Multifaceted insights into the environmental adaptability of Arnebia guttata under drought stress.

Introduction: Global warming has led to increased environmental stresses on plants, notably drought. This affects plant distribution and species adaptability, with some medicinal plants showing enhanced drought tolerance and increased medicinal components. In this pioneering study, we delve into the intricate tapestry of Arnebia guttata, a medicinal plant renowned for its resilience in arid environments. By fusing a rich historical narrative with cutting-edge analytical methodologies, this research endeavors to demystify the plant's intricate response to drought stress, illuminating its profound implications for medicinal valorization. Methods: The methodology includes a comprehensive textual research and resource investigation of A. guttata, regionalization studies, field sample distribution analysis, transcriptome and metabolome profiling, rhizosphere soil microbiome analysis, and drought stress experiments. Advanced computational tools like ArcGIS, MaxEnt, and various bioinformatics software were utilized for data analysis and modeling. Results: The study identified significant genetic variations among A. guttata samples from different regions, correlating with environmental factors, particularly precipitation during the warmest quarter (BIO18). Metabolomic analysis revealed marked differences in metabolite profiles, including shikonin content, which is crucial for the plant's medicinal properties. Soil microbial community analysis showed variations that could impact plant metabolism and stress response. Drought stress experiments demonstrated A. guttata's resilience and its ability to modulate metabolic pathways to enhance drought tolerance. Discussion: The findings underscore the complex interplay between genetic makeup, environmental factors, and microbial communities in shaping A. guttata's adaptability and medicinal value. The study provides insights into how drought stress influences the synthesis of active compounds and suggests that moderate stress could enhance the plant's medicinal properties. Predictive modeling indicates future suitable growth areas for A. guttata, aiding in resource management and conservation efforts. The research contributes to the sustainable development of medicinal resources and offers strategies for improving the cultivation of A. guttata.

Patients with ASPSCR1-TFE3 fusion achieve better response to ICI based combination therapy among TFE3-rearranged renal cell carcinoma.

BACKGROUND: TFE3-rearranged renal cell carcinoma (TFE3-rRCC) is a rare but highly heterogeneous renal cell carcinoma (RCC) entity, of which the clinical treatment landscape is largely undefined. This study aims to evaluate and compare the efficacy of different systemic treatments and further explore the molecular correlates. METHODS: Thirty-eight patients with metastatic TFE3-rRCC were enrolled. Main outcomes included progression-free survival (PFS), overall survival, objective response rate (ORR) and disease control rate. RNA sequencing was performed on 32 tumors. RESULTS: Patients receiving first-line immune checkpoint inhibitor (ICI) based combination therapy achieved longer PFS than those treated without ICI (median PFS: 11.5 vs. 5.1 months, P = 0.098). After stratification of fusion partners, the superior efficacy of first-line ICI based combination therapy was predominantly observed in ASPSCR1-TFE3 rRCC (median PFS: not reached vs. 6.5 months, P = 0.01; ORR: 67.5% vs. 10.0%, P = 0.019), but almost not in non-ASPSCR1-TFE3 rRCC. Transcriptomic data revealed enrichment of ECM and collagen-related signaling in ASPSCR1-TFE3 rRCC, which might interfere with the potential efficacy of anti-angiogenic monotherapy. Whereas angiogenesis and immune activities were exclusively enriched in ASPSCR1-TFE3 rRCC and promised the better clinical outcomes with ICI plus tyrosine kinase inhibitor combination therapy. CONCLUSIONS: The current study represents the largest cohort comparing treatment outcomes and investigating molecular correlates of metastatic TFE3-rRCC based on fusion partner stratification. ICI based combination therapy could serve as an effective first-line treatment option for metastatic ASPSCR1-TFE3 rRCC patients. Regarding with other fusion subtypes, further investigations should be performed to explore the molecular mechanisms to propose pointed therapeutic strategy accordingly.

An ethnobotanical survey on the medicinal and edible plants used by the Daur people in China.

BACKGROUND: The Daur people are one of the 55 minority ethnic groups in China and have lived in Northern China for 300 years. In traditional Daur medicine, medicinal and edible plants (MEPs) are utilised for health benefits and therapeutic purposes; however, related ethnobotanical knowledge is rarely reported, which is disadvantageous for the sustainable development of these MEPs. METHODS: Semi-structured interviews with 122 informants, six focus group discussions, and a resource survey were conducted in a Daur minority nationality area in Inner Mongolia from 2015 to 2020, and the data statistics were analysed. In this study, we simulated a system dynamics model aimed at understanding the multiple feedback mechanisms involved in the relationships between the cultural influences and socioeconomic factors, sustainable environment, and development of MEPs. RESULTS: A total of 52 species of MEPs were identified and relevant ethnobotanical knowledge was assessed using Daur medicinal species data from Inner Mongolia and the Xinjiang region, with the literature and Ewenki ethnic group data used for comparison. The most commonly used medicinal plant species by the Daur were found to be Betula pendula subsp. mandshurica, Artemisia integrifolia, Crataegus pinnatifida, Saposhnikovia divaricata, Artemisia argyi, and Jacobaea cannabifolia. The MEPs most frequently targeted the digestive and rheumatic immunity systems, as well as infectious diseases or parasitic infections and other common diseases and basic health issues. MEP knowledge was primarily limited to older generations; thus, the valuable ethnobotanical knowledge on traditional medicines must be protected from future losses. CONCLUSIONS: Our findings provide insights for future research aimed at exploiting the rich phytochemical diversity in traditional medicine and promote its use in modern lifestyles. Effective assessment and management of plant resources will lead to their application for the improvement of dietary diversity, nutrition, and health care.

Integrated analysis of intestinal microbiota and transcriptome reveals that a coordinated interaction of the endocrine, immune system and gut microbiota response to heat stress in Litopenaeus vannamei.

Due to the ongoing global warming, the risk of heatwaves in the oceans is continuously increasing while our understanding of the physiological response of Litopenaeus vannamei under extreme temperature conditions remains limited. Therefore, this study aimed to evaluate the physiological responses of L. vannamei under heat stress. Our results indicated that as temperature rose, the structure of intestinal and hepatopancreatic tissues was damaged sequentially. Activity of immune-related enzymes (acid phosphatase/alkaline phosphatase) initially increased before decreased, while antioxidant enzymes (superoxide dismutase and glutathione-S transferase) activity and malondialdehyde content increased with rising temperature. In addition, the total antioxidant capacity decreased with rising temperature. With the rising temperature, there was a significant increase in the expression of caspase-3, heat shock protein 70, lipopolysaccharide-induced tumor necrosis factor-α, transcriptional enhanced associate domain and yorkie in intestinal and hepatopancreatic tissues. Following heat stress, the number of potentially beneficial bacteria (Rhodobacteraceae and Gemmonbacter) increased which maintain balance and promote vitamin synthesis. Intestinal transcriptome analysis revealed 852 differentially expressed genes in the heat stress group compared with the control group. KEGG functional annotation results showed that the endocrine system was the most abundant in Organismal systems followed by the immune system. These results indicated that heat stress leads to tissue damage in shrimp, however the shrimp may respond to stress through a coordinated interaction strategy of the endocrine system, immune system and gut microbiota. This study revealed the response mechanism of L. vannamei to acute heat stress and potentially provided a theoretical foundation for future research on shrimp environmental adaptations.

Prognostic significance of circulating tumor DNA in urothelial carcinoma: a systematic review and meta-analysis.

BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a noninvasive technique that provides valuable insights into molecular profiles and tumor disease management. This study aimed to evaluate the prognostic significance of circulating tumor DNA (ctDNA) in urothelial carcinoma (UC) through a systematic review and meta-analysis. METHODS: A comprehensive search was conducted in MEDLINE, EMBASE, and the Cochrane Library from the inception to December 2023. Studies investigating the prognostic value of ctDNA in UC were included. Hazard ratios (HRs) of disease-free survival (DFS) and overall survival (OS) were extracted. Overall meta-analysis and subgroup exploration stratified by metastatic status, ctDNA sampling time, treatment type, and detection method was performed using the R software (version 4.2.2). RESULTS: A total of 16 studies with 1725 patients were included. Fourteen studies assessed the association between baseline ctDNA status and patient outcomes. Patients with elevated ctDNA levels exhibited significantly worse DFS (HR=6.26; 95% CI: 3.71-10.58, P <0.001) and OS (HR=4.23; 95% CI: 2.72-6.57, P <0.001) regardless of metastatic status, ctDNA sampling time, treatment type, and detection methods. Six studies evaluated the prognostic value of ctDNA dynamics in UC. Patients who showed a decrease or clearance in ctDNA levels during treatment or observation demonstrated more favorable DFS (HR=0.26, 95% CI: 0.17-0.41, P <0.001) and OS (HR=0.21, 95% CI: 0.11-0.38, P <0.001) compared to those who did not. The association remained consistent across the subgroup analysis based on metastatic status and detection methods. In the immune checkpoint inhibitor-treated setting, both lower baseline ctDNA level and ctDNA decrease during the treatment were significantly associated with more favorable oncologic outcomes. Furthermore, specific gene mutations such as FGFR3 identified in ctDNA also demonstrated predictive value in UC patients. CONCLUSION: This meta-analysis demonstrates a strong association of ctDNA status and its dynamic change with survival outcomes in UC, suggesting substantial clinical utility of ctDNA testing in prognosis prediction and decision making in this setting.

The factors affecting the development of medicinal plants from a value chain perspective.

MAIN CONCLUSION: From a value chain perspective, this paper examines the important factors from the selection of planting areas to storage, which restrict the development of medicinal plants. The purpose of this paper is to provide theoretical basis for the sustainable development of medicinal plants. Medicinal plants have significant economic and medicinal value. Due to the gradual depletion of wild medicinal plant resources, cultivators of medicinal plants must resort to artificial cultivation to cope. However, there are still many problems in the production process of medicinal plants, resulting in decreases in both yield and quality, thus hindering sustainable development. To date, research on the value chain of medicinal plants is still limited. Therefore, this paper analyzes the factors affecting the development of medicinal plants from the perspective of the value chain, including the selection of growing areas to the storage process of medicinal plants, and summarizes the challenges faced in the production process of medicinal plants. The purpose of this paper is to provide theoretical basis for the sustainable development of medicinal plants.

Mechanism study of toluene removal using iron/nickel bimetallic catalysts supported on biochar.

The present study utilized rice husk biomass as a carrier to synthesize rice husk biochar loaded with iron and nickel. Mono-metallic and bimetallic catalysts were prepared for the removal of toluene as the tar model. The efficiency of the catalysts for the removal of toluene was investigated, and finally, the removal mechanisms of mono-metallic and bimetallic catalysts for toluene were revealed. The experimental results showed that the bimetallic-loaded biochar catalysts had excellent toluene removal performance, which was closely related to the ratio of loaded Fe and Ni. Among them, the catalyst DBC-Fe2.5 %-Ni2.5 % (2.5 wt% iron loading and 2.5 wt% nickel loading) obtained through secondary calcination at 700 °C achieved the highest toluene removal efficiency of 92.76 %. The elements of Fe and Ni in the catalyst were uniformly dispersed on the surface and in the pores of the biochar, and the catalyst had a layered structure with good adsorption. Under the interaction of Fe and Ni, the agglomeration and sintering of Ni were reduced, and the surface acidity of the catalyst was increased, the surface acidity was favorable for toluene removal. The iron­nickel catalyst did not form significant alloys when calcined at 400 °C, whereas strong metal interactions occurred at 700 °C, resulting in the formation of Fe0.64Ni0.36 alloy and NiFe2O4 alloy. This NiFe alloy had abundant active sites to enhance the catalytic cracking of toluene and provide lattice oxygen for the reaction. Furthermore, the functional groups on the catalyst surface also had an impact on toluene removal. The catalyst prepared in this paper reduces the cost of tar removal, can be applied to the removal of industrial pollutant tars, reduces the pollution of the environment, and provides theoretical guidance and technical reference for the efficient removal of tar.

Memory/Active T-Cell Activation Is Associated with Immunotherapeutic Response in Fumarate Hydratase-Deficient Renal Cell Carcinoma.

PURPOSE: Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare and lethal subtype of kidney cancer. However, the optimal treatments and molecular correlates of benefits for FH-deficient RCC are currently lacking. EXPERIMENTAL DESIGN: A total of 91 patients with FH-deficient RCC from 15 medical centers between 2009 and 2022 were enrolled in this study. Genomic and bulk RNA-sequencing (RNA-seq) were performed on 88 and 45 untreated FH-deficient RCCs, respectively. Single-cell RNA-seq was performed to identify biomarkers for treatment response. Main outcomes included disease-free survival (DFS) for localized patients, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) for patients with metastasis. RESULTS: In the localized setting, we found that a cell-cycle progression signature enabled to predict disease progression. In the metastatic setting, first-line immune checkpoint inhibitor plus tyrosine kinase inhibitor (ICI+TKI) combination therapy showed satisfactory safety and was associated with a higher ORR (43.2% vs. 5.6%), apparently superior PFS (median PFS, 17.3 vs. 9.6 months, P = 0.016) and OS (median OS, not reached vs. 25.7 months, P = 0.005) over TKI monotherapy. Bulk and single-cell RNA-seq data revealed an enrichment of memory and effect T cells in responders to ICI plus TKI combination therapy. Furthermore, we identified a signature of memory and effect T cells that was associated with the effectiveness of ICI plus TKI combination therapy. CONCLUSIONS: ICI plus TKI combination therapy may represent a promising treatment option for metastatic FH-deficient RCC. A memory/active T-cell-derived signature is associated with the efficacy of ICI+TKI but necessitates further validation.

Enhancement of Carrier Mobility in Multilayer InSe Transistors by van der Waals Integration.

Two-dimensional material indium selenide (InSe) holds great promise for applications in electronics and optoelectronics by virtue of its fascinating properties. However, most multilayer InSe-based transistors suffer from extrinsic scattering effects from interface disorders and the environment, which cause carrier mobility and density fluctuations and hinder their practical application. In this work, we employ the non-destructive method of van der Waals (vdW) integration to improve the electron mobility of back-gated multilayer InSe FETs. After introducing the hexagonal boron nitride (h-BN) as both an encapsulation layer and back-gate dielectric with the vdW interface, as well as graphene serving as a buffer contact layer, the electron mobilities of InSe FETs are substantially enhanced. The vdW-integrated devices exhibit a high electron mobility exceeding 103 cm2 V-1 s-1 and current on/off ratios of ~108 at room temperature. Meanwhile, the electron densities are found to exceed 1012 cm-2. In addition, the fabricated devices show an excellent stability with a negligible electrical degradation after storage in ambient conditions for one month. Electrical transport measurements on InSe FETs in different configurations suggest that a performance enhancement with vdW integration should arise from a sufficient screening effect on the interface impurities and an effective passivation of the air-sensitive surface.

Correlational analysis of occupational accidents and the safety policies in the Chinese coal mining industry from 2008 to 2021.

This study investigates the correlation between previous coal mine safety policies and accidents in China. Data on coal mine accidents and government regulatory information from 2008 to 2021 are collected. The characteristics of coal mine accidents are analyzed, and safety policy indexes are identified. An ordinary least squares (OLS) regression model is established to quantitatively analyze the correlation between accidents and safety policy. The study finds that safety policies have some impact on accident occurrence in coal mines. Although there has been a decrease in accidents and deaths over time, higher mortality rates are observed during periods of increased production intensity and on weekends. Gas accidents are the most common, followed by roof and flood accidents. The study concludes that national safety policies with wider coverage and a stronger system are effective in preventing accidents, but caution should be exercised to avoid reduced vigilance with decreasing death rates.