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Pangolins are endangered animals in urgent need of protection. Identifying and cataloguing the viruses carried by pangolins is a logical approach to evaluate the range of potential pathogens and help with conservation. This study provides insight into viral communities of Malayan Pangolins (Manis javanica) as well as the molecular epidemiology of dominant pathogenic viruses between Malayan Pangolin and other hosts. A total of 62,508 de novo assembled contigs were constructed, and a BLAST search revealed 3600 ones (≥300 nt) were related to viral sequences, of which 68 contigs had a high level of sequence similarity to known viruses, while dominant viruses were the Sendai virus and Coronavirus. This is the first report on the viral diversity of pangolins, expanding our understanding of the virome in endangered species, and providing insight into the overall diversity of viruses that may be capable of directly or indirectly crossing over into other mammals.

Recurrent spontaneous abortion (RSA) refers to the unintentional termination of two or more consecutive pregnancies that severely threatens human reproductive health. Our previous study has shown that miR-184 is expressed more highly in RSA than in normal pregnancy, whether in the villus or decidua. In this study, compared with normal pregnant women, the expression of miR-184 in decidual stromal cells (DSCs) and decidual immune cells (DICs), as well as in peripheral blood, from RSA patients was enhanced similarly. Moreover, we found miR-184 could promote the apoptosis and repress the proliferation of trophoblast cells. Further exploration indicated that miR-184 upregulated the expression of Fas by targeting WIG1 thus inducing cell apoptosis. Finally, after miR-184 overexpression in vivo, the embryo resorption rate in pregnant mice was increased significantly. Therefore, our study outlines the pivotal role of miR-184 in maintaining successful pregnancy, providing a new diagnostic and therapeutic target for RSA.

A bstract Enhanced glycolysis in cancer cells has been linked to cell protection from DNA damaging signals, although the mechanism is largely unknown. The 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) catalyzes the generation of fructose-2,6-bisphosphate, a potent allosteric stimulator of glycolysis. Intriguingly, among the four members of PFKFB family, PFKFB3 is uniquely localized in the nucleus, although the reason remains unclear. Here we show that chemotherapeutic agent cisplatin promotes glycolysis, which is suppressed by PFKFB3 deletion. Mechanistically, cisplatin induces PFKFB3 acetylation at lysine 472 (K472), which impairs activity of the nuclear localization signal (NLS) and accumulates PFKFB3 in the cytoplasm. Cytoplasmic accumulation of PFKFB3 facilitates its phosphorylation by AMPK, leading to PFKFB3 activation and enhanced glycolysis. Inhibition of PFKFB3 sensitizes tumor to cisplatin treatment in a xenograft model. Our findings reveal a mechanism for cells to stimulate glycolysis to protect from DNA damage and potentially suggest a therapeutic strategy to sensitize tumor cells to genotoxic agents by targeting PFKFB3. Enhanced glycolysis in cancer cells has been associated with protection from DNA damage. Here the authors show that DNA damaging signals induce acetylation of PFKFB3 at lysine K472 and promote its cytosolic accumulation, which enhances glycolysis, resulting in protection from cisplatin-induced cell death.

Pre-metastatic niche formation is critical for the colonization of disseminated cancer cells in distant organs. Here we find that lung mesenchymal stromal cells (LMSCs) at pre-metastatic stage possess potent metastasis-promoting activity. RNA-seq reveals an upregulation of complement 3 (C3) in those LMSCs. C3 is found to promote neutrophil recruitment and the formation of neutrophil extracellular traps (NETs), which facilitate cancer cell metastasis to the lungs. C3 expression in LMSCs is induced and sustained by Th2 cytokines in a STAT6-dependent manner. LMSCs-driven lung metastasis is abolished in Th1-skewing Stat6 -deficient mice. Blockade of IL-4 by antibody also attenuates LMSCs-driven cancer metastasis to the lungs. Consistently, metastasis is greatly enhanced in Th2-skewing T-bet -deficient mice or in nude mice adoptively transferred with T-bet -deficient T cells. Increased C3 levels are also detected in breast cancer patients. Our results suggest that targeting the Th2-STAT6-C3-NETs cascade may reduce breast cancer metastasis to the lungs. The formation of the pre-metastatic niche enables the colonisation of disseminated cancer cells in distant organs. Here, the authors show that Th2 cytokines induce Complement 3 production in lung mesenchymal stromal cells, which recruits neutrophils and promotes the formation neutrophil extracellular traps, facilitating breast cancer cell metastasis to the lungs.

Metal-to-insulator transition (MIT) behaviors accompanied by a rapid reversible phase transition in vanadium dioxide (VO2) have gained substantial attention for investigations into various potential applications and obtaining good materials to study strongly correlated electronic behaviors in transition metal oxides (TMOs). Although its phase-transition mechanism is still controversial, during the past few decades, people have made great efforts in understanding the MIT mechanism, which could also benefit the investigation of MIT modulation. This review summarizes the recent progress in the phase-transition mechanism and modulation of VO2 materials. A representative understanding on the phase-transition mechanism, such as the lattice distortion and electron correlations, are discussed. Based on the research of the phase-transition mechanism, modulation methods, such as element doping, electric field (current and gating), and tensile/compression strain, as well as employing lasers, are summarized for comparison. Finally, discussions on future trends and perspectives are also provided. This review gives a comprehensive understanding of the mechanism of MIT behaviors and the phase-transition modulations.

Triboelectric polymer with high charge density is the foundation to promote the wide range of applications of triboelectric nanogenerators. This work develops a method to produce triboelectric polymer based on repeated rheological forging. The fluorinated ethylene propylene film fabricated by repeated forging method not only has excellent mechanical properties and good transmittance, but also can maintain an ultrahigh tribo-charge density. Based on the film with a thickness of 30 μm, the output charge density from contact-separation nanogenerator reaches 352 μC·m −2 . Then, the same film is applied for the nanogenerator with air-breakdown mode and a charge density of 510 μC·m −2 is further achieved. The repeated forging method can effectively regulate the composition of surface functional groups, the crystallinity, and the dielectric constants of the fluorinated ethylene propylene, leading to the superior capability of triboelectrification. Finally, we summarize the key parameters for elevating the electrification performance on the basis of molecular structure and related fabrication crafts, which can guide the further development of triboelectric polymers. High charge density is the foundation to promote a wide range of applications of triboelectric nanogenerators. Here, authors propose a processing method based on the repeated rheological forging of triboelectric polymers achieving an enhanced triboelectricity and further study its mechanism.

Air pollution constitutes a significant stimulus of asthma exacerbations; however, the impacts of exposure to major air pollutants on asthma-related hospital admissions and emergency room visits (ERVs) have not been fully determined. We sought to quantify the associations between short-term exposure to air pollutants [ozone (O3), carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), and particulate matter ≤10 μm (PM10) and PM2.5] and the asthma-related emergency room visits (ERV) and hospitalizations. Systematic computerized searches without language limitation were performed. Pooled relative risks (RRs) and 95% confidence intervals (95%CIs) were estimated using the random-effect models. Sensitivity analyses and subgroup analyses were also performed. After screening of 246 studies, 87 were included in our analyses. Air pollutants were associated with significantly increased risks of asthma ERVs and hospitalizations [O3: RR(95%CI), 1.009 (1.006, 1.011); I2 = 87.8%, population-attributable fraction (PAF) (95%CI): 0.8 (0.6, 1.1); CO: RR(95%CI), 1.045 (1.029, 1.061); I2 = 85.7%, PAF (95%CI): 4.3 (2.8, 5.7); NO2: RR(95%CI), 1.018 (1.014, 1.022); I2 = 87.6%, PAF (95%CI): 1.8 (1.4, 2.2); SO2: RR(95%CI), 1.011 (1.007, 1.015); I2 = 77.1%, PAF (95%CI): 1.1 (0.7, 1.5); PM10: RR(95%CI), 1.010 (1.008, 1.013); I2 = 69.1%, PAF (95%CI): 1.1 (0.8, 1.3); PM2.5: RR(95%CI), 1.023 (1.015, 1.031); I2 = 82.8%, PAF (95%CI): 2.3 (1.5, 3.1)]. Sensitivity analyses yielded compatible findings as compared with the overall analyses without publication bias. Stronger associations were found in hospitalized males, children and elderly patients in warm seasons with lag of 2 days or greater. Short-term exposures to air pollutants account for increased risks of asthma-related ERVs and hospitalizations that constitute a considerable healthcare utilization and socioeconomic burden.

Dysregulated extravillous trophoblast invasion and proliferation are known to increase the risk of recurrent spontaneous abortion (RSA); however, the underlying mechanism remains unclear. Herein, in our retrospective observational case-control study we show that villous samples from RSA patients, compared to healthy controls, display reduced succinate dehydrogenase complex iron sulfur subunit (SDHB) DNA methylation, elevated SDHB expression, and reduced succinate levels, indicating that low succinate levels correlate with RSA. Moreover, we find high succinate levels in early pregnant women are correlated with successful embryo implantation. SDHB promoter methylation recruited MBD1 and excluded c-Fos, inactivating SDHB expression and causing intracellular succinate accumulation which mimicked hypoxia in extravillous trophoblasts cell lines JEG3 and HTR8 via the PHD2-VHL-HIF-1α pathway; however, low succinate levels reversed this effect and increased the risk of abortion in mouse model. This study reveals that abnormal metabolite levels inhibit extravillous trophoblast function and highlights an approach for RSA intervention. Abnormal placentation is associated with recurrent spontaneous abortion (RSA) risk. Here the authors report that low embryonic villous succinate level associates with risk of RSA in patients, and increasing succinate levels is sufficient to reduce the incidence rate in a mouse model of spontaneous abortion.

Lightweight flexible piezoelectric polymers are demanded for various applications. However, the low instinctively piezoelectric coefficient ( i.e . d33) and complex poling process greatly resist their applications. Herein, we show that introducing dynamic pressure during fabrication is capable for poling polyvinylidene difluoride/barium titanate (PVDF/BTO) composites with d33 of ~51.20 pC/N at low density of ~0.64 g/cm 3 . The melt-state dynamic pressure driven energy implantation induces structure evolutions of both PVDF and BTO are demonstrated as reasons for self-poling. Then, the porous material is employed as pressure sensor with a high output of ~20.0 V and sensitivity of ~132.87 mV/kPa. Besides, the energy harvesting experiment suggests power density of ~58.7 mW/m 2 can be achieved for 10 N pressure with a long-term durability. In summary, we not only provide a high performance lightweight, flexible piezoelectric polymer composite towards sustainable self-powered sensing and energy harvesting, but also pave an avenue for electrical-free fabrication of piezoelectric polymers. Lightweight flexible piezoelectric polymers are demanded for various applications, but restricted by the low instinctively piezoelectric coefficient and complex poling process. Here, the authors develop a high performance lightweight, flexible self-poled piezoelectric polymer composite towards sustainable self-powered sensing and energy harvesting.

Liquid-liquid phase separation (LLPS) plays important roles in various cellular processes, facilitating membrane-less organelles construction, chromatin condensation, signal transduction on inner membrane and many other processes. Current perception is that LLPS relies on weak multivalent interactions and crowded environments intracellularly. In this study, we demonstrate that heparan sulfate can serve as a platform to induce the phase separation of basic fibroblast growth factor on cell surface. The phase separation model provides an alternative mechanism how bFGF is enriched to its receptors, therefore triggering the signaling transduction. The research provides insights on the mechanism how growth factors can be recruited to cell surface by heparan sulfate and execute their functions, extending people’s view on phase separation from intracellular to extracellular proteins at cellular level. Liquid-liquid phase separation (LLPS) is reported to occur in the intracellular environment. Here the authors show that heparan sulphate serves as a platform for basic fibroblast growth factor to undergo LLPS on the cell surface, therefore facilitating downstream signalling