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Abstract Developing facile and direct synthesis routes for enantioselective construction of cyclic π-conjugated molecules is crucial. However, originate chirality from the distorted structure around heptagon-containing polyarenes is largely overlooked, the enantioselective construction of all-carbon heptagon-containing polyarenes remains a challenge. Herein, we present a highly enantioselective synthesis route for fabricating all carbon heptagon-containing polyarenes via palladium-catalyzed carbene-based cross–coupling of benzyl bromides and N-arylsulfonylhydrazones. A wide range of nonplanar, saddle-shaped tribenzocycloheptene derivatives are efficiently prepared in high yields with excellent enantioselectivities using this approach. In addition, stereochemical stability experiments show that these saddle-shaped tribenzocycloheptene derivatives have high inversion barriers.

Human immunodeficiency virus-1 (HIV-1) infection can cause chronic activation, exhaustion, and anergy of the immune system. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is an immune checkpoint molecule, which plays an important role in immune homeostasis and disease. CTLA-4 expression is elevated in HIV-1-infected patients and is associated with disease progression. However, the mechanism controlling expression of CTLA-4 in HIV-1 infection is poorly characterized. In this study, we used a SIV-infected Chinese rhesus macaque (ChRM) model to explore CTLA-4 expression in SIV infection. Results showed that SIV infection significantly increased CTLA-4 expression in all T cell subsets, especially central memory T cells. CTLA-4+CD4+ T cell frequency was significantly associated with disease progression markers. Activation of the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway regulated CTLA-4 expression in CD4+T cells, as confirmed by stimulation with dibutyryl cyclic adenosine monophosphate, forskolin, and 3-isobutyl-1-methylxanthine, and inhibition with H-89 ex vivo. Simultaneously, cAMP concentration in PBMCs and PKA activity in both PBMCs and CD4+ T cells were increased in acute SIV-infected ChRMs, accompanied by an increase in adenylate cyclase 6 expression and a decrease in cAMP-phosphodiesterase 3A (PDE3A), PDE4B, and PDE5A expression in PBMCs. In addition, selective inhibition of PDE4B and PDE5A activity enhanced CTLA-4 expression in CD4+ T cells. These results suggest that SIV infection alters cAMP metabolism and increases cAMP-PKA signaling pathway activation, which up-regulates the expression of CTLA-4 in acute SIVmac239-infected ChRMs. Thus, regulation of the cAMP-PKA signaling pathway may be a potential strategy for the restoration of T cell function and therapy for AIDS.

Viral infections are major threats to human health (1,2). Because of the advent of high-throughout sequencing, researchers are identifying new viruses with an unprecedented speed (3), and continuous attempts at [...]

Induction implant welding (IIW) of thermoplastic composites (TPC) is a new technology which uses the heat from the electromagnetic induction heating element implanted in the lap region of TPC laminate under the action of high-frequency alternating magnetic field to melt the thermoplastic resin in the interface area to achieve the connection of TPC structure. The technology has the advantages of simple operation, green efficiency, non-contact, etc., and has received extensive attention from the industrial sector in the past 30 years. Focusing on the IIW process of TPC, the influence of heat generation mechanism, heating effect, welding process parameters on the performance of welding joints was systematically introduced in this paper. Among them, the causes of uneven temperature in the welding area were explained, the method of regulating the temperature distribution in the welding area was presented, and the relationship between the uniformity of the temperature field and the quality of the welded joint was revealed. Finally, some problems faced by the APC structure IIW technology and its future development directions were also discussed.

Carbon fiber reinforced polymer composites (CFRP) are widely used in the aerospace field. The efficient bonding technology has an important effect on the manufacturing cost and safety of CFRP components. In this paper, carbon fiber reinforced polyetherimide resin matrix composites (CF/PEI) were welded by ultrasonic welding technology. The effects of ultrasonic welding pressure and welding time on the strength of ultrasonic welded joints were studied by single lap shear strength (LSS) test, and the micro morphology of section was characterized by scanning electron microscope. The experimental data were analyzed by linear fitting, and the time pressure parameters were optimized and the joint strength was predicted by combining BP neural network and genetic algorithm. Finally, the influence mechanism of holding time on joint strength was studied. The results show that when the welding time is 2.5 s and the welding pressure is 0.45 MPa, the maximum LSS is 25.6 MPa, and it is found that the higher welding strength is due to the formation of dense and stable structure on the joint surface. The experimental data are refined by BP neural network. The LSS value simulated by genetic algorithm is 24.8 MPa, and the error between the simulation and the experimental results is only 3%.With the increase of the holding time, the strength of ultrasonic welding joint increases rapidly first and then tends to be stable. When the holding time is 5 s, the molten resin at the welding interface is basically cured completely, and the PEI resin and carbon fiber form a dense structure, and the strength of ultrasonic welding joint is stable.

We identified a novel circovirus (human-associated circovirus 2 [HuCV2]) from the blood of 2 intravenous drug users in China who were infected with HIV-1, hepatitis C virus, or both. HuCV2 is most closely related to porcine circovirus 3. Our findings underscore the risk for HuCV2 and other emerging viruses among this population.

Abstract Effective drugs with broad spectrum safety profile to all people are highly expected to combat COVID-19 caused by SARS-CoV-2. Here we report that nelfinavir, an FDA approved drug for the treatment of HIV infection, is effective against SARS-CoV-2 and COVID-19. Preincubation of nelfinavir could inhibit the activity of the main protease of the SARS-CoV-2 (IC50 = 8.26 μM), while its antiviral activity in Vero E6 cells against a clinical isolate of SARS-CoV-2 was determined to be 2.93 μM (EC50). In comparison with vehicle-treated animals, rhesus macaque prophylactically treated with nelfinavir had significantly lower temperature and significantly reduced virus loads in the nasal and anal swabs of the animals. At necropsy, nelfinavir-treated animals had a significant reduction of the viral replication in the lungs by nearly three orders of magnitude. A prospective clinic study with 37 enrolled treatment-naive patients at Shanghai Public Health Clinical Center, which were randomized (1:1) to nelfinavir and control groups, showed that the nelfinavir treatment could shorten the duration of viral shedding by 5.5 days (9.0 vs. 14.5 days, P = 0.055) and the duration of fever time by 3.8 days (2.8 vs. 6.6 days, P = 0.014) in mild/moderate COVID-19 patients. The antiviral efficiency and clinical benefits in rhesus macaque model and in COVID-19 patients, together with its well-established good safety profile in almost all ages and during pregnancy, indicated that nelfinavir is a highly promising medication with the potential of preventative effect for the treatment of COVID-19.

The beneficial microorganisms in food are diverse and complex in structure. These beneficial microorganisms can produce different and unique flavors in the process of food fermentation. The unique flavor of these fermented foods is mainly produced by different raw and auxiliary materials, fermentation technology, and the accumulation of flavor substances by dominant microorganisms during fermentation. The succession and metabolic accumulation of microbial flora significantly impacts the distinctive flavor of fermented foods. The investigation of the role of microbial flora changes in the production of flavor substances during fermentation can reveal the potential connection between microbial flora succession and the formation of key flavor compounds. This paper reviewed the evolution of microbial flora structure as food fermented and the key volatile compounds that contribute to flavor in the food system and their potential relationship. Further, it was a certain guiding significance for food industrial production.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by the SFTS virus (SFTSV) and with a high fatality rate. Thrombocytopenia is a major clinical manifestation observed in SFTS patients, but the underlying mechanism remains largely unclear. Here, we explored the effects of SFTSV infection on platelet function in vivo in severely infected SFTSV IFNar−/− mice and on mouse and human platelet function in vitro. Results showed that SFTSV-induced platelet clearance acceleration may be the main reason for thrombocytopenia. SFTSV-potentiated platelet activation and apoptosis were also observed in infected mice. Further investigation showed that SFTSV infection induced platelet reactive oxygen species (ROS) production and mitochondrial dysfunction. In vitro experiments revealed that administration of SFTSV or SFTSV glycoprotein (Gn) increased activation, apoptosis, ROS production, and mitochondrial dysfunction in separated mouse platelets, which could be effectively ameliorated by the application of antioxidants (NAC (N-acetyl-l-cysteine), SKQ1 (10-(6′-plastoquinonyl) decyltriphenylphosphonium) and resveratrol). In vivo experiments showed that the antioxidants partially rescued SFTSV infection-induced thrombocytopenia by improving excessive ROS production and mitochondrial dysfunction and down-regulating platelet apoptosis and activation. Furthermore, while SFTSV and Gn directly potentiated human platelet activation, it was completely abolished by antioxidants. This study revealed that SFTSV and Gn can directly trigger platelet activation and apoptosis in an ROS-MAPK-dependent manner, which may contribute to thrombocytopenia and hemorrhage during infection, but can be abolished by antioxidants.