Dynamics of NK,CD8 and Tfh cell mediated the production of cytokines and antiviral antibodies in Chinese patients with moderate COVID‐19

Recent studies have demonstrated a marked decrease in peripheral lymphocyte levels in patients with coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Few studies have focused on the changes of NK, T‐ and B‐cell subsets, inflammatory cytokines and virus‐specific antibodies in patients with moderate COVID‐19. A total of 11 RT‐PCR‐confirmed convalescent patients with COVID‐19 and 11 patients with non‐SARS‐CoV‐2 pneumonia (control patients) were enrolled in this study. NK, CD8⁺ T, CD4⁺ T, Tfh‐like and B‐cell subsets were analysed using flow cytometry. Cytokines and SARS‐CoV‐2‐specific antibodies were analysed using an electrochemiluminescence immunoassay. NK cell counts were significantly higher in patients with COVID‐19 than in control patients (P = 0.017). Effector memory CD8⁺ T‐cell counts significantly increased in patients with COVID‐19 during a convalescent period of 1 week (P = 0.041). TIM‐3⁺ Tfh‐like cell and CD226⁺ Tfh‐like cell counts significantly increased (P = 0.027) and decreased (P = 0.022), respectively, during the same period. Moreover, ICOS⁺ Tfh‐like cell counts tended to decrease (P = 0.074). No abnormal increase in cytokine levels was observed. The high expression of NK cells is important in innate immune response against SARS‐CoV‐2. The increase in effector memory CD8⁺ T‐cell counts, the up‐regulation of inhibitory molecules and the down‐regulation of active molecules on CD4⁺ T cells and Tfh‐like cells in patients with COVID‐19 would benefit the maintenance of balanced cellular and humoural immune responses, may prevent the development of severe cases and contribute to the recovery of patients with COVID‐19.     

Repellent,Insecticidal and Antimicrobial Activities of Leaf Essential Oils from Three Eucalyptus Species

Developing effective and eco‐friendly antimicrobials and pesticides has become a highly important issue. The repellent, insecticidal and antimicrobial activity of essential oils (EOs) isolated by hydrodistillation from dried leaves of the three Eucalyptus species (E. cloeziana, E. umbellata and E. benthamii) were investigated. During GC/MS analysis, α‐pinene (47.36 %), 1,8‐cineol (38.53 %) and α‐pinene (35.31 %) were identified as major components of E. cloeziana, E. umbellata and E. benthamii, respectively. The EOs from E. cloeziana exhibited the longest effective protection time (465 min, at 50.0 % w/w) for humans among the EOs studied. The effective protection time was 30 min and 300 min at concentrations of 12.5 % (w/w) and 25.0 % (w/w), respectively. Fumigating insecticidal activity of EOs from three Eucalyptus species was tested by airtight fumigation in conical flask, which indicated that essential oils had a highly and rapidly insecticidal activity on Culex pipiens quinquefasciatus. The antimicrobial activity of EOs was evaluated by using disc diffusion and agar dilution methods. There was no significant difference in the antibacterial activity of EOs from E. cloeziana and E. umbellate and they had the same MICs (20 mL/L) on Staphylococcus aureus, Salmonella typhi, Bacillus subtilis and Escherichia coli. E. benthamii had the worst microbial inhibitory effect among the three Eucalyptus essential oils and the MIC value for the test species is 40 mL/L except for Rhodotorula Harrison (10 mL/L).     

Antiphospholipid antibody‐activated NETs exacerbate trophoblast and endothelial cell injury in obstetric antiphospholipid syndrome

Despite the widespread use of antiplatelets and anticoagulants, women with antiphospholipid syndrome (APS) may face pregnancy complications associated with placental dysplasia. Neutrophil extracellular traps (NETs) are involved in the pathogenesis of many autoimmune diseases, including vascular APS; however, their role in obstetric APS is unclear. Herein, we investigated the role of NETs by quantifying cell‐free DNA and NET marker levels. Live‐cell imaging was used to visualize NET formation, and MAPK signalling pathway proteins were analysed. Cell migration, invasion and tube formation assays were performed to observe the effects of NETs on trophoblasts and human umbilical vein endothelial cells (HUVECs). The concentrations of cell‐free DNA and NETs in sera of pregnant patients with APS were elevated compared with that of healthy controls (HCs) matched to gestational week. APS neutrophils were predisposed to spontaneous NET release and IgG purified from the patients (APS‐IgG) induced neutrophils from HCs to release NETs. Additionally, APS‐IgG NET induction was abolished with inhibitors of reactive oxygen species, AKT, p38 MAPK and ERK1/2. Moreover, NETs were detrimental to trophoblasts and HUVECs. In summary, APS‐IgG‐induced NET formation deserves further investigation as a potential novel therapeutic target in obstetrical APS.     

Reduced Sirtuin1 signalling exacerbates diabetic mice hindlimb ischaemia injury and inhibits the protective effect of a liver X receptor agonist

Diabetes mellitus causes endothelial dysfunction, which further exacerbates peripheral arterial disease (PAD). Improving endothelial function via reducing endothelial oxidative stress (OS) may be a promising therapy for diabetic PAD. Activation of liver X receptor (LXR) inhibits excessive OS and provides protective effects on endothelial cells in diabetic individuals. Therefore, we investigated the effects of LXR agonist treatment on diabetic PAD with a focus on modulating endothelial OS. We used a streptozotocin-induced diabetes mouse model combined with a hindlimb ischaemia (HLI) injury to mimic diabetic PAD, which was followed by LXR agonist treatment. In our study, the LXR agonist T0901317 protected against HLI injury in diabetic mice by attenuating endothelial OS and stimulating angiogenesis. However, a deficiency in endothelial Sirtuin1 (SIRT1) largely inhibited the therapeutic effects of T0901317. Furthermore, we found that the underlying therapeutic mechanisms of T0901317 were related to SIRT1 and non-SIRT1 signalling, and the isoform LXRβ was involved in LXR agonist-elicited SIRT1 regulation. In conclusion, LXR agonist treatment protected against HLI injury in diabetic mice via mitigating endothelial OS and stimulating cellular viability and angiogenesis by LXRβ, which elicited both SIRT1-mediated and non-SIRT1-mediated signalling pathways. Therefore, LXR agonist treatment may be a promising therapeutic strategy for diabetic PAD.     

Interleukin‐38 protects against sepsis by augmenting immunosuppressive activity of CD4+CD25+ regulatory T cells

Naturally occurring CD4⁺CD25⁺ regulatory T cells (Tregs) are required to limit immune‐induced pathology and to maintain homeostasis during the early‐phase of sepsis. This study aimed to investigate the role of interleukin (IL)‐38, a newly described member of the IL‐1 cytokine family, in mediated immune response of CD4⁺CD25⁺ Tregs in sepsis. Here, we provide evidence that expressions of IL‐38 and its receptor were detected in murine CD4⁺CD25⁺ Tregs. Stimulation of CD4⁺CD25⁺ Tregs with LPS markedly up‐regulated the expression of IL‐38. Treatment with rmIL‐38 dramatically enhanced the immunosuppressive activity of CD4⁺CD25⁺ Tregs after LPS stimulation and in septic mice induced by CLP, resulting in amplification of helper T cell (Th) 2 response and reduction in the proliferation of effector T cells. These effects were robustly abrogated when anti–IL‐38 antibody was administered. Administration of rmIL‐38 improved the survival rate of CLP mice. In addition, CD4⁺CD25⁺ Tregs depletion before the onset of sepsis obviously abolished IL‐38–mediated protective response. These findings suggest that IL‐38 enhances the immunosuppressive activity of CD4⁺CD25⁺ Tregs, which might contribute to the improvement of host immune function and prognosis in the setting of sepsis.     

Absent in melanoma 2 enhances anti‐tumour effects of CAIX promotor controlled conditionally replicative adenovirus in renal cancer

Conditionally replicative adenoviruses (CRAds) were promising approach for solid tumour treatment, but its oncolytic efficiency and toxicity are still not satisfactory for further clinical application. Here, we developed the CAIX promotor (CAIX^promotor)‐controlled CRAd armed with a tumour suppressor absent in melanoma 2 (AIM2) to enhance its oncolytic potency. The CAIX^promotor‐AIM2 adenoviruses (Ad‐CAIX^promotor‐AIM2) could efficiently express E1A and AIM2 in renal cancer cells. Compared with Ad‐CAIX^promotor, Ad‐CAIX^promotor‐AIM2 significantly inhibited cell proliferation and enhanced cell apoptosis and cell killing, thus resulting in the oncolytic efficiency in 786‐O cells or OSRC‐2 cells. To explore the therapeutic effect, various Ads were intratumourally injected into OSRC‐2‐xenograft mice. The tumour growth was remarkably inhibited in Ad‐CAIX^promotor‐AIM2‐treated group as demonstrated by reduced tumour volume and weight with a low toxicity. The inflammasome inhibitor YVAD‐CMK resulted in the reduction of anti‐tumour activity by Ad‐CAIX^promotor‐AIM2 in vitro or in vivo, suggesting that inflammasome activation response was required for the enhanced therapeutic efficiency. Furthermore, lung metastasis of renal cancer mice was also suppressed by Ad‐CAIX^promotor‐AIM2 treatment accompanied by the decreased tumour fossil in lung tissues. These results indicated that the tumour‐specific Ad‐CAIX^promotor‐AIM2 could be applied for human renal cancer therapy. The therapeutic strategy of AIM2‐based CRAds could be a potential and promising approach for the therapy of primary solid or metastasis tumours.     

Heterotopic ossification of tendon and ligament

Much of the similarities of the tissue characteristics, pathologies and mechanisms of heterotopic ossification (HO) formation are shared between HO of tendon and ligament (HOTL). Unmet need and no effective treatment has been developed for HOTL, primarily attributable to poor understanding of cellular and molecular mechanisms. HOTL forms via endochondral ossification, a common process of most kinds of HO. HOTL is a dynamic pathologic process that includes trauma/injury, inflammation, mesenchymal stromal cell (MSC) recruitment, chondrogenic differentiation and, finally, ossification. A variety of signal pathways involve HOTL with multiple roles in different stages of HO formation, and here in this review, we summarize the progress and provide an up-to-date understanding of HOTL.     

Two New Abietane Diterpenoids from Selaginella moellendorffii Hieron.

Two new abietane diterpenoids, (3S,5R,10S)‐3‐hydroxy‐12‐O‐demethyl‐11‐deoxy‐19(4→3)‐abeo‐cryptojaponol, 12,19‐dihydroxyabieta‐8,11,13‐trien‐7‐one, were isolated from Selaginella moellendorffii Hieron., together with one known abietane diterpenoid and four known tetracyclic triterpenoids. Their structures were characterized by their 1D‐ and 2D‐NMR, ECD and mass spectral studies. All compounds were tested for their inhibitory effects on proliferation of three human cancer cells (human non‐small‐cell lung carcinoma cell lines A549 and human breast adenocarcinoma cell lines MDA‐MB‐231 and MCF‐7) in vitro. Among them, three compounds displayed modest cytotoxic activities against the above three human cancer cell lines with IC₅₀ values ranging from 16.28 to 40.67 μM.     

Caesalpanins A–C,Three Dimeric Cassane Diterpenoids from the Seeds of Caesalpinia sappan L.

Three dimeric cassane diterpenoids, caesalpanins A–C, were isolated from the seeds of Caesalpinia sappan L., as well as three known compounds. Their structures were determined via analysis of 1D‐, 2D‐NMR, and HR‐ESI‐MS data. Caesalpanins A and B were the second and third compounds that presented a nitrogen‐containing cassane diterpenoid dimer linked through one ether bond between C‐19 and C‐20′. Caesalpanin B exhibited moderate cytotoxic activity against MCF‐7 cell lines with IC₅₀ value of 29.98 μm . Caesalpanins A and B had weak inhibitory effects against LPS‐induced nitric oxide (NO) production in RAW 264.7 macrophages at 50 μm with inhibitory rate of 36.01 % and 32.93 %, respectively.     

Retarded Charge–Carrier Recombination in Photoelectrochemical Cells from Plasmon‐Induced Resonance Energy Transfer

N‐type metal oxides such as hematite (α‐Fe₂O₃) and bismuth vanadate (BiVO₄) are promising candidate materials for efficient photoelectrochemical water splitting; however, their short minority carrier diffusion length and restricted carrier lifetime result in undesired rapid charge recombination. Herein, a 2D arranged globular Au nanosphere (NS) monolayer array with a highly ordered hexagonal hole pattern (hereafter, Au array) is introduced onto the surface of photoanodes comprised of metal oxide films via a facile drying and transfer‐printing process. Through plasmon‐induced resonance energy transfer, the Au array provides a strong electromagnetic field in the near‐surface area of the metal oxide film. The near‐field coupling interaction and amplification of the electromagnetic field suppress the charge recombination with long‐lived photogenerated holes and simultaneously enhance the light harvesting and charge transfer efficiencies. Consequently, an over 3.3‐fold higher photocurrent density at 1.23 V versus reversible hydrogen electrode (RHE) is achieved for the Au array/α‐Fe₂O₃. Furthermore, the high versatility of this transfer printing of Au arrays is demonstrated by introducing it on the molybdenum‐doped BiVO₄ film, resulting in 1.5‐fold higher photocurrent density at 1.23 V versus RHE. The tailored metal film design can provide a potential strategy for the versatile application in various light‐mediated energy conversion and optoelectronic devices.