Constructing immune and prognostic features associated with ADCP in hepatocellular carcinoma and pan-cancer based on scRNA-seq and bulk RNA-seq.

Aim: Despite the significant therapeutic outcomes achieved in systemic treatments for liver hepatocellular carcinoma (LIHC), it is an objective reality that only a low proportion of patients exhibit an improved objective response rate (ORR) to current immunotherapies. Antibody-dependent cellular phagocytosis (ADCP) immunotherapy is considered the new engine for precision immunotherapy. Based on this, we aim to develop an ADCP-based LIHC risk stratification system and screen for relevant targets. Method: Utilizing a combination of single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data, we screened for ADCP modulating factors in LIHC and identified differentially expressed genes along with their involved functional pathways. A risk scoring model was established by identifying ADCP-related genes with prognostic value through LASSO Cox regression analysis. The risk scoring model was then subjected to evaluations of immune infiltration and immunotherapy relevance, with pan-cancer analysis and in vitro experimental studies conducted on key targets. Results: Building on the research by Kamber RA et al., we identified GYPA, CLDN18, and IRX5 as potential key target genes regulating ADCP in LIHC. These genes demonstrated significant correlations with immune infiltration cells, such as M1-type macrophages, and the effectiveness of immunotherapy in LIHC, as well as a close association with clinical pathological staging and patient prognosis. Pan-cancer analysis revealed that CLDN18 was prognostically and immunologically relevant across multiple types of cancer. Validation through tissue and cell samples confirmed that GYPA and CLDN18 were upregulated in liver cancer tissues and cells. Furthermore, in vitro knockdown of CLDN18 inhibited the malignancy capabilities of liver cancer cells. Conclusion: We have identified an ADCP signature in LIHC comprising three genes. Analysis based on a risk scoring model derived from these three genes, coupled with subsequent experimental validation, confirmed the pivotal role of M1-type macrophages in ADCP within LIHC, establishing CLDN18 as a critical ADCP regulatory target in LIHC.

A soybean bZIP transcription factor is involved in submergence resistance.

Although the functions of basic leucine zipper (bZIP) family transcription factors in the regulation of various abiotic stresses are beginning to be unveiled, the precise roles of bZIP proteins in plants coping with submergence stress remain unclear. Here we identified a bZIP gene GmbZIP71-4 from soybean, which localized in the nucleus. The GmbZIP71-4 over-expressed tabocco line showed reduced submergence resistance due to the decreased abscisic acid (ABA) content. GO and KEGG pathway analysis based on chromatin immunoprecipitation assay sequencing (ChIP-seq) indicated that the differences expressed genes between submergence treatment and control groups were specially enriched in plant hormone signal transduction items, especially those in response to ABA. Electrophoretic mobility shift assays (EMSA) demonstrated that GmbZIP71-4 bound to the promoter of GmABF2 gene, which is consistent with the ChIP-qPCR results. GmbZIP71-4 function as a negative regulator of soybean in responding to submergence stress through manipulating ABA signaling pathway. This findings will set a solid foundation for the understanding of submergence resistance in plants.

Ruthenium Nanoclusters and Single Atoms on α-MoC/N-Doped Carbon Achieves Low-input/Input-free Hydrogen Evolution via Decoupled/Coupled Hydrazine Oxidation.

The hydrazine oxidation-assisted H2 evolution method promises low-input and input-free hydrogen production. However, developing high-performance catalysts for hydrazine oxidation (HzOR) and hydrogen evolution (HER) is challenging. Here, we introduce a bifunctional electrocatalyst α-MoC/N-C/RuNSA, merging ruthenium (Ru) nanoclusters (NCs) and single atoms (SA) into cubic α-MoC nanoparticles-decorated N-doped carbon (α-MoC/N-C) nanowires, through electrodeposition. The composite showcases exceptional activity for both HzOR and HER, requiring -80 mV and -9 mV respectively to reach 10 mA cm-2. Theoretical and experimental insights confirm the importance of two Ru species for bifunctionality: NCs enhance the conductivity, and its coexistence with SA balances the H adsorption for HER and facilitates the initial dehydrogenation during the HzOR. In the overall hydrazine splitting (OHzS) system, α-MoC/N-C/RuNSA excels as both anode and cathode materials, achieving 10 mA cm-2 at just 64 mV. The zinc hydrazine (Zn-Hz) battery assembled with α-MoC/N-C/RuNSA cathode and Zn foil anode can exhibit 96% energy efficiency, as well as temporary separation of hydrogen gas during the discharge process. Therefore, integrating Zn-Hz with OHzS system enables self-powered H2 evolution, even in hydrazine sewage. Overall, the amalgamation of NCs with SA achieves diverse catalytic activities for yielding multifold hydrogen gas through advanced cell-integrated-electrolyzer system.

A wild rice CSSL population facilitated identification of salt tolerance genes and rice germplasm innovation.

Salt stress is one of the major factors that limits rice production. Therefore, identification of salt-tolerant alleles from wild rice is important for rice breeding. In this study, we constructed a set of chromosome segment substitution lines (CSSLs) using wild rice as the donor parent and cultivated rice Nipponbare (Nip) as the recurrent parent. Salt tolerance germinability (STG) was evaluated, and its association with genotypes was determined using this CSSL population. We identified 17 QTLs related to STG. By integrating the transcriptome and genome data, four candidate genes were identified, including the previously reported AGO2 and WRKY53. Compared with Nip, wild rice AGO2 has a structure variation in its promoter region and the expression levels were upregulated under salt treatments; wild rice WRKY53 also has natural variation in its promoter region, and the expression levels were downregulated under salt treatments. Wild rice AGO2 and WRKY53 alleles have combined effects for improving salt tolerance at the germination stage. One CSSL line, CSSL118 that harbors these two alleles was selected. Compared with the background parent Nip, CSSL118 showed comprehensive salt tolerance and higher yield, with improved transcript levels of reactive oxygen species scavenging genes. Our results provided promising genes and germplasm resources for future rice salt tolerance breeding.

Global, regional, and national burden of stroke attributable to extreme low temperatures, 1990-2019: A global analysis.

BACKGROUND: Extreme ambient temperatures have been linked to increased risks of stroke morbidity and mortality. However, global estimates of the burden of stroke due to extreme low temperatures are not well-defined. AIMS: This study aimed to determine the global burden of stroke due to extreme low temperatures and its spatiotemporal trend from 1990 to 2019. METHODS: Based on the Global Burden of Disease Study 2019, we obtained global, regional, and national data on deaths, disability-adjusted life years (DALYs), age-standardized mortality rate (ASMR), and age-standardized rate of DALYs (ASDR) of stroke attributed to extreme low temperatures, further stratified by age, sex, and sociodemographic index (SDI). RESULTS: Globally, in 2019, an estimated 474,000 stroke deaths with the corresponding ASMR (6.2 (95% uncertainty interval (UI): 4.6-7.9)) and ASDR (103.9 (95% UI: 77.0-134.5)) per 100,000 population, were attributable to extreme low temperatures. The most significant burden was observed in Central Asia, followed by Eastern Europe and East Asia. From 1990 to 2019, the global burden of stroke and its subtypes (ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage) attributable to extreme low temperatures exhibited a decrease in both ASMR and ASDR. Significant decreases in stroke burden occurred in the high-SDI regions, high-income Asia Pacific, and subarachnoid hemorrhage cases. Moreover, the ASMR and ASDR increased with age and were higher in males than females. CONCLUSION: The global stroke burden due to extreme low temperatures remains high despite a decreasing trend over the past three decades. The stroke burden due to extreme low temperatures was more notable for Central Asia, older people, and the male sex.

Melanoma differentiation-associated protein 5 prevents cardiac hypertrophy via apoptosis signal-regulating kinase 1-c-Jun N-terminal kinase/p38 signaling.

Pathological cardiac hypertrophy (CH) is driven by maladaptive changes in myocardial cells in response to pressure overload or other stimuli. CH has been identified as a significant risk factor for the development of various cardiovascular diseases, ultimately resulting in heart failure. Melanoma differentiation-associated protein 5 (MDA5), encoded by interferon-induced with helicase C domain 1 (IFIH1), is a cytoplasmic sensor that primarily functions as a detector of double-stranded ribonucleic acid (dsRNA) viruses in innate immune responses; however, its role in CH pathogenesis remains unclear. Thus, the aim of this study was to examine the relationship between MDA5 and CH using cellular and animal models generated by stimulating neonatal rat cardiomyocytes with phenylephrine and by performing transverse aortic constriction on mice, respectively. MDA5 expression was upregulated in all models. MDA5 deficiency exacerbated myocardial pachynsis, fibrosis, and inflammation in vivo, whereas its overexpression hindered CH development in vitro. In terms of the underlying molecular mechanism, MDA5 inhibited CH development by promoting apoptosis signal-regulating kinase 1 (ASK1) phosphorylation, thereby suppressing c-Jun N-terminal kinase/p38 signaling pathway activation. Rescue experiments using an ASK1 activation inhibitor confirmed that ASK1 phosphorylation was essential for MDA5-mediated cell death. Thus, MDA5 protects against CH and is a potential therapeutic target.

Impact of Straw Incorporation on the Physicochemical Profile and Fungal Ecology of Saline-Alkaline Soil.

Improving the soil structure and fertility of saline-alkali land is a major issue in establishing a sustainable agro-ecosystem. To explore the potential of different straw returning in improving saline-alkaline land, we utilized native saline-alkaline soil (SCK), wheat straw-returned saline-alkaline soil (SXM) and rapeseed straw-returned saline-alkaline soil (SYC) as our research objects. Soil physicochemical properties, fungal community structure and diversity of saline-alkaline soils were investigated in different treatments at 0-10 cm, 10-20 cm and 20-30 cm soil depths. The results showed that SXM and SYC reduced soil pH and total salinity but increased soil organic matter, alkali-hydrolyzable nitrogen, available phosphorus, total potassium, etc., and the enhancement effect of SYC was more significant. The total salinity of the 0-10 cm SCK soil layer was much higher than that of the 10-30 cm soil layers. Fungal diversity and abundance were similar in different soil layers in the same treatment. SXM and SYC soil had higher fungal diversity and abundance than SCK. At the genus level, Plectosphaerella, Mortierella and Ascomycota were the dominant groups of fungal communities in SXM and SYC. The fungal diversity and abundance in SXM and SYC soils were higher than in SCK soils. Correlation network analysis of fungal communities with environmental factors showed that organic matter, alkali-hydrolyzable nitrogen and available phosphorus were the main environmental factors for the structural composition of fungal communities of Mortierella, Typhula, Wickerhamomyces, Trichosporon and Candida. In summary, straw returning to the field played an effective role in improving saline-alkaline land, improving soil fertility, affecting the structure and diversity of the fungal community and changing the interactions between microorganisms.

An innovative fluorescent probe based on dicyanoisoflurone derivatives for differential detection of Hg2+ and Cu2+ and its applications in bacteria, cell imaging and food analysis.

BACKGROUND: Heavy metal pollution has become one of the world's most important environmental pollution, especially Hg2+ is enriched, it is easy to enter the human body through the food chain, bind to the sulfhydryl group in the protein, cause mercury poisoning. Traditional methods for detecting Hg2+ have obvious drawbacks, such as poor selectivity and long detection time. Fluorescence detection has attracted attention because of its good sensitivity and specificity detection ability. In previously reported probes for detecting Hg2+, Cu2+ often interferes. Therefore, it is of great practical significance to synthesize a fluorescent probe that can distinguish between Hg2+ and Cu2+. RESULTS: We have successfully synthesized the probe DFS, a fluorescent probe that can differentially detect Hg2+ and Cu2+, and the probe DFS has good selectivity and anti-interference ability for Hg2+ and Cu2+. The fluorescence intensity at 530 nm increased rapidly when Hg2+ was detected; during the Cu2+ detection, the fluorescence intensity at 636 nm gradually decreased, fluorescence quenching occurred, and the detection limits of Hg2+ and Cu2+ were 7.29 × 10-9 M and 2.13 × 10-9 M, respectively. Through biological experiments, it was found that probe DFS can complete the fluorescence imaging of Hg2+ and Cu2+ in Staphylococcus aureus and HUVEC cells, which has certain research value in the field of environmental monitoring and microbiology, and the probe DFS has low cytotoxicity, so it also has broad application prospects in the field of biological imaging. In addition, the probe DFS also has good applicability for Hg2+ and Cu2+ detection in actual samples. SIGNIFICANCE AND NOVELTY: This is a fluorescent probe that can distinguish between Hg2+ and Cu2+, the fluorescence emission peak appears at 530 nm when Hg2+ is detected; when detecting Cu2+, fluorescence quenching occurs at 636 nm, the fluorescence emission peak distance between Hg2+ and Cu2+ differs by 106 nm. This reduces mutual interference between Hg2+ and Cu2+ during detection, it provides a new idea for the detection of Hg2+ and Cu2+.

Dual-modality probe nanodrug delivery systems with ROS-sensitivity for atherosclerosis diagnosis and therapy.

Most acute cardiovascular and cerebrovascular diseases are caused by atherosclerotic plaque rupture leading to blocked arteries. Targeted nanodelivery systems deliver imaging agents or drugs to target sites for diagnostic imaging or the treatment of various diseases, providing new insights for the detection and treatment of atherosclerosis. Based on the pathological characteristics of atherosclerosis, a hydrogen peroxide-sensitive bimodal probe PPIS@FC with integrated diagnosis and treatment function was designed. Bimodal probes Fe3O4@SiO2-CDs (FC) were prepared by coupling superparamagnetic iron oxide and carbon quantum dots synthesized with citric acid, and self-assembled with hydrogen peroxide stimulus-responsive amphiphilic block polymer PGMA-PEG modified with simvastatin (Sim) and target molecule ISO-1 to obtain drug-loaded micelles PGMA-PEG-ISO-1-Sim@FC (PPIS@FC). PPIS@FC could release Sim and FC in an H2O2-triggered manner, achieving the goal of releasing drugs using the special microenvironment at the plaque. At the same time, in vivo magnetic resonance and fluorescence imaging results proved that PPIS@FC possessed targeting ability, magnetic resonance imaging and fluorescence imaging effects. The results of the FeCl3 and ApoE-/- model showed that PPIS@FC had an excellent therapeutic effect and in vivo safety. Therefore, dual-modality imaging drug delivery systems with ROS response will become a promising strategy for the diagnosis and treatment of atherosclerosis.

An innovative near-infrared fluorescent probe with FRET effect for the continuous detection of Zn2+ and PPi with high sensitivity and selectivity, and its application in bioimaging.

As the second most abundant transition metal element in the human body, zinc ions play an important role in the normal growth and development of the human body. We have successfully synthesized a near-infrared fluorescent probe with FRET effect for the detection of Zn2+. Probe DR6G has good selectivity and anti-interference ability for Zn2+. When Zn2+ is added to the probe DR6G solution, it responds completely within seconds, releasing red fluorescence with a detection limit of 2.02 × 10-8 M. As the main product of ATP hydrolysis, PPi is indispensable in various metabolic activities in cells and the human body. Due to the strong binding ability of Zn2+ and PPi, it is easy to form ZnPPi precipitation, so we added PPi to the solution to complete the Zn2+ detection, and realized the continuous detection of PPi, and the detection limit was 2.06 × 10-8 M. Since Zn2+ and PPi play an important role in vivo, it is of great practical significance to design and synthesize a fluorescent probe that can continuously detect Zn2+ and PPi. Biological experiments have shown that the probe DR6G has low cytotoxicity and can complete the detection of exogenous Zn2+ and PPi in cells and living mice in vitro. Bacterial experiments have shown that the DR6G probe also has certain research value in the field of environmental monitoring and microbiology. Due to the constant variation of the fluorescence signals of Zn2+ and PPi during detection, we designed the logic gate program. In practical applications, the probe DR6G can quantitatively detect Zn2+ in zinc-containing oral liquids and qualitatively detect PPi in toothpaste.

Lawn or spontaneous groundcover? Residents' perceptions of and preferences for alternative lawns in Xianyang, China.

Within urban green spaces, spontaneous groundcovers, as potential alternatives for traditional lawns, have garnered attention due to their ecological adaptability. However, little attention has been paid to whether spontaneous groundcovers can serve as suitable replacements for lawns in terms of the aesthetic values and human preferences for each. Based on questionnaires accompanied by photo elicitation, this study explored the perceptions of and preferences for seven kinds of lawns and six kinds of spontaneous groundcovers in China. The effects of social backgrounds on people's perceptions of and preferences for ground covers were also analyzed. The results indicated a general equivalence in preferences for the lawn and spontaneous groundcover. The Taraxacum mongolicum - Cynodon dactylon - Conyza canadensis community was significantly preferred most among all of the selected ground covers. Spontaneous groundcovers were regarded as more natural, wild, variable, and species-richer compared to lawns, while lawns were perceived as better kept than spontaneous groundcovers. Ground covers were preferred which were perceived to have high ecological aesthetic value and low wildness. Industry and attention to herbaceous plants mostly affected human perceptions and preferences among the social background factors, and gender, age, education level, and occupation also had significant effects. The results thus provide the support for the application of spontaneous groundcovers in moderately developed cities, but such application should consider the comprehensive development of ecological aesthetic value and the applicability of different groups of residents.

Field investigation of non-uniform environment in a Venlo-type greenhouse in Yangling, China.

Non-uniform environmental conditioning has established substantial energy-saving and conditioning effects in residential buildings, however, few studies on the technology applied in greenhouses have been conducted. Semi-enclosed greenhouse development is hindered by energy consumption. To better apply non-uniform environmental conditioning technology in greenhouses, it is necessary to investigate the non-uniform characteristics of field environment parameters. Therefore, spatial and temporal measurements of indoor temperature and relative humidity in a Venlo-type greenhouse in Yangling, China, were conducted on June 5-11, 2022. Temperature and humidity sensors were arranged in the greenhouse at 4.5 m intervals, in the canopy, cultivation, center, and root areas. Temperature and humidity measurement points on the greenhouse walls were selected. The measurement results showed large fluctuations in the indoor temperature and relative humidity over time. The difference between indoor and outdoor average temperatures ranged from -5-10 °C and temperatures unsuitable for tomato growth were identified, although some passive conditioning methods such as ventilation and water spraying were employed, which indicates the necessity of active heating and cooling. Based on the measured data, the nonuniformity coefficients of temperature and relative humidity in different directions in the greenhouse were calculated. A larger non-uniformity in the vertical direction was found compared to that in the horizontal direction. These results suggest the possibility of non-uniform environmental conditioning. A rough estimation of the energy consumption by the two different condition modes, namely zone-specific and overall conditioning, was made. A huge energy saving of 69.6 % by the zone-specific conditioning mode was revealed compared to the overall conditioning. This implies a huge advantage in energy efficiency by non-unform environmental conditioning technologies applied in greenhouses. The study provides useful data for understanding non-uniform environments in greenhouses and the application of non-uniform environmental conditioning technologies.

Broadening the Substrate Specificity of Cellobiose Phosphorylase from Clostridium thermocellum for Improved Transformation of Cellodextrin to Starch.

Cellobiose phosphorylase (CBP) catalyzes the reversible phosphorolysis of cellobiose into α-glucose 1-phosphate and glucose. A CBP with a broadened substrate specificity would be more desirable when utilized to convert cellulose into amylose (PNAS, 110: 7182-7187, 2013) and to construct yeast that can phosphorolytically use cellodextrin to produce ethanol. Based on the structure differences in the catalytic loops of CBP and cellodextrin phosphorylase from Clostridium thermocellum (named CtCBP and CtCDP, respectively), CtCBP was mutated to change its substrate specificity. A single-site mutant S497G was identified to exhibit a 5.7-fold higher catalytic efficiency with cellotriose as a substrate in the phosphorolytic reaction compared to the wild type, without any loss of catalytic efficiency on its natural substrate, cellobiose. When the S497G variant was used in the transformation of mixed cellodextrin (cellobiose + cellotriose) to amylose, the amylose yield was significantly increased compared to that of wild-type CtCBP. A structure change in the substrate-binding pocket of the S497G variant accounted for its capacity to accept longer cellodextrins than cellobiose. Taken together, the modified CtCBP, S497G was confirmed to acquire a promising feature favorable to those application scenarios involving cellodextrin's phosphorolysis.

Amorphization-Induced Cation Exchange in Indium Oxide Nanosheets for CO2-to-Ethanol Conversion.

Cation exchange (CE) in metal oxides under mild conditions remains an imperative yet challenging goal to tailor their composition and enable practical applications. Herein, we first develop an amorphization-induced strategy to achieve room-temperature CE for universally synthesizing single-atom doped In2O3 nanosheets (NSs). Density functional theory (DFT) calculations elucidate that the abundant coordination-unsaturated sites present in a-In2O3 NSs are instrumental in surmounting the energy barriers of CE reactions. Empirically, a-In2O3 NSs as the host materials successfully undergo exchange with unary cations (Cu2+, Co2+, Mn2+, Ni2+), binary cations (Co2+Mn2+, Co2+Ni2+, Mn2+Ni2+), and ternary cations (Co2+Mn2+Ni2+). Impressively, high-loading single-atom doped (over 10 atom %) In2O3 NSs were obtained. Additionally, Cu/a-In2O3 NSs exhibit an excellent ethanol yield (798.7 µmol g-1 h-1) with a high selectivity of 99.5% for the CO2 photoreduction. This work offers a new approach to induce CE reactions in metal oxides under mild conditions and constructs scalable single-atom doped catalysts for critical applications.

IL-33 priming and antigenic stimulation synergistically promote the transcription of proinflammatory cytokine and chemokine genes in human skin mast cells.

BACKGROUND: Antigenic stimulation through cross-linking the IgE receptor and epithelial cell-derived cytokine IL-33 are potent stimuli of mast cell (MC) activation. Moreover, IL-33 primes a variety of cell types, including MCs to respond more vigorously to external stimuli. However, target genes induced by the combined IL-33 priming and antigenic stimulation have not been investigated in human skin mast cells (HSMCs) in a genome-wide manner. Furthermore, epigenetic changes induced by the combined IL-33 priming and antigenic stimulation have not been evaluated. RESULTS: We found that IL-33 priming of HSMCs enhanced their capacity to promote transcriptional synergy of the IL1B and CXCL8 genes by 16- and 3-fold, respectively, in response to combined IL-33 and antigen stimulation compared to without IL-33 priming. We identified the target genes in IL-33-primed HSMCs in response to the combined IL-33 and antigenic stimulation using RNA sequencing (RNA-seq). We found that the majority of genes synergistically upregulated in the IL-33-primed HSMCs in response to the combined IL-33 and antigenic stimulation were predominantly proinflammatory cytokine and chemokine genes. Moreover, the combined IL-33 priming and antigenic stimulation increase chromatin accessibility in the synergy target genes but not synergistically. Transcription factor binding motif analysis revealed more binding sites for NF-κB, AP-1, GABPA, and RAP1 in the induced or increased chromatin accessible regions of the synergy target genes. CONCLUSIONS: Our study demonstrates that IL-33 priming greatly potentiates MCs' ability to transcribe proinflammatory cytokine and chemokine genes in response to antigenic stimulation, shining light on how epithelial cell-derived cytokine IL-33 can cause exacerbation of skin MC-mediated allergic inflammation.

Shear Stress and ROS Dual-Responsive RBC-Hitchhiking Nanoparticles for Atherosclerosis Therapy.

Atherosclerosis (AS), a leading cause of death worldwide, is a chronic inflammatory disease rich in lipids and reactive oxygen species (ROS) within plaques. Therefore, lowering lipid and ROS levels is effective in treating AS and reducing AS-induced mortality. In this study, an intelligent biomimetic drug delivery system that specifically responded to both shear stress and ROS microenvironment was developed, consisting of red blood cells (RBCs) and cross-linked polyethyleneimine nanoparticles (SA PEI) loaded with a lipid-lowering drug simvastatin acid (SA), and RBCs were self-assembled with SA PEI to obtain biresponsive SA PEI@RBCs for the treatment of AS. SA PEI could achieve sustained release of SA in response to ROS and reduce ROS and lipid levels to achieve the purpose of treating AS. Shear stress model experiments showed that SA PEI@RBCs could respond to the high shear stress level (100 dynes/cm2) at plaques, realizing the desorption and enrichment of SA PEI and improving the therapeutic efficiency of SA PEI@RBCs. In vitro and in vivo experiments have confirmed that SA PEI@RBCs exhibits better in vivo safety and therapeutic efficacy than SA PEI and free SA. Therefore, shaping SA PEI@RBCs into a biomimetic drug delivery system with dual sensitivity to ROS and shear stress is an effective strategy and treatment to facilitate their delivery into plaques.

Stromal cells in the tumor microenvironment: accomplices of tumor progression?

The tumor microenvironment (TME) is made up of cells and extracellular matrix (non-cellular component), and cellular components include cancer cells and non-malignant cells such as immune cells and stromal cells. These three types of cells establish complex signals in the body and further influence tumor genesis, development, metastasis and participate in resistance to anti-tumor therapy. It has attracted scholars to study immune cells in TME due to the significant efficacy of immune checkpoint inhibitors (ICI) and chimeric antigen receptor T (CAR-T) in solid tumors and hematologic tumors. After more than 10 years of efforts, the role of immune cells in TME and the strategy of treating tumors based on immune cells have developed rapidly. Moreover, ICI have been recommended by guidelines as first- or second-line treatment strategies in a variety of tumors. At the same time, stromal cells is another major class of cellular components in TME, which also play a very important role in tumor metabolism, growth, metastasis, immune evasion and treatment resistance. Stromal cells can be recruited from neighboring non-cancerous host stromal cells and can also be formed by transdifferentiation from stromal cells to stromal cells or from tumor cells to stromal cells. Moreover, they participate in tumor genesis, development and drug resistance by secreting various factors and exosomes, participating in tumor angiogenesis and tumor metabolism, regulating the immune response in TME and extracellular matrix. However, with the deepening understanding of stromal cells, people found that stromal cells not only have the effect of promoting tumor but also can inhibit tumor in some cases. In this review, we will introduce the origin of stromal cells in TME as well as the role and specific mechanism of stromal cells in tumorigenesis and tumor development and strategies for treatment of tumors based on stromal cells. We will focus on tumor-associated fibroblasts (CAFs), mesenchymal stem cells (MSCs), tumor-associated adipocytes (CAAs), tumor endothelial cells (TECs) and pericytes (PCs) in stromal cells.

Cooperative Ni(Co)-Ru-P Sites Activate Dehydrogenation for Hydrazine Oxidation Assisting Self-powered H2 Production.

Water electrolysis for H2 production is restricted by the sluggish oxygen evolution reaction (OER). Using the thermodynamically more favorable hydrazine oxidation reaction (HzOR) to replace OER has attracted ever-growing attention. Herein, we report a twisted NiCoP nanowire array immobilized with Ru single atoms (Ru1 -NiCoP) as superior bifunctional electrocatalyst toward both HzOR and hydrogen evolution reaction (HER), realizing an ultralow working potential of -60 mV and overpotential of 32 mV for a current density of 10 mA cm-2 , respectively. Inspiringly, two-electrode electrolyzer based on overall hydrazine splitting (OHzS) demonstrates outstanding activity with a record-high current density of 522 mA cm-2 at cell voltage of 0.3 V. DFT calculations elucidate the cooperative Ni(Co)-Ru-P sites in Ru1 -NiCoP optimize H* adsorption, and enhance adsorption of *N2 H2 to significantly lower the energy barrier for hydrazine dehydrogenation. Moreover, a self-powered H2 production system utilizing OHzS device driven by direct hydrazine fuel cell (DHzFC) achieve a satisfactory rate of 24.0 mol h-1 m-2 .