (STC) exerts a significant negative impact on the patient's quality of life, highlighting the significance of the increasing number of studies on STC. However, bibliometric analyses in this research field are scarce. Thus, this study aims to provide a comprehensive knowledge structure and identify the research trends of STC through bibliometrics. Methods: Articles related to STC from 2000 to 2022 were sourced from the Web of Science Core Collection database. VOSviewer 1.6.16, CiteSpace 6.1.6, GraphPad Prism 8.2.1 and R-package "bibliometrix" were used to analyse the data and generate knowledge maps. Results: A total of 930 studies on STC from 2000 to 2022 were included. The findings revealed a consistent yet upward trend in the number of annual publications in this field. The United States, China and Turkey were the most prolific and influential countries contributing to this field, with the University of Illinois, the University of Maryland and the National Institute of Standards & Technology being the most notable research institutions. Key journals include World Neurosurgery [Impact Factor (IF) = 2.210], Journal of Vascular Surgery (IF = 4.860) and Journal of Neurosurgery-Spine (IF = 3.467). Additionally, Tarlov Mj, Tarlov E and Zachariah Mr exhibit the highest number of publications, making them the leading authors in this field. A twenty-year retrospection of research trends using keyword analysis reveals four principal directions, namely "definition", "pathogenesis", "diagnosis" and "treatment". Currently, therapeutic surgical intervention is the key treatment for this disease, with future treatments primarily hinging on minimally invasive methodologies rooted in microendoscopic and endoscopic techniques. Conclusion: This pioneering, comprehensive scientific bibliometric study provides a holistic summary of STC research trends and hot spots spanning the past 22 years. The results identify existing research frontiers and chart maps for future studies, serving as a valuable reference for scholars vested in this field.