The emergence of a series of SARS-CoV-2 variants has necessitated the search for broad-spectrum antiviral targets. The aryl hydrocarbon receptor (AhR) senses tryptophan metabolites and is an immune regulator. However, the role of AhR in SARS-CoV-2 infection and whether AhR can be used as the target of antiviral therapy against SARS-CoV-2 and its variants are yet unclear. Here, we show that infection with SARS-CoV-2 activates AhR signaling and facilitates viral replication by interfering with IFN-I–driven antiviral immunity and up-regulating ACE2 receptor expression. The pharmacological AhR blockade or AhR knockout reduces SARS-CoV-2 and its variants’ replication in vitro. Drug targeting of AhR with AhR antagonists markedly reduced SARS-CoV-2 and its variants’ replication in vivo and ameliorated lung inflammation caused by SARS-CoV-2 infection in hamsters. Overall, AhR was a SARS-CoV-2 proviral host factor and a candidate host-directed broad-spectrum target for antiviral therapy against SARS-CoV-2 and its variants, including Delta and Omicron, and potentially other variants in the future.

Modern research has found that Ganoderma lucidum polysaccharides (GLP) and Polyporus umbellatus polysaccharides (PUP) mainly exhibit immunoregulation. However, the immune function of a polysaccharide composition consisting of GLP and PUP has not been studied. In this study, we developed a polysaccharide composition consisting of GLP and PUP in a ratio of 3:1 (named GPP). The immunoregulation of GPP was detected in RAW264.7 macrophages. Then, the acute oral toxicity of GPP and the effect of GPP on immunoregulation in mice was detected. The results showed that GPP enhanced the function of macrophage RAW264.7 cells through improving phagocytic ability, nitric oxide (NO) production and the mRNA expression of inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α. GPP belonged to the non-toxic grade in mice. Moreover, GPP significantly improved macrophage phagocytic function and the activity of natural killer (NK) cells after being administered to mice at a dose of 0, 3.6, 120, 360 mg/kg body weight (mg/kg BW) orally for 30 days. Taken together, these findings suggested that GPP moderately regulated immune function in mice, which contributes to the further development and utilization of GLP and PUP in immune function.

Major depressive disorder (MDD) is a chronic mental disorder characterized by mixed symptoms and complex pathogenesis. With long history of practical application, traditional Chinese medicine (TCM) offers many herbs for the treatment and rehabilitation of chronic disease. In this study, we developed a modified Chinese herbal formula using Panax ginseng, Angelica Sinensis, Polygala tenuifolia Willd, and Ziziphi spinosae Semen (PAPZ), based on an ancient TCM prescription. The antidepressant effects of PAPZ were investigated with a corticosterone (CORT) model of depression in mice. Our results showed that administration of PAPZ ameliorated depression-like phenotypes in the CORT model. An anatomic study showed that chronic PAPZ administration upregulated the protein expression of brain-derived neurotrophic factor (BDNF) in hippocampal tissue. The enzyme activity of superoxide dismutase was enhanced in hippocampal tissue, in line with a decreased malondialdehyde level. Taken together, these findings suggested that PAPZ has therapeutic effects in a mice depression model through increasing protein expression of BDNF and improving the anti-oxidation ability of the brain.

Soluble host factors in the upper respiratory tract can serve as the first line of defense against SARS-CoV-2 infection. In this study, we described the identification and function of a human airway trypsin–like protease (HAT), capable of reducing the infectivity of ancestral SARS-CoV-2. Further, in mouse models, HAT analogue expression was upregulated by SARS-CoV-2 infection. The antiviral activity of HAT functioned through the cleavage of the SARS-CoV-2 spike glycoprotein at R682. This cleavage resulted in inhibition of the attachment of ancestral spike proteins to host cells, which inhibited the cell-cell membrane fusion process. Importantly, exogenous addition of HAT notably reduced the infectivity of ancestral SARS-CoV-2 in vivo. However, HAT was ineffective against the Delta variant and most circulating Omicron variants, including the BQ.1.1 and XBB.1.5 subvariants. We demonstrate that the P681R mutation in Delta and P681H mutation in the Omicron variants, adjacent to the R682 cleavage site, contributed to HAT resistance. Our study reports what we believe to be a novel soluble defense factor against SARS-CoV-2 and resistance of its actions in the Delta and Omicron variants.

Purpose. Few studies have focused on long-term postoperative visual quality. This study aimed to evaluate the long-term visual quality after microincision cataract surgery (MICS). Methods. 96 patients (144 eyes) diagnosed with age-related cataracts were enrolled in this one-year study. The patients underwent MICS and received aspheric monofocal intraocular lens implants. Uncorrected distance visual acuity (UDVA) was evaluated together with best-corrected distance visual acuity (BCDVA), best-corrected near visual acuity (BCNVA), contrast sensitivity, and surgically induced astigmatism (SIA). Results. Compared to preoperative measurements, UDVA, BCDVA, and BCNVA were significantly better after surgery (P<0.001), and they remained stable throughout follow-up. Contrast sensitivity was also significantly better after surgery (P<0.001). Mean SIA during follow-up was 0.57 ± 0.33 D at 1 week, 0.36 ± 0.25 D at 3 months, and 0.18 ± 0.16 D at 1 year. SIA decreased significantly during the postoperative period (P<0.001). The 1-year postoperative absolute residual diopter value was 0.32 ± 0.28 D. Conclusion. MICS can provide excellent visual quality as soon as on postoperative day 1, which persists during the follow-up period of 1 year. In contrast to previous studies, SIA decreases over time and may not completely stabilize for as long as 1 year postoperatively.

Chikungunya virus (CHIKV) is now prevalent in multiple regions worldwide, posing a serious threat to human health. In this study, we have successfully established a rhesus macaque model of Chikungunya virus infection. Notably, while no viral load was detected in liver tissue on day 7 post-infection, significant pathological damage was observed. Single-cell RNA sequencing of liver tissue revealed a reduction in B cells following infection. Among T cells, CD8⁺ T and NKT cells mediated major cytotoxic effects, whereas CD4⁺ T and memory T cells primarily exerted regulatory functions that further enhanced the activation of CD8⁺ T and NKT cells. In macrophages, inflammatory macrophages fc gamma R-mediated phagocytosis upregulated, with multiple key activation-related genes being highly upregulated. Furthermore, we observed that there might be a potential bidirectional activation effect between T cells and macrophages. These results indicate that CHIKV-induced indirect liver injury is likely mediated not only by the virus itself but also, in part, by the activation of hepatic immune cells.