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In autoimmune hepatitis (AIH), the persisting inflammation contributes to fibrosis progression, for which conventional biochemical markers manifest relatively unsatisfactory prediction. Herein, we assessed the value of serum CD48 (sCD48) as an indicator for inflammation and fibrosis in AIH type 1. The levels of sCD48 were detected first in an exploratory cohort using ELISA. In this cohort, compared with healthy controls (4.90 ng/mL, P 0.0001), primary biliary cholangitis (7.32 ng/mL, P 0.0001), and non-alcoholic fatty liver disease (7.76 ng/mL, P 0.0001), sCD48 levels were elevated in AIH (12.81 ng/mL) and correlated with histological inflammation and fibrosis. Further using multivariate logistic regression analysis, sCD48 was identified as an independent predictor for both significant inflammation (G3-4) and advanced fibrosis (S3-4). Two predictive scores, based on sCD48, were constructed for diagnosing significant inflammation and advanced fibrosis (sCD48-AIH-SI and sCD48-AIH-AF, respectively). Using these data as a premise, predictive abilities were subsequently evaluated and verified in a validation cohort. In the exploratory cohort, the area under the receiver operating characteristic curve of sCD48 and sCD48-AIH-SI, for significant inflammation, were 0.748 and 0.813, respectively. Besides, during treatment follow-up, sCD48 levels gradually decreased from immunosuppression initiation to re-evaluation biopsy, in parallel with aspartate transaminase, total sera IgG, and fibrosis-4 score. For AIH patients in a re-evaluation biopsy cohort, sCD48 could predict significant fibrosis (S2-4). Further using immunohistochemistry, hepatic CD48 expression was elevated in AIH patients and decreased after treatment. In conclusion, sCD48 and sCD48-based predictive scores predict histological inflammation and fibrosis in AIH-1. Detecting sCD48 might help in the clinical management of AIH.

Kailian He,1,2,&ast; Xiashuang Zhang,1,2,&ast; Dong Yang,3 Xiaofeng Fu,3 Yulu Chen,1,2 Ziqi Chen,1,2 Jinglin Mo,3 Lingmi Zhou,3 Fang Xu,3 Xiuli Jiang,3 Wuxiang Shi,4 Liang Cao,1,5 You Li1,2 1Department of Environmental Health and Occupational Medicine, School of Public Health, Guilin Medical University, Guilin, Guangxi, 541199, People’s Republic of China; 2Guangxi Health Commission Key Laboratory of Entire Lifecycle Health and Care (Guilin Medical University), Guilin, Guangxi, 541199, People’s Republic of China; 3Department of AIDS Control and Prevention, Guilin Center for Disease Control and Prevention, Guilin, Guangxi, 541000, People’s Republic of China; 4Health Management Unit, Faculty of Humanities and Management, Guilin Medical University, Guilin, Guangxi, 541199, People’s Republic of China; 5Department of Experimental Teaching Center, School of Public Health, Guilin Medical University, Guilin, Guangxi, 541199, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: You Li; Liang Cao, Email liyou121300@163.com; caoliang00552@163.comPurpose: The purpose of our study is to understand the current status of depression and medical social support in elderly HIV/AIDS, as well as the role of social support on depression, so as to provide a certain reference for reducing the occurrence of depression in the population.Methods: A total of 115 participants with PLWHA (people living with HIV/AIDS) aged 50 years or older were collected in Guilin from December 2021 to July 2022. Depression and medical social support were assessed using the Center for Streaming Depression Scale (CES-D) and the Medical Social Support Scale (MOS-SSS). The structural equation model was used to examine the relationship between medical social support and depression.Results: Sixty-one of 115 participants developed depressive symptoms with a prevalence of 53.0%. The results of univariate analysis showed that ethnicity, health status, mean monthly income, antiviral treatment status, and medical social support influenced PLWHA depression (P< 0.05). Simple linear regression showed that health status (95% CI: − 9.901~-2.635), and antiviral treatment status (95% CI: − 12.969~-3.394) influent depression (P< 0.05). There were associations between total medical social support, practical support dimension, message and emotional support dimension, social interactive cooperation dimension, emotional support dimension and depression (unadjusted and adjusted for contextual factors) (P < 0.05). Using multiple linear regression analyses, we found that medical-social support was negatively associated with depression with a standardized effect value of − 0.223. PLWHA with higher medical social support had lower prevalence of depression.Conclusion: The results indicate that the prevalence of depression among HIV/AIDS patients in Guilin is high. So the joint efforts of individuals, families, and society are needed to improve the physical and mental health of the PLWHA.Keywords: older people living with HIV/AIDS, medical social support, depression, structural equation model, SEM

Background Respiratory syncytial virus (RSV) is a leading cause of respiratory disease in young children. A number of mathematical models have been used to assess the cost-effectiveness of RSV prevention strategies, but these have not been designed for ease of use by multidisciplinary teams working in low-income and middle-income countries (LMICs). Methods We describe the UNIVAC decision-support model (a proportionate outcomes static cohort model) and its approach to exploring the potential cost-effectiveness of two RSV prevention strategies: a single-dose maternal vaccine and a single-dose long-lasting monoclonal antibody (mAb) for infants. We identified model input parameters for 133 LMICs using evidence from the literature and selected national datasets. We calculated the potential cost-effectiveness of each RSV prevention strategy (compared to nothing and to each other) over the lifetimes of all children born in the year 2025 and compared our results to a separate model published by PATH. We ran sensitivity and scenario analyses to identify the inputs with the largest influence on the cost-effectiveness results. Results Our illustrative results assuming base case input assumptions for maternal vaccination ($3.50 per dose, 69% efficacy, 6 months protection) and infant mAb ($3.50 per dose, 77% efficacy, 5 months protection) showed that both interventions were cost-saving compared to status quo in around one-third of 133 LMICs, and had a cost per DALY averted below 0.5 times the national GDP per capita in the remaining LMICs. UNIVAC generated similar results to a separate model published by PATH. Cost-effectiveness results were most sensitive to changes in the price, efficacy and duration of protection of each strategy, and the rate (and cost) of RSV hospital admissions. Conclusions Forthcoming RSV interventions (maternal vaccines and infant mAbs) are worth serious consideration in LMICs, but there is a good deal of uncertainty around several influential inputs, including intervention price, efficacy, and duration of protection. The UNIVAC decision-support model provides a framework for country teams to build consensus on data inputs, explore scenarios, and strengthen the local ownership and policy-relevance of results.

Shasha Duan,1– 3,&ast; Chao Wang,1,2,&ast; Xiangli Xu,4 Xiaoshan Zhang,3 Gaofeng Su,1,2 You Li,1,2 Shuai Fu,1,2 Ping Sun,1,2 Jiawei Tian1 1Department of Ultrasound, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China; 2The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin, Heilongjiang Province, People’s Republic of China; 3Department of Ultrasound, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, People’s Republic of China; 4Department of Ultrasound, the Second Hospital of Harbin city, Harbin, Heilongjiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiawei Tian; Ping Sun, Department of Ultrasound, the Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu Road, Nangang District, Harbin, Heilongjiang Province, 150086, People’s Republic of China, Tel +86 451-86605811, Fax +86 451-86605745, Email jwtian2004@163.com; sunpinghmu@163.comPurpose: Angiogenesis is required for improving myocardial function and is a key factor in long-term prognosis after an acute myocardial infarction (AMI). Although exosomes are known to play a crucial role in angiogenesis, the role of peripheral exosomes in angiogenic signal transduction in patients with AMI remains unclear. Here, we explored the effect of exosomes extracted from the peripheral serum of AMI patients on angiogenesis and elucidated the downstream pathways.Patients and Methods: Serum exosomes were obtained from patients with AMI (AMI-Exo) and healthy individuals (Con-Exo). The exosomes were cocultured with human umbilical vein endothelial cells (HUVECs) in vitro, with aortic rings ex vivo, and were used to treat mouse hind-limb ischemia and mouse AMI model in vivo.Results: AMI-Exo raised HUVEC proliferation, tube formation, and migration, and enhanced microvessel sprouting from aortic rings compared to Con-Exo, both in vitro and ex vivo. Quantitative reverse transcription-polymerase chain reaction revealed that the abundance of miR-126-3p, a crucial regulator of angiogenesis, was increased in AMI-Exo. The inhibition of miR-126-3p decreased the benefits of AMI-Exo treatment, and miR-126-3p upregulation enhanced the benefits of Con-Exo treatment in HUVECs, aortic rings, the mouse hind-limb ischemia model, and the mouse AMI model. Knockdown and overexpression analyses revealed that miR-126-3p regulated angiogenesis in HUVECs by directly targeting tuberous sclerosis complex 1 (TSC1). Moreover, we found that miR-126-3p could inhibit TSC1 expression, which further activated mTORC1 signaling and increased HIF-1α and VEGFA expression, ultimately promoting angiogenesis.Conclusion: Collectively, our results provide a novel understanding of the function of exosomes in angiogenesis post AMI. We demonstrated that exosomes from the peripheral serum of AMI patients promote angiogenesis via the miR-126-3p/TSC1/mTORC1/HIF-1α signaling pathway.Keywords: acute myocardial infarction, angiogenesis, exosomes, miR-126-3p, tuberous sclerosis complex 1

Pulmonary embolism (PE) is a fatal clinical syndrome that is generally caused by an embolus from unstable deep venous thrombosis (DVT). However, clinical and biochemical factors that are related to the stability of DVT are not fully understood.To evaluate the relationships between plasma antigen levels of factor XII (FXII:Ag) and factor XI (FXI:Ag) with the stability of DVT.Patients with DVT and no PE, DVT and PE, and controls with no DVT or PE that matched for age, gender, and comorbidities were included in this study. FXII:Ag and FXI:Ag in peripheral venous blood were measured using enzyme-linked immunosorbent assays.Using the 95Higher plasma FXI:Ag might be a marker for unstable DVT, which might be associated with PE in these patients.

Cardiovascular diseases, also known as circulatory diseases, are diseases of the heart and blood vessels, and its etiology is hyperlipidemia, thick blood, atherosclerosis, and hypertension. Due to its high prevalence, disability, and mortality, it seriously threatens human health. According to reports, the incidence of cardiovascular disease is still on the rise. Rhodiola rosea is a kind of traditional Chinese medicine, which has the effects of antimyocardial ischemia-reperfusion injury, lowering blood fat, antithrombosis, and antiarrhythmia. Rhodiola rosea has various chemical components, and different chemical elements have the same pharmacological effects and medicinal values for various cardiovascular diseases. This article reviews the research on the pharmacological effects of Rhodiola rosea on cardiovascular diseases and provides references for the clinical treatment of cardiovascular diseases.

Cyclo (Phe-Phe) ameliorated hepatic injury and dysplasia induced by oxidative stress, and the mechanism is mainly via promoting Nrf2 translocation as well as activating the Nrf2 pathway through binding Keap1.

Two anaerobic membrane bioreactors (AnMBRs) equipped with different membrane pore size (0.4 or 0.05 µm) were operated at 25˚C and fed with domestic wastewater. The hydraulic retention time (HRT) of the reactors was shortened. The microbial communities of the two AnMBRs were investigated by 16S rRNA gene amplicon sequencing to see the effects of HRT. The predominant Archaea was an aceticlastic methanogen Methanosaeta. The composition of hydrogenotrophic methanogens changed with the HRTs: the population of Methanobacterium was higher for longer HRTs, whereas the population of unclassified Methanoregulaceae was higher for shorter HRTs. The Anaerolineae, Bacteroidia and Clostridia bacteria were dominant in both of the reactors, with a combined relative abundance of over 55%. The relative abundance of Anaerolineae was proportional to the biogas production performance. The change in the population of hydrogenotrophic methanogens or Anaerolineae can be used as an indicator for process monitoring. The sum of the relative abundance of Anaerolineae and Clostridia fluctuated slightly with changes in the HRT in both AnMBRs when the reactor was stably operated. The co-occurrence analysis revealed the relative abundance of the operational taxonomic units belonging to Anaerolineae and Clostridia was functionally equivalent during the treatment of real domestic sewage. A principal coordination analysis revealed that the changes in the microbial community in each reactor were consistent with the change of HRT. In addition, both the HRT and the stability of the process are important factors for maintaining microbial community structures.

ObjectivesTo evaluate COVID-19 vaccines in primary prevention against infections and lessen the severity of illness following the most recent outbreak of the SARS-CoV-2 Omicron variant in Shanghai.Data sourcesData from 153,544 COVID-19 patients admitted to the Shanghai “Four-Leaf Clover” Fangcang makeshift shelter hospital were collected using a structured electronic questionnaire, which was then merged with electronic medical records of the hospital. For healthy controls, data on vaccination status and other information were obtained from 228 community-based residents, using the same structured electronic questionnaire.MethodsTo investigate whether inactivated vaccines were effective in protecting against SARS-CoV-2 virus, we estimated the odds ratio (OR) of the vaccination by comparing cases and matched community-based healthy controls. To evaluate the potential benefits of vaccination in lowering the risk of symptomatic infection (vs. asymptomatic), we estimated the relative risk (RR) of symptomatic infections among diagnosed patients. We also applied multivariate stepwise logistic regression analyses to measure the risk of disease severity (symptomatic vs. asymptomatic and moderate/severe vs. mild) in the COVID-19 patient cohort with vaccination status as an independent variable while controlling for potential confounding factors.ResultsOf the 153,544 COVID-19 patients included in the analysis, the mean age was 41.59 years and 90,830 were males (59.2%). Of the study cohort, 118,124 patients had been vaccinated (76.9%) and 143,225 were asymptomatic patients (93.3%). Of the 10,319 symptomatic patients, 10,031 (97.2%), 281 (2.7%), and 7 (0.1%) experienced mild, moderate, and severe infections, respectively. Hypertension (8.7%) and diabetes (3.0%) accounted for the majority of comorbidities. There is no evidence that the vaccination helped protect from infections (OR = 0.82, p = 0.613). Vaccination, however, offered a small but significant protection against symptomatic infections (RR = 0.92, p ConclusionInactivated COVID-19 vaccines helped provide small but significant protection against symptomatic infections and halved the risk of moderate/severe illness among symptomatic patients. The vaccination was not effective in blocking the SARS-CoV-2 Omicron Variant community spread.

Objective The molecular mechanism that triggers polycystic ovary syndrome (PCOS) is mysterious. Abnormal development of ovarian granulosa cells(GCs) is one of the causes of PCOSMethods The study was carried out by using RNA-seq to detect the different gene expression levels in ovarian GCs between 3 patients with PCOS and 4 normal controls. To further verify the above results, GCs from 22 patients with PCOS and 21 controls with normal ovulation were collected to perform the RT-PCR analysisResults The results found Hedgehog signaling pathway(Hh) members, Ihh and Ptch2 were abnormally highly expressed in the PT. The qPCR results also indicated that the expression levels of other Hh signaling pathway downstream members, Ptch1, Gli1, and Gli2 in the PCOS group (PT) were significantly higher than those in the control group (NT). Besides, the expression of TNF-α mRNA in PCOS patients was higher than that in the control group. Finally, the Hh signaling pathway inhibitor, cyclopamine, can decrease the apoptosis of PCOS ovarian granulosa cellsConclusions These results suggest that abnormally activated Hh signaling pathway, especially Ihh signal, may have a profound influence on PCOS.

ImportanceThere are no approved treatments for nonalcoholic fatty liver disease (NAFLD) despite its association with obesity and increased risk of cardiovascular disease (CVD).ObjectiveTo examine the association between bariatric surgery and CVD risk in individuals with severe obesity and NAFLD.Design, Setting, and ParticipantsThis large, population-based retrospective cohort study obtained data from the MarketScan Commercial Claims and Encounters database from January 1, 2007, to December 31, 2017. Participants included insured adults aged 18 to 64 years with NAFLD and severe obesity (body mass index ≥40) without a history of bariatric surgery or CVD before NAFLD diagnosis. Baseline characteristics were balanced between individuals who underwent surgery (surgical group) and those who did not (nonsurgical group) using inverse probability of treatment weighting. Data were analyzed from March 2020 to April 2021.ExposuresBariatric surgery (Roux-en-Y gastric bypass, sleeve gastrectomy, and other bariatric procedures) vs nonsurgical care.Main Outcomes and MeasuresThe main outcome was the incidence of cardiovascular events (primary or secondary composite CVD outcomes). The primary composite outcome included myocardial infarction, heart failure, or ischemic stroke, and the secondary composite outcome included secondary ischemic heart events, transient ischemic attack, secondary cerebrovascular events, arterial embolism and thrombosis, or atherosclerosis. Cox proportional hazards regression models with inverse probability treatment weighting were used to examine the associations between bariatric surgery, modeled as time varying, and all outcomes.ResultsThe study included 86 964 adults (mean [SD] age, 44.3 [10.9] years; 59 773 women [68.7%]). Of these individuals, 30 300 (34.8%) underwent bariatric surgery and 56 664 (65.2%) received nonsurgical care. All baseline covariates were balanced after applying inverse probability treatment weighting. In the surgical group, 1568 individuals experienced incident cardiovascular events compared with 7215 individuals in the nonsurgical group (incidence rate difference, 4.8 [95% CI, 4.5-5.0] per 100 person-years). At the end of the study, bariatric surgery was associated with a 49% lower risk of CVD (adjusted hazard ratio [aHR], 0.51; 95% CI, 0.48-0.54) compared with nonsurgical care. The risk of primary composite CVD outcomes was reduced by 47% (aHR, 0.53 [95% CI, 0.48-0.59), and the risk of secondary composite CVD outcomes decreased by 50% (aHR, 0.50; 95% CI, 0.46-0.53) in individuals with vs without surgery.Conclusions and RelevanceResults of this study suggest that, compared with nonsurgical care, bariatric surgery was associated with significant reduction in CVD risk in individuals with severe obesity and NAFLD.

Five hydroxamate siderophores, chaetomadramines A-E (1-5), along with seven known compounds were isolated from the fermented rice culture of the fungus Chaetomium madrasense cib-1. Compounds 1-5 were structurally elucidated on the basis of spectroscopic data, which were a group of unusual hydroxamate siderophores, bearing a long fatty acyl on the α-NH

A novel two-stage process comprising pre-denitrification and single-stage partial nitritation/anammox was developed to treat swine manure digestate with a constant nitrogen loading rate of 1.0 gN/L/d. As the influent NH

Acute kidney injury (AKI) in cirrhosis, including hepatorenal syndrome (HRS), is a common and serious complication in cirrhotic patients, leading to significant morbidity and mortality. AKI is separated into two categories, non-HRS AKI and HRS-AKI. The most recent definition and diagnostic criteria of AKI in cirrhosis and HRS have helped diagnose and prognosticate the disease. The pathophysiology behind non-HRS-AKI and HRS is more complicated than once theorized and involves more processes than just splanchnic vasodilation. The common biomarkers clinicians use to assess kidney injury have significant limitations in cirrhosis patients; novel biomarkers being studied have shown promise but require further studies in clinical settings and animal models. The overall management of non-HRS AKI and HRS-AKI requires a systematic approach. Although pharmacological treatments have shown mortality benefit, the ideal HRS treatment option is liver transplantation with or without simultaneous kidney transplantation. Further research is required to optimize pharmacologic and nonpharmacologic approaches to treatment. This article reviews the current guidelines and recommendations of AKI in cirrhosis.

The anaerobic ammonia oxidation (anammox) process is a promising biological nitrogen removal technology. However, owing to the sensitivity and slow cell growth of anammox bacteria, long startup time and initially low nitrogen removal rate (NRR) are still limiting factors of practical applications of anammox process. Moreover, nitrogen removal efficiency (NRE) is often lower than 88 %. This review summarizes the most common methods for improving NRR by increasing microorganism concentration, and modifying reactor configuration. Recent integrated anammox-based systems were evaluated, including hydroxyapatite (HAP)-enhanced one-stage partial nitritation/anammox (PNA) process for a high NRR of over 2 kg N/m

For the deep reduction of nitrogen, the microbial fuel cell-constructed wetland (MFC-CW) was conducted for treating carbon constraint wastewater. Results indicated that nitrogen removal decreased from 94.96% to 24.96% with influent COD/TN (chemical oxygen demand/total nitrogen) from 4 to 0. MFC-CW was seriously affected by low organic wastewater. Wetland plants contributed to denitrification, with TN removal increasing from 46.13% to 64.87%. The bioenergy output showed a linear relationship with influent COD, and the maximum power density of 1.17 mW/m

The aging-induced decrease in intestinal barrier function contributes to many age-related diseases. Studies on preventive measures for "leaky gut" may help improve the quality of life of geriatric patients. The potent anti-aging effect of Gastrodia elata and parishin, which is one of its active ingredients, has been reported previously. However, their effects on the gut remain elusive, and the effect of parishin on mammals has not been studied.We used quantitative RT-PCR, western blotting, immunohistochemical analysis, and 16S rRNA sequencing to investigate the effect of G. elata and parishin on the intestinal barrier function of D-Gal-induced aging mice.G. elata and parishin prevented the decrease in tight junction protein (TJP) expression and morphological changes, modulated the composition of fecal microbiota to a healthier state, and reversed the translocation of microbial toxins and systemic inflammation. The correlation analyses showed that TJP expression and systemic inflammation were significantly positively or negatively correlated with the composition of fecal microbiota after G. elata and parishin administration. Additionally, TJP expression was also correlated with systemic inflammation. Moreover, G. elata and parishin administration reversed the decreased or increased expression of aging-related biomarkers, such as FOXO3a, SIRT1, CASPASE3 and P21, in the gut.These results suggested that G. elata and parishin could prevent gut aging and ameliorate the "leaky gut" of aged mice and that the underlying mechanism is related to the mutual correlations among barrier function, fecal microbiota composition, and inflammation.

Ischemic stroke is a very dangerous disease with high incidence, fatality and disability rate in human beings. Massive evidence has indicated that oxidative stress and inflammation are intimately correlated with progression of ischemic stroke. Additionally, LncRNAs were reported to be involved in ischemic stroke. Here, we aim to explore the effects and molecular mechanism of lncRNA OIP5-AS1 on oxidative stress and inflammation in ischemic stroke.HMC3 and SH-SY5Y cells were under the condition of oxygen-glucose deprivation/reoxygenation (OGD/R) treatment to establish cell models of ischemic stroke. Commercial kits were employed to detect the indicators of oxidative stress including ROS, MDA and SOD. The expression of OIP5-AS1, miR-155-5p and IRF2BP2 mRNA was determined using RT-qPCR. The protein levels of inflammatory factors including TNF-α, IL-1β and IL-6 and IRF2BP2 were assessed by western blot and/or ELISA. Luciferase activity assay was employed to validate their correlations among OIP5-AS1, miR-155-5p and IRF2BP2.In OGD/R-induced HMC3 and SH-SY5Y cells, the expression of OIP5-AS1 and IRF2BP2 was reduced while miR-155-5p was elevated. OGD/R induction promoted oxidative stress and inflammatory response in HMC3 and SH-SY5Y cells, while OIP5-AS1 or IRF2BP2 sufficiency as well as miR-155-5p inhibitor attenuated OGD/R-induced these influences. In addition, IRF2BP2 knockdown abolished the suppressive impacts of OIP5-AS1 overexpression on oxidative stress and inflammatory response in OGD/R-induced HMC3 and SH-SY5Y cells. Mechanistically, OIP5-AS1 enhanced IRF2BP2 expression via sponging miR-155-5p.OIP5-AS1 suppressed oxidative stress and inflammatory response to alleviate cell injury caused by OGD/R induction in HMC3 and SH-SY5Y cells through regulating miR-155-5p/IRF2BP2 axis, which might offer novel targeted molecules for ischemic stroke therapy.

The practical application of anaerobic ammonium oxidation (anammox) technology was seriously limited by lack of anammox seeding sludge. In this work, a pilot-scale expanded granular sludge bed (EGSB) reactor was used for rapid proliferation of anaerobic ammonium oxidizing bacteria (AnAOB) using anammox-hydroxyapatite (anammox-HAP) technology. The excellent settleability of anammox-HAP granular sludge (with an excellent settling velocity of 395 m/h) supported the up-flow velocity of 9.6 m/h with recirculation ratio of 19. A high nitrogen loading rate (NLR) of 26.4 g N/L/d was achieved in the pilot-scale reactor, with a cell yield of 0.23 g VSS/g NH

Alzheimer's disease (AD) is an insidious and progressive neurodegenerative disease with few disease-modifying treatments. A variety of peptide/protein drugs have neuroprotective effects, which brings new hope for the treatment of AD. However, the application of these drugs is limited because of their low specificity and difficulty in crossing the blood-brain barrier. Herein, using the phage display technology, we identified the Aβ oligomer binding peptide (KH) and the brain targeting peptide (IS). We combined these peptides to develop a bifunctional nanoparticle (IS@NP/KH) for the delivery of Aβ1-42 oligomer binding peptide into the brain. Intranasal administration of IS@NP/KH significantly attenuated the cognitive and behavioral deficits and reduced the Aβ deposition in the brain of an AD animal model (APPswe/PS 1d9 double-transgenic mice). Our results suggest that intranasal IS@NP/KH administration could be a novel therapeutic strategy for the treatment of AD.

BACKGROUND Ips is a bark beetle genus of 45 species, many of which are pests of conifer forests and plantations under stress. Twelve Ips species are recorded from China and presumably native there. From 2016 to 2018, specimens suspected to be Ips calligraphus and Ips grandicollis, were collected from traps with ethanol as a sole lure in Zhuhai, Guangdong, China. Both species originate in North America and infest various species of native or introduced pines. Since Ips species are known to cause or exacerbate problems in pine plantations, and a regional survey using traps baited with attractants were implemented in this study to investigate the extent of the introduction. RESULTS Both I. calligraphus and I. grandicollis have been collected repeatedly from several traps with Ips attractants in Zhuhai, Guangdong, China since 2016. Potential distributions of these two species in Asia, inferred using MaxEnt, is extensive, given the high projected environmental suitability in North America, South America, Mediterranean Europe, Northern Africa, and Eastern Asia. The host plant of I. calligraphus from Zhuhai was identified as slash pine Pinus elliottii using DNA barcoding of gut contents from trapped individuals. CONCLUSION This is the first report of the establishment of two American pine bark beetles, I. calligraphus and I. grandicollis in continental Asia. The gut content of both species suggests that these pest feeds on a non-native host. Whether the two species present high-risk to Asian forests will become clear with more research on their interactions with native pines.

BACKGROUND Pure natural orifice transluminal endoscopic surgery (NOTES) for colorectal cancer is a complex procedure and rarely used in clinical practice because of the ethical concerns and technical challenges, including loss of triangulation, in-line orientation, and instrument collision. Transvaginal (v) NOTES, however, can overcome these technical challenges. We report a case of pure vNOTES right hemicolectomy for colon cancer, attached with surgical video. CASE SUMMARY A 65-year-old woman with a 2-year history of intermittent diarrhea was diagnosed with ascending colon adenocarcinoma by colonoscopy and biopsy. Pure vNOTES right hemicolectomy was performed with complete mesocolic excision by well-experienced surgeons. The operative time was 200 min and the estimated blood loss was 30 mL. No intraoperative or postoperative complications occurred within 30 d after the surgery. The visual analog scale pain score on postoperative day 1 was 1 and dropped to 0 on postoperative days 2 and 3. The patient was discharged at postoperative day 6. The pathologic specimen had sufficient clear resection margins and 14 negative harvested lymph nodes. CONCLUSION vNOTES right hemicolectomy, performed by well-experienced surgeons, overcomes the technical challenges of pure NOTES and may be feasible for colon cancer.

Time perception has been known to depend on the temporal frequency of the stimulus. Previously, the effect of temporal frequency modulation was assumed to be monotonically lengthening or shortening. However, this study shows that temporal frequency affects time perception in a non-monotonic and modality-dependent manner. Four experiments investigated the time distortion effects induced by modulation of temporal frequency across auditory and visual modalities. Critically, the temporal frequency was parametrically manipulated across four levels (steady stimulus, 10-Hz, 20-Hz, and 30/40-Hz intermittent auditory/visual stimulus). Experiment 1, 2, and 3 consistently showed that a 10-Hz auditory stimulus was perceived as shorter than a steady auditory stimulus. Meanwhile, as the temporal frequency increased, the perceived duration of the intermittent auditory stimulus was lengthened. A 40-Hz auditory stimulus was perceived as longer than a 10-Hz auditory stimulus, but did not differ significantly from a steady one. Experiment 4 showed that, for the visual modality, a 10-Hz visual stimulus was perceived as longer than a steady stimulus, and the perceived duration was lengthened as temporal frequency increased. The present study demonstrated that, within the scope of the temporal frequencies examined in this study, there were differential distortion effects observed across sensory modalities.

Autoimmune hepatitis (AIH) is characterized by interface hepatitis, elevated serum alanine aminotransferase and aspartate aminotransferase levels, circulating autoantibodies, and elevated predominantly immunoglobulin G (IgG) levels. The goal in the treatment of autoimmune hepatitis (AIH) is complete disease remission. Here we took advantage of a large cohort of AIH patients to clarify predictors associated with biochemical and histological remission. Of 705 patients with complete follow-up, 569 (80.7%) patients achieved complete biochemical remission. Lower IgG levels (17.8 vs. 25 g/L, p

It is difficult for drug delivery systems to release drugs as expected, often leading to undesired side effects. To solve this problem, a CuS@MSN/DOX@MnO2@membrane (CMDMm) was reasonably designed. It was introduced to release the drug by a double response, similar to using two keys to open two locks at the same time for one door. CuS@MSN was used as a photothermal therapy (PTT) material and carrier, and then the surface of CuS@MSN/DOX was sealed by MnO2 to prevent drug release in advance. MnO2 could be reduced and degraded in a tumor microenvironment. It was applied in MR imaging due to the T1 magnetism of Mn2+ following the reduction of MnO2. Finally, the 4T1 cell membrane was extracted and coated onto the surface of CuS@MSN/DOX@MnO2, which served as a target for 4T1 tumor cells. A noteworthy phenomenon was that the fluorescence of DOX was quenched by the coordination between DOX and CuS, and this greatly improved the interaction between DOX and CuS@MSN. However, the coordination was weakened when DOX was protonated in a tumor microenvironment (∼pH 5.0), leading to the release of DOX and fluorescence recovery. The drug release experiments showed that the release efficiency was higher at pH 5.0 with 10 mmol L-1 GSH. Through in vitro laser confocal imaging, it was successfully observed that DOX was reliably released in specific tumor cells according to the fluorescence recovery, and that there was no leakage in other cells. In short, effective double response drug release was successfully confirmed.

Background: Tauopathies refer to a group of neurodegenerative disorders caused by the accumulation of insoluble hyperphosphorylated Tau protein in the brain. Previous work has shown that hexapeptide 306VQIVYK311 (PHF6) located in the repeat domain 3 of Tau protein drives Tau aggregation and itself forms a β-sheet structure similar to that of Tau oligomers and neurofibrillary tangles (NFTs). The inhibition and interruption of PHF6 and Tau aggregation are considered important strategies to ameliorate the neurodegenerative process. Methods: A mirror image phage display technology was used to target PHF6 fibrils to screen protease-resistant and low-immunogenic D-enantiomeric peptides. The effect of peptide on PHF6 aggregation was evaluated by ThT fluorescence assay and TEM. The therapeutic potential of peptide was verified by western blot and immunostaining in vivo and in vitro. Findings: Seven sets of peptides were obtained by repeated phage biopanning and a highly specific peptide p-NH with the sequence N-I-T-M-N-S-R-R-R-R-N-H was selected. p-NH interacted with PHF6 fibrils mainly through van der Waals forces and hydrogen bonding, and could inhibit PHF6 aggregation in a D configuration and concentration-dependent manner. In vitro, p-NH was able to enter into mouse neuroblastoma cells (N2a cells) to inhibit Tau hyperphosphorylation and aggregation. Intranasal administration of p-NH reduced NFTs and improved the cognitive ability of TauP301S transgenic mice. Interpretation: Our data suggest that p-NH significantly improved the cognitive ability of TauP301S transgenic mice by inhibiting Tau hyperphosphorylation and aggregation. These findings represent a straightforward methodology to find therapeutic peptides with potential applications in tauopathies. Funding Statement: This study was financially supported by the Natural Science Foundation of China (81771174, 81301102, 81600941, 81971015 and 31970967), the Basic Scientific Research Fund of Northeastern University, China (N2020002), the 111 Project (B16009), and the Fundamental Research Funds for the Central Universities of China (N2020004). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: All animal procedures were conducted in accordance with the Guidelines for Care and Use of Laboratory Animals of Northeastern University and approved by the Animal Ethics Committee of College of Life and Health Sciences of Northeastern University

By using the prominent merit of poly(N-isopropylacrylamide) (PNIPAm) that can reversibly switch from a linear state to a coiled state with the change in temperature, in this work, gelatin was grafted with carboxylic end-capped PNIPAm as the matrix material to fabricate a physical entanglement crosslinked hydrogel microneedles (MNs) patch that can control drug release after application on the skin. The crystallization of the drug during the fabrication process of MNs was decreased due to the thermo-reversible sol-gel transition of the matrix materials. In addition, to increase the mechanical strength of the MNs and to decrease the application time, the gelatin-g-PNIPAm (GP) MNs patch was mounted onto solid MNs to fabricate a rapidly separating MNs system (RS-GP-MNs). The combination of the rapidly separating technique and the thermosensitive hydrogel provides the combined ability to efficiently deliver drug-loaded MNs into the skin within few seconds and to control drug release within the skin. Through a series of tests, we found that RS-GP-MNs showed suitable lower critical solution temperature and adequate crosslinking speed for practical application. The hypoglycemic effect in diabetic mice was characteristically controlled by insulin release through RS-GP-MNs as compared to the MNs made from unmodified gelatin. The proposed RS-GP-MNs system is potentially applicable to various hydrophilic small molecular and peptide medicines that require frequent dosing, thus providing an effective, noninvasive, and painless administration method with minimal safety concerns. STATEMENT OF SIGNIFICANCE: 1. Hydrogel microneedles that can be reversibly triggered and controllably release drugs at body temperature were fabricated. 2. Hydrogel microneedles prepared from gelatin-g-PNIPAm can avoid the use of a molecular crosslinker that is toxic and difficult to be completely removed. 3. Gelatin-g-PNIPAm with thermosensitive property showed appropriate molecular interactions with the drug and slowed down the crystallization speed of the drug in the solution.

Dairy product wastewater contains high-strength organic matter suitable for anaerobic treatment, but excessive protein degradation may lead to an ammonia inhibition problem. This work studied protein-rich dairy product wastewater treatment in the anaerobic membrane bioreactor. The results showed that a temporary self-detoxification phase of ammonia inhibition from the change of pH buffer system was vital for rapid reactor recovery by substrate dilution. The ammonia washout from the reactor was simulated by a kinetic model. After ammonia inhibition, the relative abundance of syntrophic lactic and propionic acids oxidising bacteria significantly reduced along with fermentative bacteria involved in mixed organic acids production. Nevertheless, the relative abundance of the protein degradation bacteria producing acetic acid and H

Dismantling and recycling e-waste has been recognized as a potential emission source of rare earth elements (REEs). However, the presence of REEs in typical regional soils has yet to be studied. Given the potential health implications of such soil contamination, it is vital to study the characteristics, spatial distribution, and pollution level of REEs caused by e-waste dismantling as well as determine the influencing mechanism. This study focused on Guiyu Town as an example site, which is a typical e-waste dismantling base. From the site, 39 topsoil samples of different types were collected according to grid distribution points. Soil profiles were also collected in the dismantling and non-dismantling areas. The REE characteristic parameters showed that the REE distribution was abnormal and was affected by multiple factors. The results of the integrated pollution index showed that approximately 61.5% of soil samples were considered to be lightly polluted. Spatial distribution and correlation analysis showed that hot spots of REE-polluted soil coincided with known, main pollution sources. Moreover, there was a significant negative correlation (p ≤0.05) between the REE concentration and the distance from the pollution source. E-waste disassembly and recycling greatly affect the physical and chemical properties of the surrounding soil as well as downward migration areas. In the disassembly area, REE accumulated more easily in the surface layer (0-20 cm). Geographical detector results showed that distance factor was the main contribution factor for both light rare earth elements (LREE) and heavy rare earth element (HREE) (q = 34.59% and 53.33%, respectively). REE distribution in soil was nonlinear enhanced by different factors. Taken together, these results showed that e-waste disassembling and recycling not only directly affected the spatial distribution of REEs, but that their distribution was also affected by land use type and soil properties.

ObjectivesThis study explored the prevalence of and individual influencing factors for metabolic syndrome (MS) as well as associated socioeconomic factors and regional aggregation.DesignFour cross-sectional surveys were analysed for trends in MS and associations with socioeconomic and individual factors through multilevel logistic regression analyses. The risk associated with nutrient intake was also assessed through a dietary survey in 2015.SettingFrom 2010 to 2018, 8–15 counties/districts of West China were included.ParticipantsA total of 28 274 adults were included in the prevalence analysis. A total of 23 708 adults were used to analyse the related factors.ResultsThe overall prevalence of MS ranged from 21.4% to 27.8% over the 8 years, remaining basically stable within the 95% CI. Our study found that the urbanisation rate and hospital beds per 1000 people were positively associated with MS, and the number of doctors in healthcare institutions per 1000 persons was negatively associated with MS. The ORs for females, people with college education and higher and unmarried or single people were 1.49, 0.67 and 0.51, respectively (pConclusionThe high burden of MS, unreasonable proportions of energy and micronutrient intake and low percentage of high levels of physical activity were the major challenges to public health in western China. Improving the human resources component of medical services, such as the number of doctors, increasing the availability of public sports facilities and E-health tools and improving individual dietary quality and education might help prevent MS.

Background Human metapneumovirus is a common virus associated with acute lower respiratory infections (ALRIs) in children. No global burden estimates are available for ALRIs associated with human metapneumovirus in children, and no licensed vaccines or drugs exist for human metapneumovirus infections. We aimed to estimate the age-stratified human metapneumovirus-associated ALRI global incidence, hospital admissions, and mortality burden in children younger than 5 years. Methods We estimated the global burden of human metapneumovirus-associated ALRIs in children younger than 5 years from a systematic review of 119 studies published between Jan 1, 2001, and Dec 31, 2019, and a further 40 high quality unpublished studies. We assessed risk of bias using a modified Newcastle-Ottawa Scale. We estimated incidence, hospital admission rates, and in-hospital case-fatality ratios (hCFRs) of human metapneumovirus-associated ALRI using a generalised linear mixed model. We applied incidence and hospital admission rates of human metapneumovirus–associated ALRI to population estimates to yield the morbidity burden estimates by age bands and World Bank income levels. We also estimated human metapneumovirus-associated ALRI in-hospital deaths and overall human metapneumovirus-associated ALRI deaths (both in-hospital and non-hospital deaths). Additionally, we estimated human metapneumovirus-attributable ALRI cases, hospital admissions, and deaths by combining human metapneumovirus-associated burden estimates and attributable fractions of human metapneumovirus in laboratory-confirmed human metapneumovirus cases and deaths. Findings In 2018, among children younger than 5 years globally, there were an estimated 14·2 million human metapneumovirus-associated ALRI cases (uncertainty range [UR] 10·2 million to 20·1 million), 643 000 human metapneumovirus-associated hospital admissions (UR 425 000 to 977 000), 7700 human metapneumovirus-associated in-hospital deaths (2600 to 48 800), and 16 100 overall (hospital and community) human metapneumovirus-associated ALRI deaths (5700 to 88 000). An estimated 11·1 million ALRI cases (UR 8·0 million to 15·7 million), 502 000 ALRI hospital admissions (UR 332 000 to 762 000), and 11 300 ALRI deaths (4000 to 61 600) could be causally attributed to human metapneumovirus in 2018. Around 58% of the hospital admissions were in infants under 12 months, and 64% of in-hospital deaths occurred in infants younger than 6 months, of which 79% occurred in low-income and lower-middle-income countries. Interpretation Infants younger than 1 year have disproportionately high risks of severe human metapneumovirus infections across all World Bank income regions and all child mortality settings, similar to respiratory syncytial virus and influenza virus. Infants younger than 6 months in low-income and lower-middle-income countries are at greater risk of death from human metapneumovirus-associated ALRI than older children and those in upper-middle-income and high-income countries. Our mortality estimates demonstrate the importance of intervention strategies for infants across all settings, and warrant continued efforts to improve the outcome of human metapneumovirus-associated ALRI among young infants in low-income and lower-middle-income countries. Funding Bill & Melinda Gates Foundation.

In this work, magnetic Fe2O3/Fe3O4 nanocomposites were prepared via a novel rapid combustion process. The silica was precipitated on the surface of Fe2O3/Fe3O4 nanocomposites. The silica-coated magnetic nanocomposites were cross-linked with glutaraldehyde, on which cellulase was covalently immobilized. The morphology, composition, and property of the prepared nanomaterials were characterized by the scanning electron microscopy (SEM), the energy dispersive spectrometry (EDS), the X-ray diffraction (XRD), the vibrating sample magnetometer (VSM), and the Fourier transform infrared (FTIR) spectroscopy. The immobilization conditions were optimized by varying operating parameters and determined to be 0.05 mL of 0.5% cellulase solution for 2 h. The catalytic stabilities of the immobilized cellulase were evaluated. The results showed that the immobilized cellulases performed higher apparent activity at pH 4.5 and exhibited good thermal stability compared with their free counterparts. The Michaelis-Menten equation showed that Km and Vmax of free cellulase were 3.46 mol·L−1 and 0.53 mol·min−1, respectively. The immobilized cellulase had higher Km and Vmax (18.99 mol·L−1 and 0.59 mol·min−1). The retained activity of the immobilized cellulase maintained over 71% of the initial activity after being used for five cycles.

In this work, magnetic Fe2O3/Fe3O4 heterostructure nanoparticles were prepared via a novel solution combustion and gel calcination process. The glutaraldehyde was cross-linked on Fe2O3/Fe3O4 heterostructure nanoparticles decorated silica. The prepared samples were characterized by TEM, EDS, XRD, VSM, SEM, XPS, TGA/DSC, BET measurement, Raman spectroscopy, Zeta potential, HR-TEM and FT-IR. The penicillin G acylase (PGA) was covalently immobilized on magnetic Fe2O3/Fe3O4@SiO2-CHO nanocomposites via the Schiff's reaction. Variations in the observed activities as a function of immobilization time and PGA concentration have been discussed, when immobilization time and concentration of PGA were 18 h and 0.2 mg·mL−1, the activity of immobilized PGA presented optimal values of 77.8 U·L−1 and 66.2 U·L−1. The effects of pH and temperature on enzyme activity were also evaluated, the activity of PGA at the temperature of 45 °C with buffer pH of 8 arrived at the highest lever. After 12 cycles of repetitive uses, the immobilized PGA still retained around 67% of initial activity. The research results indicated that PGA immobilized on magnetic Fe2O3/Fe3O4@SiO2-CHO nanocomposites showed excellent thermal stability, pH stability, and reusability compared with free enzyme.

This research paper was to investigate the influence of soybean peptides addition on viable count of lactic acid bacteria, physicochemical parameters, flavor, and sensory evaluation of yoghurt. The number of fermenting strains (Streptococcus thermophilus + Lactobacillus delbrueckii subsp. bulgaricus) cells in yoghurt (stored at 4 °C for 19 days) added with 0.2% (w/v) of soybean peptides (808.34 Da) reached 1.4 times higher bacterial number than in the control group. A total of 34 volatile substances were detected in this study, while there were 22 volatiles occurred in the control group yoghurt, 30 volatiles were detected in yoghurt added with 0.2% soybean peptides. There was no significant difference in sensory evaluation (p > 0.05) between the yoghurt with and without soybean peptides. In our study, the addition of soybean peptides (0.2%) can be effective both in maintaining the viable bacterial count and yoghurt quality.

Background: Nowadays, antidepressants still are the mainstay of treatment for depression in Parkinson's disease (PD) but some recent studies report that medication might aggravate motor symptoms in PD patients. This meta-analysis aims to assess the effect of non-pharmacological treatments for depression in patients with PD.Materials and Methods: Only randomized controlled trials (RCTs) were included. The participants were PD patients with comorbid depression (dPD). The interventions had the equivalent effect of non-pharmacological treatments alone compared with control(s). Scores of depression scale were selected as the primary outcome, while scores of Unified Parkinson's Disease Rating Scale part III and the incidence of side effects were the secondary outcome. The statistics were pooled and presented as weighted mean differences (WMDs), standardized mean differences (SMDs), or risk ratios (RRs) with their 95% confidence intervals (CIs).Results: Fifteen articles were eventually included; twelve studies reported on repetitive transcranial magnetic stimulation (rTMS) and three used cognitive behavioral therapy (CBT). Other interventions failed to have qualified studies. Our data indicated that both rTMS and CBT could significantly improve depression scores in a short term (SMD = -0.621, 95% CI [-0.964, -0.278]; SMD = -1.148, 95% CI [-1.498, -0.798], respectively). In addition, rTMS could alleviate motor symptom (WMD = -2.617, 95% CI [-4.183, -1.051]) and was relatively safe (RR = 1.054, 95% CI [0.698, 1.592]).Conclusion: Our data suggest that rTMS can safely alleviate depression and motor symptoms in dPD at least for a short period. Moreover, compared with clinical monitoring, CBT can improve depressive symptoms.

There is increasing evidence suggesting that dysregulation of miR-155 and its target angiotensin receptor type 1 (AT1R) are linked to the incidence of ischemic stroke (IS), but the underlying mechanisms remain to be clarified. In this study, we therefore sought to investigate how miR-155 and AT1R polymorphisms affect IS risk. We included 579 IS patients and 509 age-matched controls in the present analysis, genotyping individuals for the rs767649 polymorphism in miR-155, as well as for the rs1492099 and rs275653 polymorphisms in AT1R via iMLDR-TM genotyping technology. The allele and genotype frequencies for the assessed polymorphisms were comparable in IS patients and controls, without any detectable association between AT1R haplotype and IS risk. We conducted additional trial of ORG 10172 in acute stroke treatment-mediated stratification, which indicated that the AT1R rs1492099 T allele was linked to a decreased risk of large-artery atherosclerosis (LAA) stroke. We further found that those with the AT1R rs275653 AA genotype had a decreased risk of small-artery occlusion (SAO) strokes. We further confirmed elevated miR-155 expression in IS patients, but observed no link between the rs767649 polymorphism and expression of this microRNA. Similarly, rs1492099 and rs275653 polymorphisms did not impact AT1R expression levels. The miR-155 rs767649 polymorphism does not seem to be a key determinant of IS risk, whereas the AT1R rs1492099 polymorphism is linked to reduced LAA-stroke risk, and the rs275653 AA genotype is potentially protective against SAO strokes.