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The molecules of Major histocompatibility class I (MHC-I) load peptides and present them on the cell surface, which provided the immune system with the signal to detect and eliminate the infected or cancerous cells. In the context of cancer, owing to the crucial immune-regulatory roles played by MHC-I molecules, the abnormal modulation of MHC-I expression and function could be hijacked by tumor cells to escape the immune surveillance and attack, thereby promoting tumoral progression and impairing the efficacy of cancer immunotherapy. Here we reviewed and discussed the recent studies and discoveries related to the MHC-I molecules and their multidirectional functions in the development of cancer, mainly focusing on the interactions between MHC-I and the multiple participators in the tumor microenvironment and highlighting the significance of targeting MHC-I for optimizing the efficacy of cancer immunotherapy and a deeper understanding of the dynamic nature and functioning mechanism of MHC-I in cancer. [ABSTRACT FROM AUTHOR]

Background. To evaluate the efficacy and safety of Shengxuening combined with conventional iron supplementation in the treatment of anemia during pregnancy. Methods. Electronic searches of Embase, Web of Science, Cochrane Library, China Biomedical Literature Database (CBM), China Knowledge Network (CNKI), Wanfang database (Wanfang), and China Science and Technology Journal Database (VIP) were conducted. A randomized controlled trial of Shengxuening combined with conventional iron supplements for the treatment of anemia in pregnancy was included. The quality of the included trials was assessed using the Cochrane Handbook's Risk of Bias Assessment Tool (version 5.1.0), and data analysis was performed using RevMan 5.4 software and Stata 15.0 statistical software. Results. A total of 150 studies were detected and 17 studies with a total of 1741 cases were finally included. Meta-analysis results showed that the effectiveness of Shengxuening combined with conventional iron supplementation was significantly better than that of conventional iron supplementation alone, and the adverse effects were significantly reduced compared with that of iron supplementation alone, and various anemia indicators such as Hb, RBC, MCV, and MCHC and iron metabolism indicators such as SI and TSAT were also significantly increased. Conclusion. The efficacy of the combination of Shengxuening and conventional iron supplementation in the treatment of anemia in pregnancy is better than that of conventional iron supplementation alone, and the adverse effects in the experimental group are much less than those in the control group, but the quality of the included studies is not high, and more high-quality randomized controlled trials are needed for further validation. [ABSTRACT FROM AUTHOR]

Objectives: Exosomes are essential mediators of intercellular communication as they transport proteins and RNAs between cells. Owing to their tumor‐targeting capacity, immune compatibility, low toxicity, and long half‐life, mesenchymal stem cell‐derived exosomes have great potential for the development of novel antitumor strategies. In this context, the role of exosomes produced by adipose‐derived mesenchymal stem cells (ADSCs) for the treatment of bladder cancer (BC) remains unclear. Here, we investigated the use of ADSCs as a source of therapeutic exosomes, as well as their efficacy in delivering the tumor suppressor miR‐138‐5p in BC. Methods: ADSCs stably expressing miR‐138‐5p were established using Lentivirus infection, and ADSC‐derived miR‐138‐5p exosomes (Exo‐miR‐138‐5p) were isolated from the cell culture medium. The effect of Exo‐miR‐138‐5p on BC cell migration, invasion, and proliferation was evaluated in vitro using wound healing, transwell invasion, and proliferation assays. The in vivo effect of Exo‐miR‐138‐5p was investigated using a subcutaneous xenograft mouse model. Results: Exo‐miR‐138‐5p prevented the migration, invasion, and proliferation of BC cells in vitro. Moreover, ADSC‐derived exosomes could penetrate tumor tissues and successfully deliver miR‐138‐5p to suppress the growth of xenograft tumors in vivo. Conclusions: The present results reveal that ADSC‐derived exosomes are an effective delivery vehicle for small molecule drugs in vivo, and exosome‐delivered miR‐138‐5p is a promising therapeutic agent for BC treatment. [ABSTRACT FROM AUTHOR]

Immune-checkpoint blockade (ICB) demonstrated inspiring effect and great promise in anti-cancer therapy. However, many obstacles, such as drug resistance and difficulty in patient selection, limited the efficacy of ICB therapy and awaited to be overcome. By timely identification and intervention of the key immune-suppressive promotors in the tumor microenvironment (TME), we may better understand the mechanisms of cancer immune-escape and use novel strategies to enhance the therapeutic effect of ICB. Myeloid-derived suppressor cell (MDSC) is recognized as a major immune suppressor in the TME. In this review, we summarized the roles MDSC played in the cancer context, focusing on its negative biologic functions in ICB therapy, discussed the strategies targeted on MDSC to optimize the diagnosis and therapy process of ICB and improve the efficacy of ICB therapy against malignancies. [ABSTRACT FROM AUTHOR]

• ASPN significantly associates with the progression and prognosis of multiple cancers. • ASPN is strongly related to tumor immunity across cancers. • ASPN is a potential therapeutic target for cancer. • ASPN regulates malignant biological functions in bladder cancer. Asporin (ASPN) has been identified as a player in tumorigenesis, but its precise roles and modulatory function are largely unknown. Methods: In the present study, ASPN expression was first explored, followed by a prognostic evaluation of ASPN and a comprehensive investigation of the connections between ASPN and immunomodulation, immune cell infiltration and potential compounds on a pancancer level. Finally, ASPN expression was validated in bladder urothelial carcinoma (BLCA) tissues, and the potential function of ASPN, including its effects on migration and invasion capabilities, was investigated in tumor cells. Results: The expression of ASPN exhibited significant variation across cancers and was found to be associated with patient prognosis. In addition, the expression level of APSN was markedly correlated with the abundances of infiltrating immune cells and cancer-associated fibroblasts and the expression levels of immunomodulatory genes based on the results of pancancer analysis. Metastasis and immune-associated signaling pathways were identified in enrichment analysis based on ASPN expression. Finally, we confirmed that ASPN expression increased with the degree of malignancy in BLCA tissues and cell lines and that low expression of ASPN hindered the migration and invasion of cells. Conclusions: ASPN has the potential to be a biomarker of cancer prognosis and a therapeutic target, and it also has predictive capability for the progression of BLCA. [ABSTRACT FROM AUTHOR]

Previous multi-proxy records have revealed the advantages of well-preserved and long-scale geological archives from the lake sediments of Barkol Lake, which is located at northeast Xinjiang in northwest China. However, the exact organic matter (OM) sources in the sediments and their response to climatic variability still remain unclear in this area. In this study, we present an 8.8 kyr n-alkane record extracted from the sediments in Barkol Lake to explore the OM sources and the relationship between n-alkanes and climatic changes. The results indicate that the n-alkane composition was dominated by long-chain n-alkanes(C27–C31), implying a dominant origination of OM from the terrestrial higher plants and emergent aquatic plants. The n-alkane data further revealed that changes in OM sources were related to the surface erosion-transportation-deposition processes controlled by climatic changes. Lake level changes, which are also regulated by climate conditions, played an important role in impacting OM accumulation. Relatively wetter conditions would result in a rising lake level that favored more aquatic OM and less terrestrial OM input, and vice versa. The regional climate patterns have been generally dominated by alternations of cold-wet and warm-dry episodes over the past ~8.8 kyr. We preliminarily concluded the dynamic changes of OM input and the hydrological changes in Barkol Lake was mainly controlled by SSTs in the North Atlantic region and melting water supply modulated by Eurasian ice sheet. [ABSTRACT FROM AUTHOR]

This study provides a 16.2-kyr record of mercury (Hg) deposition derived from a lacustrine sedimentary sequence in Dahu Swamp, eastern Nanling Mountains. Results indicate that changes in climatic conditions had a significant effect on Hg concentrations (Hg – C) and accumulation rates (Hg -AR). Multi-proxy records including dry density, grain size, geochemical elements, organic matter and pollen indicators were compared with Hg accumulation. The results revealed that the contributions of detrital input and atmospheric deposition were minor, and Hg accumulation in the sediments was closely related to changes in climatic conditions: relatively drier and colder climate would result in shrinkage of the lake water body thus favoring increased formation of organic-rich peat or gyttja and leading to enhanced absorption of Hg by organic matter and result in increases of Hg – C and Hg -AR in sediments, and vice versa. Our results indicate that variations of Hg accumulation in Dahu Swamp were greatly impacted by climate under the influences of solar insolation changes and shrinkage or expansion of ice sheets in high latitudes to the north. The results of this study provide an insight into the response of Hg accumulation to low latitude climate processes in the East Asian summer monsoon region. [ABSTRACT FROM AUTHOR]

• DFT-ML assisted rapid screening of HER electrocatalysts is presented. • Six TM-doped metal phosphides are predicted as promising HER catalyst. • The prediction of DFT-ML model is supported by reported experimental studies. Transition metals (TM) doped metal phosphides usually exhibits promising reactivity towards acidic hydrogen evolution reaction (HER). However, the experimental screening of highly active TM-doped metal phosphides catalyst is time-consuming and challenging. In this study, a density functional theory combined machine learning (DFT-ML) framework is proposed to accelerate the screening and predicting TM-doped metal phosphides-based HER electrocatalysts. In this framework, the ML database is constructed using critical catalyst features and DFT-calculated adsorption energy of HER intermediates. Also, local average electronegativity of the adsorption site and the surrounding atoms as catalyst feature is proposed to describe the reaction sites in this ML model. Using the HER energetics on the state-of-art highly active Pt (111) as benchmark catalyst model, a set of 10 potential active HER catalysts is predicted. By performing the H* adsorption Gibbs free energy change analysis on these ML-predicted catalysts, six promising TM-doped metal phosphides HER catalysts are determined in the sample space. This study provides a facile and effective approach for the quick screening of high-performance HER electrocatalysts. [Display omitted] [ABSTRACT FROM AUTHOR]

We show, from a 16.6 ka record of lead isotopes from a core sediments in Dahu Swamp in eastern Nanling Mountains, that the chemical weathering responds to changes in climatic conditions. Pb isotopic signals reveal that the local weathered granitoid was the dominant source of Pb deposition. However, two isotopic excursions appeared from 15.5–15.2 and 5.2–4.8 ka BP, which coincide with the dry/cold H1 event and the mid- and late-Holocene respectively, likely suggesting an additional contribution of aeolian dust from North China. Even more, more radiogenic Pb signal of E2 exhibits a mixed contribution of enhanced anthropogenic mining. We expect strong enough EAWM would dominate these two intervals. Supported by multi-proxy records, we conclude that variations Pb isotopic signals (e.g., 206Pb/204Pb, 207Pb/204Pb and 208Pb/204Pb ratios) are closely related to climate-induced chemical weathering. Synchronous variations of 208Pb/204Pb, 206Pb/204Pb and 207Pb/204Pb ratios in the core display a congruent Pb isotope signals released from both U- and Th-rich accessory minerals. During intensive chemical weathering under wetter/warmer conditions (e.g., the Bølling and Allerød events, and the Holocene Optimum period), more preferential release of radiogenic 206Pb, 207Pb and 208Pb can be absorbed by fine detritus and then eroded to the lake thus resulting in increased 208Pb/204Pb, 206Pb/204Pb and 207Pb/204 ratios in sediments, and vice versa if a drier/colder climate dominates (e.g., the H1, the Older and Younger Dryas events, and the mid- & late-Holocene). The inferred changes in chemical weathering from Dahu sediments have varied in tandem with multi-regional monsoonal proxies in China, and exhibited a sensitive response of chemical weathering to global climate change. [ABSTRACT FROM AUTHOR]

Understanding the responses of vegetation composition to climate, fire regimes and human disturbance is crucial to provide valuable insights to protect current and future ecosystems. However, relevant studies were poorly performed on the heavily forested montane areas in subtropic East Asia. In this study, we present pollen and charcoal records from a 95-cm long peat core in the subalpine Daping swamp in the western Nanling Mountains in subtropic China, to discuss the possible interactions among vegetation, fire, climatic change, and human activities in the late-Holocene. Our results suggest that the vegetation in the study area was composed of deciduous–evergreen mixed forests with few fire events during 3140–630 cal yr BP, and its changes were mainly controlled by climate with rare human impacts reflected by low concentrations of charcoals, low proportions of Poaceae pollen, and high AP/NAP ratios. After 630 cal yr BP, pollen data indicate an obvious shift from dense forests to more open landscape. The sharp increase of charcoal concentrations, the extremely low AP/NAP and increased Poaceae percentages suggest that this vegetation shift is not only impacted by the dry climate conditions, but also by the intensified deforestation due to enhanced human activities such as the slash-and-burn cultivation, etc. This study reveals a vital transitional timing from the natural to the superimposed anthropogenic forcing of vegetation composition and fire regimes at ~630 cal yr BP. Regional comparison of charcoal records indicates that the onset timing of intensified human disturbance in the inland montane areas is much later than that in the coastal areas in subtropic China. We infer the obstacle impacts of the montane terrain and the different responses of the dissemination of agriculture and enhanced population migration have played a crucial role in this asynchronous spreading pattern. [ABSTRACT FROM AUTHOR]

In this study, we used a ~47.0-kyr record of Sr–Nd isotopic data derived from lake sediments in Dahu swamp in the eastern Nanling Mountains to explore the possible changes in the source of sediments, and to provide insights into the East Asian winter monsoon (EAWM) driven climatic signals. Based on Sr–Nd isotopic results, we argued that local weathered granitic residues were the dominant source of sediments throughout the past ∼47.0 kyr. However, variations of 87Sr/86Sr and 144Nd/143Nd ratios were likely disturbed by the mixture of an additional input from Chinese Loess Plateau (CLP). During some dry/cold millennial periods (e.g., Heinrich event 5, 4, and 2, and the 26.0–24.0 kyr B.P), similar Sr–Nd isotopic signatures between the lake sediments and the fine fraction (<20 μm) of the loess from CLP implied an aeolian dust source. Thus, variability of Sr-Nd isotopic ratios indirectly indicated two modes of climate patterns: the wet and warm intervals during which the sediments were mainly derived from the local weathered residues were expressed in increased 87Sr/86Sr and decreased 144Nd/143Nd ratios, whereas during the dry and cold intervals the increased input of fine dust from CLP transported by strengthened EAWM winds would favor declined 87Sr/86Sr and increased 144Nd/143Nd ratios. Our Sr‒Nd isotopic records revealed an anti-phase between the EAWM and the summer monsoon, and displayed a good consistency with the record of mean grain size of quartz of loess from CLP, which was regarded as a reliable proxy of EAWM, suggested they can indirectly reflect variability of EAWM strength. [ABSTRACT FROM AUTHOR]

There are differences in the response of long-term mercury (Hg) deposition to climate change, so it is necessary to clarify the influencing factors of Hg deposition in different locations. The Dahu and Daping Swamps are located in the eastern and western parts of the Nanling Mountains in South China, respectively. They are asynchronous variations of Hg deposition reflected by the two swamps since the last deglaciation. Based on the comprehensive comparative analysis of physical, chemical, and biological proxies, it is indicated that Hg deposition changes in the Dahu and Daping mainly record the changes in Hg content in the catchment input from organic matter. The differences in organic matter sources, core surrounding environment, Hg sources and atmospheric sedimentation contribution are reasons associated with the catchment environment for the observed differences in swamp Hg deposition and the response to climate. In cold/dry periods, Hg adsorption by terrestrial organic matter in Dahu Swamp were more significant, while in warm/humid periods, Hg adsorption by endogenous organic matter in Daping Swamp and wet deposition of nearby Hg sources, were the main climate-related processes for their asynchronous response. In addition, Dahu and Daping Swamps show similarities and differences in their Hg deposition variations. In both swamps, multi-millennial (∼1000−2200yr) and multi-centennial cycles (∼300–500yr) were observed and may be related to the harmonic period of the Earth's precession cycle and the solar activity cycle. This study helps to understand the differences in response between sedimentary Hg and climate, and to understand the regional and global proxies used to record climate and environmental changes. • Hg deposition investigated in two swamps in the Nanling Mountains in South China. • Hg deposition in subtropical swamps responds to climate changes since the Last Deglaciation. • Changes in Hg deposition are asynchronous in the two swamps. • Low latitude climate processes affect EASM strength and Hg deposition in South China. • Millennial and centennial scale cycles in Hg deposition are also recorded. [ABSTRACT FROM AUTHOR]

Chondrite‐normalized rare earth element (REE) data of a ~47.0‐ka lake sedimentary sequence from the Dahu Swamp in the eastern Nanling Mountain area were used to determine climatic variations within the region. These sediments proved to be valuable proxies of climatic changes and their origin is discussed. The influences of grain size, organic matter absorption and Fe‐Mn oxides on REE composition were determined to not be significant. The dominant source of sediments was ascertained to be the weathered granite residues from the catchment, enriched in light rare earth elements (LREE). Intensified East Asian summer monsoon (EASM) resulted in intensive chemical weathering, leading to enhanced REE and LREE fractionations in the weathered residues; this caused the increase in REE and LREE, and decrease in heavy rare earth element (HREE) fractionation degrees in the sediment. Therefore, our results indicate that changes in LREE/HREE, (La/Yb)N, (La/Sm)N) and (Gd/Yb)N, the proxies of REE, LREE, and HREE fractionations, can serve as proxies of regional climate‐induced chemical weathering and thus serve to constrain EASM changes. [ABSTRACT FROM AUTHOR]

[Display omitted] • Efficient bifunctional electrocatalyst toward HER/OER reaction is developed. • Introduction of CeO 2 on (Ni, Co) 2 P nanosheets promotes HER/OER activity. • Low HER (151 mV) and OER (257 mV) overpotential is achieved at100 mA·cm−2. • Low cell voltage of 1.70 V is required for overall water splitting at 100 mA·cm−2. Developing low-cost and high-performance electrocatalysts for water splitting is crucial for hydrogen production. In this study, a high-performance hydrogen and oxygen evolution reaction (HER/OER) bifunctional electrocatalyst is developed by introducing oxygen-deficient CeO 2 nanoparticles on (Ni, Co) 2 P nanosheets. The introduction of defective CeO 2 modulates the electronic structure of the CeO 2 @(Ni, Co) 2 P/NF interface, which offers a synergistic effect promoting the HER/OER reaction in the alkaline water splitting process. Specifically, the CeO 2 @(Ni, Co) 2 P/NF electrode exhibits an overpotential of 151 mV for HER and 257 mV for OER at current density of 100 mA·cm−2. In the overall water electrolysis test, it exhibits excellent stability performance at a cell voltage of 1.70 V around 100 mA·cm−2. This work shows an alternative strategy for the development of active bifunctional water splitting electrocatalysts. [ABSTRACT FROM AUTHOR]

Mounting evidence has suggested that inflammation is associated with IL-6/Stat3 pathway in dendritic cells (DCs) and Th17 cells, which are critical for development of allergic contact dermatitis (ACD). Paeoniflorin (PF) has been clinically proved to be effective in the treatment of inflammatory skin diseases such as ACD. We have previously demonstrated the effect of PF on DCs stimulated with 1-chloro-2,4-dinitrobenze (DNCB) and naïve CD4 + CD45RA + T cells for Th17 cell differentiation. However, whether PF down-regulates IL-6/Stat3 in DCs and Th17 cells remains to be explored. In this study, we show clearly that PF markedly decreases IL-6/Stat3 in DCs stimulated with DNCB at both gene and protein levels compared with control DCs in vitro. Meanwhile, PF up-regulates suppressor of cytokine signaling 3 (Socs3). Such decreased expression of IL-6/Stat3 is abolished in DCs that were transfected with Socs3 short interfering RNA (siRNA). When mice CD4 + CD45 RA + T cells were co-cultured with PF-treated DCs stimulated with/without DNCB, the gene expression of the Th17 cell markers such as retinoic acid-related orphan nuclear hormone receptor γt (RORγt), IL-17A, and IL-23R decreased, in accordance with the less secretions of IL-17 and IL-23 in vitro and in vivo. Finally, the suppressed Th17 differentiation induced by PF can be abolished by additional recombinant mouse IL-6. Our results suggest that the anti-inflammatory mechanisms introduced by depletion of Socs3 expression or inactivation of the negative regulator such as Socs3 may represent a promising strategy for the prevention of ACD. [ABSTRACT FROM AUTHOR]

Previous multi-proxy records have revealed the advantages of well-preserved and long-scale geological archives from the lake sediments of Daping swamp in the western Nanling Mountains in South China. However, the exact organic matter (OM) sources in the sediments and their response to climatic variability still remain unclear. In this study, we present a 15.3-kyr n -alkane record extracted from lacustrine sediments in this swamp to explore the OM sources and the relationship between OM input and climatic changes. The results indicated that the n -alkane composition in sediments was dominated by long-chain n -alkanes (C 27 -C 31), implying that the OM mainly originated from the terrestrial higher plants and emergent aquatic plants. The n -alkane data further verified that changes in OM sources were related to the surface erosion-transportation-deposition processes controlled by climatic changes. Lake level change, which was also regulated by climate conditions, played an important role in impacting OM accumulation; warmer and wetter conditions would result in rising lake levels that favored more aquatic OM and less terrestrial OM input, and vice versa. Variability of the Asian summer monsoon intensity regulated by the dynamic variations in low-latitude processes (e.g., solar insolation, intertropical convergence zone, and El Niño/Southern Oscillation), as well as high-latitude processes (e.g., meltwater input in the North Atlantic), was closely related to the OM accumulation in sediments. • A 2.36-m n -alkane records from the subalpine Daping Swamp in western Nanling Mountains (South China) were reported. • n -Alkane proxies revealed the OM source mainly originated from terrestrial higher plants and emergent aquatic plants. • The OM accumulation is closely related to climatic/environmental conditions. • The warm and wet conditions favor increased aquatic/autochthonous and decreased terrestrial/allochthonous OM input, and vice versa. [ABSTRACT FROM AUTHOR]