Low viscosity and low temperature curing reactive POSS/epoxy hybrid resin with enhanced toughness and comprehensive thermal performance.

The mechanical and high-temperature resistance properties of epoxy resins cured at low temperatures (Tcuring ≤ 100 °C) are often inferior, and the most toughening modification methods for epoxy resins tend to compromise thermal resistance, which significantly limit the practical applications of it. Therefore, this work reported a low viscosity and low-temperature curing epoxy hybrid resin system (OPEP), adopting E-51 as a resin matrix, liquid anhydride (MHHPA) as a curing agent, tertiary amine (DMBA) as a curing accelerator, and reactive octa-epoxy terminated polyhedral oligomeric silsesquioxane (OG-POSS) as a toughening modifier. Results demonstrated that the OPEP system has excellent processability with low viscosity and long processing window period and satisfies the practical requirements of low-temperature curing. The OG-POSS exhibits superior compatibility and reactivity with the resin matrix, and its addition slightly reduces the Eα of the curing reaction and has a certain promotive effect on the curing of epoxy resin. In addition, the curing reaction rate of the OPEP resin complies with the Sesták-Berggren autocatalytic kinetics model. The impact strength, flexural strength, tensile strength, and elongation at break of the OPEP resin reached a maximum of 15.55 kJ m-2, 121.65 MPa, 90.36 MPa, and 2.48%, representing increases of 55.97%, 3.1%, 64.68%, and 26.51% compared to those of the pure resin, respectively. Notably, due to the heat-resistant inorganic silicon cage structure of OG-POSS, the thermal decomposition temperature (Td5), glass transition temperature (Tg), and heat distortion temperature (THDT) of the OPEP0.02 resin were 313.2 °C, 123.7 °C, and 102.0 °C, showing increases of 13.0 °C, 2.3 °C, and 6.8 °C compared to the pure resin, respectively, which is difficult to achieve for the general thermosetting resin toughening modification method. This research utilized organic-inorganic nanohybrid materials (POSS) to optimize the toughness and thermal stability of the resin in a coordinated manner, providing guidance for the preparation of high-performance epoxy resins that cure at low temperatures.

Examination of the relationship between agricultural carbon emission efficiency and food quality and safety: from the perspective of environmental regulation.

An important breakthrough in the coordinated development of China's low-carbon goals and food security strategies is agricultural development oriented toward quality, safety, green, and low carbon. This study integrated command-control and market-incentive environmental regulation (ER), agricultural eco-efficiency (ACEE), and food quality and safety (FQS) into a unified theoretical framework. The unexpected output-oriented Super-SBM model was used to calculate the ACEE of China's provinces and cities from 2011 to 2020 and test the bidirectional causality between ACEE and FQS through the system generalized moment estimation model. A dynamic panel smooth transition (PSTR) model was used to explore the nonlinear impact mechanisms of different types of ERs on ACEE and FQS. The results showed that there was a long-term, two-way causal relationship between ACEE and FQS. The impact of environmental regulations on ACEE and FQS has a nonlinear relationship. Among them, the role of market-incentivized ER is more significant. Therefore, building an interregional coordinated development mechanism, improving the utilization rate of agricultural resources such as fertilizers and pesticides, and coordinating the positive effects of different types of ERs are the keys to improving the ACEE and ensuring the coordinated development of FQS.

Pyroptosis: A road to next-generation cancer immunotherapy.

The goal of cancer immunotherapy is to clear tumor cells by activating antitumor immunity, especially by mobilizing tumor-reactive CD8+T cells. Pyroptosis, programmed lytic cell death mediated by gasdermin (GSDM), results in the release of cellular antigens, damage-associated molecular patterns (DAMPs) and cytokines. Therefore, pyroptotic tumor cell-derived tumor antigens and DAMPs not only reverse immunosuppression of the tumor microenvironment (TME) but also enhance tumor antigen presentation by dendritic cells, leading to robust antitumor immunity. Exploring nanoparticles and other approaches to spatiotemporally control tumor pyroptosis by regulating gasdermin expression and activation is promising for next-generation immunotherapy.

Visual analysis of the prevention and control measures of COVID-19 in Chinese ports.

In 2022, COVID-19 solutions in China have entered a normal stage, and the solutions imported from ports have been transformed from emergency prevention and control measures to investigative long-term prevention and control measures. Therefore, it is necessary to study solutions for COVID-19 at border ports. In this study, 170 research papers related to the prevention and control measures of COVID-19 at ports from 2020 to September 2022 were retrieved from Wanfang database, HowNet database, Wip database, and WoS core collection. Citespace 6.1.R2 software was used to research institutions visualize and analyze researchers and keywords to explore their research hotspots and trends. After analysis, the overall volume of documents issued in the past 3 years was stable. The major contributors are scientific research teams such as the Chinese Academy of Inspection and Quarantine Sciences (Han Hui et al.) and Beijing Customs (Sun Xiaodong et al.), with less cross-agency cooperation. The top five high-frequency keywords with cumulative frequency are as follows: COVID-19 (29 times), epidemic prevention and control (29 times), ports (28 times), health quarantine (16 times), and risk assessment (16 times). The research hotspots in the field of prevention and control measures for COVID-19 at ports are constantly changing with the progress of epidemic prevention and control. Cooperation between research institutions needs to be strengthened urgently. The research hotspots are the imported epidemic prevention and control, risk assessment, port health quarantine, and the normalized epidemic prevention and control mechanism, which is the trend of research and needs further exploration in the future.

Neutralizing IL-8 potentiates immune checkpoint blockade efficacy for glioma.

Malignant gliomas are largely refractory to immune checkpoint blockade (ICB) therapy. To explore the underlying immune regulators, we examine the microenvironment in glioma and find that tumor-infiltrating T cells are mainly confined to the perivascular cuffs and express high levels of CCR5, CXCR3, and programmed cell death protein 1 (PD-1). Combined analysis of T cell clustering with T cell receptor (TCR) clone expansion shows that potential tumor-killing T cells are mainly categorized into pre-exhausted/exhausted and effector CD8+ T subsets, as well as cytotoxic CD4+ T subsets. Notably, a distinct subpopulation of CD4+ T cells exhibits innate-like features with preferential interleukin-8 (IL-8) expression. With IL-8-humanized mouse strain, we demonstrate that IL-8-producing CD4+ T, myeloid, and tumor cells orchestrate myeloid-derived suppressor cell infiltration and angiogenesis, which results in enhanced tumor growth but reduced ICB efficacy. Antibody-mediated IL-8 blockade or the inhibition of its receptor, CXCR1/2, unleashes anti-PD-1-mediated antitumor immunity. Our findings thus highlight IL-8 as a combinational immunotherapy target for glioma.

IL-2 regulates tumor-reactive CD8+ T cell exhaustion by activating the aryl hydrocarbon receptor.

CD8+ T cell exhaustion dampens antitumor immunity. Although several transcription factors have been identified that regulate T cell exhaustion, the molecular mechanisms by which CD8+ T cells are triggered to enter an exhausted state remain unclear. Here, we show that interleukin-2 (IL-2) acts as an environmental cue to induce CD8+ T cell exhaustion within tumor microenvironments. We find that a continuously high level of IL-2 leads to the persistent activation of STAT5 in CD8+ T cells, which in turn induces strong expression of tryptophan hydroxylase 1, thus catalyzing the conversion to tryptophan to 5-hydroxytryptophan (5-HTP). 5-HTP subsequently activates AhR nuclear translocation, causing a coordinated upregulation of inhibitory receptors and downregulation of cytokine and effector-molecule production, thereby rendering T cells dysfunctional in the tumor microenvironment. This molecular pathway is not only present in mouse tumor models but is also observed in people with cancer, identifying IL-2 as a novel inducer of T cell exhaustion.

Gasdermin E-mediated target cell pyroptosis by CAR T cells triggers cytokine release syndrome.

Cytokine release syndrome (CRS) counteracts the effectiveness of chimeric antigen receptor (CAR) T cell therapy in cancer patients, but the mechanism underlying CRS remains unclear. Here, we show that tumor cell pyroptosis triggers CRS during CAR T cell therapy. We find that CAR T cells rapidly activate caspase 3 in target cells through release of granzyme B. The latter cleaves gasdermin E (GSDME), a pore-forming protein highly expressed in B leukemic and other target cells, which results in extensive pyroptosis. Consequently, pyroptosis-released factors activate caspase 1 for GSDMD cleavage in macrophages, which results in the release of cytokines and subsequent CRS. Knocking out GSDME, depleting macrophages, or inhibiting caspase 1 eliminates CRS occurrence in mouse models. In patients, GSDME and lactate dehydrogenase levels are correlated with the severity of CRS. Notably, we find that the quantity of perforin/granzyme B used by CAR T cells rather than existing CD8+ T cells is critical for CAR T cells to induce target cell pyroptosis.

Visualization of perforin/gasdermin/complement-formed pores in real cell membranes using atomic force microscopy.

Different types of pores ubiquitously form in cell membranes, leading to various types of cell death that profoundly influence the fate of inflammation and the disease status. However, these pores have never truly been visualized to date. Atomic force microscopy (AFM), which is emerging as a powerful tool to analyze the mechanical properties of biomolecules and cells, is actually an excellent imaging platform that allows biological samples to be visualized by probing surface roughness at the level of atomic resolution. Here, membrane pore structures were clearly visualized using AFM. This visualization not only describes the aperture and depth of the pore complexes but also highlights differences among the pores formed by perforin and gasdermins in tumor cell membranes and by complement in immune cell membranes. Additionally, this type of visualization also reveals the dynamic process of pore formation, fusion, and repair.

Genetic Polymorphism Study on Aedes albopictus of Different Geographical Regions Based on DNA Barcoding.

Aedes albopictus is a very important vector for pathogens of many infectious diseases including dengue fever. In this study, we explored the genetic polymorphism of Aedes albopictus strains in different geographical regions using DNA barcoding of mitochondrial COI (MT-COI) gene. We collected MT-COI sequence of 106 Aedes albopictus mosquitos from 6 provinces in China including Fujian, Guangdong, Hainan, Yunnan, and Taiwan. The length of the sequences is 709bp with the content of A+T (67.7%) greater than that of G+C (32.3%). We identified mutations in 90 (13.68%) loci, of which 57 (63.33%) are transitions, 28 (31.11%) are transversions, and 5 (5.56%) are hypervariable loci. In addition, we obtained 42 haplotypes, 4 (9.52%) of which are shared among different populations. The haplotype diversity of Aedes albopictus is 0.882 and nucleotide diversity is 0.01017. Moreover, the pedigree network diagram shows that most haplotypes are under parallel evolution, suggesting a local expansion of Aedes albopictus in history. Finally, the Neighbor-Joining tree of MT-COI haplotypes reveals a certain correlation between haplotype clusters and geographical distribution, and there are differences among Aedes albopictus in different geographical regions. In conclusion, DNA barcoding of MT-COI gene is an effective method to study the genetic structure of Aedes albopictus.

A DNA Barcoding Based Study to Identify Main Mosquito Species in Taiwan and its Difference from Those in Mainland China.

AIM AND OBJECTIVE: Mosquitoes can transmit many types of viruses such as West Nile virus and Zika virus and are responsible for a number of virus-causing diseases including malaria, dengue fever, yellow fever, lymphatic filariasis, and Japanese B encephalitis. On January 19, 2016, the first case of Zika virus infection was identified in Taiwan, which presents the need for studying the mosquito species in the Taiwan Strait and evaluating the risk of the outbreak of this infection. MATERIALS AND METHOD: In this study, we have collected 144 mosquito specimens from 42 species belonging to nine genera from both sides of the Taiwan Strait during 2013 and 2014. We then applied the COI DNA Barcoding technique to classify the specimens and performed a phylogenetic analysis to infer the evolutionary history of these mosquitoes. Based on the analyses, we found that though the mosquitoes from different sides of the Taiwan Strait share a lot of commonality, they have a few regional specificities. RESULTS: Our results also suggested a very small divergences (1%~9%) between specimens from the same mosquito species and relatively large divergences (8%~25%) between specimens from different mosquito species. Within the same species, the divergence of specimens from the same region is significantly smaller than that between two regions. A few highly divergent species between Fujian and Taiwan (e.g., An.maculatus and Ae.elsiae) might be formed due to the so-called "cryptic evolutionary events", in which the species has differentiation into cryptic species due to geographical differences without changing morphological characteristics. CONCLUSION: In conclusion, the phylogenetic analyses showed a very similar taxonomy to the historical one based on morphological characteristics, validating again the application of COI DNA Barcoding technique in classifying mosquito species. However, there are also some inconsistencies between COI DNA Barcoding and historical taxonomy, which points out the differences between mosquito DNA and morphological characteristics and suggests the possibility to improve mosquito taxonomy based on DNA techniques.

Melatonin alleviates cadmium-induced liver injury by inhibiting the TXNIP-NLRP3 inflammasome.

Cadmium (Cd) is a persistent environmental and occupational contaminant that accumulates in the liver and induces oxidative stress and inflammation. Melatonin possesses potent hepatoprotective properties against the development and progression of acute and chronic liver injury. Nevertheless, the molecular mechanism underlying the protective effects of melatonin against Cd-induced hepatotoxicity remains obscure. In this study, we aimed to investigate the effects of melatonin on Cd-induced liver inflammation and hepatocyte death. Male C57BL/6 mice were intraperitoneally injected with melatonin (10 mg/kg) once a day for 3 days before exposure to CdCl2 (2.0 mg/kg). We found that Cd induced hepatocellular damage and inflammatory infiltration as well as increased serum ALT/AST enzymes. In addition, we showed that Cd triggered an inflammatory cell death, which is mediated by the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome. Moreover, melatonin treatment significantly alleviated Cd-induced liver injury by decreasing serum ALT/AST levels, suppressing pro-inflammatory cytokine production, inhibiting NLRP3 inflammasome activation, ameliorating oxidative stress, and attenuating hepatocyte death. Most importantly, melatonin markedly abrogated Cd-induced TXNIP overexpression and decreased the interaction between TXNIP and NLRP3 in vivo and in vitro. However, treatment with siRNA targeting TXNIP blocked the protective effects of melatonin in Cd-treated primary hepatocytes. Collectively, our results suggest that melatonin confers protection against Cd-induced liver inflammation and hepatocyte death via inhibition of the TXNIP-NLRP3 inflammasome pathway.

Mosquito (Diptera: Culicidae) Habitat Surveillance by Android Mobile Devices in Guangzhou, China.

In 2014, Guangzhou City, South China, suffered from its worst outbreak of dengue fever in decades. Larval mosquito habitat surveillance was carried out by using android mobile devices in four study sites in May 2015. The habitats with larval mosquitoes were recorded as photo waypoints in OruxMaps or in videos. The total number of potential mosquito habitats was 342, of which 166 (49%) were found to have mosquito larvae or pupae. Small containers were the most abundant potential habitats, accounting for 26% of the total number. More mosquito larvae and pupae, were found in small containers than in other objects holding water, for example, potted or hydroponic plants (p < 0.05). Mosquito larvae were collected from all plastic road barriers, used tires, and underground water. Aedes albopictus larvae were found from small and large containers, stumps, among others. The overall route index (RI) was 11.3, which was 14.2 times higher than the grade C criteria of the National Patriotic Health Campaign Committee (NPHCC), China. The higher RIs were found from the bird and flower markets, schools, and underground parking lots. The results indicated that Android mobile devices are a convenient and useful tool for surveillance of mosquito habitats, and the enhancement of source reduction may benefit the prevention and control of dengue vector mosquitoes.

Exposure to nickel oxide nanoparticles induces pulmonary inflammation through NLRP3 inflammasome activation in rats.

With recent advances in the manufacture and application of nickel oxide nanoparticles (NiONPs), concerns about their adverse effects on the respiratory system are increasing. However, the underlying cellular and molecular mechanisms of NiONP-induced pulmonary toxicity remain unclear. In this study, we focused on the impacts of NiONPs on pulmonary inflammation and investigated whether the NLRP3 inflammasome is involved in NiONP-induced pulmonary inflammation and injury. NiONP suspensions were administered by single intratracheal instillation to rats, and inflammatory responses were evaluated at 3 days, 7 days, or 28 days after treatment. NiONP exposure resulted in sustained pulmonary inflammation accompanied by inflammatory cell infiltration, alveolar proteinosis, and cytokine secretion. Expression of Nlrp3 was markedly upregulated by the NiONPs, which was accompanied by overexpression of the active form of caspase-1 (p20) and interleukin (IL)-1ß secretion in vivo. NiONP-induced IL-1ß secretion was partially prevented by co-treatment with a caspase-1 inhibitor in macrophages. Moreover, siRNA-mediated Nlrp3 knockdown completely attenuated NiONP-induced cytokine release and caspase-1 activity in macrophages in vitro. In addition, NiONP-induced NLRP3 inflammasome activation requires particle uptake and reactive oxygen species production. Collectively, our findings suggest that the NLRP3 inflammasome participates in NiONP-induced pulmonary inflammation and offer new strategies to combat the pulmonary toxicity induced by NiONPs.

A Dynamic 3D Graphical Representation for RNA Structure Analysis and Its Application in Non-Coding RNA Classification.

With the development of new technologies in transcriptome and epigenetics, RNAs have been identified to play more and more important roles in life processes. Consequently, various methods have been proposed to assess the biological functions of RNAs and thus classify them functionally, among which comparative study of RNA structures is perhaps the most important one. To measure the structural similarity of RNAs and classify them, we propose a novel three dimensional (3D) graphical representation of RNA secondary structure, in which an RNA secondary structure is first transformed into a characteristic sequence based on chemical property of nucleic acids; a dynamic 3D graph is then constructed for the characteristic sequence; and lastly a numerical characterization of the 3D graph is used to represent the RNA secondary structure. We tested our algorithm on three datasets: (1) Dataset I consisting of nine RNA secondary structures of viruses, (2) Dataset II consisting of complex RNA secondary structures including pseudo-knots, and (3) Dataset III consisting of 18 non-coding RNA families. We also compare our method with other nine existing methods using Dataset II and III. The results demonstrate that our method is better than other methods in similarity measurement and classification of RNA secondary structures.

Cadmium induces NLRP3 inflammasome-dependent pyroptosis in vascular endothelial cells.

Cadmium (Cd) is an important and common environmental pollutant that has been linked to cardiovascular diseases, such as atherosclerosis and hypertension. Increasing evidence demonstrates that Cd impairs the cardiovascular system by targeting vascular endothelial cells, but the underlying mechanisms remain obscure. In human umbilical vein endothelial cells (HUVECs), we observed that Cd treatment led to cell death and the generation of inflammatory cytokines. The Cd-induced cell death was identified as pyroptosis, a novel pro-inflammatory form of cell death depending on caspase-1 activation. In addition, exposure of HUVECs to Cd resulted in NLRP3 inflammasome activation as evidenced by cleavage of caspase-1 and downstream interleukin (IL)-1ß production. Moreover, knockdown of NLRP3 by small interfering RNA efficiently suppressed Cd-induced caspase-1 cleavage, IL-1ß production and pyroptosis in HUVECs. Additional experiments demonstrated that treatment with Cd significantly increased the levels of mitochondrial reactive oxygen species (mtROS) and intracellular ROS in HUVECs. Accordingly, pre-treatment with mtROS scavenger or total ROS scavenger reduced Cd-induced activation of NLRP3 inflammasome and pyroptotic cell death. Taken together, our data suggest that NLRP3 inflammasome, activated by the generation of mtROS, mediates Cd-induced pyroptosis in HUVECs. Our results provide novel insights into Cd-induced cytotoxicity and the underlying mechanism by which Cd induces endothelial injury.