Visible-Light Photocatalytic C-H Amination of Arenes Utilizing Acridine-Lewis Acid Complexes.

This report describes the development of a visible-light photocatalytic system for C(sp2)-H amination that leverages in situ-generated photocatalysts. We demonstrate that the combination of acridine derivatives and Lewis acids forms potent photooxidants that promote the C-H amination of electronically diverse arenes upon irradiation with visible-light (440 nm). A first-generation photocatalyst composed of Sc(OTf)3 and acridine effects the C-H amination of substrates with oxidation potentials ≤ +2.5 V vs SCE with pyrazole, triazole, and pyridine nucleophiles. Furthermore, the simplicity and modularity of this system enable variation of both Lewis acid and acridine to tune reactivity. This enabled the rapid identification of two second-generation photocatalysts (derived from (i) Al(OTf)3 and acridine or (ii) Sc(OTf)3 and a pyridinium-substituted acridine) that catalyze a particularly challenging transformation: C(sp2)-H amination with benzene as the limiting reagent.

Association of scrub typhus with the risk of venous thromboembolism and long-term mortality: a population-based cohort study.

BACKGROUND: The existing literature lacks studies examining the epidemiological link between scrub typhus and deep vein thrombosis (DVT) or pulmonary embolism (PE), and the long-term outcomes. The objective of this study is to explore the potential association between scrub typhus and the subsequent risk of venous thromboembolism, and long-term mortality. METHOD: This nationwide cohort study identified 10,121 patients who were newly diagnosed with scrub typhus. Patients with a prior DVT or PE diagnosis before the scrub typhus infection were excluded. A comparison cohort of 101,210 patients was established from the general population using a propensity score matching technique. The cumulative survival HRs for the two cohorts were calculated by the Cox proportional hazards model. RESULT: After adjusting for sex, age, and comorbidities, the scrub typhus group had an adjusted HR (95% CI) of 1.02 (0.80-1.30) for DVT, 1.11 (0.63-1.93) for PE, and 1.16 (1.08-1.25) for mortality compared to the control group. The post hoc subgroup analysis revealed that individuals younger than 55 years with a prior scrub typhus infection had a significantly higher risk of DVT (HR: 1.59; 95% CI: 1.12-2.25) and long-term mortality (HR: 1.75; 95% CI, 1.54-1.99). CONCLUSION: The scrub typhus patients showed a 16% higher risk of long-term mortality. For those in scrub typhus cohort below 55 years of age, the risk of developing DVT was 1.59 times higher, and the risk of mortality was 1.75 times higher. Age acted as an effect modifier influencing the relationship between scrub typhus and risk of new-onset DVT and death.

Association between serum vitamin E and bacterial vaginitis in women: a cross-sectional study.

INTRODUCTION: Bacterial vaginitis (BV) is a common vaginal disease. Vitamin E has been shown to reduce BV by enhancing immune function, but no studies have analyzed the relationship between vitamin E and BV at different BMIs and ages. METHOD: This study used 2242 participants from four cycles of NHANES 1999-2006 in American. Participants' vitamin E levels were divided into four groups, and analyses such as study population description, stratified analysis, multiple logistic regression analysis, and curve fitting were performed. To perform data processing, the researchers used the statistical package R (The R Foundation; http://www.r-project.org ; version 3.6.3) and Empower Stats software ( www.empowerstats.net , X&Y solutions, Inc. Boston, Massachusetts). RESULT: The concentrations of serum vitamin E were negatively correlated with the risk of BV, especially when vitamin E were at 1198-5459ug/dL with (OR = -0.443, 95%CI = 0.447-0.923, P = 0.032) or without (OR = -0.521, 95%CI = 0.421-0.837, P = 0.006) adjustment for variables. At the same time, at lower levels, there was no significant association. Vitamin E supplementation may significantly reduce the risk of BV (p < 0.001). In addition, the risk of having BV decreased and then increased with increasing vitamin E concentrations at high BMI levels (p < 0.01). CONCLUSION: Vitamin E at moderate to high concentrations may significantly reduce BV risk, says the study, providing clinical evidence for the prevention and the treatment of BV.

A Low-Cost, Sensitive Reporter System Using Membrane-Tethered Horseradish Peroxidase for Efficient Gene Expression Analysis.

Reporter gene assays are essential for high-throughput analysis, such as drug screening or determining downstream signaling activation/inhibition. However, use of this technology has been hampered by the high cost of the substrate (e.g., d-Luciferin (d-Luc)) in the most common firefly luciferase (FLuc) reporter gene assay. Although alternate luciferase is available worldwide, its substrate has remained expensive, and a more affordable option is still in demand. Here, we present a membrane-tethered horseradish peroxidase (mHRP), a new reporter system composed of a cell membrane expressing HRP that can preserve its enzymatic function on the cell surface, facilitates contact with HRP substrates (e.g., ABTS and TMB), and avoids the cell lysis process and the use of the high-priced luciferase substrate. An evaluation of the light signal sensitivity of mHRP compared to FLuc showed that both had comparable signal sensitivity. We also identified an extended substrate half-life of more than 5-fold that of d-Luc. Of note, this strategy provided a more stable detection signal, and the cell lysis process is not mandatory. Furthermore, with this strategy, we decreased the total amount of time taken for analysis and increased the time of detection limit of the reporter assay. Pricing analysis showed a one-third to one twenty-eighth price drop per single test of reporter assay. Given the convenience and stability of the mHRP reporter system, we believe that our strategy is suitable for use as an alternative to the luciferase reporter assay.

Analysis of Multimorbidity of Moderate to Severe Allergic Rhinitis in Children: A Real-World Study.

INTRODUCTION: Allergic rhinitis (AR) in children is associated with various comorbidities, posing challenges for treatment and management. There have been few investigations of these multimorbidities in Chinese children with AR. Here, we investigated the prevalence of multimorbidities in children with moderate to severe AR and analyzed the influencing factors using real-world data. METHODS: In total, 600 children who visited the outpatient clinic of our hospital and were diagnosed with moderate-severe AR were prospectively enrolled. All children underwent allergen detection and electronic nasopharyngoscopy. Parents or guardians completed a questionnaire that included age, sex, mode of delivery, feeding pattern, and familial history of allergy. The multimorbidities investigated included atopic dermatitis (AD), asthma, allergic conjunctivitis (AC), chronic rhinosinusitis (CRS), adenoid hypertrophy (AH), tonsil hypertrophy (TH), recurrent epistaxis, and recurrent respiratory tract infections (RRTIs). RESULTS: The AR multimorbidities reported in children were as follows: recurrent epistaxis (46.5%), AC (46.3%), AD (40.7%), asthma (22.5%), RRIs (21.3%), CRS (20.5%), AH (19.7%), and TH (12.5%). In univariate logistic regression analysis, age (<6 years), birth mode, familial history of allergy, and single dust mite allergy were associated with AR multimorbidity (p < 0.05). Multivariate logistic regression revealed that a familial history of allergy was an independent risk factor for AC (odds ratio [OR] = 1.539, 95% confidence interval [CI]: 1.104-2.145) and AH (OR = 1.506, 95% CI: 1.000-2.267) (p < 0.05). Age (<6 years) was independently associated with the risk of AD (OR = 1.405, 95% CI: 1.003-1.969) and RRTIs (OR = 1.869, 95% CI: 1.250-2.793) (p < 0.05), cesarean section with AR and CRS risk (OR = 1.678, 95% CI: 1.100-2.561), and single dust mite allergy with asthma (OR = 1.590, 95% CI: 1.040-2.432) and CRS (OR = 1.600, 95% CI: 1.018-2.515) risk (p < 0.05). Further, non-dust mite allergy was independently associated with AR and CRS (OR = 2.056, 95% CI: 1.084-3.899). CONCLUSION: AR was found to be accompanied by different comorbidities, including both allergic and non-allergic comorbidities, complicating disease treatment. These findings demonstrated that age (<6 years), familial history of allergy, types of allergens, and cesarean section were risk factors for different multimorbidities associated with AR.

Clinical analysis of 78 patients with nonclassical 21-hydroxylase deficiency.

PURPOSE: Retrospectively analyze the clinical characteristics of patients with nonclassical 21-hydroxylase deficiency (NC21OHD) as well as the relationship between the gene mutations and endocrine hormones. In addition, the relationship between different basal 17-hydroxyprogesterone (17OHP) levels and patients' glucolipid metabolism, hormone levels, pregnancy, and treatment outcomes were examined. METHODS: Clinical data of 78 females with NC21OHD from January 2012 to July 2022 in the Department of Endocrinology and Metabolism of the Third Affiliated Hospital of Guangzhou Medical University were retrospectively analyzed. Diagnosis was based on the 17OHP level combined with clinical manifestations, imaging, and other endocrine hormones and the cytochrome P450 c21, steroid 21-hydroxylase (CYP21A2) gene. RESULTS: The age at diagnosis of the 78 patients was 29.1 ± 4.2 years; 83.3% (65/78) of the patients had menstrual abnormalities, 70 patients were of childbearing age, and 97.1% (68/70) had a history of infertility with a median time of infertility of 3.6 years. Moreover, 71.8% (56/78) of the patients had polycystic ovaries, 26.9% (21/78) had hyperandrogenemia manifestations on physical examination, 66.7% (52/78) had adrenal hyperplasia, 32.1% (25/78) had combined dyslipidemia, and 41.0% (32/78) had combined insulin resistance. Pathogenic mutations were detected in 78.2% (61/78) of the patients with both CYP21A2 alleles; 14.1% (11/78) of the patients had only one allele and 7.7% (6/78) had no pathogenic mutations. The levels of total testosterone (TT), progesterone (P) (0 min, 30 min), and 17-OHP (0 min, 30 min, 60 min) in the adrenocorticotropic hormone (ACTH) stimulation test varied between the groups. Furthermore, patients with NC21OHD were divided into 17OHP < 2 ng/ml, 2 ng/ml < 17OHP < 10 ng/ml, and 17OHP ≥ 10 ng/ml groups according to their different basal 17OHP levels. The 17OHP ≥ 10 ng/ml group had significantly higher TT, FT4, basal and post-stimulation progesterone, and 17OHP, net value added of 17-hydroxyprogesterone (△17OHP), net value added of 17-hydroxyprogesterone/net value added of cortisol ratio (△17OHP/△F), the incidence of adrenal hyperplasia, and number of gene mutations compared to those of the 17OHP < 2 ng/ml group (P < 0.05). NC21OHD infertile patients who received low-dose glucocorticoids showed a significant increase in pregnancy and live birth rates, and a significant decrease in miscarriage rate (all P < 0.05). CONCLUSION: Comprehensive analysis is important as NCCAH diagnoses may be false positive or false negative based on clinical characteristics, hormone levels, and gene detection. Females with NC21OHD showed varying degrees of fertility decline; thus, low doses of glucocorticoid treatment for infertile females with NC21OHD can improve fertility and fertility outcomes.

The Synergistic Effect of Electrical Stimulation and Dermal Fibroblast Cells-Laden 3D Conductive Hydrogel for Full-Thickness Wound Healing.

Clinically, most patients with poor wound healing suffer from generalized skin damage, usually accompanied by other complications, so developing therapeutic strategies for difficult wound healing has remained extremely challenging until now. Current studies have indicated that electrical stimulation (ES) to cutaneous lesions enhances skin regeneration by activating intracellular signaling cascades and secreting skin regeneration-related cytokine. In this study, we designed different concentrations of graphene in gelatin-methacrylate (GelMa) to form the conductive composite commonly used in wound healing because of its efficiency compared to other conductive thermo-elastic materials. The results demonstrated the successful addition of graphene to GelMa while retaining the original physicochemical properties of the GelMa bioink. In addition, the incorporation of graphene increased the interactions between these two biomaterials, leading to an increase in mechanical properties, improvement in the swelling ratio, and the regulation of degradation characteristics of the biocomposite scaffolds. Moreover, the scaffolds exhibited excellent electrical conductivity, increasing proliferation and wound healing-related growth factor secretion from human dermal fibroblasts. Overall, the HDF-laden 3D electroconductive GelMa/graphene-based hydrogels developed in this study are ideal biomaterials for skin regeneration applications in the future.

[Aucubin combined with ADSCs-exos protects TBHP-induced nucleus pulposus cells via TLR4/NF-κB pathway].

This paper aims to investigate the effects and mechanisms of adipose-derived stem cells-exosomes(ADSCs-exos) toge-ther with aucubin in protecting human-derived nucleus pulposus cells(NPCs) from inflammatory injury, senescence, and apoptosis. The tert-butyl hydroperoxide(TBHP)-induced NPCs were assigned into normal, model, aucubin, ADSCs-exos, and aucubin+ADSCs-exos groups. The cell viability was examined by cell counting kit-8(CCK-8), cell proliferation by EdU staining, cell senescence by senescence-associated-ß-galactosidase(SA-ß-Gal), and cell cycle and apoptosis by flow cytometry. Enzyme-linked immunosorbent assay was employed to examine the expression of interleukin-1ß(IL-1ß), IL-10, and tumor necrosis factor-α(TNF-α). Real-time fluorescence quantitative PCR and Western blot were employed to determine the mRNA and protein levels of aggregated proteoglycan(aggrecan), type Ⅱ collagen alpha 1(COL2A1), Toll-like receptor 4(TLR4), and nuclear factor-kappa B(NF-κB). The results showed that compared with the model group, the aucubin or ADSCs-exos group showed enhanced viability and proliferation of NPCs, decreased proportion of G_0/G_1 phase cells, increased proportion of S phase cells, reduced apoptosis and proportion of cells in senescence, lowered IL-1ß and TNF-α levels, elevated IL-10 level, down-regulated mRNA and protein levels of TLR4 and NF-κB, and up-regulated mRNA and protein levels of aggrecan and COL2A1. Compared with the aucubin or ADSCs-exos group, the aucubin+ADSCs-exos combination further increased the viability and proliferation of NPCs, decreased the proportion of G_0/G_1 phase cells, increased the proportion of S phase cells, reduced the apoptosis and proportion of cells in senescence, lowered the IL-1ß and TNF-α levels, elevated the IL-10 level, down-regulated the mRNA and protein levels of TLR4 and NF-κB, and up-regulated the mRNA and protein levels of aggrecan and COL2A1. In summary, both aucubin and ADSCs-exos could exert protective effects by inhibiting inflammatory responses, reducing apoptosis and senescence of NPCs, improving cell viability and proliferation as well as extracellular matrix synthesis, which may be associated with the inhibition of TLR4/NF-κB signaling pathway activation. The combination of both plays a synergistic role in the protective effects.

Age-specific spectrum of etiological pathogens for viral diarrhea among children in twelve consecutive winter-spring seasons (2009-2021) in China.

Viral diarrhea is one of the leading causes of morbidity and mortality in children. This study was conducted to disclose the etiological cause and epidemiological features of viral diarrhea among children in China. From 2009 to 2021, active surveillance was performed on pediatric patients with acute diarrhea and tested for five enteric viruses. Positive detection was determined in 65.56% (3325/5072) patients and an age-specific infection pattern was observed. A significantly higher positive rate was observed in 12-23-month-old children for rotavirus (47.46%) and adenovirus (7.06%), while a significantly higher positive rate was observed for norovirus (37.62%) in 6-11-month-old patients, and for astrovirus (11.60%) and sapovirus (10.79%) in 24-47-month-old patients. A higher positive rate of rotavirus in girls and norovirus in boys was observed only among 6-11 months of patients. We also observed more norovirus among patients from rural areas in the 0-5- and 36-47-month groups and more rotavirus among those from rural areas in the 12-23-month group. Diarrhea severity was greater for rotavirus in the 6-23-month group and norovirus in the 6-11-month group. Coinfections were observed in 29.26% (973/3325) of positive patients, and were most frequently observed between rotavirus and others (89.31%). Our findings could help the prediction, prevention, and potential therapeutic approaches to viral diarrhea in children.

Efficiency and Safety of Dextran-PAMAM/siMMP-9 Complexes for Decreasing Matrix Metalloproteinase-9 Expression and Promoting Wound Healing in Diabetic Rats.

Difficult healing of diabetic foot ulcers is associated with overexpression of matrix metalloproteinase 9 (MMP-9) in the local wound. Therefore, strategies aimed at downregulation of MMP-9 levels in ulcer sites may promote tissue regeneration and accelerate healing of diabetic foot ulcers (DFU). To fulfill this aim, we exploited dextran conjugated with poly(amidoamine) (Dextran-PAMAM) as a gene carrier to deliver MMP-9 targeted siRNA (siMMP-9). The prepared complexes could be efficiently endocytosed with low cytotoxicity to HaCat cells. Dextran-PAMAM could efficiently deliver siMMP-9 and significantly inhibit MMP-9 expression in vitro. Diabetic rats wound models showed that topical application of the Dextran-PAMAM/siMMP-9 complex effectively knocked down MMP-9 expression in skin wound tissue, thus accelerating wound healing. Taken together, this study demonstrates that the Dextran-PAMAM/siMMP-9 complex possesses high potential for wound healing and could serve as a promising regenerative platform for improving DFU healing.

Engineering a High-Affinity Anti-Methoxy Poly(ethylene glycol) (mPEG) Antibody for Sensitive Immunosensing of mPEGylated Therapeutics and mPEG Molecules.

Sensitive quantification of methoxy poly(ethylene glycol) (mPEG)-conjugated therapeutics for pharmacokinetic determination is critical for mPEGylated drug development. However, sensitive measurement of low-molecular-weight (lmw) mPEG compounds remains challenging due to epitope competition between backbone-specific anti-PEG antibodies. Here, we engineered a high-affinity methoxy-specific anti-mPEG antibody for sensitive quantification of free mPEG molecules and mPEGylated therapeutics. The affinity-enhanced h15-2Y antibody variant shows a 10.3-fold increase in mPEG-binding activity compared to parental h15-2b. h15-2Y-based sandwich ELISA can effectively quantify lmw mPEG5K and high-molecular-weight (hmw) mPEG20K at concentrations as low as 3.4 and 5.1 ng mL-1, respectively. Moreover, lmw mPEG compounds (560, 750, 1000, and 2000 Da) can be efficiently quantified via h15-2Y-based competitive ELISA with detection limits at nanomolar levels. This study provides a promising approach for application in the quantitative analysis of the various sizes of mPEG molecules to accelerate the timeline of mPEG-conjugated drug development.

An Unsupervised Deep Learning Approach for Dynamic-Exponential Intravoxel Incoherent Motion MRI Modeling and Parameter Estimation in the Liver.

BACKGROUND: Dynamic-exponential intravoxel incoherent motion (IVIM) imaging is a potential technique for prediction, monitoring, and differential diagnosis of hepatic diseases, especially liver tumors. However, the use of such technique at voxel level is still limited. PURPOSE: To develop an unsupervised deep learning approach for voxel-wise dynamic-exponential IVIM modeling and parameter estimation in the liver. STUDY TYPE: Prospective. POPULATION: Ten healthy subjects (4 males; age 28 ± 6 years). FIELD STRENGTH/SEQUENCE: Single-shot spin-echo echo planar imaging (SE-EPI) sequence with monopolar diffusion-encoding gradients (12 b-values, 0-800 seconds/mm2 ) at 3.0 T. ASSESSMENT: The proposed deep neural network (DNN) was separately trained on simulated and in vivo hepatic IVIM datasets. The trained networks were compared to the approach combining least squares with Akaike information criterion (LSQ-AIC) in terms of dynamic-exponential modeling accuracy, inter-subject coefficients of variation (CVs), and fitting residuals on the simulated subsets and regions of interest (ROIs) in the left and right liver lobes. The ROIs were delineated by a radiologist (H.-X.Z.) with 7 years of experience in MRI reading. STATISTICAL TESTS: Comparisons between approaches were performed with a paired t-test (normality) or a Wilcoxon rank-sum test (nonnormality). P < 0.05 was considered statistically significant. RESULTS: In simulations, DNN gave significantly higher accuracy (91.6%-95.5%) for identification of bi-exponential decays with respect to LSQ-AIC (79.7%-86.8%). For tri-exponential identification, DNN was also superior to LSQ-AIC despite not reaching a significant level (P = 0.08). Additionally, DNN always yielded comparatively low root-mean-square error for estimated parameters. For the in vivo IVIM measurements, inter-subject CVs (0.011-0.150) of DNN were significantly smaller than those (0.049-0.573) of LSQ-AIC. Concerning fitting residuals, there was no significant difference between the two approaches (P = 0.56 and 0.76) in both the simulated and in vivo studies. DATA CONCLUSION: The proposed DNN is recommended for accurate and robust dynamic-exponential modeling and parameter estimation in hepatic IVIM imaging. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Short-Term Repeatability of in Vivo Cardiac Intravoxel Incoherent Motion Tensor Imaging in Healthy Human Volunteers.

BACKGROUND: Intravoxel incoherent motion (IVIM) tensor imaging is a promising technique for diagnosis and monitoring of cardiovascular diseases. Knowledge about measurement repeatability, however, remains limited. PURPOSE: To evaluate short-term repeatability of IVIM tensor imaging in normal in vivo human hearts. STUDY TYPE: Prospective. POPULATION: Ten healthy subjects without history of heart diseases. FIELD STRENGTH/SEQUENCE: Balanced steady-state free-precession cine sequence and single-shot spin-echo echo planar IVIM tensor imaging sequence (9 b-values, 0-400 seconds/mm2 and six diffusion-encoding directions) at 3.0 T. ASSESSMENT: Subjects were scanned twice with an interval of 15 minutes, leaving the scanner between studies. The signal-to-noise ratio (SNR) was evaluated in anterior, lateral, septal, and inferior segments of the left ventricle wall. Fractional anisotropy (FA), mean diffusivity (MD), mean fraction (MF), and helix angle (HA) in the four segments were independently measured by five radiologists. STATISTICAL TESTS: IVIM tensor indexes were compared between observers using a one-way analysis of variance or between scans using a paired t-test (normal data) or a Wilcoxon rank-sum test (non-normal data). Interobserver agreement and test-retest repeatability were assessed using the intraclass correlation coefficient (ICC), within-subject coefficient of variation (WCV), and Bland-Altman limits of agreements. RESULTS: SNR of inferior segment was significantly lower than the other three segments, and inferior segment was therefore excluded from repeatability analysis. Interobserver repeatability was excellent for all IVIM tensor indexes (ICC: 0.886-0.972; WCV: 0.62%-4.22%). Test-retest repeatability was excellent for MD of the self-diffusion tensor (D) and MF of the perfusion fraction tensor (fp ) (ICC: 0.803-0.888; WCV: 1.42%-9.51%) and moderate for FA and MD of the pseudo-diffusion tensor (D* ) (ICC: 0.487-0.532; WCV: 6.98%-10.89%). FA of D and fp and HA of D presented good test-retest repeatability (ICC: 0.732-0.788; WCV: 3.28%-8.71%). DATA CONCLUSION: The D and fp indexes exhibited satisfactory repeatability, but further efforts were needed to improve repeatability of D* indexes. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Effectiveness of Vitamin C Solution in Reducing Adverse Reactions Caused by Painless Lugol Chromoendoscopy: A Multicenter Randomized Controlled Trial.

GOAL: The purpose of this study was to evaluate the effectiveness of vitamin C solution (VCS) in reducing adverse reactions caused by painless Lugol chromoendoscopy. BACKGROUND: Lugol chromoendoscopy is an effective method for screening superficial esophageal squamous cell carcinoma, although Lugol iodine solution (LIS) causes mucosal irritation. STUDY: In 4 hospitals in China, patients were randomized and divided into a distilled water (DW) group, an sodium thiosulfate solution (STS) group and a VCS group. Patients' esophageal mucosal surfaces were stained with either 1.2% or 0.5% LIS and then sprayed with DW, STS, or VCS at various concentrations. For the current randomized study, 1610 patients were enrolled in the 1.2% LIS group and 1355 patients were enrolled in the 0.5% LIS group. In addition, 150 patients were enrolled to assess the discoloration effect. The primary outcome for evaluation was the incidence of acute or late adverse reactions after Lugol iodine staining. The secondary outcome for evaluation was the discoloration effect on esophageal iodine-stained mucosa. RESULTS: VCS significantly reduced the occurrence of acute adverse reactions due to staining from 1.2% LIS. The effect of VCS was similar to that of STS but better than that of DW ( P <0.05). Regarding 0.5% LIS staining, VCS reduced the incidence of acute adverse reactions and heartburn within 1 week ( P <0.05). Both VCS and STS had similar effects. In addition, compared with spraying NS, VCS caused rapid decolorization of iodine-stained esophageal mucosa. After 120 seconds of deiodination, the color of the esophageal mucosa faded by 90%, which is similar to the results seen in the STS group. This contrasts with the results seen in the DW group, which showed fading by only 50.97% ( P <0.05). CONCLUSION: VCS can effectively reduce adverse reactions caused by different concentrations of LIS, indicating its important clinical application in the screening of superficial esophageal squamous cell carcinoma.

Vasoactive intestinal peptide: a potential target for antiviral therapy.

Viral infection is clinically common and some viral diseases, such as the ongoing global outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), have high morbidity and mortality. However, most viral infections are currently lacking in specific therapeutic agents and effective prophylactic vaccines, due to inadequate response, increased rate of drug resistance and severe adverse side effects. Therefore, it is urgent to find new specific therapeutic targets for antiviral defense among which "peptide-based therapeutics" is an emerging field. Peptides may be promising antiviral drugs because of their high efficacy and low toxic side effects. Vasoactive intestinal peptide (VIP) is a prospective antiviral peptide. Since its successful isolation in 1970, VIP has been reported to be involved in infections of SARS-CoV-2, human immune deficiency virus (HIV), vesicular stomatitis virus (VSV), respiratory syncytial virus (RSV), Zika virus (ZIKV) and cytomegalovirus (CMV). Additionally, given that viral attacks sometimes cause severe complications due to overaction of inflammatory and immune responses, the potent anti-inflammatory and immunoregulator properties of VIP facilitate it to be a powerful and promising candidate. This review summarizes the role and mechanisms of VIP in all reported viral infections and suggests its clinical potential as an antiviral therapeutic target.

[Neuro-immune interactions in respiratory diseases].

The nervous system and the immune system are relatively independent but interactional, and neuro-immune regulation is very important for the respiratory system to resist external harmful stimuli and to maintain homeostasis. Neuro-immune interaction is involved in the occurrence and development of respiratory diseases, and is essential for monitoring and modulating inflammation and tissue repair. This article summaries the neuro-immune regulation of respiratory system and discusses its role in respiratory diseases, aiming to provide a theoretical basis for further understanding the crosstalk between the nervous and immune systems, to explore the underlying mechanism in respiratory diseases, and to provide new thoughts for the prevention and treatment of respiratory diseases.

Publishing clinical prActice GuidelinEs (PAGE): Recommendations from editors and reviewers.

Transparency Ecosystem for Research and Journals in Medicine (TERM) working group summarized the essential recommendations that should be considered to review and publish a high-quality guideline. These recommendations from editors and reviewers included 10 components of essential requirements: systematic review of existing relevant guidelines, guideline registration, guideline protocol, stakeholders, conflicts of interest, clinical questions, systematic reviews, recommendation consensus, guideline reporting and external review. TERM working group abbreviates them as PAGE (essential requirements for Publishing clinical prActice GuidelinEs), and recommends guideline authors, editors, and peer reviewers to use them for high-quality guidelines.

The Impact of Weather and Air Pollution on Viral Infection and Disease Outcome Among Pediatric Pneumonia Patients in Chongqing, China, from 2009 to 2018: A Prospective Observational Study.

BACKGROUND: For pediatric pneumonia, the meteorological and air pollution indicators have been frequently investigated for their association with viral circulation but not for their impact on disease severity. METHODS: We performed a 10-year prospective, observational study in 1 hospital in Chongqing, China, to recruit children with pneumonia. Eight commonly seen respiratory viruses were tested. Autoregressive distributed lag (ADL) and random forest (RF) models were used to fit monthly detection rates of each virus at the population level and to predict the possibility of severe pneumonia at the individual level, respectively. RESULTS: Between 2009 and 2018, 6611 pediatric pneumonia patients were included, and 4846 (73.3%) tested positive for at least 1 respiratory virus. The patient median age was 9 months (interquartile range, 4‒20). ADL models demonstrated a decent fitting of detection rates of R2 > 0.7 for respiratory syncytial virus, human rhinovirus, parainfluenza virus, and human metapneumovirus. Based on the RF models, the area under the curve for host-related factors alone was 0.88 (95% confidence interval [CI], .87‒.89) and 0.86 (95% CI, .85‒.88) for meteorological and air pollution indicators alone and 0.62 (95% CI, .60‒.63) for viral infections alone. The final model indicated that 9 weather and air pollution indicators were important determinants of severe pneumonia, with a relative contribution of 62.53%, which is significantly higher than respiratory viral infections (7.36%). CONCLUSIONS: Meteorological and air pollution predictors contributed more to severe pneumonia in children than did respiratory viruses. These meteorological data could help predict times when children would be at increased risk for severe pneumonia and when interventions, such as reducing outdoor activities, may be warranted.

Enantioselective Nickel-Catalyzed Alkyne-Azide Cycloaddition by Dynamic Kinetic Resolution.

The triazole heterocycle has been widely adopted as an isostere for the amide bond. Many native amides are α-chiral, being derived from amino acids. This makes α-N-chiral triazoles attractive building blocks. This report describes the first enantioselective triazole synthesis that proceeds via nickel-catalyzed alkyne-azide cycloaddition (NiAAC). This dynamic kinetic resolution is enabled by a spontaneous [3,3]-sigmatropic rearrangement of the allylic azide. The 1,4,5-trisubstituted triazole products, derived from internal alkynes, are complementary to those commonly obtained by the related CuAAC reaction. Initial mechanistic experiments indicate that the NiAAC reaction proceeds through a monometallic Ni complex, which is distinct from the CuAAC manifold.

1-(4-Amino-2-hydroxyphenyl)ethanone from Phomopsis liquidambari showed quorum sensing inhibitory activity against Pseudomonas aeruginosa.

Phomopsis liquidambari S47 is an endophytic fungus isolated from the leaves of Punica granatum. Here, we are the first to report a quorum sensing (QS) inhibitor 1-(4-amino-2-hydroxyphenyl)ethanone (AHE) isolated and identified from the metabolites of P. liquidambari S47. Exposure to AHE at sub-MIC concentrations notably suppressed the secretion of acyl-homoserine lactones and virulence factors in Pseudomonas aeruginosa PAO1. To investigate the metabolic variations of P. aeruginosa PAO1 exposed to AHE, magnetic resonance imaging-based metabolomic analysis was performed. AHE treatment created a disturbance in the QS system by suppressing the expressions of QS-related genes. The disturbed QS system resulted in the inhibited activity of antioxidant enzymes and thus enhanced oxidative stress. The vegetable infection assay showed that the virulence of P. aeroginosa PAO1 was attenuated which could be due to the impacts to the amino acid and nucleotide metabolism by enhanced oxidative stress. These findings suggest that AHE has a potential to become an antivirulence "agent" to tackle P. aeruginosa infection. KEY POINTS: • AHE treatment inhibited AHL secretion and virulence factors production. • AHE treatment aggravated oxidative stress and disturbed metabolism. • AHE suppressed QS-related gene expressions and reduced virulence of P. aeruginosa.