Abstract
The successive emergences and accelerating spread of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages and evolved resistance to some ongoing clinical therapeutics ...increase the risks associated with the coronavirus disease 2019 (COVID-19) pandemic. An urgent intervention for broadly effective therapies to limit the morbidity and mortality of COVID-19 and future transmission events from SARS-related coronaviruses (SARSr-CoVs) is needed. Here, we isolate and humanize an angiotensin-converting enzyme-2 (ACE2)-blocking monoclonal antibody (MAb), named h11B11, which exhibits potent inhibitory activity against SARS-CoV and circulating global SARS-CoV-2 lineages. When administered therapeutically or prophylactically in the hACE2 mouse model, h11B11 alleviates and prevents SARS-CoV-2 replication and virus-induced pathological syndromes. No significant changes in blood pressure and hematology chemistry toxicology were observed after injections of multiple high dosages of h11B11 in cynomolgus monkeys. Analysis of the structures of the h11B11/ACE2 and receptor-binding domain (RBD)/ACE2 complexes shows hindrance and epitope competition of the MAb and RBD for the receptor. Together, these results suggest h11B11 as a potential therapeutic countermeasure against SARS-CoV, SARS-CoV-2, and escape variants.
Therapeutic blockade of the immune checkpoint proteins programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA4) has transformed cancer treatment. However, the overall ...response rate to these treatments is low, suggesting that immune checkpoint activation is not the only mechanism leading to dysfunctional anti-tumour immunity. Here we show that butyrophilin-like protein 2 (BTNL2) is a potent suppressor of the anti-tumour immune response. Antibody-mediated blockade of BTNL2 attenuates tumour progression in multiple in vivo murine tumour models, resulting in prolonged survival of tumour-bearing mice. Mechanistically, BTNL2 interacts with local γδ T cell populations to promote IL-17A production in the tumour microenvironment. Inhibition of BTNL2 reduces the number of tumour-infiltrating IL-17A-producing γδ T cells and myeloid-derived suppressor cells, while facilitating cytotoxic CD8
T cell accumulation. Furthermore, we find high BTNL2 expression in several human tumour samples from highly prevalent cancer types, which negatively correlates with overall patient survival. Thus, our results suggest that BTNL2 is a negative regulator of anti-tumour immunity and a potential target for cancer immunotherapy.
The nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is an important part of the natural immune system that plays an important role in many diseases. Estrogen is ...a sex hormone that plays an important role in controlling reproduction and regulates many physiological and pathological processes. Recent studies have indicated that estrogen is associated with disease progression. Estrogen can ameliorate some diseases (e. g, sepsis, mood disturbances, cerebral ischemia, some hepatopathy, Parkinson's disease, amyotrophic lateral sclerosis, inflammatory bowel disease, spinal cord injury, multiple sclerosis, myocardial ischemia/reperfusion injury, osteoarthritis, and renal fibrosis) by inhibiting the NLRP3 inflammasome. Estrogen can also promote the development of diseases (e.g., ovarian endometriosis, dry eye disease, and systemic lupus erythematosus) by upregulating the NLRP3 inflammasome. In addition, estrogen has a dual effect on the development of cancers and asthma. However, the mechanism of these effects is not summarized. This article reviewed the progress in understanding the effects of estrogen on the NLRP3 inflammasome and its mechanisms in recent years to provide a theoretical basis for an in-depth study.
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Estrogen deficiency elevates NLRP3 inflammasome levels.Estrogen ameliorates some diseases by inhibiting the NLRP3 inflammasome.Estrogen promotes the development of diseases by upregulating the NLRP3 inflammasome.Estrogen has a dual effect on the development of diseases.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The TAGAP gene locus has been linked to several infectious diseases or autoimmune diseases, including candidemia and multiple sclerosis. While previous studies have described a role of TAGAP in T ...cells, much less is known about its function in other cell types. Here we report that TAGAP is required for Dectin-induced anti-fungal signaling and proinflammatory cytokine production in myeloid cells. Following stimulation with Dectin ligands, TAGAP is phosphorylated by EPHB2 at tyrosine 310, which bridges proximal Dectin-induced EPHB2 activity to downstream CARD9-mediated signaling pathways. During Candida albicans infection, mice lacking TAGAP mount defective immune responses, impaired Th17 cell differentiation, and higher fungal burden. Similarly, in experimental autoimmune encephalomyelitis model of multiple sclerosis, TAGAP deficient mice develop significantly attenuated disease. In summary, we report that TAGAP plays an important role in linking Dectin-induced signaling to the promotion of effective T helper cell immune responses, during both anti-fungal host defense and autoimmunity.
With the continuous improvement of people's health needs, the public's requirements for medical care are also getting higher and higher. Work engagement is a positive psychological state related to ...the work. It is very important to maintain nurses' work engagement, however, due to many factors, the level of nurses' work engagement is not high and nursing managers should identify the influencing factors of work engagement, and take positive measures to fully improve nurses' work engagement.
To explore the influence of compassion fatigue, professional identity and sense of coherence on nurses' work engagement.
From January 2022 to June 2022, convenience sampling was used to select clinical nurses from 9 tertiary hospitals in Henan Province of China as the research objects for a questionnaire survey. Statistical methods included descriptive statistical analysis, Pearson correlation analysis and the PROCESS Macro Model 4 and 7 in regression analysis.
The results showed that compassion fatigue was significantly negatively correlated with sense of coherence, professional identity and work engagement (P<0.01), professional identity was significantly positively correlated with sense of coherence and work engagement (P<0.01), and there was a significant positive correlation between sense of coherence and work engagement (P<0.01). Professional identity played a partial mediating role between compassion fatigue and work engagement, accounting for 46.40% of the total effect; meanwhile, sense of coherence moderated the effect of compassion fatigue on professional identity and formed a moderated mediation model.
Compassion fatigue has a negative predictive effect on nurses' work engagement. Professional identity and sense of coherence further explained the relationship of compassion fatigue on compassion fatigue and work engagement through mediating and moderating effects.
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IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UL, UM, UPUK, VSZLJ
Background
Smartphone addiction (SA) has become a social problem that affects peoples’ quality of life and is frequently reported to be correlated with alexithymia, avoidant or anxious attachment ...styles, and subjective well-being. This study aimed to investigate the relationship between SA and alexithymia, attachment style, and subjective well-being.
Methods
A meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The following electronic databases were searched: PubMed, Web of Science, Embase, PsycINFO, PsycArticles, China National Knowledge Infrastructure (CNKI), WANFANG DATA, and Chongqing VIP Information Co., Ltd. (VIP). Stata 16.0 was used to analyze the overall effect and test the moderating effect.
Results
One hundred and ten studies were included, involving a total of 96,680 participants. SA had a significantly high positive correlation with alexithymia (
r
= 0.40), attachment anxiety (
r
= 0.37), and negative emotions (
r
= 0.31), and a low positive correlation with attachment avoidance (
r
= 0.17). In addition, there was a high negative correlation between SA and subjective well-being (
r
= –0.33) and a low negative correlation between SA, life satisfaction (
r
= –0.17), and positive emotions (
r
= –0.18). A moderation analysis revealed that age significantly moderated the relationship between SA and positive emotions. The tools for measuring SA significantly moderated the relationship between SA, alexithymia, attachment anxiety, and subjective well-being. Meanwhile, subjective well-being measurement tools significantly moderated the relationships between SA, subjective well-being, and negative emotions.
Conclusion
SA was closely related to alexithymia, attachment style, and subjective well-being. In the future, longitudinal research can be conducted to better investigate the dynamic changes in the relationship between them.
Systematic review registration
www.crd.york.ac.uk/PROSPERO/
, identifier CRD42022334798.
Background
Previous studies have not investigated the role of resilience and coping style on the association between maladaptive perfectionism and academic procrastination among nursing ...undergraduates. However, how to mobilize the learning enthusiasm of nursing students and reduce the incidence of academic procrastination is an important factor to reduce nursing loss and improve nursing quality.
Objectives
To investigate the influence of maladaptive perfectionism, resilience and coping style on academic procrastination among Chinese undergraduate nursing students.
Methods
A cross-sectional study was conducted. A convenience sampling method was used to select 665 nursing undergraduates from March to May 2022 in China. Maladaptive perfectionism, coping style, resilience, and academic procrastination were measured using questionnaires. The descriptive analysis, Pearson’s correlation analysis and the Hayes’ PROCESS Macro in SPSS 25.0 were used to test the model.
Results
The results showed that nursing undergraduates’ maladaptive perfectionism, resilience, positive coping style and academic procrastination were significantly correlated between every two variables, with coefficients ranging between −0.290 and 0.584. In addition, resilience played a partial mediating role in maladaptive perfectionism and academic procrastination, accounting for 15.70% of the total effect; in the meantime, this process was moderated by positive coping style.
Conclusion
Maladaptive perfectionism positively predicted nursing undergraduates’ academic procrastination; as a mediating mechanism with moderating, resilience and positive coping style further explained how maladaptive perfectionism promoted the academic procrastination of nursing undergraduates. Understanding this mechanism is of great significance for nursing educators to reduce the risk of academic procrastination in nursing undergraduates.
Posttraumatic growth (PTG) has been correlated with coping style among patients with breast cancer. However, to date, there is no consensus on the extent to which coping style is associated with PTG ...in patients with breast cancer. Therefore, we performed a meta-analysis to quantitatively synthesize previous findings. Based on the PRISMA method, this study employed a random effects model using the Stata software (version 16.0) to calculate the pooled correlation coefficient and examined a range of moderators: cancer stage, publication type, participants’ age, and coping style measurement tools. Relevant studies, published from inception to 9 March 2022, were identified through a systematic search in PubMed, Embase, Web of Science, PsycINFO, WANFANG DATA, Chinese National Knowledge Infrastructure (CNKI), and China Science and Technology Journal Database (VIP) databases. Finally, 20 studies involving 3,571 breast cancer patients were included in this investigation. The results showed a high positive relation between confrontation coping and PTG and a moderate positive relation between avoidance coping and PTG (confrontation:
r
= 0.456; avoidance:
r
= 0.291). Additionally, a moderate negative relation was identified between acceptance–resignation coping and PTG (
r
= –0.289). Publication type and coping style measurement tools moderated the relation between coping style and PTG among breast cancer patients. The findings indicated that breast cancer patients should either confront the disease or avoid coping with it according to their disease state, which would facilitate better growth. More studies, especially, large prospective studies, are warranted to verify our findings.
Systematic review registration
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022319107
, identifier CRD42022319107.
Genistein is a naturally occurring phytoestrogen (soy or soybean products) that is classified as an isoflavone, and its structure is similar to that of endogenous estrogens; therefore, genistein can ...exert an estrogen-like effect via estrogen receptors. Additionally, genistein is a tyrosine kinase inhibitor, which enables it to block abnormal cell growth and proliferation signals through the inhibition of tyrosine kinase. Genistein is also an angiogenesis inhibitor and an antioxidant. Genistein has effects on kidney cells, some of the kidney’s physiological functions, and a variety of kidney diseases. First, genistein exerts a protective effect on normal cells by reducing the inflammatory response, inhibiting apoptosis, inhibiting oxidative stress, inhibiting remodeling, etc., but after cell injury, the protective effect of genistein decreases or even has the opposite effect. Second, genistein can regulate renin intake to maintain blood pressure balance, regulate calcium uptake to regulate Ca2+ and Pi balances, and reduce vasodilation to promote diuresis. Third, genistein has beneficial effects on a variety of kidney diseases (including acute kidney disease, kidney cancer, and different chronic kidney diseases), such as reducing symptoms, delaying disease progression, and improving prognosis. Therefore, this paper reviews animal and human studies on the protective effects of genistein on the kidney in vivo and in vitro to provide a reference for clinical research in the future.
Taurine, a sulfur-containing amino acid, has a wide range of biological effects, such as bile salt formation, osmotic regulation, oxidative stress inhibition, immunomodulation and neuromodulation. ...Taurine has been proved to be synthesized and abundant in male reproductive organs. Recently, accumulating data showed that taurine has a potential protective effect on reproductive function of male animals. In physiology, taurine can promote the endocrine function of the hypothalamus-pituitary-testis (HPT) axis, testicular tissue development, spermatogenesis and maturation, delay the aging of testicular structure and function, maintain the homeostasis of the testicular environment, and enhance sexual ability. In pathology, taurine supplement may be beneficial to alleviate pathological damage of male reproductive system, including oxidative damage of sperm preservation
, testicular reperfusion injury and diabetes -induced reproductive complications. In addition, taurine acts as a protective agent against toxic damage to the male reproductive system by exogenous substances (e.g., therapeutic drugs, environmental pollutants, radiation). Related mechanisms include reduced oxidative stress, increased antioxidant capacity, inhibited inflammation and apoptosis, restored the secretory activity of the HPT axis, reduced chromosomal variation, enhanced sperm mitochondrial energy metabolism, cell membrane stabilization effect, etc. Therefore, this article reviewed the protective effect of taurine on male reproductive function and its detailed mechanism, in order to provide reference for further research and clinical application.
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