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In order to reveal the relationship between new urbanization and carbon emission to provide reference opinions for the construction of low-carbon urbanization, an evaluation system between new urbanization and carbon emission was constructed. Then their matching degree relationship was analyzed by coupling coordination degree model based on the data from 2012 to 2021 in Anhui Province, and their development trend from 2023 to 2032 was predicted by gray prediction model. The results show that: (1) New urbanization and carbon emission have the co-trend effect, and the consistency of core impact factors is relatively significant. Among them, the level of new urbanization increases from 0.058 in 2012 to 0.699 in 2021 and carbon emission development increases from 0.023 in 2012 to 0.165 in 2021, which both showing an upward trend. Meanwhile, social urbanization and population carbon emission are the core influencing factors. (2) The coupling coordination degree between new urbanization and carbon emission is low, but the synergy trend is optimistic and there is a large room for improvement. Among them, the coupling coordination coefficient of the coupling system rises from 0.136 in 2012 to 1.412 in 2021 (antagonistic phase), and then reaches 0.820 by 2032 (highly coordinated phase) by forecast. It shows that their current development is unbalanced, but the development trend is good, and there is a chance for improvement. This paper deepens the understanding of the logical correlation between new urbanization and carbon emission, and the following views are formed: (1) Low-carbon development is still the mainstream of new urbanization; (2) The coordination development of new urbanization and carbon emission reduction should be strengthened.
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Neutralizing antibodies (NAbs) hold great promise for clinical interventions against SARS-CoV- 2 variants of concern (VOCs). Understanding NAb epitope-dependent antiviral mechanisms is crucial for developing vaccines and therapeutics against VOCs. Here we characterized two potent NAbs, EH3 and EH8, isolated from an unvaccinated pediatric patient with exceptional plasma neutralization activity. EH3 and EH8 cross-neutralize the early VOCs and mediate strong Fc-dependent effector activity in vitro. Structural analyses of EH3 and EH8 in complex with the receptor-binding domain (RBD) revealed the molecular determinants of the epitope-driven protection and VOC-evasion. While EH3 represents the prevalent IGHV3-53 NAb whose epitope substantially overlaps with the ACE2 binding site, EH8 recognizes a narrow epitope exposed in both RBD-up and RBD-down conformations. When tested in vivo, a single-dose prophylactic administration of EH3 fully protected stringent K18-hACE2 mice from lethal challenge with Delta VOC. Our study demonstrates that protective NAbs responses converge in pediatric and adult SARS-CoV-2 patients.
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Objective:To compare peripheral blood tenascin-C (TN-C) level in patients with Kawasaki disease (KD) on admission, after treatment and at recovery, and to assess the potential of TN-C as a novel predictor for coronary artery lesion.Methods:Retrospective study.Blood samples of 44 KD patients [including 21 patients with coronary artery lesions (CAL + group) and 23 patients without coronary artery lesions(CAL - group)], 39 anaphylactoid purpura patients and 36 non-infected and non-vasculitis controls in the Affiliated Hospital of North Sichuan Medical College during January 1, 2018 and November 1, 2018 were collected.TN-C level was measured by enzyme-linked immunosorbent assay.Normally distributed data were compared by the t test; otherwise, they were compared by the Mann- Whitney U test. Pearson product-moment correlation coefficient or Spearman rank correlation coefficient was used to analyze the correlation between TN-C and other laboratory indexes. Results:For KD patients, TN-C levels on admission [(32.0±13.8) μg/L] and after treatment [(33.5±11.4) μg/L] were significantly higher than that at recovery [(23.3±10.8) μg/L](all P<0.01), which was positively correlated with C-reactive protein ( r=0.317, P=0.038), and negatively correlated with sodium level ( r=-0.472, P=0.004). No significant difference in TN-C level was found between CAL + group and CAL - group [on admission: (31.7±15.4) μg/L vs.(32.3±12.5) μg/L; after treatment: (32.2±11.6) μg/L vs.(34.8±11.3) μg/L; at recovery: (22.6±7.3) μg/L vs.(24.0±13.4) μg/L; all P>0.05]. In addition, TN-C level in patients with KD [(32.0±13.8) μg/L] and anaphylactoid purpura [(37.2±18.2) μg/L] was significantly higher than that of control children [(24.0±8.05) μg/L] (all P<0.01). Conclusions:The study findings are able to prove the potential of peripheral blood TN-C as a predictor for coronary artery lesion in KD patients, nor as a maker of vascular injury.Nevertheless, it may be used as an indicator of immune response in the acute phase of KD.
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SARS-CoV-2 variants of concern harbor mutations in the Spike (S) glycoprotein that confer more efficient transmission and dampen the efficacy of COVID-19 vaccines and antibody therapies. S mediates virus entry and is the primary target for antibody responses. Structural studies of soluble S variants have revealed an increased propensity towards conformations accessible to receptor human Angiotensin-Converting Enzyme 2 (hACE2). However, real-time observations of conformational dynamics that govern the structural equilibriums of the S variants have been lacking. Here, we report single-molecule Forster Resonance Energy Transfer (smFRET) studies of S variants containing critical mutations, including D614G and E484K, in the context of virus particles. Investigated variants predominantly occupied more open hACE2-accessible conformations, agreeing with previous structures of soluble trimers. Additionally, these S variants exhibited decelerated transitions in hACE2-accessible/bound states. Our finding of increased S kinetic stability in the open conformation provides a new perspective on SARS-CoV-2 adaptation to the human population.
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Objective:To understand the real experience of emotional labor of hospice nurses.Methods:A total of 8 hospice nurses from Shanghai, Shenzhen and Lianyungang hospice care units took part in the field study. They were observed and interviewed for one week.Results:The emotional labor of hospice nurses included natural expression, surface expression and deep expression. The emotional labor of nurses was affected by individual factors, organizational factors and social factors, including factors of the setting of hospice nursing posts was not clear, the proportion of multi-disciplinary team was insufficient, public awareness of hospice care was insufficient, and social security policy was imperfect, which was easy to make the role of nurses maladjustment, increase nurses' occupational fatigue and make nurses' emotional labor behavior lack of stable and long-term power source, thus affect the expression of their emotional labor behavior.Conclusions:We should pay attention to the expression and outcome of emotional labor of hospice nurses, to intervene and improve the individual factors, organizational factors and social factors that affect the expression of nurses' emotional labor.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have resulted in a number of severe cases of COVID-19 and deaths worldwide. However, knowledge of SARS-CoV-2 infection, diseases and therapy remains limited, underlining the urgency of fundamental studies and drug development. Studies have shown that induction of autophagy and hijacking of autophagic machinery are essential for infection and replication of SARS-CoV-2; however, the mechanism of this manipulation and function of autophagy during SARS-CoV-2 infection remain unclear. In the present study, we identified ORF3 as an inducer of autophagy and revealed that ORF3 localizes to the ER and induces FAM134B-related ERphagy through the HMGB1-Beclin1 pathway. As a consequence, ORF3 induces ER stress and inflammatory responses through ERphagy and sensitizes cells to ER stress-induced cell death, suggesting that SARS-CoV-2 ORF3 hijacks ERphagy and then harms ER homeostasis to induce inflammatory responses through excessive ER stress. These findings reveal a sequential induction of ERphagy, ER stress and acute inflammatory responses during SARS-CoV-2 infection and provide therapeutic potential for ERphagy and ER stress-related drugs for COVID-19 treatment and prevention. ImportanceSARS-CoV-2 infection and replication require autophagosome-like double-membrane vacuoles. Inhibition of autophagy suppresses viral replication, indicating the essential role of autophagy in SARS-CoV-2 infection. However, how SARS-CoV-2 hijacks autophagy and the function of autophagy in the disease progression remain unknown. Here, we reveal that SARS-CoV-2 ORF3 induces ERphagy and consequently induces ER stress to trigger acute inflammatory responses and enhance sensitivity to ER stress-induced apoptosis. Our studies uncover ERphagy-induced inflammatory responses during SARS-CoV-2 infection and provide a promising therapeutic approach for treating SARS-CoV-2 infection and inflammatory responses in COVID-19 by manipulating autophagy and ER stress.
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Melanoma differentiation-associated gene-5 (MDA5) acts as a cytoplasmic RNA sensor to detect viral dsRNA and mediates type I interferon (IFN) signaling and antiviral innate immune responses to infection by RNA viruses. Upon recognition of viral dsRNA, MDA5 is activated with K63-linked polyubiquitination and then triggers the recruitment of MAVS and activation of TBK1 and IKK, subsequently leading to IRF3 and NF-{kappa}B phosphorylation. Great numbers of symptomatic and severe infections of SARS-CoV-2 are spreading worldwide, and the poor efficacy of treatment with type I interferon and antiviral agents indicates that SARS-CoV-2 escapes from antiviral immune responses via an unknown mechanism. Here, we report that SARS-CoV-2 nonstructural protein 8 (NSP8) acts as an innate immune suppressor and inhibits type I IFN signaling to promote infection of RNA viruses. It downregulates the expression of type I IFNs, IFN-stimulated genes and proinflammatory cytokines by binding to MDA5 and impairing its K63-linked polyubiquitination. Our findings reveal that NSP8 mediates innate immune evasion during SARS-CoV-2 infection and may serve as a potential target for future therapeutics for SARS-CoV-2 infectious diseases. ImportanceThe large-scale spread of COVID-19 is causing mass casualties worldwide, and the failure of antiviral immune treatment suggests immune evasion. It has been reported that several nonstructural proteins of severe coronaviruses suppress antiviral immune responses; however, the immune suppression mechanism of SARS-CoV-2 remains unknown. Here, we revealed that NSP8 protein of SARS-CoV-2 directly blocks the activation of the cytosolic viral dsRNA sensor MDA5 and significantly downregulates antiviral immune responses. Our study contributes to our understanding of the direct immune evasion mechanism of SARS-CoV-2 by showing that NSP8 suppresses the most upstream sensor of innate immune responses involved in the recognition of viral dsRNA.
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Objective@#To observe the change and clinical significance of the peripheral blood T-lymphocytes CD45RA+ and CD45RO+ in children with Henoch-Schonlein purpura (HSP) under different clinical classification.@*Methods@#From October 2015 to July 2017, the clinical data of 80 children with HSP in the Affiliated Hospital of North Sichuan Medical College were retrospectively analyzed.According to the clinical classification, they were divided into three groups: skin involvement group (35 cases), abdominal type group (36 cases), and renal type group (9 cases). Another 80 healthy children were selected as the control group.The changes and clinical significance of peripheral blood T-lymphocytes CD45RA+ , CD45RO+ and CD45RA+ /CD45RO+ ratio were analyzed.@*Results@#Among the 80 children, 40 cases were male and 40 cases were female, with age of (7.2±2.3)years old.The CD45RA+ and CD45RO+ rates in the HSP group were (13.19±7.09)%, (12.07±3.46)%, respectively, which were significantly lower than those in the control group [(23.26±6.01)%, (21.74±3.46)%], the differences were statistically significant (t=9.69, 16.42, all P<0.05). The CD45RA+ ratio, CD45RA+ count and CD45RA+ /CD45RO+ ratio of the kidney type group were (8.02±3.63)%, (2.19±0.33)/μL, (-0.28±0.19), respectively, which were significantly lower than those of the skin group [(15.74±7.71)%, (2.55±0.33)/μL, (0.27±0.12)], the differences were statistically significant(t=3.085, 2.709, 4.013, all P<0.05). The ratio of CD45RA+ /CD45RO+ in the abdominal group was significantly lower than that in the skin group[(-0.07±0.27)vs.(0.27±0.12), t=2.989, P<0.05].@*Conclusion@#Peripheral blood T lymphocyte subsets CD45RA+ and CD45RO+ may play a role in the generation and development of immune function changes in children with HSP, and the decrease of CD45RA+ T cells may be related to the risk of HSP nephritis.
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Objective To evaluate the effects of extracts of Semen Coicis (ESC) on a BALB/c mouse model of atopic dermatitis (AD),and to explore its potential mechanism.Methods Forty specific pathogen-free (SPF) female BABL/c mice were randomly divided into blank group (8 mice,receiving no treatment) and AD model group (32 mice).The mice in the model group were topically treated with 2,4-dinitrochlorobenzene (DNCB) in acetone/olive oil to establish the mouse model of AD.After modeling,8 mice in the blank group and 8 in the model group were sacrificed immediately.The other 24 mice in the model group were randomly and equally divided into 3 groups:model control group receiving no treatment,ESC group and ESC vehicle group topically treated with ESC and ESC vehicle respectively once every day on the back and aural region of the mice for 28 consecutive days.Changes in skin lesions were observed by naked eyes every day.A thickness tester was used to measure the thickness of skin lesions on the left ear before modeling,at completion of modeling and 12 hours after the final treatment.At 12 hours after the final treatment,the mice in the above 3 groups were sacrificed,and the eyeballs were removed for collecting blood.Then,the sera were isolated,and skin tissue specimens were obtained from the skin lesions on the back.These tissue sections were subjected to hematoxylin and eosin (HE) staining and toluidine blue staining for observing the infiltration of inflammatory cells in skin lesions.An immunohistochemical study was performed to determine the expression of aquaporin 3 (AQP3),Toll-like receptor 2 (TLR2) and TLR4,and enzyme-linked immunosorbent assay (ELISA) to detect the serum levels of IgE,interleukin-4 (IL-4) and interferon-/ (IFN-γ).Results After 28-day treatment,skin lesions were improved in the ESC group.Compared with the model control group,the ESC group showed a significantly lower clinical symptom score (1.50 ± 0.58 vs.2.50 ± 0.58,P ＜ 0.05),decreased lesional thickness on the left ear ([0.31 ± 0.01] mm vs.[0.33 ± 0.01] mm,P ＜ 0.05),and lower number of infiltrating mast cells per high-power field (15.18 ± 1.64 vs.28.94 ± 1.28,P ＜ 0.05).Immunohistochemical findings indicated that the ESC group showed significantly lower expression of AQP3,TLR2 and TLR4 compared with the model control group,and decreased AQP3 expression in the spinous layer.Compared with the model control group,the ESC group showed significantly lower total serum IgE and IL-4 levels,but higher IFN-γ levels (all P ＜ 0.05).Conclusion Topical ESC is effective for the treatment of skin lesions in mouse models of AD,likely by regulating serum levels of IgE,IL-4 and IFN-γ and affecting the expression of AQP3,TLR2 and TLR4.
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Objective:In order to investigate the therapeutic effect of combined adjacent and distal acupoints in the treatment of vertebroarterial pattern of cervical spondylopathy. Methods: 140 cases were randomly divided into the acupuncture group and medication group, 70 cases in each group. The acupuncture group was treated by the acupoints selected upon TCM pattern identification plus the spots decided upon the anatomical feature in modern medicine. The medication group was treated with oral Dragon-Bone Cervical Vertebra Capsules, and Flunarizine Hydrochloride Capsules, to observe the integral of the clinical symptoms and signs and improvement of the vertebrobasilar blood flow before and after the treatment.Results and Conclusion: The total effective rate was significantly higher in the acupuncture group (100%) than in the medication group (61.4%) (P＜0.01). There was a significant difference (P＜0.05) in the integral of clinical symptoms and sighs and in the improvement of the vertebrobasilar blood flow in comparison between the two groups before and after the treatment, but the improvement was more remarkable in the acupuncture group (P＜0.05) than in the medication group, and the long-term therapeutic effect was better in the acupuncture group than in the medication group, but without significant difference (P＞ 0.2).