The COVID-19 pandemic has infected millions of people worldwide and many countries have been suffering from a large number of deaths. Acknowledging the ability of SARS-CoV-2 to mutate into distinct strains as an RNA virus and investigating its potential to cause reinfection is important for future health policy guidelines. It was thought that individuals who recovered from COVID-19 generate a robust immune response and develop protective immunity; however, since the first case of documented reinfection of COVID-19 in August 2020, there have been a number of cases with reinfection. Many cases are lacking genomic data of the two infections, and it remains unclear whether they were caused by different strains. In the present study, we undertook a rapid systematic review to identify cases infected with different genetic strains of SARS-CoV-2 confirmed by PCR and viral genome sequencing. A total of 17 cases of genetically confirmed COVID-19 reinfection were found. One immunocompromised patient had mild symptoms with the first infection but developed severe symptoms resulting in death with the second infection. Overall, 68.8% (11/16) had similar severity; 18.8% (3/16) had worse symptoms; and 12.5% (2/16) had milder symptoms with the second episode. Our case series shows that reinfection with different strains is possible, and some cases may experience more severe infections with the second episode. The findings also suggest that COVID-19 may continue to circulate even after achieving herd immunity through natural infection or vaccination, suggesting the need for longer-term transmission mitigation efforts.

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Secukinumab, an interleukin (IL)-17A antagonist, was associated with disease exacerbations in Crohn’s disease, and de novo cases of inflammatory bowel disease (IBD) have been reported in studies of rheumatoid diseases. However, there has been no detailed report demonstrating the linkage between secukinumab therapy and new-onset IBD. We present a unique case of rapid-onset fulminant colitis after receiving 1 dose of secukinumab infusion followed by improvement with combination antibiotics, corticosteroids, and calcineurin inhibition. Health care providers should be aware of the possible association between IL-17 antagonist therapy and the risk of developing new-onset fulminant IBD.

Summary Background New onset IBD has been reported with the use of anti‐IL‐17 agents, but it remains unclear to what extent this is attributed to treatment or to underlying disease. Aim To evaluate the risk of new onset IBD with the use of anti‐IL‐17 agents Methods Electronic databases were searched for randomised controlled trials (RCT) of anti‐IL‐17 agents (brodalumab, ixekizumab and secukinumab). Risk of new onset IBD was compared to placebo by Mantel‐Haenszel (MH) risk difference (RD). Sensitivity analyses including meta‐analysis using fixed‐effect model, MH and Peto odds ratio and MH risk ratio were performed due to incidence of rare adverse events. The risk of diarrhoea was also assessed due to the possibility of underdiagnosis of IBD. Results Thirty‐eight RCTs including 16 690 patients treated with anti‐IL‐17 agents were included. Twelve cases of new onset IBD were reported with anti‐IL‐17 agents in five studies, whereas no cases were reported with placebo. There was no difference in the risk of developing new onset IBD with anti‐IL‐17 agents compared to placebo (MH RD 0.00062, 95% CI −0.00072‐0.0021, P = 0.35). Sensitivity analyses demonstrated no consistent risk with any method. There was no difference in the risk of diarrhoea (MH RD 0.0013, 95% CI −0.0014‐0.0041, P = 0.34). Conclusions New onset IBD with the use of anti‐IL‐17 agents was rare. Interpretation of the results needs caution due to the presence of many zero‐event studies.

Objective To investigate the role and possible molecular mechanism of Krüppel-like factor 7 (KLF7) in the TLR4/NF-κB/IL-6 inflammatory signaling pathway activated by free fatty acids (FFA). Methods The mRNA and protein expression levels of KLF7 and the factors of TLR4/NF-κB/IL-6 inflammatory signal pathways were detected by qRT-PCR and Western blotting after cell culture with different concentrations of palmitic acid (PA). The expression of KLF7 or TLR4 in adipocytes was upregulated or downregulated; after that, the mRNA and protein expression levels of these key factors were detected. KLF7 expression was downregulated while PA stimulated adipocytes, and then the mRNA and protein expressions of KLF7/p65 and downstream inflammatory cytokine IL-6 were detected. The luciferase reporter assay was used to determine whether KLF7 had a transcriptional activation effect on IL-6. Results (1) High concentration of PA can promote the expression of TLR4, KLF7, and IL-6 in adipocytes. (2) TLR4 positively regulates KLF7 expression in adipocytes. (3) KLF7 positively regulates IL-6 expression in adipocytes. (4) PA promotes IL-6 expression via KLF7 in adipocytes. (5) KLF7 has a transcriptional activation on IL-6. Conclusion PA promotes the expression of the inflammatory cytokine IL-6 by activating the TLR4/KLF7/NF-κB inflammatory signaling pathway. In addition, KLF7 may directly bind to the IL-6 promoter region and thus activate IL-6.

The phenotypic modulation of vascular smooth muscle cells (VSMCs) plays a pivotal role in hypertension-induced vascular changes including vascular remodeling. The precise mechanisms underlying VSMC phenotypic modulation remain elusive. Here we test the role of peroxisome proliferator-activated receptor (PPAR)-␥ in the VSMC phenotypic modulation during hypertension. Both spontaneously hypertensive rat (SHR) aortas and SHR-derived VSMCs exhibited reduced PPAR-␥ expression and excessive VSMC phenotypic modulation identified by reduced contractile proteins, ␣-smooth muscle actin (␣-SMA) and smooth muscle 22␣ (SM22␣), and enhanced proliferation and migration. PPAR-␥ overexpression rescued the expression of ␣-SMA and SM22␣, and inhibited the proliferation and migration in SHR-derived VSMCs. In contrast, PPAR-␥ silencing exerted the opposite effect. Activating PPAR-␥ using rosiglitazone in vivo up-regulated aortic ␣-SMA and SM22␣ expression and attenuated aortic remodeling in SHRs. Increased activation of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling was observed in SHR-derived VSMCs. PI3K inhibitor LY294002 rescued the impaired expression of contractile proteins, and inhibited proliferation and migration in VSMCs from SHRs, whereas constitutively active PI3K mutant had the opposite effect. Overexpression or silencing of PPAR-␥ inhibited or excited PI3K/Akt activity, respectively. LY294002 counteracted the PPAR-␥ silencing induced proliferation and migration in SHR-derived VSMCs, whereas active PI3K mutant had the opposite effect. In contrast, reduced proliferation and migration by PPAR-␥ overexpression were reversed by the active PI3K mutant, and further inhibited by LY294002. We conclude that PPAR-␥ inhibits VSMC phenotypic modulation through inhibiting PI3K/Akt signaling. Impaired PPAR-␥ expression is responsible for VSMC phenotypic modulation during hypertension. These findings highlight an attractive therapeutic target for hypertension-related vascular disorders.Hypertension and hypertension-induced vascular remodeling underlie numerous cardiovascular disorders. Activated vascular smooth muscle cells (VSMCs) 2 are essential contributors to this vascular remodeling (1). Unlike other muscle cells, VSMCs do not terminally differentiate. They can switch from a differentiated phenotype (also known as contractile or quiescent phenotype) to a dedifferentiated phenotype (also known as synthetic or activated phenotype) in response to vascular injury. In this process, VSMCs regain their proliferative and migratory capacities, secrete matrix proteins, and down-regulate smooth muscle contractile proteins, such as ␣-smooth muscle actin (␣-SMA), smooth muscle 22␣ (SM22␣), smooth muscle myosin heavy chain, and calponin (2). Although this phenotypic modulation is undoubtedly required for vascular repair, inappropriate modulation is associated with increased vascular resistance and aggravates vascular injury. However, despite intensive research efforts, the precise mechanisms underlying VSMC phenotypic modula...

The COVID-19 pandemic has infected millions of people worldwide and many countries have been suffering from a large number of deaths. Acknowledging the ability of SARS-CoV-2 to mutate into distinct strains as an RNA virus and investigating its potential to cause reinfection is important for future health policy guidelines. It was thought that individuals who recovered from COVID-19 generate a robust immune response and develop protective immunity, however, since the first case of documented reinfection of COVID-19 in August 2020, there have been a number of cases with reinfection. Many cases are lacking genomic data of the two infections and it remains unclear whether they were caused by different strains. In the present study, we undertook a rapid systematic review to identify cases infected with different genetic strains of SARS-CoV-2 confirmed by polymerase-chain reaction and viral genome sequencing. A total of 17 cases of genetically confirmed COVID-19 reinfection were found. One immunocompromised patient had mild symptoms with the first infection, but developed severe symptoms resulting in death with the second infection. Overall, 68.8% (11/16) had similar severity, 18.8% (3/16) had worse symptoms, and 12.5% (2/16) had milder symptoms with the second episode. Our case series shows that reinfection with different strains is possible and some cases may experience more severe infections with the second episode. The findings also suggest that COVID-19 may continue to circulate even after achieving herd immunity through natural infection or vaccination suggesting the need for longer term transmission mitigation efforts.

We investigate the stability of the orange band photoluminescence (PL) of bifunctional nanoparticles of Mn2+-doped ZnS at 5% (ZnS:0.05Mn). These 4-nm nanoparticles are synthesized via a one-step inorganic chemical route under ambient conditions. The phase, crystallinity, and morphology are analyzed via X-ray and electron diffractions and high-resolution electron microscopy. Based on the thermally activated carrier-transfer model, it is found that orange emission is rather stable at low temperatures and possesses thermal activation energy of ∼18 meV. The analysis of the PL decay curves suggests the coexistence of multiple lifetimes, that the shortening observed in PL lifetime is not due to the Mn2+ ions, and that the orange band decay is stable in temperature range from 10 K to 300 K. The measured M-H hysteresis loops demonstrate that ZnS:0.05Mn nanoparticles exhibit ferromagnetic ordering below 30 K, unlike its bulk counterpart. No magnetic field dependence of the Mn2+ PL intensity is observed up to 1 T. The stability of the PL signal when subject to an applied magnetic field is discussed. This study offers experimental evidence to test low-dimensional dilute magnetic semiconductor models and widens the range of applications of ZnS:Mn nanostructures beyond optoelectronics.