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Background Natural killer (NK) cell-based immunotherapies have demonstrated substantial potential for the treatment of hematologic malignancies. However, its application is limited due to the difficulty in the production of a large number of NK cells in vitro and the insufficient therapeutic efficacy against solid tumors in vivo. Engineered antibodies or fusion proteins targeting activating receptors and costimulatory molecules of NK cells have been developed to encounter these problems. They are mostly produced in mammalian cells with high cost and long processing times. Yeast systems, such as Komagataella phaffii, present a convenient manipulation of microbial systems with the key advantages of improved folding machinery and low cost. Results In this study, we designed an antibody fusion protein scFvCD16A-sc4-1BBL, composed of the single chain variant fragment (scFv) of anti-CD16A antibody and the three extracellular domains (ECDs) of human 4-1BBL in a single-chain format (sc) with the GS linker, aiming to boost NK cell proliferation and activation. This protein complex was produced in the K. phaffii X33 system and purified by affinity chromatography and size exclusion chromatography. The scFvCD16A-sc4-1BBL complex showed comparable binding abilities to its two targets human CD16A and 4-1BB as its two parental moieties (scFvCD16A and monomer ECD (mn)4-1BBL). scFvCD16A-sc4-1BBL specifically stimulated the expansion of peripheral blood mononuclear cell (PBMC)-derived NK cells in vitro. Furthermore, in the ovarian cancer xenograft mouse model, adoptive NK cell infusion combined with intraperitoneal (i.p) injection of scFvCD16A-sc4-1BBL further reduced the tumor burden and prolonged the survival time of mice. Conclusion Our studies demonstrate the feasibility of the expression of the antibody fusion protein scFvCD16A-sc4-1BBL in K. phaffii with favourable properties. scFvCD16A-sc4-1BBL stimulates PBMC-derived NK cell expansion in vitro and improves the antitumor activity of adoptively transferred NK cells in a murine model of ovarian cancer and may serve as a synergistic drug for NK immunotherapy in future research and applications.

Global transcriptomic analysis on primary CD49a+ and CD49a- NK cells.

Background Innate immune responses play essential roles in skeletal muscle recovery after injury. Programmed cell death protein 1 (PD-1) contributes to skeletal muscle regeneration by promoting macrophage proinflammatory to anti-inflammatory phenotype transition. Interferon (IFN)-γ induces proinflammatory macrophages that appear to hinder myogenesis in vitro. Therefore, we tested the hypothesis that blocking IFN-γ in PD-1 knockout mice may dampen inflammation and promote skeletal muscle regeneration via regulating the macrophage phenotype and neutrophils. Methods Anti-IFN-γ antibody was administered in PD-1 knockout mice, and cardiotoxin (CTX) injection was performed to induce acute skeletal muscle injury. Hematoxylin and eosin (HE) staining was used to view morphological changes of injured and regenerated skeletal muscle. Masson’s trichrome staining was used to assess the degree of fibrosis. Gene expressions of proinflammatory and anti-inflammatory factors, fibrosis-related factors, and myogenic regulator factors were determined by real-time polymerase chain reaction (PCR). Changes in macrophage phenotype were examined by western blot and real-time PCR. Immunofluorescence was used to detect the accumulation of proinflammatory macrophages, anti-inflammatory macrophages, and neutrophils. Results IFN-γ blockade in PD-1 knockout mice did not alleviate skeletal muscle damage or improve regeneration following acute cardiotoxin-induced injury. Instead, it exacerbated skeletal muscle inflammation and fibrosis, and impaired regeneration via inhibiting macrophage accumulation, blocking macrophage proinflammatory to anti-inflammatory transition, and enhancing infiltration of neutrophils. Conclusion IFN-γ is crucial for efficient skeletal muscle regeneration in the absence of PD-1.

Clinicopathological characteristics of patients in each cohort

The details and characteristics of each patient enrolled in Cohort 1

Total number of NK cells significantly reduces in the intratumoral region of HCC tissues.

Figure S1 shows (A) Cumulative percentage of CD160 or BTLA on CD8+ T cells from representative normal liver, PT and IT of HCC patient; (B) Cumulative percentage of CD160+ or BTLA+ CD8+ T cells in healthy liver, IT and PT of HCC patients; (C) Absolute count of CD160+ or BTLA+ CD8+ T cells in healthy liver, IT and PT of HCC patients; and (D) The strategy for gating liver-infiltrating leukocytes and NK cells via flow cytometry.

Figure S3 shows (A) Cumulative percentage of IFN-γ on sorted CD160- or CD160+ NK cells of peripheral blood; (B) Scatterplot of global gene expression profiles of CD160+ and CD160- NK subsets; (C) Distribution by functional category of up- or down-regulated genes in CD160+ NK cells compared to CD160- NK cells; (D) Overview of functional pathway analysis; (E) Chemokine- or (F) cytokine- related profiles of CD160+ and CD160- NK cells; and (G) GSEA of genes up-regulated in CD160+ NK cells overlapping with gene sets from IL-2-stimulated NK cells, IL-15-stimulated NK cells and CD57- NK cells.

We previously reported that deficiencies in natural killer (NK)–cell number and function play an important role in the progression of hepatocellular carcinoma (HCC). However, the mechanisms underlying this phenomenon remain obscure. In this study, we analyzed the expression of CD160 on intrahepatic NK cells by evaluating peritumoral and intratumoral tissues of 279 patients with HCC and 20 healthy livers. We observed reduced expression of CD160 on intratumoral NK cells, and patients with lower CD160 cell densities within tumors exhibited worse disease and a higher recurrence rate. High-resolution microarray and gene set enrichment analysis of flow cytometry–sorted primary intrahepatic CD160+ and CD160− NK cells of healthy livers indicated that human CD160+ NK cells exhibited functional activation, high IFNγ production, and NK-mediated immunity. In addition, global transcriptomic analysis of sorted peritumoral and intratumoral CD160+ NK cells revealed that intratumoral CD160+ NK cells are more exhausted than peritumoral CD160+ NK cells and produce less IFNγ. High levels of TGFβ1 interfered with production of IFNγ by CD160+ NK cells, blocking of which specifically restored IFNγ production in CD160+ NK cells to normal levels. These findings indicate that reduced numbers of CD160+ NK cells, together with the functional impairment of CD160+ NK cells by TGFβ1, contribute to tumor immune escape. In addition, restoring the expression of CD160 and blocking TGFβ1 appear a promising therapeutic strategy against liver cancer.Significance:These findings show that reduced number and function of CD160+ NK cells in the tumor microenvironment contributes to immune escape of HCC; blocking TGFβ1 restores IFNγ production of CD160+ NK cells.

Summary and details of HCC patients in cohort 1 and 2.

Clinicopathological characteristics of each cohort in the study.

Figure S4 shows (A) Correlation between peritumoral IOD/area of CD160 and OS or DFS of HCC patients; and (B-C) FACS analysis of CD160 expression in circulating NK cells from HCs, patients with CHB, LC or HCC.

Univariate analysis of DFS and OS among patients with liver cancer according to clinical or immune parameters.

Figure S5 shows (A) Cumulative percentage and MFI of CD160+ NK cells following co-culturing with medium alone, TGF-β1, IL-10, or HCC patient plasma treated with or without anti-TGF-β1 or isotype control for 72h; and (B) CD160 expression level on NK cells from each HC cultured with medium alone at 0h and 72h.

Figure S2 shows (A) Correlation between the percentage of CD160+ NK cells and the percentage of TIM3+, CD96+, NKG2A+, LAG3+, TIGIT+, or CD226+ NK cells in the tissue; and (B) Correlation between the percentage of CD160+ NK cells in the tissue and the intracellular IFN-γ, CD107a, granzyme B or perforin production.

Immunotherapy based on natural killer (NK) cells is a promising approach for treating a variety of cancers. Unlike T cells, NK cells recognize target cells via a major histocompatibility complex (MHC)-independent mechanism and, without being sensitized, kill the cells directly. Several strategies for obtaining large quantities of NK cells with high purity and high cytotoxicity have been developed. These strategies include the use of cytokine-antibody fusions, feeder cells or membrane particles to stimulate the proliferation of NK cells and enhance their cytotoxicity. Various materials, including peripheral blood mononuclear cells (PBMCs), umbilical cord blood (UCB), induced pluripotent stem cells (iPSCs) and NK cell lines, have been used as sources to generate NK cells for immunotherapy. Moreover, genetic modification technologies to improve the proliferation of NK cells have also been developed to enhance the functions of NK cells. Here, we summarize the recent advances in expansion strategies with or without genetic manipulation of NK cells derived from various cellular sources. We also discuss the closed, automated and GMP-controlled large-scale expansion systems used for NK cells and possible future NK cell-based immunotherapy products.

The catalytic hydrolysis/alcoholysis of biomass carbohydrates into levulinic acid/levulinate esters (alkyl levulinates) as green biofuels and value-added chemicals holds great promise for achieving the goals of sustainable chemistry. Bifunctional catalysts...

Conversion of levulinic acid and its esters into versatile γ-valerolactone (GVL) is a pivotal and challenging step in biorefineries, limited by high catalyst cost, the use of hydrogen atmosphere, or tedious catalyst preparation and recycling process. Here we have successfully synthesized a ternary magnetic nanoparticle catalyst (Al2O3-ZrO2/Fe3O4(5)), over which biomass-derived methyl levulinate (ML) can be quantitively converted to GVL with an extremely high selectivity of > 99% and yield of ~98% in the absence of molecular hydrogen. Al2O3-ZrO2/Fe3O4(5) incorporates simultaneously inexpensive alumina and zirconia onto magnetite support by a facile coprecipitation method, giving rise to a core-shell structure, well-distributed acid-base sites, and strong magnetism, as evidenced by the X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-angle annular dark-field scanning-TEM (HAADF-STEM), SEM-energy dispersive X-ray spectroscopy (SEM-EDX), temperature-programmed desorption of ammonia (NH3-TPD), temperature-programmed desorption of carbon dioxide (CO2-TPD), pyridine-adsorption infrared spectra (Py-IR), and vibrating sample magnetometry (VSM). Such characteristics enable it to be highly active and easily recycled by a magnet for at least five cycles with a slight loss of its catalytic activity, avoiding a time-consuming and energy-intensive reactivation process. It is found that there was a synergistic effect among the metal oxides, and the high efficiency and selectivity originating from such synergism are evidenced by kinetic studies. Furthermore, a reaction mechanism regarding the hydrogenation of ML to GVL is proposed by these findings, coupled with gas chromatography-mass spectrometry (GC-MS) analysis. Accordingly, this readily synthesized and recovered magnetic nanocatalyst for conversion of biomass-derived ML into GVL can provide an eco-friendly and safe way for biomass valorization.

In order to evaluate the applicability of Fengyun 2G and GPM IMERG satellite precipitation products in the Lancang River Basin, four evaluation indicators are selected in this paper. The results show that: (1) In terms of correlation coefficient (CC), the GPM IMERG products are better than Fengyun 2G. Among them, GPM IMERG Late Run is better than Early Run, and Final Run is better than Late Run; (2) In terms of root mean square error (RMSE) and mean absolute error (MAE), the values of GPM products are higher; (3) The GPM IMERG products show that the CC of the lower reaches is better than that of the upper reaches; (4) The RMSE and MAE are better in the upper reaches than in the lower reaches, and the high value of the error is mainly concentrated in the lower reaches. This study provides a more reliable precipitation data guarantee for the cascade management of Lancang River Basin, and has certain scientific significance and practical value.

Inter-basin water transfer projects are powerful measures for resolving the uneven distribution of water resources, but their scale directly affects the associated investment and income. Therefore, determining the scale of an inter-basin water transfer project is essential. Based on the inter-basin agricultural water transfer project in the Sanjiang Plain, Northeast China, combined with the suitable development scale of the irrigation area with the joint allocation of existing water sources, this research proposes a technique to demonstrate the scale of an inter-basin water transfer project based on dynamic trial feedback under the condition of the optimization method of despiking of the groundwater allocation; the water transfer project scale is demonstrated for each section in reverse order. According to the water demand prediction results in the study area, the scale of water transfer project BC is demonstrated, and the scale of water transfer project AB is demonstrated on the basis of the BC scale. The final AB and BC water transfer scales decrease by 15% and 13%, respectively, compared with the conventional method under the premise that the water supply guarantee rate is 75%. When the water is transferred, the process is stable, and the utilization rate of the canal is high, thereby saving investment funds and facilitating project scheduling and management.

Immune cells are involved in skeletal muscle regeneration. The mechanism by which Treg cells are involved in the regeneration of injured skeletal muscle is still unclear. The purpose of this study was to explore the role of programmed death-1 in contused skeletal muscle regeneration, and to clarify the regulation of programmed death-1 on Treg cell generation and macrophage polarization, in order to deepen our understanding of the relationship between the immune system and injured skeletal muscle regeneration. The results show that programmed death-1 knockdown reduced the number of Treg cells and impaired contused skeletal muscle regeneration compared with those of wild-type mice. The number of pro-inflammatory macrophages in the contused skeletal muscle of programmed death-1 knockout mice increased, and the expression of pro-inflammatory factors and oxidative stress factors increased, while the number of anti-inflammatory macrophages and the expression of anti-inflammatory factors, antioxidant stress factors, and muscle regeneration-related factors decreased. These results suggest that programmed death-1 can promote contused skeletal muscle regeneration by regulating Treg cell generation and macrophage polarization., Immune cells are involved in skeletal muscle regeneration, but the mechanisms are unclear. In this paper, the authors show that programmed death-1 (PD-1), a key immunosuppressive receptor that is involved in adaptive immune responses, can promote contused skeletal muscle regeneration by regulating Treg cell generation and macrophage polarization.

Maize (Zea mays L.) is one of the most important crops in China. Since 2020, a new leaf spot disease has occurred in southwest China in areas such as Yunnan, Sichuan and Hubei provinces. Typical symptoms appeared after tasseling. The spots are scattered on the leaf surface, round to oval in shape with diameter range 3-20 mm. Spots are initially water-soaked, gradually turning yellow or white. In 2021, diseased leaf samples with typical white spot were collected for pathogen isolation and identification in Qujing, Yunnan province. Four small pieces of leaf tissue (about 0.25 cm2 in area) were excised from the edge of the necrotic lesion of each plant, surface sterilized with 75% ethanol for 1 min, rinsed three times with sterile distilled water, and soaked in sterile distilled water for 5 min. The solution was plated on Luria Broth medium (LB) plate (Shin et al. 2022) . After incubation at 28°C for 24 h, round, smooth-edged yellow colonies appeared in the LB plate. The bacterium isolated was gram-negative, negative for oxidase, positive for peroxidase, indole, citrate (Wells et al. 1987). Three strains (PA21QJ01, PA21QJ02 and PA21QJ03) showed identical colony morphology. PA21QJ01 was used for further molecular analyses. DNA was extracted from fresh colonies cultured in LB(Shin et al. 2022), and the fragments at the 16S rDNA, gyrB and rpoB loci were amplified using primers 27F/1492R (Galkiewicz and Kellogg 2008), UP-1/UP-2r (Yamamoto and Harayama 1995) and rpoBCM81-F/rpoBCM32b-R (Brady et al. 2008), respectively. The sequences of fragments of 16S rDNA, gyrB and rpoB from isolate PA21QJ01 were was deposited in GenBank (accession number: OM184301.1, OM302500, OM302499). A search for homologous sequences using BLAST resulted in 99.9, 99.6 and 99.8% identity of 16S rDNA, gyrB and rpoB, respectively, with sequences from the NN08200 of Pantoea ananatis (GenBank accession numbers: MK415050.1 for 16S rDNA, CP035034.1 for gyrB and CP035034.1.1 for rpoB). Above molecular results indicated that PA21QJ01 isolated from maize white spot is P. ananatis. Pathogenicity tests were performed on tasseled plants of the suscptible maize variety Wugu1790. After culture in LB medium plate at 30°C for 12 h, the bacterial solution was used for inoculation at a concentration of 1 × 108 CFU ml-1. After 7 days of inoculation, the leaves of the plants appeared water-soaked. After 10 days, white spot developed with brown margin. In contrast, the control plants remained healthy and symptomless. The same P. ananatis was reisolated in the inoculated maize plants, fulfilled Koch's law. In the last decade, P. ananatis has been reported to cause maize white spot in South Africa, Mexico, Poland, Argentina, Brazil (Sauer et al. 2015), and Ecuador (Toaza et al.2021). It has caused crop diseases with other crops, such as onion, rice, pineapple, melon, and sorghum, and others (Sauer et al. 2015). It caused leaf blight and leaf steak in rice in China (Yu et al. 2021). This is the first report of maize white spot caused by P. ananatis in China. However, to our knowledge, this is the first report of maize white spot disease in China. Attentions should be paid to screening for disease-resistant resources and breeding disease-resistant hybrids. Reference: Wells, J. M. et al. 1987. Int. J. Syst. Bacteriol. 37:136-143. Shin, G. Y. et al. 2022. Plant Dis. Doi: 10.1094/PDIS-08-21-1810-SC. Brady, C., et al. 2008. Syst. Appl. Microbiol. 31:447. Galkiewicz, J. P., and Kellogg, C. A. 2008. APPL ENVIRON MICROB, 74.24: 7828-7831. Toaza, A. et al. 2021. Plant Dis. Doi:10.1094/PDIS-02-21-0298-PDN Yamamoto, S., and Harayama, S. 1995. APPL ENVIRON MICROB, 61:1104.L. Sauer, A. V. et al. 2015. Agronomy Science and Biotechnology. Doi:10.33158/ASB.2015v1i1p21 Yu et al. 2021. Plant Dis. Doi:10.1094/PDIS-05-21-0988-PDN.

Understanding changes in the intensity and frequency of extreme precipitation is vital for flood control, disaster mitigation, and water resource management. In this study, 12 extreme precipitation indices and the best-fitting extreme value distribution were used to analyze the spatiotemporal characteristics of extreme precipitation in the upper reaches of the Hongshui River Basin (UHRB). The possible links between extreme precipitation and large-scale circulation were also investigated. Most extreme precipitation indices increased from west to east in the UHRB, indicating that the eastern region is a humid area with abundant precipitation. The indices for consecutive wet days (CWD) and precipitation events (R0.1) decreased significantly, indicating that the UHRB tends to be dry, with few precipitation events. The probability distribution functions of most extreme precipitation indices, especially that of R0.1, shifted significantly to the left in 1988–2016 compared with 1959–1987, further indicating that the UHRB has experienced a significant drying trend in recent decades. The East Asian summer monsoon and the El Niño–Southern Oscillation/Pacific Decadal Oscillation were confirmed to influence extreme precipitation in the UHRB. These findings are helpful for understanding extreme precipitation variation trends in the UHRB and provide references for further research. HIGHLIGHTS We do not focus on the Pearl River Basin (453,690 km2) but pay attention to a sub-basin (98,500 km2) within it.; Most extreme precipitation indices decreased slightly and nonsignificantly in the UHRB.; The number of consecutive wet days and precipitation events decreased significantly.; The UHRB has tended to be dry, with few precipitation events.; The El Niño–Southern Oscillation /Pacific Decadal Oscillation and East Asian summer monsoon have strong effects on extreme precipitation.

Because of the distinct and complex anatomy of the ampullary region, the exact origin of the periampullary tumors was often difficult to ascertain. In this study, we evaluated 78 patient samples, including 26 small intestinal adenocarcinomas, 35 pancreatic ductal adenocarcinomas, and 17 cholangiocarcinomas by immunohistochemical detection of cadherin-17 (CDH17), CDX2, CK20, and CK19 protein expression. The result showed that CDH17 and CDX2 expression was higher in small intestinal adenocarcinoma (73.1% and 65.4%) than in pancreatic (14.3% and 2.9%) and bile duct (41.2% and 23.5%) cancers, respectively. CK20 expression was low in 78 tumor tissues, but relatively high in small intestinal adenocarcinoma (42.3%). CK19 showed a strong positive expression in all 78 adenocarcinoma tissues. The CDH17-high/CDX2-high pattern was predominantly expressed in small intestinal cancer tissues (75%), whereas the CDH17-low/CDX2-low pattern was observed in pancreatic cancers (63.8%) and bile duct cancers (20.9%). The study concluded that CDH17-high/CDX2-high adenocarcinomas more likely originated from small intestine versus pancreas or bile duct, whereas CDH17-low/CDX2-low ones are more likely of pancreatic origin. The combined use of CDH17 and CDX2 could be helpful in providing support for the histologic origin of periampullary adenocarcinoma.

Agkisacucetin, a snake C-type lectin-like protein isolated from the venom of Deinagkistrodon acutus (formerly Agkistrodon acutus), is a novel antithrombotic drug candidate in phase 2 clinical trials. Agkisacucetin specifically recognizes the platelet surface receptor glycoprotein Ib α chain (GPIbα) to block GPIb and von Willebrand factor (VWF). In this study, we solved the crystal structure of the GPIbα N-terminal domain (residues 1-305) in complex with agkisacucetin to understand their molecular recognition mechanism. The crystal structure showed that agkisacucetin primarily contacts GPIbα at the C-terminal part of the conserved leucine-rich repeat (LRR) domain (LRR-6 to LRR-8) and the previously described “β-switch” region through the β chain. In addition, we found that agkisacucetin α chain contacts part of the GPIbα C-terminal peptide after the LRR domain through complementary charge interactions. This C-terminal peptide plays a key role in GPIbα and thrombin recognition. Therefore, our structure revealed that agkisacucetin can sterically block the interaction between the GPIb receptor and VWF and thrombin proteins to inhibit platelet function. Our structural work provides key molecular insights into how an antithrombotic drug candidate recognizes the GPIb receptor to modulate platelet function to inhibit thrombosis.

Cellulose triacetate (CTA) was successfully synthesized from corn stover cellulose (CSC) in the presence of [PyPS]3PW12O40 (IL-POM). The effects of IL-POM contents, reaction temperature, and reaction time on the yield and degree of substitution of CTA were investigated. The synthesized CTA was characterized by SEM, FTIR, and TGA, and the degree of polymerization and solubility in various organic solvents were evaluated. Results showed that the optimum reaction conditions were as follows: 0.04 g of IL-POM, reaction temperature of 140 °C, and reaction time of 45 min, for 0.4 g of CSC and 9 mL of glacial acetic acid. The yield of CTA under optimum reaction conditions was as high as 79.27%, and the degree of substitution was 2.95. SEM and FTIR results showed that the cellulose acetylation occurred, and CTA was synthesized. The TGA results revealed that the decomposition temperature of CTA increased by about 30 °C when compared with that of CSC. A simple, environment-friendly, and efficient process for the preparation of CTA from CSC was constructed, which provides a new pathway for the high-value utilization of corn stover.

Background Valorization of lignocellulosic biomass to obtain clean fuels and high-value chemicals is attractive and essential for sustainable energy and chemical production, but the complex structure of biomass is recalcitrant to catalytic processing. This recalcitrance can be overcome by pretreating biomass into deconstructable components, which involves altering the structural complexities and physicochemical properties. However, the impact of these alterations on biomass deconstruction varies considerably, depending on the pretreatment and subsequent conversion type. Here, we systematically describe the changes in structure and properties of corn stover after ball milling as well as their influence on the following enzymatic saccharification and acid-catalyzed alcoholysis, with the aim of elucidating the relationships between structures, properties and deconstructable potential of lignocellulosic biomass. Results Ball milling causes dramatic structural changes, since the resistant plant cell walls are destroyed with size reduction to a cellular scale, leading to the increase in surface area and reducing ends, and decrease in crystallinity and thermal stability. As a result, ball-milled corn stover is more susceptible to enzymatic saccharification to fermentable sugars and provides more industrially viable processing approaches, as it is effective at high solids loading and minor enzyme loading, without any other pretreatment. Acid-catalyzed alcoholysis of corn stover to biofuels, on the other hand, is also enhanced by ball milling, but additional processing parameters should be tailored to the needs of efficient conversion. Further, a detailed examination of process variables coupled with a kinetic study indicates that acid-catalyzed alcoholysis is limited by the process variables rather than by the substrate parameters, whereas ball milling facilitates this reaction to some extent, especially under mild conditions, by lowering the activation energy of corn stover decomposition. Conclusions The efficient catalytic conversion of biomass is closely related to its structure and properties, an understanding of which offers prospects for the rational improvement of methods aimed at more economic commercial biorefineries.

This paper focuses on determining the spatial and temporal characteristics of the sensitivity coefficients (SCs) between potential evapotranspiration (ET0) and key climatic factors across the Shiyang River Basin (SYRB) from 1981 to 2015. Penman–Monteith equation and a sensitivity analysis were used to calculate ET0 and the SCs for key climatic factors. Sen's slope was used to analyze the observed series. According to the results, the sensitivity significances were in the order of relative humidity (RH) > net solar radiation (NSR) > wind speed (WS) > maximum air temperature (Tmax) > minimum air temperature (Tmin). The SCs for the RH and NSR were larger in the upper mountainous region, while the other three coefficients were larger in the middle and lower reaches. All five climatic factors for the ET0 SCs showed increasing trends in the mountainous region, and the Tmax, WS and RH SCs increased in the middle and lower reaches. Over the past 35 years, the change in ET0 was dominated by the air temperature (T), RH and NSR, and the increase in ET0 during the studied period was mainly due to the increases in T and NSR. HIGHLIGHTS Determined the spatial and temporal characteristics of the sensitivity coefficients between ET0 and key climatic factors across the SYRB.; Explored the causes of ET0 changes and their responses to climate change in the SYRB.; Quantified the contribution rate of each climatic element to ET0 in the SYRB from 1981 to 2015.

Water conservancy projects are one of the main sources of carbon emissions. Nearly 60% of river revetments in developed countries are treated with ecological slope protection technologies to reduce carbon emissions. Ecological river revetment has been widely adopted as a measure for slope protection. Presently, the study on carbon emission reduction mainly focuses on agricultural production, petroleum exploitation, residential life, and transportation. No significant research has been made on the effects of river revetment protection projects on carbon emissions. This study evaluates the carbon emissions from structural and ecological revetments, and its impact on China's climate. Results show that the ecological revetment can reduce carbon emissions significantly, by 93% as compared to the structural revetment. Moreover, the construction cost of an ecological slope is 37% cheaper than that of a structural slope. This research proves that ecological river slope protection technologies are vital for reducing China's carbon emission. HIGHLIGHTS At present, the research on carbon emission reduction does not contribute much to the research on carbon emission of river slope protection projects.; This study evaluates the carbon emissions from the structural slope and the ecological slope.; Quantify the carbon emissions from the structural slope and the ecological slope construction.; Consider the carbon storage capacity of green plants to compare the carbon emissions of the structural and ecological slope.; We study the contribution of ecological slope in reducing the carbon emissions and improving the climate and environment.

This study compared characteristics of different animal manure and examined non-parametric multivariate analysis tools’ suitability for their data mining. This can provide data and methodology support for scientific research and utilization of animal manure raw materials’ characteristics. Distribution profile testing, statistical calculation, and Spearman correlation analysis—using characteristics of 788 animal manure samples of layer, broiler, pig, dairy, and beef, with fertilizer nutrient compositions, proximate compositions, ultimate compositions, and calorific values—were conducted. Latent associations between different animal manure types’ characteristics were examined through five non-parametric multivariate analyses. All samples’ physicochemical characteristics samples showed different non-normal distributions except potassium. Volatile matter (VM), fixed carbon (FC), ash, carbon, hydrogen, oxygen, and higher/lower heating value (HHV/LHV) were correlated, and nitrogen was positively correlated with phosphorus, potassium, and sulfur. Non-parametric principal component analysis (PCA), non-parametric exploratory factor analysis (EFA), hierarchical cluster analysis (HCA), and non-metric multidimensional scaling (NMDS) obtained similar results: VM, FC, carbon, hydrogen, oxygen, HHV, and LHV had associated attributes (“energy utilization”); phosphorus, potassium, ash, nitrogen, and sulfur had intrinsic associated attributes (“fertilizer utilization”). Animal manure characteristics should be mined and analyzed using non-parametric statistical analysis methods. Non-parametric PCA, non-parametric EFA, HCA, and NMDS are suitable for this purpose.

To investigate the effect of ultrafine grinding pretreatment on the isolation of wheat straw cellulose fibers and nanocrystals, wheat straw at cellular scale (50–30 m) were produced with different ultrafine grinding time prior to extract cellulose fibers and nanocrystals. Cellulose fibers were obtained by 4% sodium hydroxide and alkaline hydrogen peroxide treatment from ultrafine ground wheat straw. Morphological changes were observed using scanning electron microscopy (SEM). Fourier transform infrared (FTIR) spectroscopy showed the removal of non-cellulosic components and the rearrangement of hydrogen bonds in cellulose. X-ray diffraction (XRD) analysis revealed the decrease of crystalline index with grinding time prolonged and the formation of cellulose II in alkali treated 8.0 h ultrafine ground wheat straw. Cellulose nanocrystals were produced from these cellulose fibers using 64% sulfuric acid hydrolysis treatment. Morphological examination through atomic force microscope (AFM) showed that the length of rod-like CNCs decreased with prolonged ultrafine grinding time in 2.0 h and then increased due to the formation of cellulose II.

The heterogeneity and complex composition of crop straw are some of the main obstacles to its scientific and efficient industrial utilization. To thoroughly reveal and identify the composition of different crop straw types and their latent attributes, in this study, 784 straw samples of rice, wheat, corn, rape and cotton were collected. Based on the large sample size, 18 composition characteristics, including chemical composition, proximate composition, ultimate composition, and heating values, were adopted to determine the profiles of the crop straw composition characteristics. Correlation analysis and 7 different types of multivariate analysis were applied and compared. The results indicated that among the 18 characteristics, hemicellulose, water-soluble carbohydrates, crude proteins, phosphorus, fixed carbon, hydrogen, nitrogen, and sulfur had non-normal distributions. Spearman method was a more suitable correlation analysis approach for the crop straw characteristics than Pearson method. The results of the different multivariate analysis methods were reflected in the different classification attributes of water-soluble carbohydrates, phosphorus, hydrogen and sulfur. Non-parametric principal component analysis and non-parametric exploratory factor analysis provided consistent results. The characteristics could be divided into 4 categories of intrinsic associated attributes, namely, (1) lignin, volatile matter, fixed carbon, carbon, hydrogen, higher heating value, and lower heating value; (2) potassium, ash, and sulfur; (3) cellulose, hemicellulose, moisture, and oxygen; and (4) water-soluble carbohydrates, crude proteins, phosphorus, and nitrogen, which exhibited combustion positive, combustion negative, biochemical conversion, and nutritional property, respectively. The study results provide data and methodology support for the development of crop straw utilization strategies.

A mild and efficient alcoholysis process for the conversion of ball milled corn stover was developed using Bronsted (B) acidic ionic liquid [Bmim-SO3H][HSO4] (SO3H-IL) and Lewis (L) acidic Al2(SO4)...

Keggin-type polyoxometalate derived ionic liquids (POM-ILs) have recently been presented as effective solvent systems for biomass delignification. To investigate the mechanism of lignin dissolution in POM-ILs, the system involving POM-IL ([C4C1Im]3[PW12O40]) and guaiacyl glycerol-β-guaiacyl ether (GGE), which contains a β-O-4 bond (the most dominant bond moiety in lignin), was studied using quantum mechanical calculations and molecular dynamics simulations. These studies show that more stable POM-IL structures are formed when [C4C1Im]+ is anchored in the connecting four terminal oxygen region of the [PW12O40]3- surface. The cations in POM-ILs appear to stabilize the geometry by offering strong and positively charged sites, and the POM anion is a good H-bond acceptor. Calculations of POM-IL interacting with GGE show the POM anion interacts strongly with GGE through many H-bonds and π-π interactions which are the main interactions between the POM-IL anion and GGE and are strong enough to force GGE into highly bent conformations. These simulations provide fundamental models of the dissolution mechanism of lignin by POM-IL, which is promoted by strong interactions of the POM-IL anion with lignin.

Pesticide residues in water is one of the most serious problems in developing countries. Surface enhanced Raman spectroscopy (SERS) is widely used in the detection and monitoring of pesticide and other trace compounds because of its low limits of detection (LODs). However, different SERS substrate synthesis methods have different economic benefits and environmental impacts. In this paper, a flexible AuNPs@CDA SERS substrate was fabricated by the gold nanoparticles (AuNPs) and the biomass-based cellulose diacetate (CDA), which had stable test performance and considerable LODs. The substrates were economically viable and environment friendly. The characterization analysis of the substrate allows us to flexibly select different test methods (drop-test or enrichment-test) as coping strategy in different situation. The results showed that the LODs of thiram pesticide in water by enrichment-test could reach 10

Increasing evidence suggests that IL-33 plays an important role in regulating tumor development. However, conflicting results, obtained from numerous studies, have highlighted the divergent functions of IL-33. The detailed mechanisms by which IL-33 modulates tumor development merit further investigation. Here, we report that IL-33 administration can effectively inhibit the development of pulmonary metastasis of breast cancer in a mouse. In our model, IL-33 promotes the production of TNF-α by macrophages, which increases IL-33 specific receptor (ST2) expression on natural killer (NK) cells and is pivotal in IL-33-induced NK cell activation. IL-33 treatment also facilitates the production of CCL5 in the lung by eosinophils and CD8+ T cells, which mediates the recruitment of NK cells to the tumor microenvironment. The systemic activation and local recruitment of NK cells result in potent tumor rejection in the lung. Our study reports a novel mechanism for the IL-33-meditated suppression of metastatic cancer and provides potential therapeutic strategies for targeting metastatic tumor.

High-intensity interval training (HIIT), a new type of exercise, can effectively prevent the progression of metabolic diseases. The aim of this study was to investigate the effects of HIIT on liver inflammation and metabolic disorders in type 2 diabetes mellitus (T2DM) mice induced by a high-fat diet (HFD) combined with streptozotocin (STZ) and to explore the possible mechanisms of macrophage polarization and mitochondrial dynamics. Our results showed that HIIT can increase fatty acid oxidation-related gene (PPARα, CPT1α, and ACOX1) mRNA levels and decrease adipogenesis-related gene (PPARγ) mRNA levels to improve liver metabolism in T2DM mice. The improvement of lipid metabolism disorder may occur through increasing liver mitochondrial biosynthesis-related genes (PGC-1α and TFAM) and restoring mitochondrial dynamics-related gene (MFN2 and DRP1) mRNA levels. HIIT can also reduce the mRNA levels of liver inflammatory factors (TNF-α, IL-6, and MCP-1) in T2DM mice. The reduction in liver inflammation may occur through reducing the expression of total macrophage marker (F4/80) and M1 macrophage marker (CD86) mRNA and protein and increasing the expression of M2 macrophage marker (CD163, CD206, and Arg1) mRNA and protein in the liver. HIIT can also increase the expression of insulin signaling pathway (IRS1, PI3K, and AKT) mRNA and protein in the liver of T2DM mice, which may be related to the improvements in liver inflammation and lipid metabolism. In conclusion, these results suggested that 8 weeks of HIIT can improve inflammation and lipid metabolism disorders in the liver of type 2 diabetes mellitus mice, macrophage M1/M2 polarization, and mitochondrial dynamics may be involved in this process.

Background Although checkpoint-based immunotherapy has shown exciting results in the treatment of tumors, around 70% of patients have experienced unresponsiveness. PVRIG is a recently identified immune checkpoint receptor and blockade of which could reverse T cell exhaustion to treat murine tumor; however, its therapeutic potential via NK cells in mice and human remains seldom reported. Methods In this study, we used patient paraffin-embedded colon adenocarcinoma sections, various murine tumor models (MC38 colon cancer, MCA205 fibrosarcoma and LLC lung cancer), and human NK cell- or PBMC-reconstituted xenograft models (SW620 colon cancer) to investigate the effect of PVRIG on tumor progression. Results We found that PVRIG was highly expressed on tumor-infiltrating NK cells with exhausted phenotype. Furthermore, either PVRIG deficiency, early blockade or late blockade of PVRIG slowed tumor growth and prolonged survival of tumor-bearing mice by inhibiting exhaustion of NK cells as well as CD8+ T cells. Combined blockade of PVRIG and PD-L1 showed better effect in controlling tumor growth than using either one alone. Depletion of NK or/and CD8+ T cells in vivo showed that both cell types contributed to the anti-tumor efficacy of PVRIG blockade. By using Rag1−/− mice, we demonstrated that PVRIG blockade could provide therapeutic effect in the absence of adaptive immunity. Further, blockade of human PVRIG with monoclonal antibody enhanced human NK cell function and inhibited human tumor growth in NK cell- or PBMC-reconstituted xenograft mice. Conclusions Our results reveal the importance of NK cells and provide novel knowledge for clinical application of PVRIG-targeted drugs in future.