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We explore the mechanisms of the attitude–behavior paradox and how multiple stakeholders strategize to compromise their attitudes and behaviors. Through an instrumental variable probit model, we examine the effect of income heterogeneity and social ties on the farmers’ attitude–behavior paradox for collective action. The empirical results demonstrate that weak and strong ties, income heterogeneity, interaction terms, education, community environment, and community rules negatively affect the paradox, whereas water stealing and water use conflicts positively affect it. After dividing the paradox into two forms, we find that weak ties, the interaction terms thereof, negatively affect the paradox for “having negative attitude but do have behavior”, while income heterogeneity negatively affects the paradox for “having positive attitude but no behavior”. We contribute to the understanding of mechanisms whereby economic incentives and social structures interplay in addressing the above paradox. We conclude by discussing the implications for policies to overcome this social dilemma.

Global cropland expansion and associated greenhouse gas (GHG) emissions are largely driven by the growing demand of animal-sourced food. Thus, options are urgently needed to enhancing feed supply at a low environmental cost. Here we explored a set of scenarios about improving domestic feed supply, using a linear optimization model. Results indicate that the total feed (energy and protein) production may be increased by 18–32% through optimizing the spatial distribution of feed crops across provinces, without additional cropland input. GHG emissions and nitrogen and phosphorus inputs per MJ of produced feed decreased by 18–25%, 18–23%, and 16–21%, respectively. The redistribution strategies provide 10–16% additional animal food, which covers the demand of 195–393 million people. Lastly, we provide suggestions for improving the effectiveness of governmental policies related to spatial planning of crops, so as to alleviate the food-feed competition for cropland and to improve environmental sustainability.

BACKGROUND Workers in fireworks production are mainly at risk for explosion injury. However, there are few reports on the consequences of methanol poisoning in fireworks laborers. CASE PRESENTATION We report on three patients with visual loss caused by inhalation exposure to high concentrations of methanol, who were engaged in the granulation process of the fireworks manufacturing industry. They presented with severe metabolic acidosis and visual impairments, accompanied by headache, chest tightness, shortness of breath, dizziness, and vomiting. All were diagnosed with acute methanol poisoning. One patient developed bilateral blindness and two patients improved after timely hemodialysis treatment. CONCLUSIONS These case reports emphasize the risk of methanol poisoning in the fireworks industry or other factories using commercial alcohol with high methanol content. Early hemodialysis intervention and metabolic acidosis correction are crucial for rescuing visual impairment caused by methanol exposure. Awareness and supervision of commercial alcohol use are indispensable for similar industrial processes.

Cisplatin is one of the most effective anti-cancer drugs, but its efficacy is limited by the development of resistance. Previous studies have shown that mitochondria play critical roles in cisplatin cytotoxicity, however, the exact mechanism of mitochondria involved in cisplatin sensitivity has not been clarified. In this study, cisplatin triggered mitochondrial oxidative stress and the decrease of mitochondria membrane potential in human cervical cancer cells. Then we screened a series of mitochondrial relevant inhibitors, including mitochondrial mPTP inhibitors DIDS and CsA, and mitochondrial respiratory complex inhibitors Rot and TTFA. Among these, only DIDS, as the inhibitor of mitochondrial outer membrane protein VDAC1, showed strong antagonism against cisplatin toxicity. DIDS mitigated cisplatin-induced MFN1-dependent mitochondrial fusion, mitochondrial dysfunction and oxidative damage. These findings demonstrated that VDAC1 may serve as a potential therapeutic target in the increase sensitivity of cisplatin, which provides an attractive pharmacological therapy to improve the effectiveness of chemotherapy.

Blockade of the immune checkpoint PD-1/PD-L1 with monoclonal antibodies demonstrated unprecedented clinical efficacies in many cancers. But the orally available low molecular weight inhibitors remain infancy. Compared to small molecules, peptide exhibits better selectivity and fewer side effects, but poor half-life and a big challenge to be orally administrated. Here, we developed a proteolysis-resistant D peptide OPBP-1 (Oral PD-L1 Binding Peptide 1) which could selectively bind PD-L1, significantly block PD-1/PD-L1 interaction and enhance IFN-γ (interferon γ) secretion from CD8+ T cells in human PBMCs (Peripheral blood mononuclear cells). OPBP-1 could significantly inhibit tumor growth in murine colorectal CT26 and melanoma B16-OVA models at a relatively low dose of 0.5 mg/kg, with enhancing the infiltration and function of CD8+ T cells. More interestingly, oral delivery of OPBP-1 loaded TMC (N, N, N-trimethyl chitosan) hydrogel (OPBP-1@TMC) showed promising OPBP-1 oral bioavailability (52.8%) and prolonged half-life (14.55 h) in rats, and also significantly inhibited tumor growth in CT26 model. In conclusion, we discovered and optimized a PD-1/PD-L1 blocking peptide OPBP-1, and subsequently loaded into a TMC based hydrogel oral delivery system, in order to maximally elevate the oral bioavailability of the peptide drug and effectively inhibit tumor growth. These results opened up a new prospect for oral drug development in cancer immunotherapy.

Most cancers contain abundant tumor-associated macrophages (TAMs). TAMs usually display a tumor-supportive M2-like phenotype; they promote tumor growth and influence lymphocyte infiltration, leading to immunosuppression. These properties have made TAMs an attractive cancer immunotherapy target. One promising immunotherapeutic strategy involves switching the tumor-promoting immune suppressive microenvironment by reprogramming TAMs. However, clinical trials of M2-like macrophage reprogramming have yielded unsatisfactory results due to their low efficacy and nonselective effects. In this article, we describe the development of M2-like macrophage-targeting nanoparticles (PNP@R@M-T) that efficiently and selectively deliver drugs to 58% of M2-like macrophages, over 39% of M1-like macrophages, and 32% of dendritic cells within 24 h in vivo. Compared with the control groups, administration of PNP@R@M-T dramatically reprogrammed the M2-like macrophages (51%), reduced tumor size (82%), and prolonged survival. Our findings indicate that PNP@R@M-T nanoparticles provide an effective and selective reprogramming strategy for macrophage-mediated cancer immunotherapy.

This study evaluated the quality of groundwater and its suitability for drinking and irrigation in the hilly area of the Taihang Mountains in Henan Province, China. Groundwater samples were collected from 43 unconfined and 20 confined wells and analyzed. The pollution index of groundwater (PIG) was estimated based on the physicochemical parameters, and seven indices, including the sodium adsorption ratio (SAR), sodium percentage (%Na), residual sodium carbonate (RSC), permeability index (PI), magnesium ratio (MR), Kelley's ratio (KR), and corrosivity ratio (CR), were calculated to qualify the groundwater within the research area for irrigation activities. Multivariate statistical techniques were performed to better understand the hydrochemical processes. Chemical analysis showed that the dominant cation and anion were Ca2+ and HCO3-, respectively, and the principal hydrochemical facies was Ca-Mg-HCO3. In terms of pH, total dissolved solids, Na+, Cl-, F-, and SO42-, most samples were well within the limits prescribed by Chinese standards for drinking water quality, but more than half of the unconfined samples exceeded the specified limits for total hardness and nitrate. The PIG values suggested the pollution level was insignificant for all confined water samples and 72.09% of unconfined water samples, but the PIG distribution map showed that the water in the south central part of the study area had low to moderate pollution. According to the computed values of SAR, %Na, RSC, PI, KR, and MR and the results of a salinity diagram, the results further indicated that most of the studied samples were appropriate for irrigation usage. Only the CR values rendered 41.86% of the unconfined samples and 20% of the confined samples unfit for irrigation. Hence, proper measures are needed to resolve the corrosivity problem. Factor analysis resulted in the extraction of 3 factors that explained 81% of the data variability, and the extracted factors pointed towards geogenic factors governing the groundwater quality.

Transition metal carbides show remarkable catalysis for MgH2, and the addition of carbon materials can attach excellent cycling stability. In this paper, Mg-doped with transition metal carbides (TiC) and graphene (G) composite (denoted as Mg–TiC–G) is designed to assess the influence of TiC and graphene on the hydrogen storage performance of MgH2. The as-prepared Mg–TiC–G samples showed favorable dehydrogenation kinetics compared to the pristine Mg system. After adding TiC and graphene, the dehydrogenation activation energy of MgH2 decreases from 128.4 to 111.2 kJ mol−1. The peak desorption temperature of MgH2 doped with TiC and graphene is 326.5 °C, which is 26.3 °C lower than the pure Mg. The improved dehydrogenation performance of Mg–TiC–G composites is attributed to synergistic effects between catalysis and confinement.

The awareness capability of output power for renewable resources is essential for enhancing the resilience of power systems. Photovoltaic (PV) forecasting technology is an essential technology for increasing the operation efficiency and controllable resources for power systems after extreme natural events. Conventional Markov chain (MC) methods often ignore the time characteristics and the actual distribution of the PV output power sequence when making PV forecasts. This article proposes improved MC methods of equal quantity and clustering‐based division methods. The methods can consider the interval distributions of the PV output power time series and select an hour as the time interval. As a sequence, the predicted power at the next moment can be closer to the expectation of the output power distributions. Such a method is combined with a similar day algorithm to calculate the forecast result. Case studies were conducted with one‐year operation data from a 25‐MW PV station. The results indicate that the proposed methods can effectively improve the accuracy of prediction results compared with traditional methods.

The initial solidification process of microalloyed steels was simulated using a confocal scanning laser microscope, and the growth behavior of austenite grain was observed in situ. The method for measuring the initial austenite grain size was studied, and the M 0 * (the parameter to describe the grain boundary migration) values at different cooling rates were then calculated using the initial austenite grain size and the final grain size. Next, a newly modified model for predicting the austenite grain size was established by introducing the relationship between M 0 * and the cooling rate, and the value calculated from the modified model closely corresponds to the measured value, with average relative error being less than 5%. Further, the relationship between Tγ (the starting temperature for austenite grain growth) and equivalent carbon content CP (CP > 0.18%) was obtained by in situ observation, and it was introduced into the modified model, which expanded the application scope of the model. Taking the continuous casting slab produced by a steel plant as the experimental object, the modified austenite grain size prediction model was used to predict the austenite grain size at different depths of oscillation mark on the surface of slab, and the predicted value was in good agreement with the actual measured value.

One of the key issues in collective action is whether stakeholders are able to realize commons governance through a trust-based mode or control-based mode. This paper, examines whether trust and control affect the commons governance for small-scale irrigation facilities, and the moderating effects of group size on the relationship between trust and control and cooperative performance. The data were collected from 504 households who participated in the collective action for small-scale irrigation facilities in Shaanxi, Gansu Province, and Ningxia Hui Autonomous Region of Northwest China. The analysis was performed by Structural Equation modeling and hierarchical regression. The findings show that trust and control are contrasting forces that influence the participation degree and the cooperative performance, although their relationship is not of a simple supplementary character but could be moderated by the group size. Both trust-based and control-based modes of irrigation management are effective in small groups, whereas only a control-based mode of management has an effect in big groups. The theoretical contribution of this paper clarifies the mechanisms through which the contrasting forces of group size are exerted on trust and control, directly and indirectly influences the participation degree and the cooperative performance in commons governance.

Diosgenin (Dios), a natural steroidal sapogenin, is a bioactive compound extracted from dietary fenugreek seeds. It has a wide range of applications, exhibiting anti‑oxidant, anti‑inflammatory and anti‑cancer activities. However, whether the extracts have beneficial effects on periodontal pathogens has so far remained elusive. The aim of the present study was to investigate the anti‑bacterial effects of Dios on Porphyromonas gingivalis (P. gingivalis) and Prevotella intermedia (P. intermedia) in vitro. The anti‑microbial effect of Dios on P. gingivalis and P. intermedia was assessed by a direct contact test (DCT) and the Cell Counting Kit (CCK)‑8 assay at 60, 90 and 120 min. In addition, counting of colony‑forming units (CFU) and live/dead cell staining were used to evaluate the anti‑bacterial effects. The results of the DCT and CCK‑8 assays indicated that Dios had beneficial dose‑dependent inhibitory effects on P. gingivalis and P. intermedia. The CFU counting results also indicated that Dios had dose‑dependent anti‑bacterial effects on P. gingivalis and P. intermedia. Of note, Dios had significant anti‑bacterial effects on the biofilms of P. gingivalis and P. intermedia in vitro as visualized by the live/dead cell staining method. In conclusion, the present results demonstrated that Dios had a marked anti‑bacterial activity against P. gingivalis and P. intermedia in vitro, both in suspension and on biofilms. The present study highlighted the potential applications of Dios as a novel natural agent to prevent and treat periodontitis through its anti‑bacterial effects.

Basic Oxygen Furnace (BOF) dust can be mixed with binders to prepare cold-bonded pellets and return to BOF for recycling, because of its high total iron and alkaline oxide content. Nevertheless, the lengthy digestion reaction of dead-burned MgO and CaO contained in BOF dust causes expansion and cracking of the pellets, which seriously affect the pellet strength. In this study, it was first proposed to use a hydration reaction between dead-burned MgO and KH2PO4 to form bonding phases based on the hydration mechanism of magnesium potassium phosphate (MKP) cementitious material, to solidify MgO contained in BOF dust and improve the pellet strength. The key issue of using MKP cementitious material as a binder to improve the pellet strength is to choose appropriate magnesium-to-phosphate molar ratio M/P and water-to-binder mass ratio w/b. Based on this, cold-bonded pellets were prepared by using different ratios of MKP binder. The compressive strength, hydration products, microstructure and thermal properties of the pellets were analyzed, and the bonding mechanism of MKP binder in the pellets was proposed. The results show that the pellets have the highest mechanical strength and the most K-Struvite crystals under M/P molar ratio of 4 and w/b mass ratio of 0.5. At high temperatures, K-Struvite crystals will not evaporate harmful phosphorus-containing substances due to the decomposition of the binder components. MKP binder is unevenly distributed in the pellets: in the binder concentrated areas, the massive and dense K-Struvite crystals wrap BOF dust particles; in the binder decentralized areas, the fine K-Struvite crystals are filled between the dust particles or adhere to the surface of dust matrix, connecting the dust particles into a whole.

Basic oxygen furnace (BOF) dust is a kind of solid waste in the metallurgical steelmaking process, which contains more than 50 pct total iron and a certain amount of overburned MgO and CaO. Based on the nonhydraulic cementitious property of MgO in BOF dust, MgCl2 is added together as a binder to prepare cold-bonded pellets returning to BOF, which is the most economical route to recycle secondary resources. In this study, we investigated the hydration and crystallization behavior of MgO-based binder prepared by MgO superheated at 1500 °C and MgCl2 in cold-bonded BOF dust pellets, to solve the problem of whether the overburned MgO can be hydrated with MgCl2 to form crystalline phases, and generated nonhydraulic cementitious structure with high strength to consolidate the pellets. The results show that the overburned MgO prepared at 1500 °C and MgCl2 can form adhesive gels to absorb BOF dust particles by hydration reaction. The gels develop to 5Mg(OH)2·MgCl2·8H2O crystalline phase with a reticular structure after solidification, and the crystalline phase produces pellet mechanical strength by wrapping and connecting bridge. The hydration reaction produced by overburned MgO is incomplete, and the hydration reaction degree is 50 to 65 pct.

Land tenure security perceived by farmers is generally considered an important precondition for rural development. In this paper, we first propose a holistic framework of land tenure security that integrates Van Gelder's tripartite view of tenure security with Ho's credibility thesis. Following this framework, we empirically investigate the interrelation between the cognitive and the affective components of tenure security perceptions, and analyze how these perceptions are influenced by psychological factors, such as personality traits and economic preferences. We apply the generalized structural equation modeling to a dataset collected in 2019 among 1359 rice farmers in three provinces in eastern China. We found that the cognitive component shows an inverse “U-shape” relationship with the affective component, indicating farmers are not necessarily worried about the possible future land reallocation even if they think it is very likely to take place and that the widely used indicator, i.e., estimated probability of land reallocation, is thereby not sufficient to reflect a farmer's overall perceived tenure security. We also found that individual differences in personality traits (e.g., neuroticism) can help explain observed variations in perceived tenure security. The results showing perceived land tenure security of rural farmers also comprises nonequivalent “feeling” and “thinking” components and their influencing psychological factors have important implications for future research and policy making on rural institutional development.

Oral squamous cell carcinoma (OSCC) is widely recognized as an optimal model for precise medicine guided molecular biomarkers of cancer, however, few clinical practices were applied till now. Based on the data from our own studies and published papers, it was found that the expression of MAL was significantly decreased in epithelial cancer as compared with normal tissues, and exhibited a opposite association with pathological grade. To study the molecular events related to deficiency of MAL during carcinogenesis, occurrence and development, a Mal knockout mouse model was constructed and consistently reproduced and bred. The Mal knockout mice are highly vulnerable to tumor induction by carcinogen of 4NQO, evidenced by their extremely earlier carcinogenesis, higher incidence, and more aggressive growth. Analysis of scRNA-seq data indicated that Mal knockout mice lost the ability in maintaining epithelial cell differentiation and get more prone to carcinogen with a remarkably higher incidence of epithelial malignancy. Further analyses identified putative co-functional genes of MAL, including DSG1, AQP3 and S100A8, which are key factors in maintaining epithelial cell differentiation. To conclude, the current study exhibits the clinical significance and explains the tumor suppressing function of MAL. The results also suggest the potential of MAL and its co-functional genes being biomarkers for designing the prevention and/or differentiation therapy strategies in OSCC.SignificanceMAL is found to be strongly opposite with tumor pathological grade from clinical and in vivo studies in OSCC. We propose MAL and its co-functional genes, including DSG1, AQP3 and S100A8, as key factors in maintaining epithelial cell differentiation and are valuable targets for designing prevention and differentiation therapy strategies in OSCC.

N6-methyladenosine (m6A) RNA methylation, one of the most widespread posttranscriptional modifications in eukaryotes, plays crucial roles in various developmental processes. The m6A modification process is catalyzed by a methyltransferase complex that includes Wilms tumor 1-associated protein (WTAP) as a key component. Whether the development of dental enamel is regulated by m6A RNA methylation in mammals remains unclear. Here, we reveal that WTAP is widely expressed from the early stage of tooth development. Specific inactivation of Wtap in mouse enamel epithelium by the Cre/loxp system leads to serious developmental defects in amelogenesis. In Wtap conditional KO mice, we determined that the differentiation of enamel epithelial cells into mature ameloblasts at the early stages of enamel development is affected. Mechanistically, loss of Wtap inhibits the expression of Sonic hedgehog (SHH), which plays an important role in the generation of ameloblasts from stem cells. Together, our findings provide new insights into the functional role of WTAP-mediated m6A methylation in amelogenesis in mammals.

Background Advanced paternal age has been associated with a variety of adverse reproductive outcomes. However, the effects of paternal age on offspring lifespan are still controversial. Result Here, we studied the correlation between parental reproductive age and offspring lifespan using a Chinese specific genealogy data. We chose a “Ding” genealogy data across 130 years during the Qing Dynasty (1726-1855). The present study showed that fathers aged more than 35 years were more likely to have male offspring with lower lifetime compared with fathers aged 20-35 years. The significant negative correlation between paternal age and male offspring lifespan existed after adjusted for maternal age. We proposed a new evidence that advanced paternal age is a risk for male offspring survival.

Background Cisplatin resistance is a major challenge for advanced head and neck cancer (HNC). Understanding the underlying mechanisms and developing effective strategies against cisplatin resistance are highly desired in the clinic. However, how tumor stroma modulates HNC growth and chemoresistance is unclear. Results We show that cancer-associated fibroblasts (CAFs) are intrinsically resistant to cisplatin and have an active role in regulating HNC cell survival and proliferation by delivering functional miR-196a from CAFs to tumor cells via exosomes. Exosomal miR-196a then binds novel targets, CDKN1B and ING5, to endow HNC cells with cisplatin resistance. Exosome or exosomal miR-196a depletion from CAFs functionally restored HNC cisplatin sensitivity. Importantly, we found that miR-196a packaging into CAF-derived exosomes might be mediated by heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1). Moreover, we also found that high levels of plasma exosomal miR-196a are clinically correlated with poor overall survival and chemoresistance. Conclusions The present study finds that CAF-derived exosomal miR-196a confers cisplatin resistance in HNC by targeting CDKN1B and ING5, indicating miR-196a may serve as a promising predictor of and potential therapeutic target for cisplatin resistance in HNC. Electronic supplementary material The online version of this article (10.1186/s13059-018-1604-0) contains supplementary material, which is available to authorized users.

Power system stabilizer plays an important role in suppressing the low frequency oscillations, but a PSS with poorly tuned parameters may produce negative damping and aggravate the system oscillation. The purpose of this paper is to study the mechanism of damping of a PSS in multi machine system and to analyze whether the PSS has produced negative damping. This paper adopts Park model for analysis. According to the concepts of complex frequency and generalized phasor, the correlation between the damping torque phasor and the real part of the complex eigenvalue is studied. With the auxiliary of Park equivalent circuits, the damping torque provided by the excitation system is separated from the electrical torque phasor. Then, the damping torque coefficient of the PSS is defined as an indicator of the damp effect of the stabilizer. Finally, the simulation results of single machine infinite bus system and 4-machine system demonstrate the validation of the proposed method for evaluating the damping effect of PSS on the system.

Premature ovarian failure (POF) is a typical form of pathological aging with complex pathogenesis and no effective treatment. Meanwhile, recent studies have reported that a high-fat and high-sugar (HFHS) diet adversely affects ovarian function and ovum quality. Here, we investigated the therapeutic effect of thymopentin (TP-5) as a treatment for murine POF derived from HFHS and its target. Pathological examination and hormone assays confirmed that TP-5 significantly improved murine POF symptoms. And, TP-5 could reduce oxidative stress injury and blood lipids in the murine POF derived from HFHS. Flow cytometry and qPCR results suggested that TP-5 attenuated activation of CD3+ T cells and type I macrophages. RNA-Seq results indicated somedifferences in gene transcription between the TP-5 intervention group and the control group. KEGG analysis indicated that the expression of genes involved in the mTOR signaling pathway was the most significantly different between the two groups. Additionally, compared with the control groups, the expression levels of interleukin, NFκB, and TNF families of genes were significantly downregulated in the POF+TP-5 group, whereas expression of the TGFβ/Smad9 genes was significantly upregulated. Finally, immunofluorescence staining and qPCR confirmed that TP-5 promoted the polarization of Mo2 cells in the ovary by activating the expression of the BMP4/Smad9 signalling pathway. Thus, our study confirmed that TP-5 has a significant therapeutic effect on POF by upregulating BMP4/Smad9 signalling pathway so as to promote the balance and polarization of immune cell and reducing the release of inflammatory factors and reduce lipid oxidative stress injury.

Lipopolysaccharide (LPS) from oral pathogenic bacteria is an important factor leading to alveolar bone absorption and the implant failure. The present study aimed to evaluate the modulation of berberine hydrochloride (BBR) on the LPS-mediated osteogenesis and adipogenesis imbalance in rat bone marrow-derived mesenchymal stem cells (BMSCs). Cell viability, osteoblastic and adipogenic differentiation levels were measured using the Cell Counting Kit-8 assay, alkaline phosphatase (ALP) staining and content assay, and oil red O staining, respectively. Reverse transcription-quantitative PCR and immunoblotting were used to detect the related gene and protein expression levels. In undifferentiated cells, BBR increased the mRNA expression levels of the osteoblastic genes (Alp, RUNX family transcription factor 2, osteocalcin and secreted phosphoprotein 1) but not the adipogenic genes (fatty acid binding protein 4, Adipsin and peroxisome proliferator-activated receptorγ). LPS-induced osteoblastic gene downregulation, adipogenic gene enhancement and NF-κB activation were reversed by BBR treatment. In osteoblastic differentiated cells, decreased ALP production by LPS treatment was recovered with BBR co-incubation. In adipogenic differentiated cells, LPS-mediated lipid accumulation was decreased by BBR administration. The mRNA expression levels of the pro-inflammatory factors (MCP-1, TNF-α, IL-6 and IL-1β) were increased by LPS under both adipogenic and osteoblastic conditions, which were effectively ameliorated by BBR. The actions of BBR were attenuated by compound C, suggesting that the role of BBR may be partly due to AMP-activated protein kinase activation. The results demonstrated notable pro-osteogenic and anti-adipogenic actions of BBR in a LPS-stimulated inflammatory environment. This indicated a potential role of BBR for bacterial infected-related peri-implantitis medication.

The east foothill of the Taihang Mountains, Hebei Province, is an important groundwater recharge and transport area in the North China Plain. It is of practical significance to study the groundwater hydrochemical characteristics of this area for rational groundwater regulation. In this study, the Chadha rectangular diagram and Piper trilinear diagram were adopted to identify the relevant hydrochemical processes, and the main groundwater hydrochemical type was the HCO3·SO4–Ca. Descriptive statistical methods, correlation analysis, major ion ratio determination and principal component analysis (PCA) were employed to analyze the formation mechanism of groundwater hydrogeochemical characteristics and to identify the sources of the main groundwater ions in the study area. The results showed that Ca2+ and HCO3− were the dominant groundwater cation and anion, respectively, and the Gibbs diagram demonstrated that the majority of groundwater samples occurred in the rock weathering-dominated area. Bivariate diagrams revealed that mineral dissolution and ion exchange controlled the groundwater geochemistry. The study area was seriously polluted by NO3–, which might be due to the application of farmland fertilizers and leakage of rural domestic sewage and garbage. PCA yielded three principal components (PCs), which represented processes influenced by salinity, human activity and fluoride impacts on the groundwater chemistry. The distribution of high-positive PC scores verified the influences of the various processes on the groundwater study area, which is an effective tool to formulate and implement management strategies for the sustainable development of groundwater areas.

Radiotherapy (RT) has been shown to cause immunogenic cell death (ICD) of cancer cells, which promote the release of tumor-associated antigens, and trigger the cancer-immunity cycle (CIC). However, ICD induced by RT usually does not occur in hypoxic tumor cells due to their resistance to radiation. Moreover, RT also induces programmed death ligand 1 (PD-L1) upregulation on tumor cells, which has an inhibitory effect on T lymphocytes. Therefore, therapy based on CIC must selectively target the restricted steps of antitumor immunity. Herein, the authors design a versatile three-in-one assembling nanoparticle that can simultaneously execute these obstacles. The amphiphilic peptide drug conjugate NIA-D1, containing the hydrophobic radio-sensitizer 2-(2-nitroimidazol-1-yl) acetic acid (NIA), a peptide substrate of matrix metalloproteinase-2, and a hydrophilic PD-L1 antagonist

Lassa virus (LASV) belongs to the Mammarenavirus genus (family Arenaviridae) and causes severe hemorrhagic fever in humans. The glycoprotein complex (GPC) contains eleven N-linked glycans that play essential roles in GPC functionalities such as cleavage, transport, receptor recognition, epitope shielding, and immune response. We used three mutagenesis strategies (asparagine to glutamine, asparagine to alanine, and serine/tyrosine to alanine mutants) to abolish individual glycan chain on GPC and found that all the three strategies led to cleavage inefficiency on the 2nd (N89), 5th (N119), or 8th (N365) glycosylation motif. To evaluate N to Q mutagenesis for further research, it was found that deletion of the 2nd (N89Q) or 8th (N365Q) glycan completely inhibited the transduction efficiency of pseudotyped particles. We further investigated the role of individual glycan on GPC-mediated immune response by DNA immunization of mice. Deletion of the individual 1st (N79Q), 3rd (N99Q), 5th (N119Q), or 6th (N167Q) glycan significantly enhanced the proportion of effector CD4+ cells, whereas deletion of the 1st (N79Q), 2nd (N89Q), 3rd (N99Q), 4th (N109Q), 5th (N119Q), 6th (N167Q), or 9th (N373Q) glycan enhanced the proportion of CD8+ effector T cells. Deletion of specific glycan improves the Th1-type immune response, and abolishment of glycan on GPC generally increases the antibody titer to the glycan-deficient GPC. However, the antibodies from either the mutant or WT GPC-immunized mice show little neutralization effect on wild-type LASV. The glycan residues on GPC provide an immune shield for the virus, and thus represent a target for the design and development of a vaccine. Electronic supplementary material The online version of this article (10.1007/s12250-021-00358-y) contains supplementary material, which is available to authorized users.

Lassa virus (LASV) belongs to the Mammarenavirus genus (family Arenaviridae) and causes severe hemorrhagic fever in humans. The glycoprotein precursor (GPC) contains eleven N-linked glycans that play essential roles in GPC functionalities such as cleavage, transport, receptor recognition, epitope shielding, and immune response. We used three mutagenesis strategies to abolish the individual glycan chains on the GPC and found that all three mutations led to cleavage inefficiency on the 2nd, 5th, and 8th glycosylation motifs. To evaluate N to Q mutagenesis for further research, it was found that deletion of the 2nd and 8th glycans completely inhibited the infectivity. We further investigated the role of glycans on GPC-mediated immune response by DNA immunization of mice. Deletion of the individual 1st, 3rd, 5th and 6th glycans significantly enhanced the proportion of effector CD4+ cells, whereas deletion of the 1st, 2nd, 3rd, 4th 5th, 6th, and 9th glycans enhanced the proportion of CD8+ effector T cells. Deletion of specific glycans improves the Th1-type immune response, and abolishment of glycan on GPC generally increases the antibody titer to the glycan-deficient GPC. However, the antibodies from either the mutant or WT GPC-immunized mice show little neutralization effect on wild-type LASV. The glycan residues on GPC provide an immune shield for the virus, and thus represent a target for the design and development of a vaccine.ImportanceAt present, there are no Food and Drug Administration-approved drugs or vaccines specific for LASV. Similar to other enveloped viruses with a heavy glycan shield, the N-linked glycans of LASV make it difficult for effector T cells and neutralization antibodies to access the glycoprotein epitope. In this study, we evaluated the effect of the individual glycan chains on GPC-mediated immune response, and found that deletion of the glycan improves the proportion of effector T cells, improving the Th1-type immune response, and increasing the antibody titer to the WT and mutant GPC, which may be beneficial to vaccine design and development.

Many water resources are threatened with nutrient pollution worldwide. This holds for rivers exporting increasing amounts of nutrients from the intensification of food production systems and further urbanization. This riverine nutrient transport causes coastal eutrophication. This study aims to identify cost-effective management options to simultaneously reach environmental targets for river export of nitrogen and phosphorus by the Yangtze River (China) in 2050. A newly developed modelling approach is used that integrates the Model to Assess River Inputs of Nutrients to seAs (MARINA) with a cost-optimization procedure, and accounts for socio-economic developments, land use and climate changes in a spatially explicit way. The environmental targets for river export of nutrients aim to reduce the gap between baseline and desirable nutrient export. Our baseline is based on MARINA projections for future river export of nutrients, while the desirable nutrient export reflects a low eutrophication potential. Results show the possibilities to close the gap in river export of both nutrients by 80–90% at a cost of 1–3 billion $ per year in 2050. Recycling of animal waste on cropland is an important cost-effective option; reducing synthetic fertilizer inputs provides an opportunity to compensate for the additional costs of the recycling and treatment of manure and wastewater. Our study provides new insights on the combination of cost-effective management options for sub-basins of the Yangtze. This can support the design of cost-effective and sub-basin specific management options for reducing future water pollution. Published

Oral cancer (OC) is the most common type of head and neck malignant tumor. Tumor‑derived exosomes induce a complex extracellular environment that affects tumor immunity. In the present study, exosomes were isolated from OC cell lines (WSU‑HN4 and SCC‑9) by ultrafiltration and the protein content of these oral cancer‑derived exosomes (OCEXs) was analyzed by mass spectrometry, which revealed the enrichment of transforming growth factor (TGF)‑β1. Natural killer (NK) cells were examined by flow cytometry following co‑culture with OCEXs. The expression of killer cell lectin like receptor K1 (KLRK1; also known as NKG2D, as used herein) and natural cytotoxicity triggering receptor 3 (NCR3; also known as NKp30, as used herein) in NK cells was found to be significantly upregulated following co‑culture with the OCEXs for 1 day, whereas this expression decreased at 7 days. Killer cell lectin like receptor C1 (KLRC1; also known as NKG2A; as used herein) expression exhibited an opposite trend at 1 day. In addition, NK cell cytotoxicity against the OC cells was enhanced at 1 day, but was attenuated at 7 days. TGF‑β1 inhibited the function of NK cells at 7 days, whereas it had no obvious effects at 1 and 3 days. On the whole, the findings of the present study reveal changes in NK cell function and provide new insight into NK cell dysfunction.

This paper investigates how land tenure reform has affected livestock production in the pastoral areas of China. County-level data for Inner Mongolia between 1985 and 2008 are used in a fixed effects model to disentangle the effects of land tenure reform on livestock production from factors related to market forces, grassland condition, technological development and environmental heterogeneity. The results show that the implementation of the land tenure reform slowed down the increase in livestock production, although it did not completely stop this increase. It therefore appears that land reform is in itself unable to offset the impact of other factors that accelerate the increase in livestock production. Moreover, the constraining effect of the land tenure reform on the increase in livestock production decreases over time, and ultimately disappears. Finally, the constraining effect of the land tenure reform was shown to be stronger on the increase of the livestock population than on that of meat output. This indicates that the land tenure reform has helped to improve livestock productivity.

Migration can make an important contribution to rural poverty reduction and overall productivity growth, but it may be limited by prevailing rural land tenure arrangements. Since 1998, the Chinese government has implemented a number of land tenure reforms with the aim of improving the tenure security and the transferability of land. Although these reforms enhanced legal tenure security, it is not clear to what extent they remove existing land tenure bottlenecks in migration. Both actual tenure security, i.e. local implementation of laws that warrant tenure security, and household perceptions of tenure security are likely to play a role. In this paper we examine the impacts of actual and perceived tenure security on rural household migration in China, taking into account the degree of development of land rental markets. We argue that actual and perceived tenure security can have both positive and negative effects on migration decisions and that the presence of land rental markets may modify these effects. A two-step control function approach that controls for endogeneity of tenure security perceptions is applied to household and village-level data collected in Jiangsu, Jiangxi, Liaoning provinces and Chongqing municipality. We find that both actual and perceived tenure security affect migration, but the impact of perceived tenure security measured by land reallocation expectations is much stronger and is positive, whereas the independent impact of actual tenure security is negative. Households perceiving a lower risk of losing land when one or more members migrate are more inclined to migrate, independent of the availability of land rental markets in their villages. Actual tenure security, as measured by absence of land reallocations and possession of land certificates, has an independent negative effect on migration only in villages with underdeveloped land rental markets.

Converter dust is a kind of solid waste in the metallurgical steelmaking process. It can make cold bonded pellets via adding binder return to converter for recycling, because of its high content of total iron (TFe) and alkaline oxide. Due to the expansion of digestion reaction of ƒ-CaO and MgO in the converter dust, the pellets are cracked and the strength is reduced. The study compared the effects of sodium silicate, sodium humate, and MgO-based binders on the strength, cracking rate, and moisture content of cold bonded pellets. The results show that the pellets prepared by the MgO-based binder have no cracking, high strength, and low moisture content. X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to clarify the principle of MgO-based binder controlling cracking. It is a hydration reaction with MgO in the converter dust, which absorbs a large amount of free water and avoids the digestion and cracking. Meanwhile, it generates the adhesive nonhydraulic gels, which form a connecting bridge after solidification to increase the pellet strength.