Search

Abstract Background Interstitial lung abnormality (ILA) has been recognized as a pertinent factor in the development and prognosis of various pulmonary conditions. However, its correlation with co-morbidities remains understudied. The current study endeavors to elucidate the association between ILA and both clinical features and co-morbidities in patients with chronic obstructive pulmonary disease (COPD). Methods A retrospective cohort comprising 1131 hospitalized patients diagnosed with COPD was examined in this observational study. Patients were dichotomously classified based on the presence or absence of ILA, and subsequent analyses scrutinized disparities in demographic, clinical, and laboratory profiles, alongside co-morbid conditions, between the two subgroups. Results Of the 1131 COPD patients, 165 (14.6%) exhibited ILA. No statistically significant differences were discerned between COPD patients with and without ILA concerning demographic, clinical, or laboratory parameters, except for levels of circulating fibrinogen and procalcitonin. Nevertheless, a notable discrepancy emerged in the prevalence of multiple co-morbidities. Relative to COPD patients devoid of ILA, those presenting with ILA manifested a diminished prevalence of lung cancer (OR = 0.50, 95% CI: 0.30–0.83, p = 0.006), particularly of the lung adenocarcinoma (OR = 0.32, 95% CI: 0.15–0.71, p = 0.005). Additionally, the presence of ILA in COPD was positively associated with heart failure (OR = 1.75, 95% CI: 1.04-3.00, p = 0.040) and cancers other than lung cancer (OR = 2.27, 95% CI: 1.16–4.39, p = 0.012). Conclusion These findings demonstrate that the presence of ILA is associated with co-morbidities of COPD, particularly lung cancer.

Abstract Background Epidural test dose for labor analgesia is controversial and varies widely in clinical practice. It is currently unclear whether using a portion of the initial dose for analgesia as the test dose delays the onset time of analgesia, compared to the traditional test dose. Methods One hundred and twenty-six parturients who chose epidural analgesia during labor were randomly assigned to two groups. The first dose in group L was 3 ml 1.5% lidocaine, and in the RF group was 10 ml 0.1% ropivacaine combined with 2 μg/ml fentanyl. After 3 min of observation, both groups received 8 ml 0.1% ropivacaine combined with 2 μg/ml fentanyl. The onset time of analgesia, motor and sensory blockade level, numerical pain rating scale, patient satisfaction score, and side effects were recorded. Results The onset time of analgesia in group RF was similar to that in group L (group RF vs group L, 7.0 [5.0–9.0] minutes vs 8.0 [5.0–11.0] minutes, p = 0.197). The incidence of foot numbness (group RF vs group L, 34.9% vs 57.1%, p = 0.020) and foot warming (group RF vs group L, 15.9% vs 47.6%, p

Introduction: Opioid overprescribing may fuel the opioid epidemic and increase the risk of complications of opioid misuse. This study examined trends and determinants of chronic and heavy opioid use among elderly community dwellers in the U.S. Methods: Medicare Current Beneficiary Surveys data from 2006 to 2019 were used. Common opioid medications were identified in the prescription medication files (n=47,264). Patients with Chronic users were defined as those receiving 6 or more opioid prescriptions within a year or on medication for 3 or more months, and heavy users were those having an average daily dose of 90 or more morphine milligram equivalents or 3,780 morphine milligram equivalents or more per continuous treatment episode. Results: One in 6 elderly community dwellers ever used opioids during the study period. Chronic users were more likely to be women than men (68.9% vs 31.1%, p

Introduction Smoking cessation (SC) clinics are a professional SC services in China. However, studies comparing the characteristics and SC rates of smoking populations in SC clinics with those using mobile SC programs are limited. We compared smokers’ characteristics, 3-month SC rates, and the factors influencing 3-month SC success, between a large hospital SC clinic and a WeChat SC miniprogram. Methods Between January and November 2021, 384 participants voluntarily enrolled in either the hospital SC clinic (Group A: n=243) or the WeChat SC miniprogram (Group B: n=141). Both groups underwent a 3-month SC intervention, and their SC status was monitored at 24 hours, 1 week, 1 month, and 3 months after quitting. SC rate was defined as the self-reported rate of continuous SC. Results The 3-month SC rate was higher in Group A (42.4%) than in Group B (24.8%). Participants with middle school education had a lower likelihood of SC success than those with primary school or lower (p=0.014). Employees in the enterprise/business/services industries were more likely to have SC success than farmers (p=0.013). Participants with SC difficulty scores of 0–60 were more successful than those with scores >60 (p=0.001, p=0.000, respectively). Participants who quit smoking due to their illness, or other reasons, had a higher likelihood of SC success than those who quit due to concerns about their own and their family's health (p=0.006, p=0.098, respectively). While the likelihood of SC success was lower in those who quit because of the influence of their environment than in those who quit due to concerns about their own and their family's health (p=0.057). Conclusions Both SC clinics and WeChat SC mini-programs achieved satisfactory SC rates. The high accessibility of mobile SC platforms, which save time spent on transportation and medical visits, renders them worth promoting and publicizing as additional SC options for smokers, particularly young smokers.

Introduction Many smokers in China desire to quit, though the success rate among adults is low. This study evaluated the effects of QuitAction, a WeChat smoking cessation platform, summarized the intervention experience of the smoking cessation platform, identified aspects of the platform that necessitated improvement, and provided references for further optimization of the smoking cessation platform. Methods This single-arm study was conducted in Hunan, China, from September 2020 to October 2021. Regular smokers, who were aged ≥15 years and willing to quit smoking using QuitAction, were recruited. An in-application questionnaire evaluated participants’ baseline smoking status and intention to quit smoking. The QuitAction program included questionnaires regarding the participants’ ongoing smoking cessation status at 24 hours, one week, one month and three months after quitting. The smoking cessation procedure was discontinued if the participant had no intention of continuing. The smoking cessation rate, influencing success factors, frequency of use satisfaction, and helpfulness of QuitAction were recorded. Results A total of 303 participants registered and logged into the QuitAction program, including 59 with incomplete information and 64 with no intention of quitting. The study finally included 180 participants. The smoking cessation rate was 33.9% at 24 hours, 27.2% at one week, 26.1% at one month, and 25.0% at three months. QuitAction was reported as helpful by 94.9% of participants and 95.7% were satisfied with the program. Participants with a quitting difficulty score of 80–100 were less likely to quit smoking than participants with a difficulty score of 0–60 (OR=0.28; 95% CI: 0.10–0.78; p=0.015). Participants using the platform ≥5 times were more likely to quit smoking than those who used the platform

Introduction Travel and living environment restrictions, which may have positive or negative effects on smoking-related behaviors, were implemented to limit the COVID-19 pandemic. This study aimed to compare the baseline clinical characteristics and smoking cessation (SC) rate at 3 months of patients in an SC clinic in Hunan Province, China before and during the COVID-19 pandemic and identify influencing factors of successful SC. Methods Healthy patients at the SC clinic aged ≥18 years before the COVID-19 pandemic and during the COVID-19 pandemic were divided into groups A and B, respectively. The two groups’ demographic data and smoking characteristics were compared, and SC interventions were applied by the same medical staff team through telephone follow-up and counselling during the SC procedure. Results Groups A and B included 306 and 212 patients, respectively, with no significant differences in demographic data. The SC rates of group A (pre COVID-19) and group B (during the COVID-19 pandemic) at 3 months were 23.5% and 30.7%, respectively, after the first SC visit. Those who chose to quit immediately or within 7 days were more successful than those who did not choose a quit date (p=0.002, p=0.000). Patients who learned about the SC clinic via network resources and other methods were more likely to succeed than those who learned about the clinic from their doctor or hospital publications (p=0.064, p=0.050). Conclusions Planning to quit smoking immediately or within 7 days of visiting the SC clinic and learning about the SC clinic via the network media or other methods improved the likelihood of successful SC. SC clinics and the harm of tobacco should be promoted via network media. During consultation, the smokers should be encouraged to quit smoking immediately and establish an SC plan, which would help them to quit smoking.

IntroductionNatural products have been shown to an important source of therapeutics for human disease. In this study, we aimed to identify natural compounds as potential therapeutics for epidermolysis bullosa acquisita (EBA), an autoimmune disease caused by autoantibodies to type VII collagen (COL7).MethodsUtilizing an in vitro experimental system, we screened a natural product library composed of 800 pure compounds for their inhibitory effect on COL7-anti-COL7 IgG immune complex (IC)-mediated neutrophil activation and on neutrophil-mediated tissue damage.ResultsThree natural compounds, namely luteolin peracetate, gossypol, and gossypolone were capable in inhibiting the IC-induced neutrophil adhesion and oxygen burst in vitro. Furthermore, luteolin peracetate and gossypolone were able to inhibit the anti-COL7 IgG induced dermal-epidermal separation in an ex vivo model for EBA.DiscussionIn summary, this study demonstrates that luteolin peracetate and gossypolone are potential therapeutics for experimental EBA, which deserves further investigation.

Abstract Background Lung cancers arising in never smokers have been suggested to be substantially different from lung cancers in smokers at an epidemiological, genetic and molecular level. Focusing on non-small cell lung cancer (NSCLC), we characterized lung cancer patients in China looking for demographic and clinical differences between the smoking and never-smoking subgroups. Methods In total, 891 patients with NSCLC, including 841 with adenocarcinoma and 50 with squamous cell carcinoma, were recruited in this study. Association of smoking status with demographic and clinical features of NSCLC was determined, and risk factors for lymph node metastasis and TNM stage were evaluated using Multivariate logistic regression analysis. Results In patients with adenocarcinoma, never smokers showed a younger age at diagnosis (54.2 ± 12.7vs. 59.3 ± 9.4, p adjusted

Abstract Apnoeic oxygenation is not only important for patients who cannot be intubated/ventilated, but also can be routinely employed when planning to secure the airway.We aimed to compare safe apnoea times between patients receiving modified nasopharyngeal oxygen therapy and those receiving high-flow nasal oxygen therapy (HFNO) following the induction of general anaesthesia.This was a single-centre, randomized controlled clinical study. Eighty-four female patients undergoing elective laparoscopic gynaecological surgery under general anaesthesia were randomly assigned to the high-flow nasal oxygen therapy group (Group HFNO) or the modified nasopharyngeal oxygen therapy group (Group Naso). A Kaplan–Meier survival curve was used to describe the apnoeic oxygenation time.The safe apnoea time of the patients in the Group Naso was higher than that of the patients in the Group HFNO (20 (19.3 to 20.0) vs. 16.5 (12.9 to 20) minutes, P

The technical condition of bridges has become a crucial issue for organizing the maintenance and repairs in bridge management systems. It is of great practical engineering significance to construct an effective model for predicting the technical condition degradation of the bridge through the use of the historical inspection data. Based on the semi-Markov random process, this paper proposes a useful deterioration prediction model for bridges in the highway network. From the historical inspection data of the prefabricated concrete box girder bridges, the degradation curves of technical condition rating are obtained. The effect of bridge length on degradation rate of the prefabricated concrete box girder bridges is analyzed. According to the Weibull distribution parameters of different condition grades, the technical state degradation models for a bridge group and an individual bridge are proposed to predict the performance of the overall bridge and superstructure of the bridge. The results show that with the increase in bridge length, the degradation rate of bridge technical condition increases. The degradation rate of the technical condition of the superstructure is faster than that of the overall bridge. The proposed semi-Markov stochastic degradation model for the bridge group can not only predict the different condition ratings of the bridges at any time, but also predict the future deterioration trend of an individual bridge under any ratings.

Abstract Background Recently, a novel humanized mouse model for systemic sclerosis (SSc) was established by transferring peripheral blood mononuclear cells (PBMC) from patients with SSc to Rag2 −/− Il2rg −/− immunodeficient mice. Here, we aimed to investigate the role of T and B cells in this humanized mouse model. Methods T and B cells were depleted in vitro from freshly isolated PBMC using anti-CD3 and anti-CD19 magnetic microbeads, respectively. Subsequently, PBMC and T or B cell-depleted PBMC were transferred into Rag2 −/− /Il2rg −/− mice via intraperitoneal injection. Twelve weeks after the transfer, mice were sacrificed and evaluated. Results Mice transferred with whole PBMC from SSc patients developed systemic inflammation in the lungs, kidneys, and liver, and 6 out of 11 mice died or had to be sacrificed during the experiment. By contrast, such inflammation and death were not observed in mice transferred with corresponding T or B cell-depleted PBMC. In line with this finding, transfer with whole PBMC restored the splenic white pulp composing of human T, B, and plasma cells and led to the production of a considerable amount of human autoantibodies in recipient mice, while those immunological features were rarely observed in mice that received T or B cell-depleted PBMC. In contrast to our previous findings demonstrating a transfer of the protective effect of a B cell therapy into the mouse, treatment of SSc patients with chemical immunosuppressive drugs did not affect the pathogenicity of PBMC. Conclusions This study demonstrates that both T and B cells are indispensable for the pathogenesis of the PBMC transfer-induced mouse model for SSc.

Abstract Background Decreasing the anaesthesia preparation time for primiparas experiencing painful uterine contractions is clinically relevant. This prospective intervention study investigated the effect of various educational methods conducted at different times on body positioning for primiparas undergoing labour analgesia. Methods Ninety primiparas who were about to receive labour analgesia were randomly divided into a verbal instruction group, a photo instructions group, and an educational video group for immediate education, and 60 primiparas who were willing to receive labour analgesia but were not in labour were randomly divided into a photo instruction group and an educational video group for advance education. The times required for body positioning were compared. Results In the immediate education cohort, the body positioning time in the verbal group (50.48 ± 28.97 s) was significantly longer than those in the photo group (30.47 ± 6.94 s) and the video group (23.14 ± 9.74 s) (P = 0.00). In the advance education cohort, the time in the photo group (17.47 ± 6.48 s) was longer than that in the video group (13.71 ± 7.01 s) (P = 0.042). Whether photos or videos are used, advance education can significantly decrease body positioning time. Conclusions Video or photo education for primiparas who are about to receive labour analgesia can decrease the body positioning time and is more effective when provided in advance.

Abstract Background Delta-opioid receptor is widely expressed in human and rodent hearts, and has been proved to protect cardiomyocytes against ischemia/reperfusion and heart failure. The antagonist of delta-opioid receptor could block the rescue effect of lipid emulsion against local anesthetic cardiotoxicity. However, no evidence is available for the direct effect of delta-opioid-receptor agonists on the cardiotoxicity of local anesthetics. Methods Anesthetized Sprague Dawley rats were divided into five groups. Group NS received 2 ml·kg−1·min−1 normal saline, group LE received 2 ml·kg−1·min−1 30% lipid emulsion and group BW received 0.1, 1.0, or 5.0 mg/kg BW373U86, a delta-opioid-receptor agonist, for 5 min. Then 0.5% bupivacaine was infused intravenously at a rate of 3.0 mg·kg−1·min−1 until asystole. The time of arrhythmia, 50% mean arterial pressure-, 50% heart rate-reduction and asystole were recorded, and the dose of bupivacaine at each time point was calculated. Results All three different doses of BW373U86 did not affect the arrhythmia, 50% mean arterial pressure-reduction, 50% heart rate-reduction and asystole dose of bupivacaine compared with group NS. 30% LE significantly increased the bupivacaine threshold of 50% mean arterial pressure-reduction (17.9 [15.4–20.7] versus 7.2 [5.9–8.7], p = 0.018), 50% heart rate-reduction (18.7 ± 4.2 versus 8.8 ± 1.7, p

Introduction China has the largest number of smokers in the world. The great majority of China’s smokers desire to quit smoking (QS); however, the success rate of self-quitting is low. This study investigated the effects of smoking cessation (SC) clinics in a cancer hospital in Hunan province and determined the influencing factors of successful SC. Methods Smokers were recruited to QS by healthcare workers in the SC clinic from February 2015 to February 2019. SC counseling was provided and telephone follow-up was conducted at 1 week, and at 1, 3 and 6 months. Patients who continued SC during the follow-up period were considered to have QS. Results Of the 344 patients included in this study, 16.3% QS at one week, 26.5% at one month, 27.6% at three months, and 31.7% at six months. Age ≥60 years, previous SC attempts, immediate quit dates, and telephone follow-up times (3–4 calls) were predictive factors for smokers to SC at six months. Conclusions Age, previous attempts to QS, immediate quit dates and telephone follow-up times were independent predictors of SC success at six months. SC clinics and frequent telephone follow-up improve the success rate of SC, especially in patients who have previously tried to QS or in those who set immediate quit dates.

BackgroundIn-vitro models of differentiated primary human airway epithelial cells are a valuable tool to study severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Through the use of these models, it has been shown that the expression of SARS-CoV-2 entry genes in human airway epithelia is influenced by various factors such as age, sex, smoking status, and pathogenic conditions. In this study, we aimed to determine the effects of cell culture conditions and donor demographic and clinical characteristics on the expression of SARS-CoV-2 entry genes including angiotensin converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2), cathepsin L (CTSL), and tyrosine protein kinase receptor UFO (AXL) in primary airway epithelial cells.MethodsEleven lung cancer patients with or without chronic obstructive pulmonary disease (COPD) or asthma were recruited. Human bronchial epithelial cells (HBEC) or small airway epithelial cells (SAEC) isolated from submerged or air-liquid interface (ALI) cultures were analyzed by quantitative real-time PCR. We also tested for correlations with clinical data.ResultsIn ALI cultures, the expression of AXL was significantly higher in HBEC than in SAEC. In addition, the expression of ACE2, TMPRSS2, and CTSL was significantly increased in both HBEC and SAEC differentiated under ALI conditions compared with the submerged culture. Negligible association was found between the expression of SARS-CoV-2 entry genes in SAEC and the age, sex, smoking status, and complication of COPD, asthma or hypertension of the cell donors.ConclusionThese results demonstrate that the expression of SARS-CoV-2 entry genes in differentiated primary airway epithelial cells in-vitro is much more influenced by individual culture conditions than by specific characteristics of individual donors.

Abstract Background The Interaction between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein with Angiotensin converting enzyme 2 (ACE2) on the host cells is a crucial step for the viral entry and infection. Therefore, investigating the molecular mechanism underlying the interaction is of great importance for the prevention of the infection of SARS-CoV-2. In this study, we aimed to establish a virus-free in vitro system to study the interaction between the spike protein and host cells of SARS-CoV-2. Results Our results show that ACE2-overexpressing HEK293T cells are captured by immobilized spike S1 protein, and the cell capturing process can be inhibited by the receptor binding domain of the spike protein or antibodies against S protein. Furthermore, spike S1 protein variant with D614G mutant show a higher cell capturing ability than wild type spike S1 protein and stronger binding capacity of its receptor ACE2. In addition, the captured cells can be eluted as living cells for further investigation. Conclusions This study provides a new in vitro system for investigating the interaction between SARS-CoV-2 and host cells and purifying ACE2-expressing cells.

Acute exacerbations show a significant impact on disease morbidity and mortality in chronic obstructive pulmonary disease (COPD). In contrast to stable COPD, the association of smoking status with clinical and laboratory characteristics in patients with acute exacerbations of COPD (AECOPD) has not been well studied. In this retrospective study, we compared never smokers and ever smokers on their demographic, clinical, and laboratory characteristics in a Chinese clinical cohort of AECOPD. In this cohort comprising 1,034 consecutive patients with AECOPD, never smokers were older (75 vs 70.5 years, padjusted < 0.001) and had a higher body mass index than smokers (21.1 ± 4.0 vs 20.3 ± 3.4, padjusted = 0.028). Furthermore, never smokers showed a decreased risk of recurrent acute exacerbation (13.0 vs 21.8%, padjusted = 0.029), a lower risk of development of emphysema (77.8 vs 89.1%, padjusted < 0.001), a lower prevalence of the co-morbidity of lung cancer (0.5 vs 6.6%, padjusted < 0.001), lower levels of circulating eosinophils (EO; 0.04 × 109/L vs 0.10 × 109/L, padjusted = 0.007) and basophils (BA; 0.02 × 109/L vs 0.03 × 109/L, padjusted = 0.019), and a higher plasma levels of D-dimer (0.62 μg/ml vs 0.51 μg/ml, padjusted = 0.02). Furthermore, multivariate logistic regression analysis identified several risk factor for the recurrent acute exacerbation, such as smoking [odds ratio (OR) = 1.84, 95% CI: 1.03–3.40, p = 0.044], urban residential area (OR = 1.43, 95% CI: 1.01–2.05, p = 0.045), and the presence of emphysema (OR = 2.31, 95% CI: 1.25–4.69, p = 0.012). In conclusion, this study demonstrates that the smoking status of patients is associated with recurrent acute exacerbations, emphysema, lung cancer, and levels of circulating EO and BA in AECOPD. Identification of cigarette smoking as a risk factor for recurrent acute exacerbation supports behavioral intervention of smoking cessation in the management of patients with AECOPD.

Abstract Paraneoplastic autoimmune encephalitis (PAE) represents a group of rare neurological syndromes associated with neoplastic diseases. Here, we report a case that multiple anti‐neuronal antibodies were present in a patient with PAE who developed both small cell lung cancer and colorectal adenocarcinoma. Furthermore, the immunopathological investigation of the colorectal adenocarcinoma revealed the formation of abnormal neuronal antigens and a massive infiltration of plasma cells in the tumor tissue. These findings support the hypothesis that expression of neuronal antigens in neoplasm initiates autoimmune responses in PAE.

Objectives: Elderly people had suffered a disproportionate burden of COVID-19. We hypothesized that males and females in different age groups might have different epidemic trajectories. Methods: Using publicly available data from South Korea, daily new COVID-19 cases were assessed using generalized additive models, assuming Poisson and negative binomial distributions. Epidemic dynamics by age and gender groups were explored using interactions between smoothed time terms and age and gender. Results: A negative binomial distribution fitted the daily case counts best. The relationship between the dynamic patterns of daily new cases and age groups was statistically significant (p

The aim of this study is to efficiently excite the radiation of phase gradient metasurface (PGM), a novel coplanar discontinuous transmission line feed is proposed for reduction of the profile, where 12 uniform discontinuous rectangular rings form the feeding structure. The unit cells of PGM are symmetrically placed on both sides of this feed structure at the same layer, and they are close enough. The measurements agree well with those of simulations in the range of 10.48–11.18 GHz.

Epidermolysis bullosa acquisita (EBA) is an autoimmune blistering disorder characterized and caused by autoantibodies against type VII collagen (COL7). Although it has been noticed that EBA in both patients and mice is associated with an increased scratching, it is not clear whether and how the scratching contributes to disease manifestation. Hence, we here aimed to validate this clinical observation and also to investigate the potential contribution of increased scratching in EBA pathogenesis in mice. Longitudinal assessment of scratching behavior revealed an increased frequency of scratching as early as 12 hours after injection of anti-COL7 IgG into the skin of mice. Subsequently, scratching events became even more frequent in mice. In contrast, mice injected with a control antibody showed an unaltered scratching behavior throughout the observation period. Based on these observations, we hypothesized that mechanical irritation may promote the induction of inflammation in experimental EBA. To challenge this assumption, the local anesthetic dyclonine hydrochloride was topically applied before injection of anti-COL7 IgG. Dyclonine hydrochloride reduced the scratching events and impaired clinical disease manifestation. In therapeutic experimental settings, i.e. administration of the local anesthetic 24 hours after injection of anti-COL7 IgG, dyclonine hydrochloride only inhibited the scratching behavior, but had no significant effect on clinical disease development. In addition, eosinophils were detected in the skin before the injection of anti-COL7 IgG and significantly increased 48 hours after the antibody injection. Collectively, our results suggest that scratching behavior contributes to the initiation phase of disease manifestation in experimental EBA.

Class I phosphoinositide 3-kinases (PI3K) have been implemented in pathogenesis of experimental epidermolysis bullosa acquisita (EBA), an autoimmune skin disease caused by type VII collagen (COL7) autoantibodies. Mechanistically, inhibition of specific PI3K isoforms, namely PI3Kβ or PI3Kδ, impaired immune complex (IC)-induced neutrophil activation, a key prerequisite for EBA pathogenesis. Data unrelated to EBA showed that neutrophil activation is also modulated by PI3Kα and γ, but their impact on the EBA has, so far, remained elusive. To address this and to identify potential therapeutic targets, we evaluated the impact of a panel of PI3K isoform-selective inhibitors (PI3Ki) on neutrophil function in vitro, and in pre-clinical EBA mouse models. We document that distinctive, and EBA pathogenesis-related activation-induced neutrophil in vitro functions depend on distinctive PI3K isoforms. When mice were treated with the different PI3Ki, selective blockade of PI3Kα (alpelisib), PI3Kγ (AS-604850), or PI3Kβ (TGX-221) impaired clinical disease manifestation. When applied topically, only TGX-221 impaired induction of experimental EBA. Ultimately, multiplex kinase activity profiling in the presence of disease-modifying PI3Ki identified unique signatures of different PI3K isoform-selective inhibitors on the kinome of IC-activated human neutrophils. Collectively, we here identify topical PI3Kβ inhibition as a potential therapeutic target for the treatment of EBA.

The requirements of 5G/6G promote progress in the miniaturization of the antenna array, which promotes the development of a closely spaced decoupling technique. However, the present techniques face the common problem of beam tilt if the spacing is close. Thus, a pattern-corrected, closely-spaced technique is proposed in this paper for the two patch antennas with the λ0/20 edge-to-edge distance of the H-plane. The corresponding structure, which is inserted at the center of the spacing, consists of a vertical wall with a single substrate and two symmetrical T-type metals, and a slot at the center is reserved to adequately accommodate the vertical wall. The vertical strip at the other end of the T-type metal is connected to the ground of the patch antenna, while the parallel strip is placed exactly above the patch substrate. After an exact analysis, a prototype was fabricated and measured, and the results showed that the measurements agreed well with those of the simulations, the decoupling coefficients in the 5.8 GHz band were below −20 dB, and the measured radiation pattern at 5.81 GHz was corrected to the broadside from 28° and the maximum realized gain was 5.30 dB.

During the last two decades, managers have been applying Building Information Modeling (BIM) to improve the quality of management as well as operation. The effectiveness of applications within a BIM environment is restrained by the limited immersive experience in virtual environments. Defined as the immersive visualization of virtual scenes, Virtual Reality (VR) is an emerging technology that can be actively explored to expand BIM to more usage. This paper highlights the need for a structured methodology for the integration of BIM/VR and gives a generic review of BIM and VR in training platforms for management in infrastructures. The rationales for fire evacuation training were formed based on the review. Then, methods of configuring BIM + VR prototypes were formulated for emergency response in highway tunnels. Furthermore, a conceptual framework integrating BIM with VR was proposed to enable the visualization of the physical context in real-time during the training. The result indicated that, extended to the training system of highway management via the “hand” of BIM, the VR solution can benefit more areas, such as the cost of fire evacuation drills in highway tunnels and the tendency of accidents to occur in the emergency response.

ObjectiveThe contribution of sustained autologous autoantibody production by B cells to the pathogenesis of systemic sclerosis (SSc) and granulomatosis with polyangiitis (GPA) is not fully understood. To investigate this, a humanized mouse model was generated by transferring patient-derived peripheral blood mononuclear cells (PBMC) into immunocompromised mice.MethodsPBMC derived from patients with SSc and GPA as well as healthy controls (HD) were isolated, characterized by flow cytometry, and infused into Rag2-/-/IL2rg-/- mice. In addition, PBMC from SSc patients treated with rituximab were transferred into mice. Twelve weeks later, human autoantibodies were determined in blood of the recipient mice and affected tissues were analyzed for pathological changes by histology and immunohistochemistry.ResultsMice engrafted with PBMC derived from SSc patients developed autoantibodies such as antinuclear antibodies (ANA) mimicking the pattern of the respective donors. Moreover, cellular infiltrates dominated by B cells were observed in lung, kidney and muscles of the recipient mice. By contrast, PBMC derived from HD or GPA patients survived in recipient mice after transfer, but neither human autoantibodies nor inflammatory infiltrates in tissues were detected. Furthermore, these pathological changes were absent in mice transferred with PBMC from rituximab-treated SSc patients.ConclusionThis humanized mouse model is indicative for cross-reactivity of human lymphocytes to murine autoantigens and argues for a pivotal role of B cells as well as of sustained autoimmunity in the pathogenesis of SSc. It provides a powerful tool to study interstitial lung disease and so far, under-recognized disease manifestations such as myositis and interstitial nephritis.

Genetic association studies have discovered the GTF2I-NCF1 intergenic region as a strong susceptibility locus for multiple autoimmune disorders, with the missense mutation NCF1 rs201802880 as the causal polymorphism. In this work, we aimed to perform a comprehensive meta-analysis of the association of the GTF2I-NCF1 locus with various autoimmune diseases and to provide a systemic review on potential mechanisms underlying the effect of the causal NCF1 risk variants. The frequencies of the two most extensively investigated polymorphisms within the locus, GTF2I rs117026326 and NCF1 rs201802880, vary remarkably across the world, with the highest frequencies in East Asian populations. Meta-analysis showed that the GTF2I-NCF1 locus is significantly associated with primary Sjögren’s syndrome, systemic lupus erythematosus, systemic sclerosis, and neuromyelitis optica spectrum disorder. The causal NCF1 rs201802880 polymorphism leads to an amino acid substitution of p.Arg90His in the p47phox subunit of the phagocyte NADPH oxidase. The autoimmune disease risk His90 variant results in a reduced ROS production in phagocytes. Clinical and experimental evidence shows that the hypoactive His90 variant might contribute to the development of autoimmune disorders via multiple mechanisms, including impairing the clearance of apoptotic cells, regulating the mitochondria ROS-associated formation of neutrophil extracellular traps, promoting the activation and differentiation of autoreactive T cells, and enhancing type I IFN responses. In conclusion, the identification of the association of NCF1 with autoimmune disorders demonstrates that ROS is an essential regulator of immune tolerance and autoimmunity mediated disease manifestations.

Biological aging is a complex process featured by declined function of cells and tissues, including those of the immune system. As a consequence, aging affects the expression and development of autoantibodies and autoreactive T cells, which can be seen in their sum as the autoimmunome of an individual. In this study we analyzed whether sets of autoimmune features are associated with specific phenotypes which form autoimmunomic signatures related to age and neurodegenerative diseases. The autoantibody profile data of healthy subjects and patients from the GEO database was used to explore autoimmunomic signatures of aging and three neurodegenerative diseases including Parkinson's disease (PD), Alzheimer disease (AD) and Multiple Sclerosis (MS). Our results demonstrate that the autoimmunomic signature of aging is featured by an undulated increase of IgG autoantibodies associated with learning and behavior and a consistent increase of IgG autoantibodies related to ribosome and translation, and the autoimmunomic signature of aging are also associated with age-related neurodegenerative diseases. Intriguingly, Differential Expression-Sliding Window Analysis (DE-SWAN) identified three waves of changes of autoantibodies during aging at an age of 30, 50, and 62 years, respectively. Furthermore, IgG autoantibodies, in particular those against ribosomal proteins, could be used as prediction markers for aging and age-related neurodegenerative diseases. Therefore, this study for the first time uncovers comprehensive autoimmunomic signatures for aging and age-related neurodegenerative diseases.

Background: More than 300 million smokers make China the largest cigarette consumer globally, which is a huge economic burden. Smoking cessation (SC) clinics can offer counseling and follow-up services. The operational experience of SC clinics in China needs to be summarized and improved based on research evidence.Purpose: The objectives of this study were to describe quit rates among attendees of SC clinics in Hunan and assess predictors of successful SC.Methods: The participants in this study were smokers who visited the SC clinic of Hunan Cancer Hospital from February 1, 2015 to September 30, 2018. Individuals who received individual counseling and assessment from the SC clinic staff and were willing to quit smoking were eligible for inclusion. Those with critical illness or cancer were excluded. Application of smoking cessation clinic registration form (unified by Chinese Center for Disease Control and Prevention) was used to assess participants at the consultation. Follow-ups and counseling were performed over telephone at 1 week, 1 month, and 3 months after the initial cessation consultation or in times of need. Successful SC was checked for at 3 months after the start of SC.Results: A total of 328 smokers (mean age 45.67 ± 12.38 years) had participated. The abstinence rate at 3 months was 28.4%. Binary regression analysis revealed significant independent predictors to be the total numbers of SC follow up sessions, previous SC attempts, and participants' decision on when to quit smoking (The relative to quit immediately group, quit within 30 days, quit after 30 days, and undecided quit were less likely to succeed in quitting. while quit within seven days had no statistical significance.Conclusion: SC clinics can achieve a desirably high quit rate. Participant's previous attempts at quitting, three or more follow-ups, and the decision to quit immediately or within seven days were factors helpful in predicting the success of SC.

Neuropathic pain is a kind of chronic pain that remains difficult to treat due to its complicated underlying mechanisms. Accumulating evidence has indicated that enhanced synaptic plasticity of nociceptive interneurons in the superficial spinal dorsal horn contributes to the development of neuropathic pain. Neuroligin1 (NL1) is a type of excitatory postsynaptic adhesion molecule, which can mediate excitatory synaptic activity, hence promoting neuronal activation. Vglut2 is the most common marker of excitatory glutamatergic neurons. To explore the role of NL1 in excitatory neurons in nociceptive regulation, we used transgenic mice with cre recombinase expression driven by the Vglut2 promoter combined with viral vectors to knockdown the expression of NL1 in excitatory neurons in the spinal dorsal horn. We found that NL1 was upregulated in the L4–L6 spinal dorsal horn in Vglut2-cre+/– mouse subjected to spared nerve injury (SNI). Meanwhile, the expression of phosphorylated cofilin (p-cofilin) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit 1 (GluR1) was also increased. Spinal microinjection of a cre-dependent NL1-targeting RNAi in Vglut2-cre+/– mouse alleviated the neuropathic pain-induced mechanical hypersensitivity and reduced the increase in p-cofilin and GluR1 caused by SNI. Taken together, NL1 in excitatory neurons regulates neuropathic pain by promoting the SNI-dependent increase in p-cofilin and GluR1 in the spinal dorsal horn. Our study provides a better understanding of the role of NL1 in excitatory neurons, which might represent a possible therapeutic target for alleviating neuropathic pain.

ObjectivesThe coordinated immune response of the host is the key of the successful combat of the body against SARS-CoV-2 infection and is decisive for the development and progression of COVID-19. In this study, we aimed to investigate whether the immunological phenotype of patients are associated with duration of illness in patients with severe COVID-19.MethodIn this single-center study, 69 patients with severe or critical COVID-19 were recruited retrospectively. Immunological parameters including counts of white blood cells, neutrophils, lymphocytes, the neutrophil-to-lymphocyte ratio, and levels of circulating cytokines and cytokine receptors were screened for their association with disease severity, survival and duration of illness of COVID-19.ResultsOur data confirmed previous results that neutrophil-to-lymphocyte ratio and circulating levels of IL-6 represent prominent biomarker for the prediction of disease severity and survival of COVID-19. However, this study shows for the first time that duration of illness in patients with severe COVID-19 is positively associated with serum levels of IL-8 (P=0.004) and soluble IL-2Rα (P=0.025).ConclusionThe significant association of duration of illness with circulating levels of IL-8 and soluble IL-2Rα in patients with severe COVID-19 implicates that neutrophils and T cells are involved in the evolution of COVID-19.

SARS-CoV-2 enters into human airway epithelial cells via membrane fusion or endocytosis, and this process is dependent on ACE2, TMPRSS2, and cathepsin L. In this study, we examined the expression profiles of the three SARS-CoV-2 entry genes in primary human airway epithelial cells isolated from smokers, non-smokers, patients with chronic obstructive pulmonary disease or lung cancer. An exhaustive search of the GEO database was performed to identify eligible data on 1st June 2020. In total, 46 GEO datasets comprising transcriptomic data of 3,053 samples were identified as eligible data for further analysis. All meta-analysis were performed using RStudio. Standardized mean difference was utilized to assess the effect size of a factor on the expression of targeted genes and 95% confidence intervals (CIs) were calculated. This study revealed that (i) cigarette smoking is associated with an increased expression of ACE2 and TMPRSS2 and a decreased expression of cathepsin L; (ii) significant alternations in expression of ACE2, TMPRSS2, and cathepsin L were observed between current smokers and former smokers, but not between former smokers and never smokers; (iii) when compared with healthy controls with identical smoking status, patients with COPD or lung cancer showed negligible changes in expression of ACE2, TMPRSS2, and cathepsin L. Therefore, this study implicates cigarette smoking might contribute to the development of COVID-19 by affecting the expression of SARS-CoV-2 entry genes, while smoking cessation could be effective to reduce the potential risk.

Background: After more than six months into the coronavirus disease (COVID-19) pandemic, as of August 10, 2020, over 734,664 people had died worldwide. The current study aims to evaluate how mitigating interventions affected the epidemic process in the 30 largest metropolitan areas in the US and whether temperature played a role in the epidemic process. Methods: Publicly available data for the time series of COVID-19 cases and deaths and weather were analyzed at the metropolitan level. The time-varying reproductive numbers (Rt) based on retrospective moving average were used to explore the trends. Student t-tests were used to compare temperature and peak Rt cross-sectionally. Results: We found that virus transmissibility, measured by instantaneous reproduction number (Rt), had declined since the end of March for all areas and almost all of them reached a Rt of 1 or below after April 15, 2020. The timing of the main decline was concurrent with the implementation of mitigating interventions. However, the Rts remained around 1 for most areas since then and there were some small and short rebounds in some areas, suggesting a persistent epidemic in those areas when interventions were relaxed. Cities with warm temperature also tended to have a lower peak Rt than that of cities with cold temperature. However, they were not statistically significant and large geographic variations existed. Conclusions: Aggressive interventions might have mitigated the current pandemic of COVID-19, while temperature might have weak effects on the virus transmission. We may need to prepare for a possible return of the coronavirus outbreak.

Objective: Health inequalities were often exacerbated during the emerging epidemic. This study examined urban and non-urban inequalities in health services among COVID-19 patients aged 65 years or above in Florida, USA, from 2 March to 27 May 2020. Methods: A retrospective time series analysis was conducted using individual patient records. Multivariable Poisson’s and logistic models were used to calculate adjusted incidence of COVID-19 and the associated rates of emergency department visits, hospitalizations, and deaths. Results: As of 27 May 2020, there were 13,659 elderly COVID-19 patients (people aged 65 years or above) in Florida and 14.9% of them died. Elderly people living in small metropolitan areas might be less likely to be confirmed with COVID-19 infection than those living in large metropolitan areas. The emergency department visit and hospitalization rates decreased significantly across metropolitan statuses for both men and women. Those patients living in small metropolitan or rural areas were less likely to be hospitalized than those living in large metropolitan areas (35% and 34% vs 41%). Elderly women aged 75 years or above living in rural areas had 113% higher adjusted incidence of COVID-19 than those living in large metropolitan areas, and the rates of hospitalizations were lower compared with those counterparts living in large metropolitan areas (29% vs 46%; odds ratio: 0.37 (0.25–0.54), p

Sjögren's syndrome (SS) is a complex rheumatoid disease that mainly affects exocrine glands, resulting in xerostomia (dry mouth) and xerophthalmia (dry eye). SS is characterized by autoantibodies, infiltration into exocrine glands, and ectopic expression of MHC II molecules on glandular epithelial cells. In contrast to the well-characterized clinical and immunological features, the etiology and pathogenesis of SS remain largely unknown. Animal models are powerful research tools for elucidating the pathogenesis of human diseases. To date, many mouse models of SS, including induced models, in which disease is induced in mice, and genetic models, in which mice spontaneously develop SS-like disease, have been established. These mouse models have provided new insight into the pathogenesis of SS. In this review, we aim to provide a comprehensive overview of recent advances in the field of experimental SS.

Abstract Background The chemokine receptors CXCR3 and CXCR4 are involved in the pathogenesis of fibrosis, a key feature of systemic sclerosis (SSc). It is hypothesized that immunoglobulin (Ig)G antibodies (abs) against these two receptors are present in patients with SSc and are associated with clinical findings. Methods Anti-CXCR3 and anti-CXCR4 ab levels were measured in 449 sera from 327 SSc patients and in 234 sera from healthy donors (HD) by enzyme-linked immunosorbent assay (ELISA). In SSc, ab levels were compared with clinical data in a cross-sectional and longitudinal setting. Protein expression of CXCR3 and CXCR4 on peripheral blood mononuclear cells (PBMCs) was analyzed in 17 SSc patients and 8 HD by flow cytometry. Results Anti-CXCR3 and anti-CXCR4 ab levels were different among SSc subgroups compared with HD and were highest in diffuse SSc patients. The ab levels strongly correlated with each other (r = 0.85). Patients with SSc-related interstitial lung disease (SSc-ILD) exhibited higher ab levels which negatively correlated with lung function parameters (e.g., r = −0.5 and r = −0.43 for predicted vital capacity, respectively). However, patients with deterioration of lung function showed lower anti-CXCR3/4 ab levels compared with those with stable disease. Frequencies and median fluorescence intensities (MFI) of CXCR3+ and CXCR4+ PBMCs were lower in SSc patients compared with HD and correlated with the severity of skin and lung fibrosis. They correlated with the severity of skin and lung fibrosis. Conclusions Anti-CXCR3/4 abs and their corresponding receptors are linked with the severity of SSc-ILD. Antibody levels discriminate patients with stable or decreasing lung function and could be used for risk stratification.

Adaptive beamforming is sensitive to steering vector (SV) and covariance matrix mismatches, especially when the signal of interest (SOI) component exists in the training sequence. In this paper, we present a low-complexity robust adaptive beamforming (RAB) method based on an interference–noise covariance matrix (INCM) reconstruction and SOI SV estimation. First, the proposed method employs the minimum mean square error criterion to construct the blocking matrix. Then, the projection matrix is obtained by projecting the blocking matrix onto the signal subspace of the sample covariance matrix (SCM). The INCM is reconstructed by replacing part of the eigenvector columns of the SCM with the corresponding eigenvectors of the projection matrix. On the other hand, the SOI SV is estimated via the iterative mismatch approximation method. The proposed method only needs to know the priori-knowledge of the array geometry and angular region where the SOI is located. The simulation results showed that the proposed method can deal with multiple types of mismatches, while taking into account both low complexity and high robustness.

Ectopic expression of MHC II molecules on glandular cells is a feature of primary Sjögren's syndrome (pSS). However, the cause of this ectopic expression and its potential role in the pathogenesis of the disease remains elusive. Here, we report that ectopic expression of MHC II molecules on glandular cells represents an early presymptomatic event in a mouse model of pSS induced by immunization of Ro60_316-335 peptide emulsified in TiterMax® as an adjuvant. Ectopic expression of MHC II was induced by TiterMax® but not by complete freund's adjuvant (CFA). Furthermore, immunization with Ro60_316-335 peptide emulsified in TiterMax®, but not in CFA, induced a pSS-like disease in mice. Our results suggests that ectopic expression of MHC II molecules on glandular cells represents a presymptomatic feature of pSS and that such ectopic expression can be induced by exogenous factors. In addition, this study also provides a novel mechanism how adjuvants can amplify immune responses.

Rheumatoid diseases are a group of systemic autoimmune diseases which affect multiple organs with largely unknown etiology. In the past decade, long non-coding RNAs (lncRNAs) have emerged as important regulators of biological processes and contribute deeply to immune cell development and immune responses. Substantial evidences have been accumulated showing that LncRNAs involved in the pathogenesis of the rheumatoid diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). In this review, we summarize literature combined with bioinformatics methods to analyze the unique and common lncRNAs patterns in rheumatoid diseases and try to reveal the important function of lncRNAs in RA, SLE and SS.

Anti-neutrophil cytoplasmic autoantibodies (ANCA) targeting proteinase 3 (PR3) and myeloperoxidase expressed by innate immune cells (neutrophils and monocytes) are salient diagnostic and pathogenic features of small vessel vasculitis, comprising granulomatosis with polyangiitis (GPA), microscopic polyangiitis, and eosinophilic GPA. Genetic studies suggest that ANCA-associated vasculitides (AAV) constitute separate diseases, which share common immunological and pathological features, but are otherwise heterogeneous. The successful therapeutic use of anti-CD20 antibodies emphasizes the prominent role of ANCA and possibly other autoantibodies in the pathogenesis of AAV. However, to elucidate causal effects in AAV, a better understanding of the complex interplay leading to the emergence of B lymphocytes that produce pathogenic ANCA remains a challenge. Different scenarios seem possible; e.g., the break of tolerance induced by a shift from non-pathogenic toward pathogenic autoantigen epitopes in inflamed tissue. This review gives a brief overview on current knowledge about genetic and epigenetic factors, barrier dysfunction and chronic non-resolving inflammation, necro-inflammatory auto-amplification of cellular death and inflammation, altered autoantigen presentation, alternative complement pathway activation, alterations within peripheral and inflamed tissue-residing T- and B-cell populations, ectopic lymphoid tissue neoformation, the characterization of PR3-specific T-cells, properties of ANCA, links between autoimmune disease and infection-triggered pathology, and animal models in AAV.

Skin mast cells (MCs), a resident immune cell type with broad regulatory capacity, play an important role in sensing danger signals as well as in the control of the local immune response. It is conceivable to expect that skin MCs regulate autoimmune response and are thus involved in autoimmune diseases in the skin, e.g., autoimmune bullous dermatoses (AIBD). Therefore, exploring the role of MCs in AIBD will improve our understanding of the disease pathogenesis and the search for novel therapeutic targets. Previously, in clinical studies with AIBD, particularly bullous pemphigoid, patients’ samples have demonstrated that MCs are likely involved in the development of the diseases. However, using MC-deficient mice, studies with mouse models of AIBD have obtained inconclusive or even discrepant results. Therefore, it is necessary to clarify the observed discrepancies and to elucidate the role of MCs in AIBD. Here, in this review, we aim to clarify discrepant findings and finally elucidate the role of MCs in AIBD by summarizing and discussing the findings in both clinical and experimental studies.

Chronic obstructive pulmonary disease (COPD), the fourth leading cause of death worldwide, is characterized by irreversible airflow limitation based on obstructive bronchiolitis, emphysema, and chronic pulmonary inflammation. Inhaled toxic gases and particles, e.g., cigarette smoke, are major etiologic factors for COPD, while the pathogenesis of the disease is only partially understood. Over the past decade, an increasing body of evidence has been accumulated for a link between COPD and autoimmunity. Studies with clinical samples have demonstrated that autoantibodies are present in sera of COPD patients and some of these antibodies correlate with specific disease phenotypes. Furthermore, evidence from animal models of COPD has shown that autoimmunity against pulmonary antigens occur during disease development and is capable of mediating COPD-like symptoms. The idea that autoimmunity could contribute to the development of COPD provides a new angle to understand the pathogenesis of the disease. In this review article, we provide an advanced overview in this field and critically discuss the role of autoantibodies in the pathogenesis of COPD.

Primary Sjögren’s syndrome (pSS) is characterized by a panel of autoantibodies, while it is not clear whether B cells and autoantibodies play an essential role in pathogenesis of the disease. Here, we report a novel mouse model for pSS which is induced by immunization with the Ro60_316-335 peptide containing a predominant T cell epitope. After immunization, mice developed several symptoms mimicking pSS, including a decreased secretion of tears, lymphocytic infiltration into the lacrimal glands, autoantibodies, and increased levels of inflammatory cytokines. Disease susceptibility to this novel mouse model varies among strains, where C3H/HeJ (H2-k) and C3H/HeN (H2-k) are susceptible while DBA/1 (H2-q) and C57BL/6 (H2-b) are resistant. Depletion of B cells using anti-CD20 monoclonal antibodies prevented C3H/HeN mice from development of the pSS-like disease. In addition, HLA-DRB1*0803, a pSS risk allele, was predicted to bind to the hRo60_308-328 which contains a predominant T cell epitope of human Ro60. Therefore, this study provides a novel mouse model for pSS and reveals an indispensable role of B cells in this model. Moreover, it suggests that T cell epitope within Ro60 antigen is potentially pathogenic for pSS.

Objective: The goal of this research is to delineate health care utilization among elderly Medicare beneficiaries with coexisting dementia and cancer compared with those with dementia alone, cancer alone, or neither condition. Method: The study cohort included 96,124 elderly patients aged 65 years and older who resided in the Mid-South region of the United States and were enrolled in Medicare during 2009. Multivariate regression analyses were used to examine health care utilizations while adjusting for sociodemographic characteristics. Results: Those with coexisting dementia and cancer diagnoses had higher rates of hospitalizations, hospital readmissions within 30 days, intensive care unit use, and emergency department visits compared with those with dementia only, cancer only, and those with neither condition. Patients with coexisting dementia and cancer also had a higher number of primary care visits and specialist visits. Conclusion: There is a greater need for developing tailored care plans for elderly with these two degenerative health conditions to address their unique health care needs and to reduce financial burden on the patients and the health care system.

OBJECTIVES:Anti-muscarinic acetylcholine type-3 receptor (anti-M3R) autoantibodies have been suggested to be pathogenic for primary Sjögren's syndrome (pSS), and the second extracellular loop of M3R is suspected to carry a disease-promoting epitope. In this study, we aimed to evaluate the pathogenicity of autoantibodies against peptides derived from the second extracellular loop of M3R in mice and to determine whether those autoantibodies could be used as biomarker for pSS. METHODS:BALB/c mice were immunized with modified linear or cyclic peptides of the second extracellular loop of M3R. The function of exocrine glands was evaluated by measuring the secretion of saliva and tears. The histological evaluations were performed by using H&E staining or direct immunofluorescence staining. Autoantibodies against linear or cyclic peptides of the second extracellular loop of M3R in human and mice were determined using ELISA. RESULTS:Immunization induced mice to produce autoantibodies against the linear or cyclic peptides of the second extracellular loop of M3R, and those autoantibodies could bind onto salivary glands. However, those mice showed neither impairment in the secretion of tears or saliva nor histological abnormality in the exocrine glands. Furthermore, passive transfer of the IgG isolated from the immunized mice into healthy mice did not induced the dysfunction of the exocrine glands. The prevalence of autoantibodies against the peptides of the second extracellular loop of M3R was low in pSS patients, and it did not differ significantly from that in healthy controls. CONCLUSIONS:Our results suggest that the autoantibodies against peptides of the second extracellular loop of M3R are not pathogenic in vivo and they are not suitable as biomarkers for pSS diagnosis.

As a clean and efficient energy, natural gas is the main driving force for China’s energy transformation and the realization of green energy development. Distributed natural gas combined cooling, heating and power (DNG-CCHP) is the main utilization method of distributed natural gas with many advantages. However, the economics of China’s DNG-CCHP system are poor, hindering the healthy and sustainable development of the system in China. Thus, this paper systematically analyzes the factors affecting the economics of DNG-CCHP system in China. Firstly, through the analysis of the development status and obstacles of China’s DNG-CCHP system, the economic impact factor set of DNG-CCHP systems involving 34 factors is constructed. Then, the integrated DEMTTEL-ISM method is used to construct the multi-level hierarchical structure of influencing factors, the influence mechanism of the factors on the economics of DNG-CCHP system is systematically and comprehensively analyzed, and the path of improving system economics is proposed accordingly. Finally, based on the research findings and the development of China’s DNG-CCHP, the coordinated development of DNG-CCHP and distributed renewable energy was discussed, and several policy suggestions are put forward to contribute to the integration of distributed natural gas and distributed renewable energy.

With the development and grid-connection of renewable energy sources such as wind power, there are more and more uncertainties in power systems, and large-scale wind power has brought many challenges to the security and stability the systems. These uncertainties have to be eliminated by means of upward or downward regulations of conventional generators and charging/discharging services of energy storage devices. Based on the analysis of the influence of wind power uncertainties on the day-ahead electricity market, this article proposes a robust clearing model for the day-ahead electricity market considering the wind power penetration, which can help to complete the dispatch of power system. Compared with the traditional models, the proposed model is a multi-objective model, which considers both the lowest operating cost and the least wind power curtailment of power system. Moreover, the obtained dual multipliers λ corresponding to the power balance constraints reflect the marginal cost of the power production in a certain period, that is, the locational marginal price (LMP), which can be used as the clearing prices. This robust market clearing model takes into consideration the economic and reliability of the system operation and accommodates as much renewable energy as possible. The simulation of three wind power producers was implemented on the IEEE 30-bus test system, which verified the rationality of the proposed approaches.

This paper aims to explore China’s contributions to global green energy and low-carbon (GELC) development based on the Belt and Road (B&R) Initiative. Basic situations of B&R countries reveal an urgent requirement for developing green energy. Carbon intensity is an efficient indicator reflecting the degree of GELC development, which is affected by many factors. By analyzing the spatial distribution of carbon intensities in 29 B&R countries excluding China, the spatial agglomeration and positive radiation effects are discovered, while the negative radiation effects are disappearing, indicating that the studied B&R countries lack an effective driving mechanism to promote GELC development. Besides, the spatial convergence results support significant absolute and conditional convergences in the 29 B&R countries, and a faster convergence speed when considering control variables. Therefore, B&R countries trend to converge to a steady stable carbon intensity to achieve the GELC development. Furthermore, the investment rate and openness play a driving role in pushing the decrease of carbon intensity growth rate, revealing that the B&R Initiative can promote reducing the global carbon emissions and developing global green energy. Moreover, the carbon intensity of the country will be positively affected by those of the surrounding areas, indicating that reducing carbon emission is a global governance issue requiring the participation of all countries. Finally, several policy suggestions are proposed to promote the global GELC development under B&R framework, according to the empirical findings.

During the “13th Five-Year Plan” period, green energy is the top priority for China. China has realized that natural gas, as a low-carbon energy source, fits with the nation’s energy demand and will play a critical role in the energy transition, but the actual industry development is slower than expected. By analyzing the major gas corporations around the world, the paper finds that the key factors of the sector are supply and price of the energy resource. A comprehensive analysis on domestic and foreign imported gas reveals a trend of oversupply in China in the future. Given the critical import dependence, China has introduced a series of gas price reforms since 2013, which have led to negative impacts on important gas consumption sectors including power generation. With the levelized cost of electricity (LCOE) model, we find that under the prevailing gas supply structure and price level, the economy of utility gas power generation will remain unprofitable, while combined cooling heating and power (CCHP) is only commercially feasible in coastal developed regions. If continuing, such a trend will not only bring forth disastrous consequences to gas power industry, but also damage the upstream gas industry, more importantly, impede the energy transition. We conclude the paper with policy implications on pricing mechanism reform, developing domestic unconventional gas and the R&D of gas turbine.

Endo-β-N-acetylglucosaminidase (EndoS) has been shown to act as a potent pathogen-derived immunomodulatory molecule in autoimmune diseases. Here we investigated how EndoS treatment reduces the pathogenicity of rabbit anti-mCOL7 IgG using different experimental models of epidermolysis bullosa acquisita (EBA). Our results show that the EndoS treatment does not interfere with the binding of the antibody to the antigen but reduces immune complex (IC)-mediated neutrophil activation by impairing the binding of the IC to FcγR on neutrophils. On the basis of this newly identified EndoS-mediated mechanism we hope to develop new strategies in the treatment of the disease.

BackgroundMitochondrial DNA (mtDNA) polymorphism is a possible factor contributing to the maternal parent-of-origin effect in multiple sclerosis (MS) susceptibility.Methods and findingsIn order to investigate the role of mtDNA variations in MS, we investigated six European MS case-control cohorts comprising >5,000 individuals. Three well matched cohorts were genotyped with seven common, potentially functional mtDNA single nucleotide polymorphisms (SNPs). A SNP, nt13708 G/A, was significantly associated with MS susceptibility in all three cohorts. The nt13708A allele was associated with an increased risk of MS (OR = 1.71, 95% CI 1.28-2.26, P = 0.0002). Subsequent sequencing of the mtDNA of 50 individuals revealed that the nt13708 itself, rather than SNPs linked to it, was responsible for the association. However, the association of nt13708 G/A with MS was not significant in MS cohorts which were not well case-control matched, indicating that the significance of association was affected by the population structure of controls.ConclusionsTaken together, our finding identified the nt13708A variant as a susceptibility allele to MS, which could contribute to defining the role of the mitochondrial genome in MS pathogenesis.