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Macrophages are heterogeneous cell populations that are present in all tissues. Macrophages can be divided into classically activated inflammatory macrophages (M1) and alternatively activated anti-inflammatory macrophages (M2). It has been generally accepted that M1 macrophages are polarised in an inflammatory environment to produce pro-inflammatory cytokines, whilst M2 macrophages are involved in anti-inflammation and aid tissue repair in wound healing. Bacterial endotoxin (lipopolysaccharide; LPS) is a potent factor in infection, which induces M1 macrophages resulting in higher levels of iNOS, TNFα and IL-12p70 which dictate inflammatory T cell responses. M2 macrophages can be transformed into M1 macrophages following LPS stimulation to promote inflammation. Candida albicans is a commensal fungal microorganism, which has been suggested to induce immune tolerance; however, the mechanism of C. albicans-induced immune tolerance has not been investigated in detail. IL-35 is a recently identified anti-inflammatory cytokine which is a heterodimeric protein consisting of the Epstein-Barr virus-induced gene 3 (EBI3) and IL-12p35. IL-35 shares the protein subunit p35, with IL-12p70. IL-12p70 is the most potent cytokine to induce Th1 responses during inflammation. In this study, we demonstrate that heat-killed C. albicans (HKC) strongly suppressed LPS-induced IL-12p70 production in M2 macrophages. Candida albicans induced a high level of EBI3 expression in M2 macrophages, which served as a mechanism for IL-12p70 suppression by competitive binding of the common protein subunit (p35) of IL-35 and IL-12p70. To demonstrate that EBI3 expression had the ability to block IL-12p70 production intracellularly, a Chinese Hamster Ovary (CHO) cell line with biscistronic expression of IL-12p40 and p35 was constructed, followed by ectopic over-expression of EBI3. The over-expression of EBI3 in the IL-12p70 producing cell line effectively suppressed IL-12p70 production. IL-35 secretion was also detected in the cell line, with suppressed IL-12p70 production by immune-precipitation Western blotting. However, this secretion was not evident in M2 macrophages following stimulation by HKC. This can be explained by the constitutive expression of IL-35 receptors (gp130 and IL-12Rβ2) in M2 macrophages for cytokine consumption. Our results have indicated that C. albicans can suppress host inflammatory responses in mucosal skin by suppressing LPS-induced IL-12p70 production. Lower IL-12p70 production may avoid an unnecessary Th1 response in order to retain immune tolerance, which may be one of the mechanisms by which C. albicans achieves a successful commensal lifestyle without having a detrimental effect on the host's health.

STING （also known as MITA） mediates the innate antiviral signaling and ubiquitination of STING is key to its function. However, the deubiquitination process of STING is unclear. Here we report that USP18 recruits USP20 to deconjugate K48-1inked ubiquitination chains from STING and promotes the stability of STING and the expression of type I IFNs and proinflammatory cytokines after DNA virus infection. USP18 deficiency or knockdown of USP20 resulted in enhanced K48-1inked ubiquitination and accelerated degradation of STING, and impaired activation of IRF3 and NF-κB as well as induction of downstream genes after infection with DNA virus HSV-1 or transfeetion of various DNA ligands. In addition, Uspl8-/- mice were more susceptible to HSV-1 infection compared with the wildtype littermates. USP18 did not deubiquitinate STING in vitro but facilitated USP20 to catalyze deubiquitination of STING in a manner independent of the enzymatic activity of USP18. In addition, reconstitution of STING into Uspl8-/- MEFs restored HSV-1-induced expression of downstream genes and cellular antiviral responses. Our findings thus uncover previously uncharacterized roles of USPI8 and USP20 in mediating virus-triggered signaling and contribute to the understanding of the complicated regulatory system of the innate antiviral responses.

Selective brain hypothermia is considered an effective treatment for neuronal injury after stroke, and avoids the complications of general hypothermia. However, the mechanisms by which selective brain hypothermia affects mitochondrial fission remain unknown. In this study, we investigated the effect of selective brain hypothermia on the expression of fission 1 (Fis1) protein, a key factor in the mitochondrial fission system, during focal cerebral ischemia/reperfusion injury. Sprague-Dawley rats were divided into four groups. In the sham group, the carotid arteries were exposed only. In the other three groups, middle cerebral artery occlusion was performed using the intraluminal filament technique. After 2 hours of occlusion, the filament was slowly removed to allow blood reperfusion in the ischemia/reperfusion group. Saline, at 4°C and 37°C, were perfused through the carotid artery in the hypothermia and normothermia groups, respectively, followed by restoration of blood flow. Neurological function was assessed with the Zea Longa 5-point scoring method. Cerebral infarct volume was assessed by 2,3,5-triphenyltetrazolium chloride staining, and apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining. Fis1 and cytosolic cytochrome c levels were assessed by western blot assay. Fis1 mRNA expression was assessed by quantitative reverse transcription-polymerase chain reaction. Mitochondrial ultrastructure was evaluated by transmission electron microscopy. Compared with the sham group, apoptosis, Fis1 protein and mRNA expression and cytosolic cytochrome c levels in the cortical ischemic penumbra and cerebral infarct volume were increased after reperfusion in the other three groups. These changes caused by cerebral ischemia/reperfusion were inhibited in the hypothermia group compared with the normothermia group. These findings show that selective brain hypothermia inhibits Fis1 expression and reduces apoptosis, thereby ameliorating focal cerebral ischemia/reperfusion injury in rats. Experiments were authorized by the Ethics Committee of Qingdao Municipal Hospital of China (approval No. 2019008).

The Chronic Care Model (CCM) is a framework that supports the proactive, planned, coordinated and patient-centered care of chronic diseases. The Patient Assessment of Chronic Illness Care (PACIC) scale is a valuable tool for evaluating patients’ perspectives on chronic care delivery based on the CCM. Few studies have examined its application in China. This study assesses hypertension care in Chinese patients and explores how PACIC scores relate to patient compliance. A cross-sectional study was conducted in Hangzhou, China, from June to August 2021, including 253 hypertensive patients from 5 county hospitals and 13 primary healthcare centers. The study used the PACIC scale to assess hypertension care delivery and the Compliance of Hypertensive Patients scale (CHPS) to measure patient compliance. Multiple linear regression analyses were used to explore the relationship between demographic characteristics and the total and domain scores of PACIC, as well as the association between CHPS and the domain scores of PACIC. The mean value of overall the PACIC score was 3.12 (out of 5). Problem solving/contextual domain had the highest average score for each item, while follow up/coordination domain had the lowest. Patient activation had negative effects on intention (β = −.18, P < .05), attitude (β = −.21, P < .05), responsibility (β = −.17, P < .05), and the total score of CHPS (β = −.24, P < .01). Delivery system design/decision support was negatively associated with lifestyle (β = −.21, P < .05) and the total score of CHPS (β = −.26, P < .01). Hypertensive patients perceived that they sometimes received hypertension care consistent with the CCM in Chinese primary healthcare settings. A higher level of PACIC score was beneficial for improving hypertensive patient compliance.

The number of confirmed COVID-19 cases has increased drastically; however, information regarding the impact of this disease on the occurrence of arrhythmias is scarce. The aim of this study was to determine the impact of COVID-19 on arrhythmia occurrence. This prospective study included patients with COVID-19 treated at the Leishenshan Temporary Hospital of Wuhan City, China, from February 24 to April 5, 2020. Demographic, comorbidity, and arrhythmias data were collected from patients with COVID-19 (n = 84) and compared with control data from patients with bacterial pneumonia (n = 84) infection. Furthermore, comparisons were made between patients with severe and nonsevere COVID-19 and between older and younger patients. Compared with patients with bacterial pneumonia, those with COVID-19 had higher total, mean, and minimum heart rates (all P<0.01). Patients with severe COVID-19 (severe and critical type diseases) developed more atrial arrhythmias compared with those with nonsevere symptoms. Plasma creatine kinase isoenzyme (CKMB) levels (P=0.01) were higher in the severe group than in the nonsevere group, and there were more deaths in the severe group than in the nonsevere group (6 (15%) vs. 3 (2.30%); P=0.05). Premature atrial contractions (PAC) and nonsustained atrial tachycardia (NSAT) were significantly positively correlated with plasma CKMB levels but not with high-sensitive cardiac troponin I or myoglobin levels. Our data demonstrate that COVID-19 patients have higher total, mean, and minimum heart rates compared with those with bacterial pneumonia. Patients with severe or critical disease had more frequent atrial arrhythmias (including PAC and AF) and higher CKMB levels and mortality than those with nonsevere symptoms.

Electroacupuncture preconditioning at acupoint Baihui (GV20) can reduce focal cerebral ischemia/reperfusion injury. However, the precise protective mechanism remains unknown. Mitochondrial fission mediated by dynamin-related protein 1 (Drp1) can trigger neuronal apoptosis following cerebral ischemia/reperfusion injury. Herein, we examined the hypothesis that electroacupuncture pretreatment can regulate Drp1, and thus inhibit mitochondrial fission to provide cerebral protection. Rat models of focal cerebral ischemia/reperfusion injury were established by middle cerebral artery occlusion at 24 hours after 5 consecutive days of preconditioning with electroacupuncture at GV20 (depth 2 mm, intensity 1 mA, frequency 2/15 Hz, for 30 minutes, once a day). Neurological function was assessed using the Longa neurological deficit score. Pathological changes in the ischemic penumbra on the injury side were assessed by hematoxylin-eosin staining. Cellular apoptosis in the ischemic penumbra on the injury side was assessed by terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling staining. Mitochondrial ultrastructure in the ischemic penumbra on the injury side was assessed by transmission electron microscopy. Drp1 and cytochrome c expression in the ischemic penumbra on the injury side were assessed by western blot assay. Results showed that electroacupuncture preconditioning decreased expression of total and mitochondrial Drp1, decreased expression of total and cytosolic cytochrome c, maintained mitochondrial morphology and reduced the proportion of apoptotic cells in the ischemic penumbra on the injury side, with associated improvements in neurological function. These data suggest that electroacupuncture preconditioning-induced neuronal protection involves inhibition of the expression and translocation of Drp1.

The antioxidant activities of flavonoid mixtures can be used to investigate the synergistic antioxidant mechanism of flavonoids. The antioxidant capacities of three flavonoids (quercetin, baicalein, and daidzein) and β-carotene in binary and ternary mixtures with kaempferol were analyzed using a 2,2-diphenyl-1-picrylhydrazyl (DPPH) inhibition assay by means of absorption spectroscopy. The results showed that the number of hydroxyl groups and o-hydroxyl groups had a significant effect on the antioxidant activity of the flavonoids, and the mixture of kaempferol, quercetin, and baicalein showed optimal synergistic antioxidant activity. Compared with quercetin and baicalein, kaempferol had the fastest inhibition rate, and multiple prolonged kinetic processes associated with the scavenging of DPPH radicals occurred in mixtures of kaempferol with the other flavonoids and β-carotene. Kaempferol has a potential synergistic antioxidant effect when mixed with daidzein and β-carotene, and the results suggested that this may be due to the regeneration of kaempferol after antioxidation. By means of classic UV-Vis spectroscopy, reaction details of the synergistic antioxidant process of DPPH radical scavenging by flavonoids can be obtained.

A calculation scheme to gain the relationship between the thickness of shrink-fit holder and thermodynamic properties. Based on the theoretical analysis of fitting molder between shrink-fit holder and tool, then the thermodynamic properties of the shrink-fit holder and cutting tool such as contact pressure, equivalent stress and deformation are analyzed at different thickness of shrink-fit holder in static, under cutting force and inducting heating by using the finite element software ANSYS. The results show that the total contact pressure and maximum equivalent stress increased and the minimum thermal displacement difference decreased with the increase of holder thickness. Under the action of cutting force, the contact stress on the tool holder no longer uniformed and the maximum contact stress significantly increased, cutting tool also deformed. Finally a method to determine the reasonable holder thickness is given and it has a practical guiding significance for the design and selection of the shrink-fit tool holder.

Reaction of 2-phenyl-1,3-dibromopropane with in situ generated ( μ -SLi) 2 Fe 2 (CO) 6 yielded a known complex [( μ -SCH 2 ) 2 CHC 6 H 5 ]Fe 2 (CO) 6 ( A ). Displacement of two carbonyls from complex A by cis -1,2-bis(diphenylphosphine)ethylene (dppv) or 1,2-bis(diphenylphosphine)ethane (dppe) in the presence of Me 3 NO·2H 2 O gave two chelate complexes [( μ -SCH 2 ) 2 CHC 6 H 5 ]Fe 2 (CO) 4 ( κ 2 -dppv), [A( κ 2 -dppv)] and [( μ -SCH 2 ) 2 CHC 6 H 5 ]Fe 2 (CO) 4 ( κ 2 -dppe), [A( κ 2 -dppe)], respectively. Protonation of the diiron centers of [A( κ 2 -dppv)] and [A( κ 2 -dppe)] using an excess of HBF 4 ·Et 2 O in dichloromethane at room temperature gave the bridging hydrides [( μ -H)A( κ 2 -dppv)]BF 4 and [( μ -H)A( κ 2 -dppe)]BF 4 . The complexes [( μ -H)A( κ 2 -dppv)]BF 4 , [A( κ 2 -dppe)] and [( μ -H)A( κ 2 -dppe)]BF 4 were characterized by elemental analysis and spectroscopic methods, and [( μ -H)A( κ 2 -dppv)]BF 4 and [( μ -H)A( κ 2 -dppe)]BF 4 were also characterized by X-ray crystallography. The electrochemical behavior of [( μ -H)A( κ 2 -dppv)]BF 4 was investigated by cyclic voltammetry, and the catalytic electrochemical reduction in protons from trifluoroacetic acid or p -methylbenzene sulfonic acid to give hydrogen was investigated.