Transcription Factor Forkhead Box O1 Mediates Transforming Growth Factor-ß1-Induced Apoptosis in Hepatocytes.

Dysregulation of hepatocyte apoptosis is associated with several types of chronic liver diseases. Transforming growth factor-ß1 (TGF-ß1) is a well-known pro-apoptotic factor in the liver, which constitutes a receptor complex composed of TGF-ß receptor I and II, along with transcription factor Smad proteins. As a member of the forkhead box O (Foxo) class of transcription factors, Foxo1 is a predominant regulator of hepatic glucose production and apoptosis. This study investigated the potential relationship between TGF-ß1 signaling and Foxo1 in control of apoptosis in hepatocytes. TGF-ß1 induced hepatocyte apoptosis in a Foxo1-dependent manner in hepatocytes isolated from both wild-type and liver-specific Foxo1 knockout mice. TGF-ß1 activated protein kinase A through TGF-ß receptor I-Smad3, followed by phosphorylation of Foxo1 at Ser273 in promotion of apoptosis in hepatocytes. Moreover, Smad3 overexpression in the liver of mice promoted the levels of phosphorylated Foxo1-S273, total Foxo1, and a Foxo1-target pro-apoptotic gene Bim, which eventually resulted in hepatocyte apoptosis. The study further demonstrated a crucial role of Foxo1-S273 phosphorylation in the pro-apoptotic effect of TGF-ß1 by using hepatocytes isolated from Foxo1-S273A/A knock-in mice, in which the phosphorylation of Foxo1-S273 was disrupted. Taken together, this study established a novel role of TGF-ß1→protein kinase A→Foxo1 signaling cascades in control of hepatocyte survival.

Hepatic p38α MAPK controls gluconeogenesis via FOXO1 phosphorylation at S273 during glucagon signalling in mice.

AIMS/HYPOTHESIS: Hyperglucagonaemia-stimulated hepatic glucose production (HGP) contributes to hyperglycaemia during type 2 diabetes. A better understanding of glucagon action is important to enable efficient therapies to be developed for the treatment of diabetes. Here, we aimed to investigate the role of p38 MAPK family members in glucagon-induced HGP and determine the underlying mechanisms by which p38 MAPK regulates glucagon action. METHODS: p38α, ß, γ and δ MAPK siRNAs were transfected into primary hepatocytes, followed by measurement of glucagon-induced HGP. Adeno-associated virus serotype 8 carrying p38α MAPK short hairpin RNA (shRNA) was injected into liver-specific Foxo1 knockout, liver-specific Irs1/Irs2 double knockout and Foxo1S273D knockin mice. Foxo1S273A knockin mice were fed a high-fat diet for 10 weeks. Pyruvate tolerance tests, glucose tolerance tests, glucagon tolerance tests and insulin tolerance tests were carried out in mice, liver gene expression profiles were analysed and serum triglyceride, insulin and cholesterol levels were measured. Phosphorylation of forkhead box protein O1 (FOXO1) by p38α MAPK in vitro was analysed by LC-MS. RESULTS: We found that p38α MAPK, but not the other p38 isoforms, stimulates FOXO1-S273 phosphorylation and increases FOXO1 protein stability, promoting HGP in response to glucagon stimulation. In hepatocytes and mouse models, inhibition of p38α MAPK blocked FOXO1-S273 phosphorylation, decreased FOXO1 levels and significantly impaired glucagon- and fasting-induced HGP. However, the effect of p38α MAPK inhibition on HGP was abolished by FOXO1 deficiency or a Foxo1 point mutation at position 273 from serine to aspartic acid (Foxo1S273D) in both hepatocytes and mice. Moreover, an alanine mutation at position 273 (Foxo1S273A) decreased glucose production, improved glucose tolerance and increased insulin sensitivity in diet-induced obese mice. Finally, we found that glucagon activates p38α through exchange protein activated by cAMP 2 (EPAC2) signalling in hepatocytes. CONCLUSIONS/INTERPRETATION: This study found that p38α MAPK stimulates FOXO1-S273 phosphorylation to mediate the action of glucagon on glucose homeostasis in both health and disease. The glucagon-induced EPAC2-p38α MAPK-pFOXO1-S273 signalling pathway is a potential therapeutic target for the treatment of type 2 diabetes.

Impact of stress hyperglycemia ratio, derived from glycated albumin or hemoglobin A1c, on mortality among ST-segment elevation myocardial infarction patients.

BACKGROUND: Stress hyperglycemia ratio (SHR), associated with adverse outcomes in patients with ST-segment elevation myocardial infarction (STEMI), has several definitions. This study aims to assess the prognostic value of SHR, derived from hemoglobin A1c (HbA1c) or glycated albumin (GA), to mortality. METHODS: The study comprised 1,643 STEMI patients who underwent percutaneous coronary intervention (PCI) in two centers. SHR1 was calculated using fasting blood glucose (FBG)/GA, while SHR2 was calculated using the formula FBG/(1.59*HbA1c-2.59). The primary endpoints were in-hospital death and all-cause mortality, with a median follow-up duration of 1.56 years. RESULTS: Higher SHR1 and SHR2 values are associated with increased risks of in-hospital death and all-cause mortality. Each standard deviation increase in SHR1 corresponded to a 39% and 22% escalation in in-hospital death and all-cause mortality, respectively. The respective increases for SHR2 were 51% and 26%. Further examinations validated these relationships as linear. Additionally, the areas under the curve (AUC) for in-hospital death were not significantly different between SHR1 and SHR2 (p > 0.05). Incorporating SHR1 or SHR2 into the base model significantly improved the discrimination and risk reclassification for in-hospital and all-cause mortality. A subgroup analysis revealed that the effects of SHR1 and SHR2 were more pronounced in patients with hypercholesteremia. CONCLUSION: SHR1 and SHR2 have emerged as robust and independent prognostic markers for STEMI patients undergoing PCI. The SHR calculation based on either HbA1c or GA can provide additional predictive value for mortality beyond traditional risk factors, helping to identify high-risk STEMI patients.

Comparative effects of vitamin and mineral supplements in the management of type 2 diabetes in primary care: A systematic review and network meta-analysis of randomized controlled trials.

Medical nutrition treatment can manage diabetes and slow or prevent its complications. The comparative effects of micronutrient supplements, however, have not yet been well established. We aimed at evaluating the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM) to inform clinical practice. Electronic and hand searches for randomized controlled trials (RCTs) were performed until June 1, 2022. We selected RCTs enrolling patients with T2DM who were treated with vitamin supplements, mineral supplements, or placebo/no treatment. Data were pooled via frequentist random-effects network meta-analyses. A total of 170 eligible trials and 14223 participants were included. Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively). Vitamin K supplements ranked best in reducing glycated hemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence. Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%). Niacin supplements ranked best in triglyceride reductions and increasing high-density lipoprotein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively). Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%). Our analyses indicated that micronutrient supplements, especially chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be more efficacious in managing T2DM than other micronutrients. Considering the clinical importance of these findings, new research is needed to get better insight into this issue.

Circ_0001312 Silencing Suppresses Doxorubicin-Induced Cardiotoxicity via MiR-409-3p/HMGB1 Axis.

Doxorubicin (DOX) is a potent cytotoxic chemotherapeutic agent limited in clinical application owing to its cumulative and irreversible cardiotoxicity. Circ_0001312 is highly expressed in patients with heart failure. However, it is still unclear whether circ_0001312 plays any roles in DOX-induced cardiotoxicity.Human AC16 cardiomyocytes in functional group were stimulated with DOX. The levels of genes and proteins were detected by qRT-PCR and western blotting. The proliferation, apoptosis, as well as inflammatory and oxidative injury in cardiomyocytes were investigated. Dual-luciferase reporter, RNA immunoprecipitation, and pull-down assays were utilized to confirm the binding between miR-409-3p and circ_0001312 or HMGB1 (high-mobility group box 1). Exosomes were isolated by using the commercial kit and identified by transmission electron microscopy (TEM) and nanoparticle-tracking analysis (NTA).DOX impaired cardiomyocyte proliferation and induced apoptotic, inflammatory, and oxidative injury in cells. Furthermore, it promoted circ_0001312 expression, and the knockdown of circ_0001312 could reverse DOX-evoked cardiomyocyte injury. In terms of mechanics, circ_0001312 bound competitively to miR-409-3p to up-regulate HMGB1, which was a target of miR-409-3p. DOX decreased the miR-409-3p but increased the HMGB1 expression in cardiomyocytes. Functionally, miR-409-3p inhibition attenuated the protective action of circ_0001312 silencing on cardiomyocytes under DOX treatment. Moreover, miR-409-3p could abate DOX-evoked apoptosis, and inflammation and oxidative stress in cardiomyocytes, and these effects were counteracted by HMGB1 overexpression. In addition, circ_0001312 was secreted by exosomes and could be transmitted via exosomes.Circ_0001312 reversed the cytotoxic effects mediated by DOX on cardiomyocytes via the miR-409-3p/HMGB1 axis. Besides, it was released to the extracellular space by exosomes.

A Novel LSTM-Based Machine Learning Model for Predicting the Activity of Food Protein-Derived Antihypertensive Peptides.

Food protein-derived antihypertensive peptides are a representative type of bioactive peptides. Several models based on partial least squares regression have been constructed to delineate the relationship between the structure and activity of the peptides. Machine-learning-based models have been applied in broad areas, which also indicates their potential to be incorporated into the field of bioactive peptides. In this study, a long short-term memory (LSTM) algorithm-based deep learning model was constructed, which could predict the IC50 value of the peptide in inhibiting ACE activity. In addition to the test dataset, the model was also validated using randomly synthesized peptides. The LSTM-based model constructed in this study provides an efficient and simplified method for screening antihypertensive peptides from food proteins.

MiR-145 participates in the development of lupus nephritis by targeting CSF1 to regulate the JAK/STAT signaling pathway.

BACKGROUND: Lupus nephritis (LN) is a chronic autoimmune disease, leading to progressive renal dysfunction. MicroRNAs (miRNAs) contribute to LN pathophysiology. Nevertheless, the potential mechanisms of miR-145 in LN remain unclear. Here, we investigated the contribution of miR-145 to LN progression. METHODS: qRT-PCR analysis determined miR-145 and CSF1 expression. Western blot tested CSF1, JAK2, p-JAK2, STAT3, p-STAT3, cleaved caspase3, Bax and Bcl-2 expression. Dual luciferase reporter assay confirmed the interaction between miR-145 and CSF1. ELISA assay detected the secretion of inflammatory molecules. Flow cytometric analysis determined cell cycle and apoptosis. MTT was conducted to test cell viability. The LN mouse model was constructed for in vivo experiments. HE and Masson staining examined the kidney pathologic changes. RESULTS: MiR-145 was down-regulated in LN patients and LPS-induced HRMCS, whereas CSF1 was up-regulated. Moreover, miR-145 overexpression inhibited HRMCS cell apoptosis and inflammatory damage. Besides, miR-145 was found to directly target CSF1. Additionally, knockdown of CSF1 inhibited HRMCS cell apoptosis and inflammatory damage by inactivating the JAK/STAT signaling pathway. Furthermore, miR-145 inhibited inflammatory damage and cell apoptosis of HRMCS by down-regulating CSF1. Finally, we verified that miR-145 suppressed LN development in vivo. CONCLUSION: Our data reveals that miR-145 regulates LN progression via CSF1 mediated JAK/STAT signaling pathway, and miR-145 may be a new therapeutic target for LN treatment.

CoO Nanoparticles Combined with MRI: Analysis of No-Reflow in Patients with Acute ST-Segment Elevation Myocardial Infarction after PCI and the Effect of Coronary Nicorandil.

Magnetic resonance imaging (MRI) has become one of the most important medical imaging techniques in the clinic due to its high degree of soft tissue resolution and no radiation damage, and it plays an important role in the early diagnosis and treatment of tumors. This article mainly studies the analysis of no-reflow in patients with acute ST-segment elevation myocardial infarction after PCI and the effect of coronary nicorandil on CoO nanoparticles combined with MRI. In this paper, the synthesized water-soluble nanoparticles are dispersed in a 2% xanthan gum or agarose solution. In an MRI analyzer, the T1 value is tested with the inversion recovery sequence, and the T2 value is tested with the hard pulse CPMG sequence. The gyroscope imaging sequence performs T1-weighted and T2-weighted imaging tests. Calculated densitometry (QCA) was used to measure the stenosis of the coronary lesions, the length of the lesions and the diameter of the lumen before stent implantation. In order to facilitate the collection of urine samples, this article adopts the method of inserting a catheter to drain the patient for sampling. From the baseline state at the time of enrollment to 150 minutes after PCI, polyethylene containing 0.1% butylated hydroxyanisole is used. Urine samples were taken from the test tube every 30 minutes, a total of 6 times were collected, and the collected urine samples were stored in a low-temperature refrigerator at -80℃ for the final inspection. This paper uses calculation software to calculate the risk of death and death/myocardial infarction in the hospital and at 6 months after discharge. The data showed that the postoperatively detected CKMB and cTnI were higher than those before the operation, but the peak value of the nicorandil group was lower than that of the control group, but there was still no statistical difference (P>0.05). The results show that nicorandil can significantly improve the no-reflow phenomenon in AMI patients during PCI.

Global research trends of immunotherapy and biotherapy for inflammatory bowel disease: a bibliometric analysis from 2002 to 2021.

BACKGROUND: It is known that inflammatory bowel disease is the result of a defective immune system, and immunotherapy and biological therapy have gradually become important means to treat it. This paper focused on the bibliometric statistical analysis of the current research progress to summarize the research status of this field and analyze the research trends in recent years. METHODS: Two visualization tools, CiteSpace and VOSviewer, were used to explore the data of journals, institutions, countries/regions, authors, references, and keywords for the literature included in the Web of Science Core Collection from January 1, 2002, to December 31, 2021. RESULTS: A total of 312 papers were published in 120 journals by 603 institutions from 40 countries/regions, with 9463 co-cited references. The United States has the most publications with the highest total citations in the world. Inflammatory Bowel Diseases published the maximum number of papers, and Gastroenterology devoted the most co-citations to immunotherapy and biological therapy for IBD. In addition, we found that the studies before 2009 mostly focused on clinical trials while researchers have paid more attention to clinical management in therapy for IBD since 2009. Combination therapy and management of the treatment for the disease have become research hotspots. CONCLUSION: The focus of immunotherapy and biotherapy for IBD has shifted from clinical trials to the management of the risks and benefits of immunotherapy.

Highly sensitive Curcumin-conjugated nanotheranostic platform for detecting amyloid-beta plaques by magnetic resonance imaging and reversing cognitive deficits of Alzheimer's disease via NLRP3-inhibition.

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disorder without effective therapy and lack diagnosis strategy for preclinical AD patients. There is an urgent need for development of both early diagnosis and therapeutic intervention of AD. RESULTS: Herein, we developed a nanotheranostics platform consisting of Curcumin (Cur), an anti-inflammatory molecule, and superparamagnetic iron oxide (SPIO) nanoparticles encapsulated by diblock 1,2-dio-leoyl-sn-glycero-3-phosphoethanolamine-n-[poly(ethylene glycol)] (DSPE-PEG) that are modified with CRT and QSH peptides on its surface. Furthermore, we demonstrated that this multifunctional nanomaterial efficiently reduced ß-amyloid plaque burden specifically in APP/PS1 transgenic mice, with the process noninvasively detected by magnetic resonance imaging (MRI) and the two-dimensional MRI images were computed into three-dimension (3D) plot. Our data demonstrated highly sensitive in vivo detection of ß-amyloid plaques which more closely revealed real deposition of Aß than previously reported and we quantified the volumes of plaques for the first time based on 3D plot. In addition, memory deficits of the mice were significantly rescued, probably related to inhibition of NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasomes. CONCLUSIONS: Gathered data demonstrated that this theranostic platform may have both early diagnostic and therapeutic potential in AD.

Understanding the Association between Online Social Support Obtainment and Coping during a Public Crisis.

This study aims to examine how the process of online support obtainment may affect cognitive and behavioral coping during a public crisis. A cross-sectional online survey (N = 555) was conducted during the early stage of the COVID-19 pandemic in the U.S. Our findings revealed that informational support, obtained primarily through passive and private online involvement, led to increased risk perceptions of COVID-19; emotional support, obtained mainly via private online involvement, appeared to elicit higher perceived efficacy to cope with the crisis. People's engagement in preventive behaviors was found to be affected by efficacy perceptions, but not by risk perceptions. The results suggested that online social support functioned as a double-edged sword to affect people's coping with a public crisis.

RNA interference of vATPase subunits A and E affects survival of larvae and adults in Plagiodera versicolora (Coleoptera: Chrysomelidae).

Vacuolar-type H+-ATPases (vATPases) are ATP-driven proton pumps and play essential roles in many physiological functions. Plagiodera versicolora (Coleoptera: Chrysomelidae) is a leaf-eating forest pest found in salicaceous trees worldwide. RNA interference (RNAi) is a powerful tool for functional identify and pest control. In this study, we used RNAi as an approach to knock down subunits A and E of the vATPase gene. The phylogenetic analysis showed that vATPase-A and vATPase-E from the same order were clustered together to form Coleoptera subclades, respectively. The expression levels of vATPase-A and vATPase-E were higher in gut, Malpighian tubules and 1st instar larvae. Ingest the dsvATPase-A and dsvATPase-E significantly inhibited the development of 1st to 3th instar larvae, incapacitated of mating and oviposition in adults. In addition, knockdown of vATPase subunit genes caused higher mortality in larvae and adults. The results demonstrate that RNAi efficiencies both vATPase-A and vATPase-E genes at various larvae stages and adults. Moreover, this research suggested that silencing of two vATPase subunits A and E offers a potential strategy to control P. versicolora.

Tocotrienol-Rich Fractions Offer Potential to Suppress Pulmonary Fibrosis Progression.

Although pulmonary fibrosis (PF) is considered a rare disease, the incidence thereof has increased steadily in recent years, while a safe and effective cure remains beyond reach. In this study, the potential of tocotrienol-rich fractions (TRF) and carotene to alleviate PF was explored. PF was induced in Sprague-Dawley rats via a single intratracheal bleomycin (BLM) (5 mg/kg) instillation. These rats were subsequently treated with TRF, carotene, pirfenidone (Pir) and nintedanib (Nin) for 28 days via gavage administration, whereafter histopathological performance, biochemical functions and molecular alterations were studied in the lung tissues. Our results showed that TRF, carotene, Nin and Pir all ameliorated PF by reducing inflammation and resisting oxidative stress to varying degrees. The related mechanisms involved the TGF-ß1/Smad, PI3K/Akt and NF-κB signaling pathways. Ultimately, our findings revealed that, when combined with TRF, the therapeutic effects of Nin and Pir on PF were enhanced, indicating that TRF may, indeed, provide promising potential for use in combination therapy in the treatment of PF.

Multiplicity and dynamics of social representations of the COVID-19 pandemic on Chinese social media from 2019 to 2020.

Documenting the emergent social representations of COVID-19 in public communication is necessary for critically reflecting on pandemic responses and providing guidance for global pandemic recovery policies and practices. This study documents the dynamics of changing social representations of the COVID-19 pandemic on one of the largest Chinese social media, Weibo, from December 2019 to April 2020. We draw on the social representation theory (SRT) and conceptualize topics and topic networks as a form of social representation. We analyzed a dataset of 40 million COVID-19 related posts from 9.7 million users (including the general public, opinion leaders, and organizations) using machine learning methods. We identified 12 topics and found an expansion in social representations of COVID-19 from a clinical and epidemiological perspective to a broader perspective that integrated personal illness experiences with economic and sociopolitical discourses. Discussions about COVID-19 science did not take a prominent position in the representations, suggesting a lack of effective science and risk communication. Further, we found the strongest association of social representations existed between the public and opinion leaders and the organizations' representations did not align much with the other two groups, suggesting a lack of organizations' influence in public representations of COVID-19 on social media in China.

ZFP36 promotes VDR mRNA degradation to facilitate cell death in oral and colonic epithelial cells.

BACKGROUND: Vitamin D receptor (VDR) plays a vital protective role in oral and colonic epithelial cells. Albeit we know that VDR expression is reduced in the mucosal epithelial layers of autoimmune diseases, the mechanism by which VDR is decreased remains elusive. METHODS: VDR and zinc finger protein 36 (ZFP36) levels in human samples and cell lines were detected by real-time PCR, western blot and immunostaining. Luciferase report assay was used to test cis-elements in VDR gene promoter, real-time PCR was applied to measure mRNA decay and western blot was performed to evaluate protein degradation. RNA affinity chromatography assay was used to test protein-mRNA interaction. Co-immunoprecipitation was used to detect protein-protein interaction. The role of ZFP36 in AU-rich elements (AREs) in the 3' untranslated region (UTR) of VDR mRNA was also measured by luciferase report assay. RESULTS: We identify ZFP36 can bind with the AREs in the 3'UTR of VDR mRNA, leading to mRNA degradation in oral and colonic epithelial cells under inflammatory circumstance. Either ZFP36 protein or AREs of VDR mRNA mutation abolishes this protein-mRNA binding process. After the key amino acid's mutation, ZFP36 fails to decrease VDR mRNA expression. We also find that VDR physically binds with Y box-binding protein 1 (YBX-1) to block YBX-1's nuclear translocation and ameliorate cell death in the presence of inflammation. CONCLUSION: These findings provide insights into the cause of VDR decrease in oral and colonic epithelial cells under inflammatory condition and explain how VDR maintains cell viability in these cells. Video abstract.

The ACE2/Ang (1-7)/MasR axis as an emerging target for antihypertensive peptides.

Food protein-derived bioactive peptides, particularly antihypertensive peptides, are important constituents of functional foods or nutraceuticals. Most antihypertensive are identified as the inhibitors of angiotensin converting enzyme (ACE), a key enzyme responsible for the generation of angiotensin II (Ang II), which is a vasoconstricting peptide. Hence, ACE has long been used as a universal target to identify antihypertensive peptides. Angiotensin converting enzyme 2 (ACE2), is a homolog of ACE but uses Ang II as its key substrate to produce angiotensin (1-7), exerting vasodilatory activity via the mas receptor (MasR). Therefore, ACE2 functions in the opposite way as ACE and is an emerging novel target for cardiovascular therapy. The potential of food protein-derived bioactive peptides in targeting ACE2 has been rarely explored. While, recently we found that IRW, an egg white ovotransferrin-derived antihypertensive peptide, reduced blood pressure in spontaneously hypertensive rats via the ACE2/Ang (1-7)/MasR axis, indicating a new mechanism of food protein-derived bioactive peptides in reducing blood pressure. The objectives of this review are to summarize the functions of the ACE2/Ang (1-7)/MasR axis and to examine its potential roles in the actions of food protein-derived antihypertensive peptides. The interaction between antihypertensive peptides and the ACE2/Ang (1-7)/MasR axis will also be discussed.

Using Reports of Symptoms and Diagnoses on Social Media to Predict COVID-19 Case Counts in Mainland China: Observational Infoveillance Study.

BACKGROUND: Coronavirus disease (COVID-19) has affected more than 200 countries and territories worldwide. This disease poses an extraordinary challenge for public health systems because screening and surveillance capacity is often severely limited, especially during the beginning of the outbreak; this can fuel the outbreak, as many patients can unknowingly infect other people. OBJECTIVE: The aim of this study was to collect and analyze posts related to COVID-19 on Weibo, a popular Twitter-like social media site in China. To our knowledge, this infoveillance study employs the largest, most comprehensive, and most fine-grained social media data to date to predict COVID-19 case counts in mainland China. METHODS: We built a Weibo user pool of 250 million people, approximately half the entire monthly active Weibo user population. Using a comprehensive list of 167 keywords, we retrieved and analyzed around 15 million COVID-19-related posts from our user pool from November 1, 2019 to March 31, 2020. We developed a machine learning classifier to identify "sick posts," in which users report their own or other people's symptoms and diagnoses related to COVID-19. Using officially reported case counts as the outcome, we then estimated the Granger causality of sick posts and other COVID-19 posts on daily case counts. For a subset of geotagged posts (3.10% of all retrieved posts), we also ran separate predictive models for Hubei province, the epicenter of the initial outbreak, and the rest of mainland China. RESULTS: We found that reports of symptoms and diagnosis of COVID-19 significantly predicted daily case counts up to 14 days ahead of official statistics, whereas other COVID-19 posts did not have similar predictive power. For the subset of geotagged posts, we found that the predictive pattern held true for both Hubei province and the rest of mainland China regardless of the unequal distribution of health care resources and the outbreak timeline. CONCLUSIONS: Public social media data can be usefully harnessed to predict infection cases and inform timely responses. Researchers and disease control agencies should pay close attention to the social media infosphere regarding COVID-19. In addition to monitoring overall search and posting activities, leveraging machine learning approaches and theoretical understanding of information sharing behaviors is a promising approach to identify true disease signals and improve the effectiveness of infoveillance.

Internet Use, Risk Awareness, and Demographic Characteristics Associated With Engagement in Preventive Behaviors and Testing: Cross-Sectional Survey on COVID-19 in the United States.

BACKGROUND: During the coronavirus disease (COVID-19) pandemic, engagement in preventive behaviors and getting tested for the virus play a crucial role in protecting people from contracting the new coronavirus. OBJECTIVE: This study aims to examine how internet use, risk awareness, and demographic characteristics are associated with engagement in preventative behaviors and testing during the COVID-19 pandemic in the United States. METHODS: A cross-sectional survey was conducted on Amazon Mechanical Turk from April 10, 2020, to April 14, 2020. Participants' internet use (in terms of the extent of receiving information pertaining to COVID-19), risk awareness (whether any immediate family members, close friends or relatives, or people in local communities tested positive for COVID-19), demographics (sex, age, ethnicity, income, education level, marital status, and employment status), as well as their engagement in preventative behaviors and testing were assessed. RESULTS: Our data included 979 valid responses from the United States. Participants who received more COVID-19-related health information online reported more frequent effort to engage in all types of preventive behaviors: wearing a facemask in public (odds ratio [OR] 1.55, 95% CI 1.34-1.79, P<.001), washing hands (OR 1.58, 95% CI 1.35-1.85, P<.001), covering nose and mouth when sneezing and coughing (OR 1.78, 95% CI 1.52-2.10, P<.001), keeping social distance with others (OR 1.41, 95% CI 1.21-1.65, P<.001), staying home (OR 1.40, 95% CI 1.20-1.62, P<.001), avoiding using public transportation (OR 1.57, 95% CI 1.32-1.88, P<.001), and cleaning frequently used surfaces (OR 1.55, 95% CI 1.34-1.79, P<.001). Compared with participants who did not have positive cases in their social circles, those who had immediate family members (OR 1.48, 95% CI 8.28-26.44, P<.001) or close friends and relatives (OR 2.52, 95% CI 1.58-4.03, P<.001) who tested positive were more likely to get tested. Participants' sex, age, ethnicity, marital status, and employment status were also associated with preventive behaviors and testing. CONCLUSIONS: Our findings revealed that the extent of receiving COVID-19-related information online, risk awareness, and demographic characteristics including sex, ethnicity, age, marital status, and employment status are key factors associated with US residents' engagement in various preventive behaviors and testing for COVID-19.

[Systemic reactions to subcutaneous immunotherapy for bronchial asthma and/or allergic rhinitis in children and their risk factors].

OBJECTIVE: To investigate the incidence of systemic reactions (SR) to subcutaneous immunotherapy (SCIT) for bronchial asthma and/or allergic rhinitis in children and their risk factors. METHODS: A retrospective analysis was performed on 198 children with bronchial and/or allergic rhinitis. According to the presence or absence of SR and local reactions (LR) during SCIT, the patients were divided into two groups: SR (with SR and LR, n=31) and control (without SR or LR, n=142). A multivariate logistic regression analysis was used to determine the risk factors associated with SR. RESULTS: Among the 198 patients who received 8 157 injections of SCIT, 25 (12.6%) experienced SR (31 times, 0.38%), including grade I SR (18 times, 58%), grade II SR (10 times, 32%), grade III SR (3 times, 10%), and no grade IV SR. The multivariate logistic regression analysis showed that multiple sensitization with both food and inhaled allergens, specific IgE to dust mites (grade 6), total IgE (grade 6), and a history of LR were independent risk factors for SR (P<0.05). CONCLUSIONS: SCIT is a safe treatment for bronchial asthma and/or allergic rhinitis in children, with a low incidence of SR. Children with multiple sensitization with both food and inhaled allergens, a hypersensitive state (specific IgE to dust mites, grade 6; total IgE, grade 6), and a history of LR have an increased risk of SR to SCIT.

MicroRNA-145 Involves in the Pathogenesis of Renal Vascular Lesions and May Become a Potential Therapeutic Target in Patients with Juvenile Lupus Nephritis.

AIMS: The current study was conducted with the central objective of investigating the expression of microRNA-145 (miR-145) in renal vascular lesions (RVLs) in juvenile lupus nephritis (JLN) and its possible mechanism. METHODS: The clinical data of 49 JLN patients confirmed by renal biopsy were collected and followed by grouping according to the RVLs score after hematoxylin-eosin staining: mild, moderate, and severe groups. In situ hybridization was used to detect the expression of miR-145 in renal vessels which was then being compared among different RVLs groups. Up-LV-miR-145 and LV-miR-NC lentiviral vectors were constructed and transfected into human vascular smooth muscle cells (HVSMCs), respectively. After HVSMCs were treated with 10.0 µg/L platelet-derived growth factor (PDGF)-BB for 24 h, the proliferation, migration, and apoptosis of endothelial cells were detected by MTT, Transwell assay, and flow cytometry, respectively. Western blot was used to detect expression of alpha-smooth muscle actin (α-SM-actin) and osteopontin (OPN). RESULTS: The expression of miR-145 in renal vascular cells was statistically significant. The higher the inner membrane ratio, the lesser the miR-145 expression. After treatment with PDGF-BB, expression of miR-145 in HVSMCs decreased, proliferation and migration ability enhanced, apoptosis decreased, α-SM-actin decreased, and OPN increased. The proliferation and migration ability of HVSMCs in the LV-miR-145 group suppressed, apoptosis enhanced, α-SM-actin increased, and OPN decreased. CONCLUSIONS: Our study revealed that miR-145 expression decreased with the increase of vascular damage. miR-145 can inhibit proliferation, migration, and differentiation phenotypic transformation of HVSMCs induced by PDGF-BB. miR-145 may be involved in the pathogenesis of RVLs and may be a new target for treatment of RVLs in lupus nephritis.