From the beginning of 2002 and 2012, severe respiratory syndrome coronavirus (SARS‐CoV) and Middle East respiratory syndrome coronavirus (MERS‐CoV) crossed the species barriers to infect humans, ...causing thousands of infections and hundreds of deaths, respectively. Currently, a novel coronavirus (SARS‐CoV‐2), which has become the cause of the outbreak of Coronavirus Disease 2019 (COVID‐19), was discovered. Until 18 February 2020, there were 72 533 confirmed COVID‐19 cases (including 10 644 severe cases) and 1872 deaths in China. SARS‐CoV‐2 is spreading among the public and causing substantial burden due to its human‐to‐human transmission. However, the intermediate host of SARS‐CoV‐2 is still unclear. Finding the possible intermediate host of SARS‐CoV‐2 is imperative to prevent further spread of the epidemic. In this study, we used systematic comparison and analysis to predict the interaction between the receptor‐binding domain (RBD) of coronavirus spike protein and the host receptor, angiotensin‐converting enzyme 2 (ACE2). The interaction between the key amino acids of S protein RBD and ACE2 indicated that, other than pangolins and snakes, as previously suggested, turtles (Chrysemys picta bellii, Chelonia mydas, and Pelodiscus sinensis) may act as the potential intermediate hosts transmitting SARS‐CoV‐2 to humans.
Highlights
The critical residues of S protein RBD binding with ACE2 indicated the potential intermediate hosts transmitting SARS‐CoV‐2 to humans.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Dendritic cells (DCs) orchestrate the initiation, programming, and regulation of anti-tumor immune responses. Emerging evidence indicates that the tumor microenvironment (TME) induces immune ...dysfunctional tumor-infiltrating DCs (TIDCs), characterized with both increased intracellular lipid content and mitochondrial respiration. The underlying mechanism, however, remains largely unclear. Here, we report that fatty acid-carrying tumor-derived exosomes (TDEs) induce immune dysfunctional DCs to promote immune evasion. Mechanistically, peroxisome proliferator activated receptor (PPAR) α responds to the fatty acids delivered by TDEs, resulting in excess lipid droplet biogenesis and enhanced fatty acid oxidation (FAO), culminating in a metabolic shift toward mitochondrial oxidative phosphorylation, which drives DC immune dysfunction. Genetic depletion or pharmacologic inhibition of PPARα effectively attenuates TDE-induced DC-based immune dysfunction and enhances the efficacy of immunotherapy. This work uncovers a role for TDE-mediated immune modulation in DCs and reveals that PPARα lies at the center of metabolic-immune regulation of DCs, suggesting a potential immunotherapeutic target.
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•Tumor-derived exosomes (TDEs) drive DC dysfunction•TDE-derived fatty acids activate PPARα to induce DC fatty acid oxidation•PPARα blockade modulates lipid metabolism and function in DCs•PPARα inhibition enhances the anti-tumor efficacy of immunotherapies
Yin et al. reveal that tumor-derived exosomes (TDEs), as fatty acid carriers, induce a metabolic shift toward oxidative phosphorylation, driving DC immune dysfunction. Transcriptomic analysis identifies PPARα as the fatty acid sensor mediating the immunosuppressive effects of TDEs on DCs. PPARα blockade effectively restores DC function and enhances the efficacy of immunotherapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Flavonoids are well known as a large class of polyphenolic compounds, which have a variety of physiological activities, including anti-influenza virus activity. The influenza A/WSN/33 infected A549 ...cells have been used to screen anti-influenza virus drugs from natural flavonoid compounds library. Unexpectedly, some flavonoid compounds significantly inhibited virus replication, while the others dramatically promoted virus replication. In this study, we attempted to understand these differences between flavonoid compounds in their antivirus mechanisms. Hesperidin and kaempferol were chosen as representatives of both sides, each of which exhibited the opposite effects on influenza virus replication. Our investigation revealed that the opposite effects produced by hesperidin and kaempferol on influenza virus were due to inducing the opposite cell-autonomous immune responses by selectively modulating MAP kinase pathways: hesperidin up-regulated P38 and JNK expression and activation, thus resulting in the enhanced cell-autonomous immunity; while kaempferol dramatically down-regulated p38 and JNK expression and activation, thereby suppressing cell-autonomous immunity. In addition, hesperidin restricted RNPs export from nucleus by down-regulating ERK activation, but kaempferol promoted RNPs export by up-regulating ERK activation. Our findings demonstrate that a new generation of anti-influenza virus drugs could be developed based on selective modulation of MAP kinase pathways to stimulate cell-autonomous immunity.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The application of nano-materials to modify construction materials has become a research hotspot in recent years, but often different scholars use different research methods and reach different ...conclusions about the same material, which is not conducive to the performance comparison between different materials. In this paper, nano-SiO
, carbon nanotubes (CNTs) and nanocrystalline cellulose (NCC) were used as raw materials to prepare cement-based composites to compare the effects of the three nanomaterials on the mechanical and water absorption properties under the same experimental conditions, and their principles were investigated via The scanning electron microscope (SEM), X-Ray Diffraction (XRD) and other microscopic analysis testing methods. At the same time, strength benefit indexes are introduced to comprehensively evaluate the economics of the strength improvement provided by the three kinds of nanomaterial. The results show that doping with nano-SiO
, CNTs and NCC can promote the hydration process of cement effectively. The composite material exhibits excellent mechanical properties at the macro level because of the nucleation and filling effect of nano-SiO
, and the bridging and strengthening effects of CNTs and NCC. The compressive strength increased by 45.13%, 28.31% and 44.19% at 7d, and 23.09%, 18.40% and 23.40% at 28d. The flexural strength of 7d increased by 31.00%, 36.22 and 54.81%, and 14.91%, 22.23% and 30.46% at 28d. The water absorption is SiO
< NCC < CNTs, and the nano-SiO
is lower than the other two materials at least 15.54%. CNTs group has the lowest compressive strength benefit, which is 16.91 yuan/m
, and the lowest flexural strength benefit is NCC, which is 3.59 yuan/m
.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
We integrate previous work on the Hegenshan–Heihe suture with our interpretation of geomagnetic anomaly and seismic reflection data to investigate the role of the Hegenshan–Heihe suture in the ...evolution of late Mesozoic extensional structures in the Wunite depression of the Erlian Basin. Sags in the Wunite depression present as NE50° trending in the western sector, N0°–NE30° trending in the central sector and NE45° trending in the eastern sector. Our results highlight the importance of the pre-existing Hegenshan–Heihe suture in the evolution of the late Mesozoic rift system and reveal the following details. (1) The NE50° extent sags in the western sector are controlled by the c. NE50°-trending suture. Moreover, the extensional deformation of the reactivated suture during Early Cretaceous time resulted in a further vertical and horizontal extension of major border faults. (2) The N0°–NE30° extent sags in the central sector are influenced by the c. NE75°-trending suture. The sinistral strike-slip component of the reactivated suture during Early Cretaceous time resulted in a strike rotation of major border faults from NEE-trending (following the suture) to NNE-trending. (3) Because of strike-slip deformation, which resulted from the deformation of the reactivated suture accrued in major border faults, light dip-slip deformation led to less vertical offset. (4) The NE45°-trending sags in the eastern sector are controlled by the c. NE45°-trending suture. Moreover, the extensional deformation of the reactivated suture during Early Cretaceous time facilitated a further vertical and horizontal prolongation of major border faults.
Dissolved oxygen (DO) in water bodies is a prerequisite for fish survival and plays a crucial role in fish growth, development, and physiological processes. However, with increasing eutrophication, ...greenhouse effects, and extreme weather conditions, DO levels in aquatic environments often become lower than normal. This leads to stress in fish, causing them to exhibit escape behavior, inhibits their growth and development, and causes tissue damage. Moreover, oxidative stress, decreased immune function, and altered metabolism have been observed. Severe hypoxia can cause massive fish mortality, resulting in significant economic losses to the aquaculture industry. In response to hypoxia, fish exhibit a series of behavioral and physiological changes that are self-protective mechanisms formed through long-term evolution. This review summarizes the effects of hypoxic stress on fish, including the asphyxiation point, behavior, growth and reproduction, tissue structure, physiological and biochemical processes, and regulation of gene expression. Furthermore, future research directions are discussed to provide new insights and references.
•The effects of hypoxic stress on fish are summarized, including behavior, growth and reproduction, physiological state, etc.•Asphyxiation points for 143 species of fish are summarized.•4 HIF-α subtypes and 1 HIF-β subtype can be identified from fish at least.•Studies on the cumulative effects of multiple stress factors are further needed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Orthogonal test method was applied to analyze the strength properties of basalt-polypropylene mortar. The effect of basalt fiber length, polypropylene fiber length, basalt fiber volume content and ...polypropylene fiber volume content on the 28 d cube compressive strength and flexural strength were investigated. Test results show that comparing with flexural strength, the influence of basalt fiber length and polypropylene fiber length on compressive strength of mortar was greater than on flexural strength. The length of polypropylene fibers contributes the highest to the flexural strength. The effect of basalt fiber on mortar strength is the largest with 6 mm length and 4% content. Polypropylene fiber length has the greatest influence on the compressive strength of fiber mortar, followed by basalt fiber volume content. Volume content of polypropylene fiber has the greatest influence on flexural strength of fiber mortar, followed by polypropylene fiber length. According to the scoring of the efficacy coefficient method, the best ratio combination for compressive and flexural strength was the basalt fiber length of 9 mm, polypropylene fiber length of 6 mm, basalt fiber volume content of 4% and polypropylene fiber volume content of 4%. Compared with the blank samples, the 28 d compressive strength and 28 d flexural strength of the cement mortar samples were increased by 27.4% and 49% respectively. According to the test results, the properties of the fiber were analyzed and evaluated and the mechanism of fiber action and fiber microstructure were analyzed.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
When properly processed, rice husk ash (RHA) comprises a large amount of SiO
, which exhibits a high pozzolanic activity and acts as a good building filler. In this paper, the effects of rice husk ...ash content, acid pretreatment, and production regions on the compressive and flexural properties and water absorption of a cement paste were studied. The experimental results showed that the compressive strength of the rice husk ash was the highest with a 10% content level, which was about 16.22% higher than that of the control sample. The rice husk after acid pretreatment displayed a higher strength than that of the sample without the acid treatment, and the rice husk from the Inner Mongolia region indicated a higher strength than that from the Guangdong province. However, the flexural strength of each group was not significantly different from that of the blank control group. The trend observed for the water absorption was similar to that of the compressive strength. The variation in the RHA proportions had the greatest influence on the properties of the paste specimens, followed by the acid pretreatments of the rice husks. The production regions of the rice husks indicated the least influence.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Gut microbiome is critical to our human health and is related to postmenopausal osteoporosis (PMO). Strontium ranelate (SrR) is an anti-osteoporosis oral drug that can promote osteoblast formation ...and inhibit osteoclast formation. However, the effect of SrR on gut microbiome has been rarely studied. Therefore, we investigated the effect of oral SrR on gut microbiome and metabolic profiles. In this study, we used ovariectomized (OVX) Sprague-Dawley rats to construct a PMO model and applied oral SrR for 6 weeks. The relative abundance of intestinal microbiome was investigated by 16S rRNA metagenomic sequencing. Ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) was used to analyze changes in metabolites of intestinal contents. Results demonstrated that 6-week oral SrR alleviated osteoporosis and significantly changed the composition of the gut microbiome and metabolic profiles of OVX rats. Ruminococcus, Akkermansia and Oscillospira were significantly enriched in the gut of OVX rats after 6-week oral SrR. Especially, the species R. albus showed the greatest importance by a random forest classifier between OVX and OVX_Sr group. The enrichment of R. albus in the gut was positively correlated with bone mineral density and the accumulation of lycopene and glutaric acid, which also significantly elevated after oral SrR. We discovered that oral SrR can improve bone health while stimulate the accumulation of gut microbe R. albus and metabolites (lycopene and glutaric acid). The results suggested possible connections between oral SrR and the gut-bone axis, which may provide new insight into the treatment/prevention of osteoporosis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Hemorrhage is common in APL-related coagulopathy while thrombosis is uncommon.•In the high-risk APL population, thrombotic complication become more frequent.•FDP/FIB and d-dimer/FIB ratios are ...useful for predicting thrombosis.
Hemorrhage is the typical manifestation of APL-related coagulopathy while thrombosis is infrequently reported. In a retrospective analysis with 33 patients with hyperleukocytic APL, we found 6 out of 33 hyperleukocytic APL patients presented with thrombosis rather than hemorrhage. A notable feature in these high-risk APL patients with thrombosis is that there were no significant abnormalities in fibrinogen (FIB), prothrombin time (PT) and activated partial thromboplastin time (APTT). Compared with the normal ranges, both the high-risk APL patients with thrombosis and the high-risk APL patients with hemorrhage had a significant increase in fibrinogen degradation product (FDP) and d-dimer levels. However, the group with hemorrhage had noticeably higher plasma levels of FDP and d-dimer than the group with thrombosis. To find a close relationship between coagulation markers and the onset of thrombotic events in patients with high-risk APL, the potential effects of FDP/FIB and d-dimer/FIB ratios as risk markers were investigated. We demonstrated that FDP/FIB and d-dimer/FIB ratios in the patients with high-risk APL with thrombosis showed higher ratios than the normal range but significantly lower ratios than the patients with high-risk APL-related hemorrhage. Our data demonstrated that the alteration in FDP/FIB and d-dimer/FIB ratios have more significant relevance than the levels of FIB, FDP or d-dimer as potential factors for predicting thrombosis and may help with designing more appropriately risk-adapted treatment protocols or personalized therapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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