Structure control and evolution of atomically precise gold clusters as heterogeneous precatalysts.

Metal clusters have distinct features from single atom and nanoparticle (>1 nm) catalysts, making them effective catalysts for various heterogeneous reactions. Nevertheless, the ambiguity and complexity of the catalyst structure preclude in-depth mechanistic studies. The evolution of metal species during synthesis and reaction processes represents another challenge. One effective solution is to precisely control the structure of the metal cluster, thus offering a well-defined pre-catalyst. The well-defined chemical formula and configurations make atomically precise metal nanoclusters optimal choices. To fabricate an atomically precise metal nanocluster-based heterogeneous catalyst with enhanced performance, careful structural design of both the nanocluster and support material, an effective assembling technique, and a pre-treatment method for these hybrids need to be developed. In this review, we summarize recent advances in in the development of heterogeneous catalysts using atomically precise gold and alloy gold nanoclusters as precursors. We will begin with a brief introduction to the structural properties of atomically precise nanoclusters and structure determination of cluster/support hybrids. We will then introduce heterogeneous catalysts prepared from medium size (tens to hundreds of metal atoms) and low nuclearity nanoclusters. We will illustrate how ligand modification, support-cluster interaction, hybrid fabrication, and heteroatom (Pt, Pd Ag, Cu, Cd, Fe) introduction affect the structural properties and pretreatment/reaction-induced structural evolution of gold nanocluster pre-catalysts. Lastly, we will highlight the synthetic method of NCs@MOF hybrids and their effectiveness in circumventing the adverse cluster structural evolution. These findings are expected to shed light on the structure-activity relationship studies and future catalyst design strategies using atomically precise metal nanocluster pre-catalysts.

Efficacy and safety of immune checkpoint inhibitors with or without radiotherapy in metastatic non-small cell lung cancer: A systematic review and meta-analysis.

Background and purpose: Although immune checkpoint inhibitors (ICIs) have become the first-line treatment for metastatic non-small cell lung cancer (mNSCLC), their efficacy is limited. Meanwhile, recent reports suggest that radiotherapy (RT) can activate the systemic antitumor immune response by increasing the release of antigens from tumor tissues. Therefore, in patients with mNSCLC treated with ICIs, investigations were performed to determine whether the addition of RT improved the outcomes. Furthermore, the adverse events rate was evaluated. Methods and materials: Pubmed, Embase, and Cochrane Library were searched using the keywords "radiotherapy," "immune checkpoint inhibitors," and "non-small cell lung cancer" from the date of inception to 2 May 2022. Randomized controlled trials (RCTs) and nonRCTs (NRCTs) comparing the efficacy and safety of RT combined with ICIs versus ICIs alone in metastatic NSCLC were assessed. The primary outcomes were progression-free survival (PFS) and overall survival (OS), and the secondary outcomes were abscopal response rate (ARR), abscopal control rate (ACR), adverse events rate, and pneumonia rate. The analyses were conducted using the Mantel-Haenszel fixed-effects or random-effects model. The I2 statistic was used to determine heterogeneity, whereas funnel plots and Egger's test were used to assess publication bias. Results: In 15 clinical studies, 713 patients received RT combined with ICIs and 1,275 patients received only ICIs. With regard to PFS and OS, the hazard ratios of RT combined with ICIs were 0.79 (0.70, 0.89) and 0.72 (0.63, 0.82), respectively. In terms of ARR and ACR, the odds ratios (ORs) of RT combined with ICIs were 1.94 (1.19, 3.17) and 1.79 (1.08, 2.97), respectively. Subgroup analyses based on study type (RCT/NRCT), RT target (intracranial/extracranial), number of RT sites (single site), previous ICI resistance (yes/no), and sequencing of RT and ICIs (concurrent/post-RT ICIs) revealed that the addition of RT significantly prolonged PFS and OS. However, subgroup analyses based on radiation dose/fractionation indicated that the addition of hypofractionated RT significantly prolonged OS but not PFS. When grouped according to the level of PD-L1 expression, the addition of RT prolonged PFS only in patients who were PD-L1-negative. Furthermore, subgroup analyses of ARR and ACR signified that the combination therapy resulted in better local control of lesions outside the irradiation field in the hypofractionated RT, extracranial RT, and ICI-naïve subgroups. In terms of adverse events, the addition of RT did not significantly increase the adverse events rate but was associated with a higher pneumonia rate [OR values were 1.24 (0.92, 1.67) and 1.76 (1.12, 2.77), respectively]. Conclusion: Meta-analysis of existing data suggests that the addition of RT can significantly prolong PFS and OS in patients with metastatic NSCLC receiving ICIs. In addition to lesions in the irradiation field, RT can improve the local control rate of lesions outside the irradiation field via immune activation. Combination therapy does not increase the overall risk of adverse reactions, except for pneumonia.

Reveal the threat of water quality risks in Yellow River Delta based on evidences from isotopic and hydrochemical analyses.

This study aims to evaluate the seasonal and spatial characteristics of hydrochemistry and DO isotopes and identify the eco-environmental threats under the background of saline intrusion and human activities in Yellow River Delta (YRD). Analyses for major ions (i.e., K+, Na+, Ca2+, Mg2+, SO42-, HCO3- and Cl-), nitrate ion (NO3-) and isotopic composition are performed for precipitation, river water, wetland water and sea water. Based on the range of δ2H and δ18O as well as their relations, the mixing between multiple sources and evaporation are confirmed. Electrical conductivity (EC), concentration of NO3-, soluble sodium percentage (SSP) and magnesium hazard (MH) are employed as indicators to reflect the ecological risks from salinity, agricultural pollutants, sodium and magnesium. By hierarchical cluster analysis (HCA), the samples of wetland water are grouped associated with those of river water. The characteristic reflects 3 patterns of risks in wetlands, including saline intrusion, human activities and their mixed influence.

Distribution of hydrogen and oxygen stable isotopes and pollution indicators in water during a monsoon transitional period in Min River Basin.

Based on 197 monthly river water and groundwater samples and 30 event-scale precipitation samples, our study reports the distribution of hydrogen and oxygen isotopes and pollution indicators in Min River Basin. The variation of δ18O and d-excess indicate that the water source in the upper main course water is more variable and that in the middle-lower part is relatively stable. Comparison between plots of δ2H versus δ18O in the river water and precipitation reflect the dominant water source is different between river water in the upper and middle-lower parts. The electrical conductivity (EC) shows a similar spatial variation trend for main course water collected in four campaigns. The pollutant concentration change at the confluences of main tributaries shows that the inflow of Heishui River and Dadu River leads to decreased NO3- and Cl-, while that of Xi River, Pu River and Fuhe River leads to a leap in NO3- and Cl-. A significant positive correlation is observed between EC and δ18O, indicating the consistent control of water sources on isotope distribution and water quality. The relationship between elevation and δ18O in the main course river water suggests that the factors affecting isotope distribution vary spatially. "Altitude effect" can only be observed in October and November for the upper steepest plateau zone due to the spatial variation in the precipitation stored during the wet season. The "inverse altitude effect" is observed for the upper part during the wet season and for the middle-lower part during the whole study period, which can be explained by the contribution of tributaries with different discharge regimes. Our findings show that water source with different discharge regimes can serve as the leading factor controlling the stream component in multi-tributary river basins with large spatial span and may mask the influence of spatial distribution of precipitation.

Using stable isotopes as tracer to investigate hydrological condition and estimate water residence time in a plain region, Chengdu, China.

The oxygen and hydrogen isotopic compositions (δ18O and δ2H) were measured on river water and precipitation collected from four sub-catchments within the upper Tuojiang River catchment. δ18O values of river water and precipitation exhibit significant seasonal variations. These seasonal variations are used for estimating the mean residence time (MRT) for four sub-catchments by an exponential model, ranging from 346 to 493 days. The correlation between catchment MRT and mean slope of the catchment (r2 = 0.29) is weak, while the correlations between catchment MRT, catchment area (r2 = 0.79) and topographic index (r2 = 0.98) are strong. These results indicate that topography and catchment area, both control the catchment MRT and the topographic index may be a reliable parameter for estimating the catchment MRT. Moreover, the relationship between land use types and MRT was investigated. The results show that paddy fields (r2 = 0.95) compared to the other land use types may have a greater impact on the MRT of the irrigation-dominated catchment. This study provides a preliminary exploration of the factors affecting MRT in the plain region and a basis for simulating MRT in the future.

Revealing the impact of water conservancy projects and urbanization on hydrological cycle based on the distribution of hydrogen and oxygen isotopes in water.

In recent years, the development and utilization of water resources have imposed great impacts on hydrological characteristics and ecological environment. In this paper, methods based on stable isotopes were used to analyze the cumulative effect of water projects and urbanization on the hydrological cycle in Qingbaijiang River Basin. Isotope evidence shows that the hydrological processes affected by water regulation and urbanized runoff generation differentiate greatly from the natural state. The annual mean isotopic values follow an order of groundwater > rainwater > river water. Consistent isotopic composition and variation trend between the near-bank groundwater and river water were only observed from May to late June 2018 and from February to April 2019 in the upper zone, indicating the dominant recharge of river to the groundwater. However, the isotopic variations between the two waters in the middle and lower zones suggested that the hydraulic exchange was limited, demonstrating the significant changes in river water level caused by the reservoir impoundment. The isotopic enrichment rate along the flow path is highest in January (0.0265‰/km), followed by October (0.0160‰/km), indicating the significant evaporation, while slight spatial changes in July (0.0027‰/km) reflected masked evaporation effect. This variability can be mainly attributed to the flow rate change and increase of water salinity in anthropic zones. Periodic regression analysis was employed to evaluate the difference in rainfall-runoff responses between hydrographic zones and estimate the mean residence time (MRT). Periodicity of isotopes in river water increased from upper to lower reaches with increasing R2 values from 0.04 in SW1 to 0.46 in SW8. The MRT grew shorter along the flow path from 870 days in SW1 to 293 days in SW8, reflecting accelerated rainfall-runoff process due to the increasing impervious surface area and drainage system. These results identify the sensitivity of stable isotopes to the land use changes, runoff generation, and topography, and have implication for the potential water and environmental risks. Based on these understandings, suggestions for sustainable water-environment management in urban and rural areas were proposed.

Prevention and treatment of radiation-induced lung injury.

Radiation-induced lung injury (RILI) is a common complication in cancer patients receiving local thoracic radiation and bone marrow transplantation conditioning. It is divided into early-stage radiation pneumonitis and advanced radiation fibrosis of the lung. This severely hampers the quality of life and survival of cancer patients. Meanwhile, RILI is a major factor limiting radiation doses in clinical practice, which affects the local control of cancer. Unfortunately, the mechanism of RILI is still not well defined, and there are no treatment options available for these patients. In this review we summarize the methods and agents used for the treatment and prevention of RILI, with the aim of increasing understanding of RILI.

[Analysis of Stable Hydrogen and Oxygen Isotope Characteristics and Vapor Sources of Event-based Precipitation in Chengdu].

Based on analysis of hydrogen and oxygen isotopes in 113 rainfall samples collected from September 2016 to October 2017 in Chengdu, which is a typical representative of humid areas affected by multiple moisture sources, the compositional characteristics of hydrogen and oxygen isotopes (2H, 18O, and 17O) and the water vapor sources of precipitation were analyzed. It was found that δD, δ18O, δ17O, d-excess, and 17O-excess in atmospheric event-based precipitation have significant seasonal variation. In the dry season they are high and in the wet season are low, reflecting the different moisture sources during two seasons (dry and wet). The slope and intercept of the Local Meteoric Water Line were small, indicating that the precipitation originated from sources with various stable isotope ratios and that raindrops were subject to secondary evaporation during their landing process. The Local Meteoric Water Line slope for the triple oxygen isotopes (δ'17O=0.5289δ'18O+0.0075) ranged between the slopes for seawater vapor and dry air, and the value of 17O-excess was far larger than that of seawater. This indicates that the Chengdu area lies in the path of marine air masses moving toward inland regions. The atmospheric precipitation mainly came from these marine air masses and the isotope had undergone serious enrichment in the process of reaching the area. The d values were close to the global average, and the extremely low value of d-excess in the dry season may be affected by artificial rainfall operations. In addition to the relative humidity of the water vapor source, 17O-excess is also affected by the upstream air mass convection; moreover, the 17O-excess of the precipitation was not affected by the meteorological factors over the whole study period, so the 17O-excess could be considered tracers of evaporative conditions at the vapor source in Chengdu. The precipitation 17O-excess in different seasons provides additional information to better understand the precipitation formation processes in Chengdu.

Effect of selenium supplements on the antioxidant activity and nitrite degradation of lactic acid bacteria.

Selenium (Se) is one of the essential trace elements in the human body, and Se-enriched lactic acid bacteria (LAB) can improve the biological utilization value of inorganic Se. The aim of this study was to isolate Se-enriched LAB and study their effects on antioxidant activity and nitrite degradation. The Se-enriched LAB L.P2, which was nitrite-tolerant and could grow in 30 µg/mL sodium selenite (Na2SeO3) medium, was isolated from the traditional fermented Chinese sauerkraut. L.P2 belonged to Lactobacillus plantarum according to the 16S rDNA analysis. The biomass and lactic acid production of L.P2 reached to a maximum (9.52 log CFU/mL and 16.99 mg/mL) when 2.0 µg/mL Na2SeO3 was supplemented in the medium. Additionally, the nitrite degradation rate reached 85.76% when the initial concentration of Na2SeO3 was 2.0 µg/mL. The Se-enriched LAB enhanced the scavenging capacity of hydroxyl radical and superoxide free radical of L.P2 and improved the lipid peroxidation and ion-chelating abilities. Moreover, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in Se 4 group (4.0 µg/mL Na2SeO3 was added) reached 48.49 and 50.35 U/mg, respectively. Thus, Se 4 concentration was significantly higher than that of Se 0 group (with no Se added). In particular, SOD and GSH-Px enzymes correlated with nitrite degradation (P < 0.01). Collectively, our results indicate that Se supplementation can enhance the antioxidant capacity of LAB, contribute to its nitrite degradation, and thus may have potential applications in functional foods.

Transplantation of Bone Marrow Mesenchymal Stem Cells Prevents Radiation-Induced Artery Injury by Suppressing Oxidative Stress and Inflammation.

The present study aims to explore the protective effect of human bone marrow mesenchymal stem cells (hBMSCs) on radiation-induced aortic injury (RIAI). hBMSCs were isolated and cultured from human bone marrow. Male C57/BL mice were irradiated with a dose of 18-Gy 6MV X-ray and randomly treated with either vehicle or hBMSCs through tail vein injection with a dose of 103 or 104 cells/g of body weight (low or high dose of hBMSCs) within 24 h. Aortic inflammation, oxidative stress, and vascular remodeling were assessed by immunohistochemical staining at 3, 7, 14, 28, and 84 days after irradiation. The results revealed irradiation caused aortic cell apoptosis and fibrotic remodeling indicated by aortic thickening, collagen accumulation, and increased expression of profibrotic cytokines (CTGF and TGF-ß). Further investigation showed that irradiation resulted in elevated expression of inflammation-related molecules (TNF-α and ICAM-1) and oxidative stress indicators (4-HNE and 3-NT). Both of the low and high doses of hBMSCs alleviated the above irradiation-induced pathological changes and elevated the antioxidant enzyme expression of HO-1 and catalase in the aorta. The high dose even showed a better protective effect. In conclusion, hBMSCs provide significant protection against RIAI possibly through inhibition of aortic oxidative stress and inflammation. Therefore, hBMSCs can be used as a potential therapy to treat RIAI.

Therapeutic effects of bone marrow-derived mesenchymal stem cells on radiation-induced lung injury.

Radiation-induced lung injury (RILI) is a fatal condition featured by interstitial pneumonitis and fibrosis. Mesenchymal stem cells (MSCs) have been widely used for treating RILI in rodent models. In the present study, we aimed to investigate whether the therapeutic effects of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) on RILI were in a dose-dependent manner. A total of 100 mice were randomly divided into: a control group (n=25), subject to lung irradiation and injection of phosphate-buffered solution (PBS) via the tail vein; and the hBM-MSC group, subject to lung irradiation followed by injection of a low dose (1x103 hBM-MSCs/g), medium dose (5x103 hBM-MSCs/g) and high dose (1x104 hBM-MSCs/g) of hBM-MSCs in PBS through the tail vein, respectively. After sacrifice, the pulmonary tissues were subject to hematoxylin and eosin (H&E) staining, Masson's trichrome staining and immunohistochemical staining to investigate the pathological changes. Immunofluorescent staining was performed to evaluate the differentiation capacity of hBM-MSCs in vivo by analyzing the expression of SPC and PECAM. hBM-MSCs improved the survival rate and histopathological features in the irradiated mice, especially in the low-dose group. Marked decrease in collagen deposition was noted in the irradiated mice treated using a low dose of hBM-MSCs. In addition, hBM-MSCs attenuated secretion and expression of IL-10 and increased the expression of TNF-α. Furthermore, hBM-MSCs had the potential to differentiate into functional cells upon lung injury. Low-dose hBM-MSCs contributed to functional recovery in mice with RILI.

ERCC2 polymorphisms and radiation-induced adverse effects on normal tissue: systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: The relationship between ERCC2 polymorphisms and the risk of radiotoxicity remains inconclusive. The aim of our study is to systematically evaluate the association between ERCC2 polymorphisms and the risk of radiotoxicity. METHODS: Publications were identified through a search of the PubMed and Web of Science databases up to August 15, 2015. The pooled odds ratios (ORs) with corresponding 95 % confidence intervals (CIs) were calculated to evaluate the association between ERCC2 polymorphisms and radiotoxicity. Trial sequential analysis (TSA) and power calculation were performed to evaluate the type 1 and type 2 errors. RESULTS: Eleven studies involving 2584 patients were ultimately included in this meta-analysis. Conventional meta-analysis identified a significant association between ERCC2 rs13181 polymorphism and radiotoxicity (OR = 0.71, 95 % CI: 0.55-0.93, P = 0.01), but this association failed to get the confirmation of TSA. CONCLUSIONS: The minor allele of rs13181 polymorphism may confer a protect effect against radiotoxicity. To confirm this correlation at the level of OR = 0.71, an overall information size of approximate 2800 patients were needed.

Association between Single Nucleotide Polymorphisms in XRCC3 and Radiation-Induced Adverse Effects on Normal Tissue: A Meta-Analysis.

The X-ray repair cross-complementing group 3 (XRCC3) protein plays an important role in the repair of DNA double-strand breaks. The relationship between XRCC3 polymorphisms and the risk of radiation-induced adverse effects on normal tissue remains inconclusive. Thus, we performed a meta-analysis to elucidate the association between XRCC3 polymorphisms and radiation-induced adverse effects on normal tissue. All eligible studies up to December 2014 were identified through a search of the PubMed, Embase and Web of Science databases. Seventeen studies involving 656 cases and 2193 controls were ultimately included in this meta-analysis. The pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the association between XRCC3 polymorphisms and the risk of radiation-induced normal tissue adverse effects. We found that the XRCC3 p.Thr241Met (rs861539) polymorphism was significantly associated with early adverse effects induced by radiotherapy (OR = 1.99, 95%CI: 1.31-3.01, P = 0.001). A positive association lacking statistical significance with late adverse effects was also identified (OR = 1.28, 95%CI: 0.97-1.68, P = 0.08). In addition, the rs861539 polymorphism was significantly correlated with a higher risk of adverse effects induced by head and neck area irradiation (OR = 2.41, 95%CI: 1.49-3.89, p = 0.0003) and breast irradiation (OR = 1.41, 95%CI: 1.02-1.95, p = 0.04), whereas the correlation was not significant for lung irradiation or pelvic irradiation. Furthermore, XRCC3 rs1799794 polymorphism may have a protective effect against late adverse effects induced by radiotherapy (OR = 0.47, 95%CI: 0.26-0.86, P = 0.01). Well-designed large-scale clinical studies are required to further validate our results.

The anti-fibrotic effects of mesenchymal stem cells on irradiated lungs via stimulating endogenous secretion of HGF and PGE2.

Radiation-induced pulmonary fibrosis is a common disease and has a poor prognosis owing to the progressive breakdown of gas exchange regions in the lung. Recently, a novel strategy of administering mesenchymal stem cells for pulmonary fibrosis has achieved high therapeutic efficacy. In the present study, we attempted to use human adipose tissue-derived mesenchymal stem cells to prevent disease in Sprague-Dawley rats that received semi-thoracic irradiation (15 Gy). To investigate the specific roles of mesenchymal stem cells in ameliorating radiation-induced pulmonary fibrosis, we treated control groups of irradiated rats with human skin fibroblasts or phosphate-buffered saline. After mesenchymal stem cells were infused, host secretions of hepatocyte growth factor (HGF) and prostaglandin E2 (PGE2) were elevated compared with those of the controls. In contrast, tumour necrosis factor-alpha (TNF-α) and transforming growth factor-beta1 (TGF-ß1) levels were decreased after infusion of mesenchymal stem cells. Consequently, the architecture of the irradiated lungs was preserved without marked activation of fibroblasts or collagen deposition within the injured sites. Moreover, mesenchymal stem cells were able to prevent the irradiated type II alveolar epithelial cells from undergoing epithelial-mesenchymal transition. Collectively, these data confirmed that mesenchymal stem cells have the potential to limit pulmonary fibrosis after exposure to ionising irradiation.

Human immunodeficiency virus-negative plasmablastic lymphoma: a comprehensive analysis of 114 cases.

Human immunodeficiency virus-negative plasma-blastic lymphoma (PBL) is an extremely rare entity. Its clinicopathological features, optimal treatment strategy and prognostic factors remain obsure. An extensive search was performed in the English language literature within the Pubmed database using the key words: 'plasmablastic lymphoma and human immunodeficiency virus-negative or immunocompetent'. Data from 114 patients from 52 articles were analyzed. The mean patient age at diagnosis was 58.90 years (range, 2-86). HIV-negative PBL showed a predilection for elderly individuals (patients older than 60 years, 56.14%) and affected more males than females (M:F, 2.29:1). Ann Arbor stage IV patients accounted for 39.22% while bone marrow involvement was less frequent (12.79%). The Ki-67 index was high with a mean expression of 83%. Epstein-Barr virus (EBV) infection was common being positive in 58.70% of the patients while herpesvirus-8 (HHV-8) infection was rare being positive in only 7.55% of the patients. Immunosuppression was noted in 28.16% of patients. The median overall survival (OS) was 19 months. The 1- and 2-year survival rates were 52.3 and 45.3%, respectively. Age, gender and primary site showed no strong relationship with OS while Immunosuppression, Ann Arbor stage IV and EBV negativity were able to predict a poorer OS. Either complete remission (CR) or partial remission (PR) was superior to the refractory group in OS (P<0.0001 and P=0.0066, respectively). For stage â…  patients, the application of radiotherapy did not improve the OS. In conclusion, HIV-negative PBL is a distinct entity likely occurring in elderly and immunosuppressed individuals. Immunosuppression status, Ann Arbor stage IV, EBV negativity and refractory to treatment are poor prognostic factors of OS in HIV-negative PBL.