Acetaldehyde Dehydrogenase 2 Deficiency Aggravates Lung Fibrosis through Mitochondrial Dysfunction and Aging in Fibroblasts.

Idiopathic pulmonary fibrosis, a fatal interstitial lung disease, is characterized by fibroblast activation and aberrant extracellular matrix accumulation. Effective therapeutic development is limited because of incomplete understanding of the mechanisms by which fibroblasts become aberrantly activated. Here, we show acetaldehyde dehydrogenase 2 (ALDH2) in fibroblasts as a potential therapeutic target for pulmonary fibrosis. A decrease in ALDH2 expression was observed in patients with idiopathic pulmonary fibrosis and bleomycin-treated mice. ALDH2 deficiency spontaneously induces collagen accumulation in the lungs of aged mice. Furthermore, young ALDH2 knockout mice exhibited exacerbated bleomycin-induced pulmonary fibrosis and increased mortality compared with that in control mice. Mechanistic studies revealed that transforming growth factor (TGF)-ß1 induction and ALDH2 depletion constitute a positive feedback loop that exacerbates fibroblast activation. TGF-ß1 down-regulated ALDH2 through a TGF-ß receptor 1/Smad3-dependent mechanism. The subsequent deficiency in ALDH2 resulted in fibroblast dysfunction that manifested as impaired mitochondrial autophagy and senescence, leading to fibroblast activation and extracellular matrix production. ALDH2 overexpression markedly suppressed fibroblast activation, and this effect was abrogated by PTEN-induced putative kinase 1 (PINK1) knockdown, indicating that the profibrotic effects of ALDH2 are PINK1- dependent. Furthermore, Alda-1-induced ALDH2 activation reversed the established pulmonary fibrosis in both young and aged mice. In conclusion, ALDH2 expression inhibits the pathogenesis of pulmonary fibrosis. Strategies to up-regulate or activate ALDH2 expression could be potential therapies for pulmonary fibrosis.

Not All Levels of Social Re-Inclusion Allow for Recovery from Negative Outcomes of Social Exclusion: The Moderating Role of Self-Esteem.

Previous studies on social exclusion have focused on its adverse effects, rarely exploring how social re-inclusion can aid recovery from exclusion-induced distress. The level of social re-inclusion that can help individuals recover from social exclusion, and whether the recovery effect is influenced by individual characteristics are unclear. The present experimental study extends the Cyberball paradigm, adding a re-inclusion stage to explore the recovery effects of four levels of social re-inclusion on affect; furthermore, it tests the moderating role of self-esteem in the recovery effect. A total of 154 Chinese college students participated in the experiment. Results showed that (1) recovery was effective when the level of re-inclusion was equal to (replica re-inclusion) or greater than (moderate and high over-re-inclusions) the pre-exclusion level of inclusion, but ineffective when it was below this level (token re-inclusion); (2) the re-inclusion level positively predicted recovery, and this was moderated by self-esteem-the prediction was effective for participants with middle and high self-esteem, but not for participants with low self-esteem. These results are discussed from a group process and self-psychology perspective.

The Reward-Related Shift of Emotional Contagion from the Observer's Perspective Correlates to Their Intimacy with the Expresser.

Although previous studies have found a bidirectional relationship between emotional contagion and reward, there is insufficient research to prove the effect of reward on the social function of emotional contagion. To explore this issue, the current study used electroencephalography (EEG) and the interactive way in which the expresser played games to help participants obtain reward outcomes. The results demonstrated a significant correlation between changes in emotional contagion and closeness, indicating that emotional contagion has a social regulatory function. Regarding the impact of reward outcomes, the results showed that compared to the context of a loss, in the context of a win, participants' closeness toward the expresser shifted to a more intimate level, their emotional contagion changed in a more positive direction, and the activity of the late positive component (LPC) of the event-related potentials (ERPs) changed to a greater extent. Significantly, the mediation results demonstrated the effect of reward and indicated that changes in the LPC elicited while experiencing the expressers' emotion predicted the subsequent shifts in closeness through alterations in emotional contagion of the anger emotion in the winning context and the happy emotion in the loss context. This study provides empirical evidence regarding the social function of emotional contagion and proves for the first time that the reward context plays a role in it.

Kick Cat Effect: Social Context Shapes the Form and Extent of Emotional Contagion.

Emotional contagion refers to the transmission and interaction of emotions among people. Researchers have mainly focused on its process and mechanism, often simplifying its social background due to its complexity. Therefore, in this study, we attempt to explore whether the presence and clarity of social context affect emotional contagion and the related neural mechanisms. In Experiment 1, participants were asked to report their subjective experiences after being exposed to the facial expressions of emotional expressers, with or without the corresponding social context being presented. The results revealed that positive or negative expressions from the expressers elicited corresponding emotional experiences in the receivers, regardless of the presence of social context. However, when the social context was absent, the degree of emotional contagion was greater. In Experiment 2, we further investigated the effect of the clarity of social contexts on emotional contagion and its neural mechanisms. The results showed an effect consistent with those in Experiment 1 and highlighted the special role of N1, N2, P3, and LPP components in this process. According to the emotions as social information theory, individuals may rely more on social appraisal when they lack sufficient contextual information. By referencing the expressions of others and maintaining emotional convergence with them, individuals can adapt more appropriately to their current environment.

Does CSR performance improve corporate immunity to the COVID-19 pandemic? Evidence from China's stock market.

This paper studies the role of corporate social responsibility (CSR) performance on corporate financial performance during the COVID-19 by examining a sample of Chinese listed firms. Based on the PSM-DID methodology, we find that the pandemic-induced decline in stock returns is stronger with more CSR engagement. The results remain robust even after the dynamic effect test and placebo test. It means CSR performance does not improve Chinese corporate immunity to the pandemic. This inadequate response of CSR could be due to the "relatively few good things effect". Furthermore, our study indicates that increasing awareness of responsible investment and improving the quality of CSR disclosure could facilitate CSR engagement in China.

Hemophagocytic lymphohistiocytosis in two patients following treatment with pembrolizumab: two case reports and a literature review.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening state of immune hyperactivation. It has the highest mortality rate among all hematological immune-related adverse events (irAEs) of immune checkpoint inhibitors (ICIs) when treating various cancers. However, the predisposing factors of HLH have rarely been mentioned in previous research. Case Description: Herein, we report 2 cases of HLH following treatment with pembrolizumab. A patient was diagnosed with thymic carcinoma (TC) and possible Sjögren's syndrome (SS), while another was diagnosed with non-small cell lung cancer (NSCLC) and Epstein-Barr virus (EBV) infection, and both were positive for antinuclear antibodies. Both cases experienced transient immune-related fever on day 7 after pembrolizumab administration and splenomegaly on day 10. Then recurrent high-grade fever appeared, and liver function impairment, highly elevated ferritin, and hypertriglyceridemia were tested. After the diagnosis of HLH, both patients were treated with dexamethasone and etoposide without relapse in our follow-up. Conclusions: Considering the widespread use of ICIs and the high mortality rate of HLH, the immune-related fever, splenomegaly, and other signs of hyperinflammation after the infusion of ICIs, are worthy of attention to the presence of HLH. Preexisting autoimmune diseases (ADs) or positive antibodies, concomitant infection, and the setting of thymic epithelial tumors (TET) may be predisposing factors for HLH. And increased caution is needed before the initiation of ICIs for patients with 2 or more predisposing factors.

Carboxymethylated pachyman induces ferroptosis in ovarian cancer by suppressing NRF1/HO-1 signaling.

Carboxymethylated pachyman (CMP) is characterized by immune regulatory, antitumor and antioxidant activities. However, whether CMP contributes to the treatment of ovarian cancer has yet to be explored. The role of CMP in ovarian cancer cell death was analyzed using CCK-8 and flow cytometry assays. The data showed that CMP induced ovarian cancer cell death in a dose-dependent manner. Furthermore, CMP-induced cell death could be largely reversed by preincubation with ferrostatin-1 (Fer-1) but not 3-methyladenine or necrostatin-1. Reverse transcription-quantitative PCR analysis indicated that CMP significantly increased prostaglandin-endoperoxide synthase 2 (PTGS2) and Chac glutathione specific γ-glutamylcyclotransferase 1 (CHAC1) mRNA levels, but preincubation with Fer-1 obviously reduced PTGS2 and CHAC1 mRNA levels in SKOV3 and Hey cells. The intracellular levels of superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA) and Fe2+ were then quantified The data showed that 100 and 200 µg/ml CMP enhanced the production of SOD, MDA and Fe2+ but decreased GSH levels in SKOV3 and HEY cells. These data indicated that CMP could induce ferroptosis in ovarian cancer cells. More importantly, in vitro and in vivo studies indicated that CMP significantly suppressed nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), cystine/glutamate antiporter system X(c)(-) (xCT) and glutathione peroxidase 4 (GPX4) expression in ovarian cancer cells and tumors. In conclusion, the present study showed novel data that CMP could induce ferroptotic death in ovarian cancer cells by suppressing Nrf2/HO-1/xCT/GPX4. All these findings indicate that CMP may have great potential in anti-ovarian cancer cell therapy by inducing ferroptosis.

A VLP-Based Vaccine Candidate Protects Mice against Japanese Encephalitis Virus Infection.

Japanese encephalitis virus (JEV) is the leading cause of epidemic encephalitis in Asia, and vaccination is the most effective way to prevent JE. Although several licensed vaccines were widely used, there is still a demand for developing safer, cheaper, and more effective JE vaccines. In the current study, a virus-like particle (VLP) vaccine candidate containing the envelope structural protein of JEV expressed by the Pichia pastoris was assembled in vitro. It elicited a robust humoral and cellular immune response in mice model, conferring immunodeficient mice complete protection against lethal doses of JEV challenge. Furthermore, pigs immunized with VLP alone without adjuvant via intramuscular produced high neutralizing antibodies against JEV. Consequently, this study showed a new design of JEV subunit vaccine based on VLP strategy and demonstrated the potential for clinical application.

Case Report: A Homozygous Mutation (p.Y62X) of Phospholipase D3 May Lead to a New Leukoencephalopathy Syndrome.

Leukodystrophies are a heterogeneous group of inherited disorders with highly variable clinical manifestations and pathogenetic backgrounds. At present, variants in more than 20 genes have been described and may be responsible for different types of leukodystrophies. Members of the phospholipase D family of enzymes catalyze the hydrolysis of membrane phospholipids. Meanwhile, phospholipase D3 (PLD3) has also been found to exhibit single stranded DNA (ssDNA) acid 5' exonuclease activity. Variants in phospholipase D3 (PLD3) may increase the risk of Alzheimer's disease and spinocerebellar ataxia, but this hypothesis has not been fully confirmed. In this study, we identified a novel homozygous mutation (NM_012268.3: c.186C>G/ p.Y62X) of PLD3 in a consanguineous family with white matter lesions, hearing and vision loss, and kidney disease by whole exome sequencing. Real-time PCR revealed that the novel mutation may lead to non-sense-mediated messenger RNA (mRNA) decay. This may be the first case report on the homozygous mutation of PLD3 in patients worldwide. Our studies indicated that homozygous mutation of PLD3 may result in a novel leukoencephalopathy syndrome with white matter lesions, hearing and vision loss, and kidney disease.

A recombinant receptor-binding domain in trimeric form generates protective immunity against SARS-CoV-2 infection in nonhuman primates.

A safe and effective vaccine is critical to combat the COVID-19 pandemic. Here, we developed a trimeric SARS-CoV-2 receptor-binding domain (RBD) subunit vaccine candidate that simulates the natural structure of the spike (S) trimer glycoprotein. Immunization with the RBD trimer-induced robust humoral and cellular immune responses, and a high level of neutralizing antibodies was maintained for at least 4.5 months. Moreover, the antibodies that were produced in response to the vaccine effectively cross-neutralized the SARS-CoV-2 501Y.V2 variant (B.1.351). Of note, when the vaccine-induced antibodies dropped to a sufficiently low level, only one boost quickly activated the anamnestic immune response, conferring full protection against a SARS-CoV-2 challenge in rhesus macaques without typical histopathological changes in the lung tissues. These results demonstrated that the SARS-CoV-2 RBD trimer vaccine candidate is highly immunogenic and safe, providing long-lasting, broad, and significant immunity protection in nonhuman primates, thereby offering an optimal vaccination strategy against COVID-19.

[Methodological study on eliminating nucleic acid contamination in molecular diagnostic laboratory].

Nucleic acid detection technique has good sensitivity and specificity and is widely used in in vitro diagnosis, animal and plant commodity quarantine, forensic identification, and other fields. However, it is susceptible to carryover contamination during the operation and leads to false-positive results, which seriously affects the detection accuracy. Therefore, finding an effective solution to prevent and eliminate nucleic acid carryover contamination has become particularly urgent. This study compared several different methods for removing nucleic acid contamination and confirmed that sodium hypochlorite solution and PCRguard reagent could effectively eliminate nucleic acid carryover in the liquid and on surfaces of different materials. Besides, the combination of sodium hypochlorite solution and PCRguard can solve the nucleic acid aerosol contamination. This study proposes solutions for the routine prevention of carryover contamination and removal of aerosol that has occurred in molecular diagnostic laboratories.

IgY antibodies against Ebola virus possess post-exposure protection in a murine pseudovirus challenge model and excellent thermostability.

Ebola virus (EBOV) is one of the most virulent pathogens that causes hemorrhagic fever and displays high mortality rates and low prognosis rates in both humans and nonhuman primates. The post-exposure antibody therapies to prevent EBOV infection are considered effective as of yet. However, owing to the poor thermal stability of mammalian antibodies, their application in the tropics has remained limited. Therefore, a thermostable therapeutic antibody against EBOV was developed modelled on the poultry(chicken) immunoglobulin Y (IgY). The IgY antibodies retaining their neutralising activity at 25°C for one year, displayed excellent thermal stability, opposed to conventional polyclonal antibodies (pAbs) or monoclonal antibodies (mAbs). Laying hens were immunised with a variety of EBOV vaccine candidates and it was confirmed that VSVΔG/EBOVGP encoding the EBOV glycoprotein could induce high titer neutralising antibodies against EBOV. The therapeutic efficacy of immune IgY antibodies in vivo was evaluated in the newborn Balb/c mice who have been challenged with the VSVΔG/EBOVGP model. Mice that have been challenged with a lethal dose of the pseudovirus were treated 2 or 24 h post-infection with different doses of anti-EBOV IgY. The group receiving a high dose of 106 NAU/kg (neutralising antibody units/kilogram) showed complete protection with no symptoms of a disease, while the low-dose group was only partially protected. Conversely, all mice receiving naive IgY died within 10 days. In conclusion, the anti-EBOV IgY exhibits excellent thermostability and protective efficacy. Anti-EBOV IgY shows a lot of promise in entering the realm of efficient Ebola virus treatment regimens.

Investigation of photocatalysis reactions on the single-crystal and polycrystalline graphenes.

Graphene has been extensive studied in the field of photocatalysis. Herein, single-crystal and polycrystalline graphenes are prepared by mechanical exfoliation and chemical vapor deposition (CVD), respectively. The photocatalytic properties of polycrystalline graphene are carefully assessed by using 4-nitrobenzenethiol (4-NBT), as a probe molecule, under incident 532 nm laser beam. Similarly, the photocatalytic properties of single-crystal graphene are also investigated with 4-aminothiophenol (PATP) under incident 633 nm laser radiation. In order to solve the problem of uneven distribution of probe molecules on graphene, the internal standard method is adopted by using 2-naphthalenethiol (2-NT), as the internal standard molecule. The experimental findings indicate that PATP can be catalyzed onto the surface of single-crystal graphene under the irradiation of 633 nm laser beam and its catalytic properties significantly increase with decreasing the number of graphene layers. In addition, when single-crystal graphene is used as the Surface-enhanced Raman scattering (SERS) enhancement substrate, the SERS enhancement was also increased with the decrease of the number of layers.

[Development and characterization of serotype-specific monoclonal antibodies against Dengue virus NS1].

Dengue virus (DENV) is the most widely transmitted arbovirus in the world. Due to the lack of diagnostic technology to quickly identify the virus serotypes in patients, severe dengue hemorrhagic fever cases caused by repeated infections remain high. To realize the rapid differential diagnosis of different serotypes of DENV infection by immunological methods, in this study, four DENV serotype NS1 proteins were expressed and purified in mammalian cells. Monoclonal antibodies (MAbs) against NS1 protein were obtained by hybridoma technology after immunizing BALB/c mice. Enzyme-linked immunosorbent assay, indirect immunofluorescence assay, dot blotting, and Western blotting were used to confirm the reactivity of MAbs to viral native NS1 and recombinant NS1 protein. These MAbs include not only the universal antibodies that recognize all DENV 1-4 serotype NS1, but also serotype-specific antibodies against DENV-1, DENV-2 and DENV-4. Double antibody sandwich ELISA was established based on these antibodies, which can be used to achieve rapid differential diagnosis of serotypes of DENV infection. Preparation of DENV serotype-specific MAbs and establishment of an ELISA technology for identifying DENV serotypes has laid the foundation for the rapid diagnosis of DENV clinical infection.

A rapid and quantitative fluorescent microsphere immunochromatographic strip test for detection of antibodies to porcine reproductive and respiratory syndrome virus.

A fluorescent microsphere-based immunochromatographic strip test (FICT) was developed for the rapid, sensitive, and quantitative detection of porcine reproductive and respiratory syndrome virus (PRRSV) antibodies at the pen-side. The assay was based on the formation of a sandwich immune-complex (anti-pig IgG-PRRSV antibodies-NSP7/N), which was validated by a comparison with IDEXX-ELISA using 3325 clinical specimens. The diagnostic specificity, sensitivity, and accuracy of FICT were 97.28, 93.41, and 94.95%, respectively. FICT showed a good correlation with the virus neutralization assay. Overall, a promising pen-side diagnostic tool was developed for the rapid and quantitative detection of PRRSV antibodies within 15 min.

Analysis of 2019 novel coronavirus infection and clinical characteristics of outpatients: An epidemiological study from a fever clinic in Wuhan, China.

BACKGROUND: Since the outbreak of 2019 novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) pneumonia, thousands of patients with fever or cough were flocked into fever clinic of designated hospitals in Wuhan, China. To date, no data have ever been reported to reflect the prevalence of coronavirus disease 2019 (COVID-19) among these outpatients. Moreover, it is almost unknown to discriminate COVID-19 and nucleic acid negative patients based on clinical features in the fever clinics. METHODS: The infectious status of SARS-CoV-2 was estimated among the outpatients. The epidemiological and clinical characteristics were compared between COVID-19 and nucleic acid negative patients. RESULTS: The nucleic acid positive rate for SARS-CoV-2 in the outpatients from our fever clinic was 67·1%, while the majority of patients with COVID-19 were mild cases. The predominant initial symptom in those patients with COVID-19 was fever (78.2%), followed by cough (15.6%). Very significantly lower number of eosinophils was characterized in patients with COVID-19 as compared with that of nucleic acid negative patients. More importantly, the proportion of subjects with eosinophil counts lower than normal levels in patients with COVID-19 was much higher than that of nucleic acid negative patients. Fever combined with bilateral ground-glass opacities in computed tomography imaging and eosinophil count below the normal level are probably a valuable indicator of COVID-19 infection in those outpatients. CONCLUSIONS: Those findings may provide critical information for the regions, such as Europe and United States that are facing the same situation as Wuhan experienced, and could be valuable to prevent those nucleic acid negative patients from misdiagnosis before antibody testing.

Clinical characteristics of COVID-19 in patients with preexisting ILD: A retrospective study in a single center in Wuhan, China.

Since the outbreak of 2019 novel coronavirus (SARS-CoV-2) pneumonia, many patients with underlying disease, such as interstitial lung disease (ILD), were admitted to Tongji hospital in Wuhan, China. To date, no data have ever been reported to reflect the clinical features of Corona Virus Disease 2019 (COVID-19) among these patients with preexisting ILD. We analyzed the incidence and severity of COVID-19 patients with ILD among 3201 COVID-19 inpatients, and compared two independent cohorts of COVID-19 patients with pre-existing ILD (n = 28) and non-ILD COVID-19 patients (n = 130). Among those 3201 COVID-19 inpatients, 28 of whom were COVID-19 with ILD (0.88%). Fever was the predominant symptom both in COVID-19 with ILD (81.54%) and non-ILD COVID-19 patients (72.22%). However, COVID-19 patients with ILD were more likely to have cough, sputum, fatigue, dyspnea, and diarrhea. A very significantly higher number of neutrophils, monocytes, interleukin (IL)-8, IL-10, IL-1ß, and D-Dimer was characterized in COVID-19 with ILD as compared to those of non-ILD COVID-19 patients. Furthermore, logistic regression models showed neutrophils counts, proinflammatory cytokines (tumor necrosis factor-alpha, IL6, IL1ß, IL2R), and coagulation dysfunction biomarkers (D-Dimer, PT, Fbg) were significantly associated with the poor clinical outcomes of COVID-19. ILD patients could be less vulnerable to SARS-CoV-2. However, ILD patients tend to severity condition after being infected with SARS-CoV-2. The prognosis of COVID-19 patients with per-existing ILD is significantly worse than that of non-ILD patients. And more, aggravated inflammatory responses and coagulation dysfunction appear to be the critical mechanisms in the COVID-19 patients with ILD.

Outpatient strategies and the changing SARS-CoV-2 epidemic.

In response to the early outbreak of SARS-CoV-2, online fever clinics were set up. Then, an online face-to-face consultation was developed to solve the extreme difficulty of getting medical services to patients with chronic diseases. http://bit.ly/3cPppai.