High-Entropy Design for 2D Halide Perovskite.

Hybrid halide perovskites are good candidates for a range of functional materials such as optical electronic and photovoltaic devices due to their tunable band gaps, long carrier diffusion lengths, and solution processability. However, the instability in moisture/air, the toxicity of lead, and rigorous reaction setup or complex postprocessing have long been the bottlenecks for practical application. Herein, we present a simultaneous configurational entropy design at A-sites, B-sites, and X-sites in the typical (CHA)2PbBr4 two-dimensional (2D) hybrid perovskite. Our results demonstrate that the high-entropy effect favors the stabilization of the hybrid perovskite phase and facilitates a simple crystallization process without precise control of the cooling rate to prepare regular crystals. Moreover, high-entropy 2D perovskite crystals exhibit tunable energy band gaps, broadband emission, and a long carrier lifetime. Meanwhile, the high-entropy composition almost maintains the initial crystal structure in deionized water for 18 h while the original (CHA)2PbBr4 crystal mostly decomposes, suggesting obviously improved humidity stability. This work offers a facile approach to synthesize humidity-stable hybrid perovskites under mild conditions, accelerating relevant preparation of optoelectronics and light-emitting devices and facilitating the ultimate commercialization of halide perovskite.

Effects of CEO water shortage experience and power intensity on corporate water performance - Evidence from China.

Corporate water performance and sustainable development are currently vital focus areas for scholars. Therefore, this paper investigates the experience of Chief Executive Officers (CEOs) with water shortage influences corporate water performance by focusing on listed companies in water-intensive and high-water-risk industries in China between 2014 and 2019. This paper manually collected information relative to the cities and provinces where CEOs grew up to evaluate their early exposure to water shortages. Furthermore, this paper develops an evaluation scale, based on the Enterprise Water Conservation Evaluation Guide (GB/T 7119-2006), to compute the enterprise water management practices scores. These results will constitute the enterprise water performance evaluation score. Moreover, this paper focuses on CEOs who have experienced water resource shortages through a positive impact on the water resource performance of their companies. As for the findings, they demonstrate that CEOs who grew up in regions with higher water scarcity have a more pronounced positive effect on their water shortage experience through corporate water performance. Furthermore, CEO power intensity positively moderates the relationship between the CEO's water shortage experience and corporate water resource performance. Further investigation reveals generational differences in the impact of CEO water shortage experience on company water performance. CEOs, who grew up during periods with a higher incidence of droughts, demonstrate a more significant promoting effect on corporate water performance. To sum up, this study expands the understanding of factors influencing corporate water resource performance and deepens the knowledge of the early life experiences of CEOs.

Expression pattern of the bone morphogenetic protein-4 and its relationship with inflammation, vascular injury in patients suffered the arterial occlusive diseases. / åŠ¨è„‰é˜»å¡žæ€§ç–¾ç— æ‚£è€ è¡€æµ†éª¨å½¢æ€å‘ç”Ÿè›‹ç™½-4çš„è¡¨è¾¾å˜åŒ–åŠå ¶ä¸Žç‚Žç—‡å’Œè¡€ç®¡æŸä¼¤çš„ç›¸å ³æ€§.

OBJECTIVES: Bone morphogenetic protein-4 (BMP4) has been proved to be an important regulatory factor for the pathological process of atherosclerosis (AS). However, there are few related clinical studies. This study aims to investigate the levels of plasma BMP4 in patients suffering from the arterial occlusive diseases (ACD) characterized by AS, and further to test the relationship between BMP4 and inflammation and vascular injury. METHODS: A total of 38 ACD patients (the ACD group) and 38 healthy people for the physical examination (the control group) were enrolled. The plasma in each subject from both groups was obtained to test the levels of BMP4, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-10, and vascular endothelial cadherin (VE-cadherin), and the relationship between BMP4 and the detected indicators above were further analyzed. RESULTS: Compared with the control group, the patients in the ACD group displayed significant elevations in the neutrophil to lymphocyte ratio [NLR, 1.63 (1.26, 1.91) vs 3.43 (2.16, 6.61)] and platelet to lymphocyte ratio [PLR, 6.37 (5.26, 7.74) vs 15.79 (7.97, 20.53)], while decrease in the lymphocyte to monocyte ratio [LMR, 5.67 (4.41, 7.14) vs 3.43 (2.07, 3.74)] (all P<0.05). Besides, the ACD patients displayed significant elevations in plasma BMP4 [581.26 (389.85, 735.64) pg/mL vs 653.97(510.95, 890.43) pg/mL], TNF-α [254.16 (182.96, 340.70) pg/mL vs 293.29(238.90, 383.44) pg/mL], and VE-cadherin [1.54 (1.08, 2.13) ng/mL vs 1.85 (1.30, 2.54) ng/mL], and decrease in IL-10 [175.89 (118.39, 219.25) pg/mL vs 135.92 (95.80, 178.04) pg/mL] (all P<0.05). While the levels of IL-1ß remained statistically comparable between the 2 groups (P=0.09). Furthermore, the plasma BMP4 levels were further revealed to be positively correlated with the levels of IL-1ß (r=0.35), TNF-α (r=0.31) and VE-cadherin (r=0.47), while they were negatively correlated with the levels of IL-10 (r=-0.37; all P<0.01). CONCLUSIONS: After ACD occurrence, the patients' plasma concentrations of BMP4 would be upregulated, which may serve as a candidate to indicate the levels of inflammation and vascular injury.

A liposomal carbohydrate vaccine, adjuvanted with an NKT cell agonist, induces rapid and enhanced immune responses and antibody class switching.

BACKGROUND: Congenital disorders of glycosylation (CDGs) are genetic diseases caused by gene defects in glycan biosynthesis pathways, and there is an increasing number of patients diagnosed with CDGs. Because CDGs show many different clinical symptoms, their accurate clinical diagnosis is challenging. Recently, we have shown that liposome nanoparticles bearing the ALG1-CDG and PMM2-CDG biomarkers (a tetrasaccharide: Neu5Ac-α2,6-Gal-ß1,4-GlcNAc-ß1,4-GlcNAc) stimulate a moderate immune response, while the generated antibodies show relatively weak affinity maturation. Thus, mature antibodies with class switching to IgG are desired to develop high-affinity antibodies that may be applied in medical applications. RESULTS: In the present study, a liposome-based vaccine platform carrying a chemoenzymatic synthesized phytanyl-linked tetrasaccharide biomarker was optimized. The liposome nanoparticles were constructed by dioleoylphosphatidylcholine (DOPC) to improve the stability and immunogenicity of the vaccine, and adjuvanted with the NKT cell agonist PBS57 to generate high level of IgG antibodies. The results indicated that the reformulated liposomal vaccine stimulated a stronger immune response, and PBS57 successfully induce an antibody class switch to IgG. Further analyses of IgG antibodies elicited by liposome vaccines suggested their specific binding to tetrasaccharide biomarkers, which were mainly IgG2b isotypes. CONCLUSIONS: Immunization with a liposome vaccine carrying a carbohydrate antigen and PBS57 stimulates high titers of CDG biomarker-specific IgG antibodies, thereby showing great potential as a platform to develop rapid diagnostic methods for ALG1-CDG and PMM2-CDG.

An ortholog of the MADS-box gene SEPALLATA3 regulates stamen development in the woody plant Jatropha curcas.

MAIN CONCLUSION: Overexpression of JcSEP3 causes defective stamen development in Jatropha curcas, in which brassinosteroid and gibberellin signaling pathways may be involved. SEPALLATAs (SEPs), the class E genes of the ABCE model, are required for floral organ determination. In this study, we investigated the role of the JcSEP3 gene in floral organ development in the woody plant Jatropha curcas. Transgenic Jatropha plants overexpressing JcSEP3 displayed abnormal phenotypes such as deficient anthers and pollen, as well as free stamen filaments, whereas JcSEP3-RNA interference (RNAi) transgenic plants had no obvious phenotypic changes, suggesting that JcSEP3 is redundant with other JcSEP genes in Jatropha. Moreover, we compared the transcriptomes of wild-type plants, JcSEP3-overexpressing, and JcSEP3-RNAi transgenic plants. In the JcSEP3-overexpressing transgenic plants, we discovered 25 upregulated genes involved in anther and pollen development, as well as 12 induced genes in brassinosteroid (BR) and gibberellin (GA) signaling pathways. These results suggest that JcSEP3 directly or indirectly regulates stamen development, concomitant with the regulation of BR and GA signaling pathways. Our findings help to understand the roles of SEP genes in stamen development in perennial woody plants.

Experimental investigation of solute transport across transition interface of porous media under reversible flow directions.

Understanding solute transport through macroscopic interfaces is essential to understand the effects of geological heterogeneity on contaminant transport in porous media. Studies of solute transport in compartmental porous media have noted the asymmetry of breakthroughs (BTCs) in solute movement across material interfaces, indicating the presence of discontinuous concentration that makes solute transport directionally dependent. Transition interfaces are more common in nature than sharp interfaces. To understand solute transport across transition interfaces, well-controlled laboratory experiments were performed. A numerical model was also built to understand mass accumulation and concentration discontinuity through transition as well as sharp interfaces. We conclude that directionally dependent asymmetry of BTCs was found with both sharp and transition interfaces. The asymmetry of BTCs was more pronounced at a transition interface than at a sharp interface. The mobile and immobile (MIM) model can better capture the directionally dependent transport of solutes through a sharp/transition interface than the advection-dispersion equation (ADE). The mobile water partition coefficient (ß) and mass transfer coefficient (ω) in MIM were lager in the direction from fine sand to coarse sand (F-C). The time difference between tracer replace and tracer input is greater in the presence of an interface, especially transition interfaces. Even at small Reynolds numbers (1 × 10-4 to 0.116), solute transport across a discontinuous interface under reversible flow directions is most likely dominated by convective dispersion rather than an assumed diffusion process.

Chemoenzymatic Synthesis of a Rhamnose-Functionalized Bispecific Nanobody as a Bispecific Antibody Mimic for Cancer Immunotherapy.

Bispecific antibodies (BsAbs) are next-generation therapeutics for complex cancer treatment. Herein, we developed a dual-targeting non-IgG format of bsAbs by using a bispecific nanobody (bsNb) that can simultaneously target EGFR and HER2 on tumor cells. Site-specific modification of the anti-EGFR-HER2 bsNb was conducted using the rhamnose (Rha) hapten via sortase A-mediated ligation to reconstitute the missing crystallizable fragment (Fc) effector biological functions. Functionally similar to bsAbs, bsNb-Rha conjugates retained dual-targeting activity and exerted potent anticancer effects via the Fc-domain-mediated engagement of endogenous anti-Rha antibodies. Further, an optimized bsNb-Rha conjugate exhibited markedly improved pharmacokinetics and efficient inhibitory effects against xenograft tumor growth in vivo. Our strategy provides a general and cost-effective platform to generate a new bsAb format for cancer immunotherapy.

Does the "10-Point Water Plan" reduce the intensity of industrial water pollution? Quasi-experimental evidence from China.

The Action Plan for Water Pollution Prevention and Control (i.e., the "10-Point Water Plan") is a regulation formulated by China to prevent and control water pollution and ensure China's water safety. To test the policy effect of the "10-Point Water Plan", we use data from 269 cities for the period from 2012 to 2017 to examine whether the implementation of the plan can help reduce the intensity of industrial water pollution. The results show that the industrial water pollution intensity in Central and Western China is significantly higher than that in other regions, and the implementation of the "10-Point Water Plan" significantly reduces industrial water pollution intensity in China. We further find that upgrading industrial structures and technological innovation are effective ways to ameliorate the intensity of industrial water pollution. In terms of spatial heterogeneity, the impact of the "10-Point Water Plan" on reducing industrial water pollution is smaller in areas with high environmental regulation intensity than in areas with low environmental regulation intensity. We also find a strong inhibitory effect of environmental regulations on industrial water pollution intensity in areas with low environmental regulation intensity. Our findings support the positive policy effect of the "10-Point Water Plan" and provide significant policy implications for water pollution prevention and control actions in China and other countries.

Chemo-enzymatic synthesis of the ALG1-CDG biomarker and evaluation of its immunogenicity.

Congenital disorders of glycosylation (CDG) are a growing group diseases that result from defects in genes involved in glycan biosynthesis pathways. One tetrasaccharide, i.e., Neu5Ac-α2, 6-Gal-ß1, 4-GlcNAc-ß1, 4-GlcNAc, was recently reported as the biomarker of ALG1-CDG, the disease caused by ALG1 deficiency. To develop a novel diagnostic method for ALG1-CDG, chemo-enzymatic synthesis of the tetrasaccharide biomarker linked to phytanyl phosphate and the biomarker's immune stimulation were investigated in this study. The immunization study using liposomes bearing phytanyl-linked tetrasaccharide revealed that they stimulated a moderate immune response. The induced antibody showed strong binding specificity for the ALG1-CDG biomarker, indicating its potential in medical applications.

How does soil pollution risk perception affect farmers' pro-environmental behavior? The role of income level.

Soil pollution is a serious environmental issue in China. As a key subject of agricultural practices, promoting Chinese farmers' Pro-Environmental Behavior (PEB) through increasing their soil pollution risk perception is an important means for soil protection, agricultural transformation and ecological development. In this study, we distinguish four dimensions of soil pollution risk perception: fact perception (FP), loss perception (LP), cause perception (CP) and response behavior ability perception (RBAP). We conceptualize a model that depicts the relationships between the four dimensions of Chinese farmers' soil pollution risk perception and their PEB and the moderating effect of farms' household income level on these relationships. Using a questionnaire survey to collect empirical data, we find: first, the four dimensions of Chinese farmers' soil pollution risk perception have positive effects on their PEB; second, Chinese farmers' household income level positively moderates the relationships between their FP, LP and CP and their PEB but its moderating effect on the relationship between their RBAP and their PEB is not significant. Relevant theory and policy implications for environmental management are discussed in the paper.

Interface Bonding Properties and Mechanism of Poplar Board-Veneered Wood Fiber/Polypropylene Composites with Chlorinated Polypropylene Films as an Intermediate Layer.

It is difficult to decorate wood plastic composites with wood veneer because their surface energy is low and there are no pores on the surface. In the present study, we developed an environmentally friendly and convenient method to decorate the wood fiber/polypropylene (WF/PP) composite board. We used chlorinated polypropylene (CPP) as an intermediate film to laminate wood veneer to WF/PP composite boards by hot-pressing at 110 °C and then cooling down. The interface bonding mechanism between the wood veneer, CPP layer, and WF/PP composite was analyzed using scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDS), surface roughness test, and attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR). The results indicated that CPP penetrated the wood pores and formed a firm anchor structure. SEM images showed small cracks at the interface between CPP and PP when WF/PP contained less WF. The results of SEM-EDS and ATR-FTIR showed that WF/PP composites with a higher WF content would have more fibers exposed at the surface, thus making the surface rough and providing more specific surface area. The veneered WF/PP composite with 80% WF content had the highest surface bond strength and water resistance.

One-step immobilization and purification of genetic engineering CBD fusion EndoS on cellulose for antibodies Fc-glycan remodeling.

The endoglycosidase (EndoS and its glycosynthase mutants D233A, D233Q) gene was fused with cellulose binding domain (CBD) using pET-35b vector and the fusion enzymes were successfully expressed in Escherichia coli. Then a simplified approach for one-step immobilization and purification of EndoS enzymes using cellulose as matrices were developed and excellent loading efficiency (81-90%) was achieved in optimal condition. The cellulose immobilized CBD-EndoS and the glycosynthase mutants presented high catalytic activity and were successfully applied in a two-step antibody Fc N-glycan remodeling, generating a therapeutic antibody with homogeneous glycoform in high efficiency. The cellulose immobilized CBD-EndoS and its mutants (D233A and D233Q) displayed excellent storage stability when stored at 4 degrees for one month. Reusability studies demonstrated that the cellulose immobilized CBD-EndoS and its mutants could be recycled for five times without obvious activity loss.

Enzymatic On-Resin Peptide Cleavage and in Situ Cyclization One-Pot Strategy for the Synthesis of Cyclopeptide and Cyclotide.

A one-pot strategy combining sortase A mediated on-resin peptide cleavage and in situ cyclization was developed for the synthesis of cyclic peptides. This strategy was applied to synthesize head-to-tail cyclic antibacterial bovine lactoferricin peptide LFcinB20-35 in a yield of 67%. The one-pot strategy was compatible with an oxidative folding reaction, and complex cyclotides containing one or two disulfide bonds, such as sunflower trypsin inhibitors-1 and α-conotoxin MII, were successfully synthesized in one pot in a yield of 77% and 61%, respectively.

Antibiotic ivermectin preferentially targets renal cancer through inducing mitochondrial dysfunction and oxidative damage.

Renal cell carcinoma (RCC) is the most aggressive type of genitourinary cancer and highly resistant to current available therapies. In this work, we investigated the effects and mechanism of anti-parasitic agent ivermectin in RCC. We show that ivermectin significantly inhibits proliferation and induces apoptosis in multiple RCC cell lines that represent different histological subtypes and various mutation status. Importantly, ivermectin is significantly less or ineffective in normal kidney cells compared with RCC cells, demonstrating the preferential toxicity of ivermectin to RCC. Ivermectin also significantly inhibits RCC tumor growth in vivo. Mechanistically, ivermectin induces mitochondrial dysfunction via decreasing mitochondrial membrane potential, mitochondrial respiration and ATP production. As a consequence of mitochondrial dysfunction, oxidative stress and damage is detected in ivermectin treated RCC cells and xenograft mouse model. The rescue of ivermectin's effect by acetyl-l-Carnitine (ALCAR, a mitochondrial fuel) or antioxidant N-acetyl-l-cysteine (NAC) confirms mitochondria as the target of ivermectin in RCC cells. Compared to normal kidney cells, RCC cells have higher mitochondrial mass and respiration, and ATP production, which might explain the preferential toxicity of ivermectin to RCC. Our work suggest that ivermectin is a promising candidate for RCC treatment and targeting mitochondrial metabolism is an alternative therapeutic strategy for RCC.

New potent and selective αvß3 integrin ligands: Macrocyclic peptides containing RGD motif synthesized by sortase A-mediated ligation.

Three 14-mer macrocyclic peptides 1-3 containing mono-, di- and tri-RGD structure motif were designed and synthesized by sortase A-mediated ligation in good yields. The results of in intro cell-based biological assays indicated that linear peptide 5 and macrocyclic peptide 1, containing di-RGD and mono-RGD motif respectively, showed remarkable potency and selectivity to αvß3 integrin.

Effects of Flow Fluctuation on Dilution and Spreading in a Self-Affine Fracture.

In this work, the spreading and dilution (mixing) processes of the miscible compound were analyzed numerically by three-dimensional Lattice Boltzmann Method (LBM) at a pore scale in a non-uniform flow field. The authors proposed an aperture-related dilution index to quantify the local dilution process in the different aperture regions. The results showed that the fluctuation of the compound spreading caused by the flow fluctuation depended on both the aqueous diffusivity and the frequency of the flow fluctuation. The flow fluctuation increased remarkably the original dilution index when the aqueous diffusivity of the miscible compound was relatively low. However, the analysis of the aperture-related dilution index showed that the degree of the dilution in smaller aperture regions was less than that in larger aperture regions, indicating that there was more incomplete dilution (mixing) in the smaller aperture region.

Synthesis and immunological studies of linear oligosaccharides of ß-glucan as antigens for antifungal vaccine development.

Antifungal vaccines have recently engendered considerable excitement for counteracting the resurgence of fungal infections. In this context, ß-glucan, which is abundantly expressed on all fungal cell surfaces, functionally necessary for fungi, and immunologically active, is an attractive target antigen. Aiming at the development of effective antifungal vaccines based on ß-glucan, a series of its oligosaccharide derivatives was designed, synthesized, and coupled with a carrier protein, keyhole limpet hemocyanin (KLH), to form new semisynthetic glycoconjugate vaccines. In this article, a convergent and effective synthetic strategy using preactivation-based iterative glycosylation was developed for the designed oligosaccharides. The strategy can be widely useful for rapid construction of large oligo-ß-glucans with shorter oligosaccharides as building blocks. The KLH conjugates of the synthesized ß-glucan hexa-, octa-, deca-, and dodecasaccharides were demonstrated to elicit high titers of antigen-specific total and IgG antibodies in mice, suggesting the induction of functional T cell-mediated immunity. Moreover, it was revealed that octa-, deca-, and dodeca-ß-glucans were much more immunogenic than the hexamer and that the octamer was the best among these. The results suggested that the optimal oligosaccharide sequence of ß-glucan required for exceptional immunogenicity was a hepta- or octamer and that longer glucans are not necessarily better antigens, a finding that may be of general importance. Most importantly, the octa-ß-glucan-KLH conjugate provoked protective immunity against Candida albicans infection in a systemic challenge model in mice, suggesting the great potential of this glycoconjugate as a clinically useful immunoprophylactic antifungal vaccine.

A Convergent Synthesis of 6-O-Branched ß-Glucan Oligosaccharides.

ß-Glucans are important carbohydrate antigens on the surface of fungal cells useful for antifungal vaccine development. This paper has described a highly convergent and efficient strategy for the synthesis of structurally defined branched ß-glucan oligosaccharides that can be used for detailed studies of ß-glucans and for the design of ß-glucan-based vaccines. The strategy was highlighted by assembling the title compounds via preactivation-based glycosylation with thioglycosides as glycosyl donors. It was used to successfully prepare ß-glucan oligosaccharides that had a ß-1,3-linked nonaglucan backbone with ß-1,6-glucotetraose, ß-1,3-glucodiose and ß-1,3-glucotetraose branches at the 6-O-position of the nonaglucan central sugar unit. The structure and size of the glycosyl donors and acceptors used in the syntheses did not significantly affect the glycosylation efficiency, suggesting that the strategy can be generally useful for the synthesis of more complex structures.

Synthesis and evaluation of monophosphoryl lipid A derivatives as fully synthetic self-adjuvanting glycoconjugate cancer vaccine carriers.

A fully synthetic carbohydrate-based cancer vaccine is an attractive concept, but an important topic in the area is to develop proper vaccine carriers that can improve the immunogenicity and other immunological properties of tumor-associated carbohydrate antigens (TACAs). In this context, four monophosphoryl derivatives of Neisseria meningitidis lipid A were synthesized via a highly convergent and effective strategy and evaluated as vaccine carriers and adjuvants. The conjugates of these monophosphoryl lipid A (MPLA) derivatives with a modified form of the sTn antigen were found to elicit high titers of antigen-specific IgG antibodies, indicating a T cell-dependent immune response, in the absence of an external adjuvant. It was concluded that MPLAs could be utilized as potent vaccine carriers and built-in adjuvants to create fully synthetic self-adjuvanting carbohydrate-based cancer vaccines. The lipid composition and structure of MPLA were shown to have a significant influence on its immunological activity, and among the MPLAs examined, natural N. meningitidis MPLA exhibited the most promising properties. Moreover, Titermax Gold, a conventional vaccine adjuvant, was shown to inhibit, rather than promote, the immunological activity of MPLA conjugates, maybe via interacting with MPLA.

Fractional derivative method for anomalous aquitard flow in a leaky aquifer system with depth-decaying aquitard hydraulic conductivity.

Aquitards significantly affect groundwater flow in multi-aquifer systems through adjacent aquifer leakage. Despite this, studies focusing on their heterogeneity and the non-conventional diffusion patterns of their flow are still limited. In this study, a factional derivative approach was first extended to explore the time-dependent behavior of flow transport in the aquitard. Two analytical solutions were derived for specific discharges in independent aquitards under different boundary conditions. The findings revealed that aquitard flow exhibits obvious anomalous diffusion behaviors, characterized by slower decay and heavy-tailed specific discharge data. The fractional derivative model provided a more accurate representation of this behavior than traditional models, as evidenced by its superior agreement with experimental data. Moreover, a transient model for pumping tests in a leaky aquifer system was developed, incorporating the memory effect of anomalous flow and vertical heterogeneity in aquitards. Relevant semi-analytical solutions were derived to explore the impacts of memory factor ß and decay exponent of aquitard hydraulic conductivity (K) on the leakage aquifer system. Theoretical results demonstrated that stronger memory effect reduces drawdowns in the aquitard and confined aquifer during mid-to-late times. A larger dimensionless decay exponent (Ad) decreases aquitard drawdown and increases aquifer drawdown at late times. Sensitivity analysis showed aquitard drawdown experiences two peaks in sensitivity to ß and Ad at early- or mid-times, affected by memory effect and decay exponent of aquitard K, signifying maximal impact at these specific intervals. This study provides a practical model to effectively manage groundwater resources by accurately reflecting aquitard memory and heterogeneity effects.