Mn(II) Promoted Divergent-Convergent Domino Reaction Giving Dinuclear Tetrasubstituted Pyrrole Complex.

Domino reaction of benzo[d]thiazole-2-methylamine (S1) has been developed in the presence of MnCl2 ⋅ 4H2O, leading to tetrasubstituted pyrrole coordinated dinuclear Mn(II) complex 1 ([MnClP]2, P-=2,3,4,5-tetrakis(benzo[d]thiazol-2-yl)pyrrol-1-ide). The reaction process has been studied by assigning a series of intermediates based on time-dependent mass spectrometry, control experiments, crystallography, and density functional theory (DFT) theoretical calculation. A plausible mechanism involving an unprecedented divergent-convergent domino sequence has been proposed. Compound S1 could be activated by MnCl2 ⋅ 4H2O via coordination, which divergently produces two intermediates imine II (1-(benzo[d]thiazol-2-yl)-N-(benzo[d]thiazol-2-ylmethyl)methanimine) and alkene C (1,2-bis(benzo[d]thiazol-2-yl)ethene) through oxidative self-condensation and free radical coupling followed by elimination, respectively. They could then react with each other convergently via formal [3+2] cycloaddition to give deprotonated tetrasubstituted pyrrole coordinated intermediate [MnClP] after aromatization. Dimerization of [MnClP] produces the final product 1. Three C-C bonds and one C-N bond are formed through this six-step domino sequence. The corresponding organic skeleton (HP: 2,2',2'',2'''-(1H-pyrrole-2,3,4,5-tetrayl)tetrakis(benzo[d]thiazole)) has been obtained from 1 and shows a higher fluorescent quantum yield (52 %) than the reported 3,4-diphenyl substituted analogue 2,2'-(3,4-diphenyl-1H-pyrrole-2,5-diyl)bis(benzo[d]thiazole) (DPB) (42 %).

Minimally invasive surgical removal of bilateral impacted mandibular supernumerary teeth using 3D surgical guide template: a case report.

Impacted supernumerary teeth are defined as the presence of one or more teeth in a patient's upper and lower jaws in addition to the normal number of teeth in the dental arch. It has an incidence rate of approximately 1%-14% and more frequently occurs in males than females, may be single or multiple, unilateral or bilateral, erupted or impacted. In this article, we describe the case of a patient with two supernumerary teeth between the roots of the mandibular second premolar and the first molar, which influenced the effectiveness of the first orthodontic treatment. The special anatomical position of the complex supernumerary teeth made tooth extraction challenging. Given the higher risk status of surgery, we implemented a novel tooth extracting technique for this patient. Thus, in this study, we describe a case of minimally invasive extraction of bilateral mandibular impacted supernumerary teeth using a digital 3D positioning guide plate.

Constructing Dynamic Anode/Electrolyte Interfaces Coupled with Regulated Solvation Structures for Long-Term and Highly Reversible Zinc Metal Anodes.

Aqueous zinc ion batteries (AZIBs) show a great potential for next-generation energy storage due to their high safety and high energy density. However, the severe side reactions of zinc negative electrode largely hinder the further application of AZIBs. Herein, trace tris(hydroxymethyl)aminomethane (Tris) additive with rich lone-pair-electrons and zincophilic sites is firstly introduced to achieve long-term and highly reversible Zn plating/stripping. Specifically, Tris not only regulates the solvation structure of Zn2+, but is also adsorbed vertically on the Zn anode surface with a changed coordination intensity during the plating/stripping process of Zn to generate an in situ dynamic adsorption layer for the first time. The dynamic adsorption layer could successively attract the solvated Zn2+ and then promote the de-solvation of the solvated Zn2+ owing to the orientation polarization with regularly-changed applied electric field, the volume rejection effect, and strong intermolecular force towards H2O of the vertically-adsorbed Tris. Therefore, an improved Zn2+-transport kinetics as well as the inhibition of side reactions of Zn anode are successfully realized. Accordingly, the Zn||Zn symmetric cell provides an ultra-long cycle life of 2600 h. Furthermore, the Zn||MnO2 full cell with Tris could demonstrate a high capacity and structural stability for practical applications.

Salt Restriction and Angiotensin-Converting Enzyme Inhibitor Improve the Responsiveness of the Small Artery in Salt-Sensitive Hypertension.

For salt-sensitive hypertension (SSH), salt restriction and angiotensin-converting enzyme (ACE) inhibitors are essential treatments, but their effect on the function of resistance arteries is unclear. Here, we present an intravital study to detect the effect of salt restriction and ACE inhibitors on the function of the mesenteric small artery (MSA) in SSH. Dahl salt-sensitive rats were randomized into the following groups: ACE inhibitor gavage, salt restriction, ACE inhibitor combined with salt restriction, and high-salt diet. After a 12-week intervention, the mesenteric vessels maintained their perfusion in vivo, and the changes in the diameter and blood perfusion of the MSAs to norepinephrine (NE) and acetylcholine (ACh) were detected. Switching from a high-salt diet to a low-salt diet (i.e., salt restriction) attenuated the vasoconstriction of the MSAs to NE and promoted the vasodilatation to ACh, while ACE inhibitor improved the vasodilatation more obviously. Pathologically, changes in local ACE, AT1R, and eNOS expression were involved in these processes induced by a high-salt diet. Our study suggests that salt restriction and ACE inhibitor treatment improve high salt intake-induced MSA dysfunction in SSH, and salt restriction is a feasible and effective treatment. Our findings may provide a scientific basis for the treatment of hypertension.

Hot-Pressing Furnace Current Monitoring and Predictive Maintenance System in Aerospace Applications.

This research combines the application of artificial intelligence in the production equipment fault monitoring of aerospace components. It detects three-phase current abnormalities in large hot-pressing furnaces through smart meters and provides early preventive maintenance. Different anomalies are classified, and a suitable monitoring process algorithm is proposed to improve the overall monitoring quality, accuracy, and stability by applying AI. We also designed a system to present the heater's power consumption and the hot-pressing furnace's fan and visualize the process. Combining artificial intelligence with the experience and technology of professional technicians and researchers to detect and proactively grasp the health of the hot-pressing furnace equipment improves the shortcomings of previous expert systems, achieves long-term stability, and reduces costs. The complete algorithm introduces a model corresponding to the actual production environment, with the best model result being XGBoost with an accuracy of 0.97.

Capsaicin enhances the antitumor activity of sorafenib in hepatocellular carcinoma cells and mouse xenograft tumors through increased ERK signaling.

Sorafenib, a small inhibitor of tyrosine protein kinases, is currently the standard chemotherapy drug for the treatment of advanced hepatocellular carcinoma (HCC). Although sorafenib improves the survival of HCC patients, its efficacy is not optimal and requires further improvement. Capsaicin, the major active component of chili peppers from the genus Capsicum, is not only the agonist of TRPV1 channel, but also displays antitumor activity and enhances the sensitivity of cancer cells to cytotoxic drugs. In this study, we investigated the antitumor effects of combined sorafenib and capsaicin on HCC cells in vitro and xenograft tumors. Treatment with capsaicin alone dose-dependently inhibited the proliferation of the HCC cell lines PLC/PRF/7, HuH7 and HepG2 with IC50 values of 137, 108 and 140.7 µmol/L, respectively. No obvious expression of TRPV1 channel was detected in the 3 HCC cell lines and TRPV1 channel blockers did not alleviate the cytotoxicity of capsaicin. By contrast, combining capsaicin and sorafenib significantly enhanced the suppression on cell proliferation, achieving a high-level synergistic effect (inhibition rates over 50%) and promoting HCC cell apoptosis. In nude mice with PLC/PRF/5 xenografts, combined administration of capsaicin and sorafenib significantly enhanced the suppression on tumor growth without apparent gross toxicity compared to either agent alone. Mechanistically, capsaicin (10-200 µmol/L) dose-dependently increased the levels of phosphorylated ERK (p-ERK) in PLC/PRF/5 cells, thus leading to enhanced sorafenib sensitivity and a synergistic suppression on the tumor cells. Taken together, our results suggest that capsaicin-increased phosphorylation of ERK contributes to the enhanced antitumor activity of sorafenib, and capsaicin may be useful in improving the efficacy of sorafenib for the treatment of HCC.

Non-invasive brain stimulation for fibromyalgia: current trends and future perspectives.

Fibromyalgia, a common and enduring pain disorder, ranks as the second most prevalent rheumatic disease after osteoarthritis. Recent years have witnessed successful treatment using non-invasive brain stimulation. Transcranial magnetic stimulation, transcranial direct current stimulation, and electroconvulsion therapy have shown promise in treating chronic pain. This article reviews the literature concerning non-invasive stimulation for fibromyalgia treatment, its mechanisms, and establishes a scientific basis for rehabilitation, and discusses the future directions for research and development prospects of these techniques are discussed.

[Acupoints compatibility rules of acupuncture for depression disease based on data mining technology].

Based on data mining technology, the acupoints compatibility rules of acupuncture for depression diseases were explored. The randomized controlled trial (RCT) articles regarding acupuncture for depression diseases published from establishment of database to September 2nd, 2022 were searched in CNKI database, Wangfang database, VIP database, SinoMed database, PubMed, EMbase, Web of Science and Cochrane Library. The use frequency of acupoints, meridian tropism, selection of special acupoints and acupoint association rules for five common depression diseases, including primary depression, post-stroke depression, menopausal syndrome, psychoneurosis and anxiety disorder, were analyzed by Python programming language. Cytoscape software was used to analyze the acupoint association and the disease-acupoint co-occurrence network. As a result, totally 387 articles were included, and 319 acupoints prescriptions for the above five common depression diseases were extracted, involving 159 acupoints. The use frequency of acupoints was 2 574 times in total. The frequently-used acupoints were Baihui (GV 20), Sanyinjiao (SP 6), Taichong (LR 3), Neiguan (PC 6), Shenmen (HT 7), Yintang (GV 24+), Zusanli (ST 36), Hegu (LI 4), Sishencong (EX-HN 1) and Taixi (KI 3), etc. The frequently involved meridians were the governor vessel, foot-taiyang bladder meridian, foot-taiyin spleen meridian, and foot-jueyin liver meridian. The frequency of the special acupoints from high to low was crossing points, five-shu points, yuan-primary points, back-shu points, luo-connecting points, and eight confluent points, etc, which were often used in combination with "Baihui (GV 20)-Yintang (GV 24+)" (the highest degree of association). At the same time, the analysis of the co-occurrence network of depression diseases and acupoints showed that the core acupoints group of acupuncture for depression diseases were Baihui (GV 20), Taichong (LR 3), Shenmen (HT 7), Zusanli (ST 36), Neiguan (PC 6) and Sanyinjiao (SP 6). In conclusion, acupuncture treatment for depression diseases has gradually formed a rule of acupoint compatibility, with special acupoint as the main body and "unblocking the governor vessel, and regulating the spirit and qi " as the main therapeutic principle.

HVT-vectored H7 vaccine protects chickens from lethal infection with the highly pathogenic H7N9 Avian influenza virus.

Since mid-2016, the highly pathogenic H7N9 subtype avian influenza virus (AIV) has threatened both public health and the poultry industry. Although a vaccination strategy has been deemed imperative to manage the virus, the most commonly used inactivated vaccines today are susceptible to interference from maternal antibodies and associated with an over-reliance on humoral immunity. In response, we developed a recombination vaccine with the herpesvirus of turkeys (HVT) as the vector to squeeze HPAI H7N9 and assessed its protective efficiency in immunized chickens. By inserting an enhanced green fluorescent protein (EGFP) expression cassette (i.e., MCMV+EGFP+SV40 polyA) into the HVT065 and HVT066 positions, we obtained the recombinant HVT expressing EGFP (i.e., rHVT-EGFP). Electroporation and EGFP tags improved the efficiency of transfection compared with transfection using expression plasmids without any fluorescent labeling and traditional liposomes. Using limiting dilution analysis and ultrasonic cell disruption techniques, we screened and purified a cell-bound herpes virus based on rHVT-EGFP and consequently constructed a recombinant HVT expressing the hemagglutinin (HA) of H7N9 (i.e., rHVT-H7HA), which was able to proliferate similarly to the parental strain, stably pass for at least 15 generations in vitro, and replicate stably in multiple organs in vivo. After chickens were immunized with rHVT-H7HA, the average antibody titers reached up to 3 log2 at 35 d post-vaccination and remained stable. Those results suggest that rHVT-H7HA can protect chickens against H7N9 with a dose-independent immune protection rate of 90% and significantly reduce the lung virus titer 4 d post-challenge.

Pharmacological targeting of Axin2 suppresses cell growth and metastasis in colorectal cancer.

BACKGROUND AND PURPOSE: The scaffold molecule Axin2 is constitutively activated in colorectal cancer (CRC) and functions as a potent promoter of CRC behaviour. Pharmacological targeting of Axin2 may therefore exert a therapeutic effect in patients with CRC. Here, we discovered a potent small-molecule inhibitor of Axin2, based on the mechanism by which Axin2 is regulated post-translationally, and investigated its antitumour effects. EXPERIMENTAL APPROACH: Compound discovery and its inhibitory action on Axin2 protein were revealed by microscale thermophoresis, in vitro kinase assay, quantitative kinetic assay, immunoblotting/immunoprecipitation, RT-qPCR and cycloheximide pulse-chase assay. Compound antitumour effects and the underlying mechanisms were evaluated in multiple cell-based assays and mouse models. KEY RESULTS: We discovered that glycogen synthase kinase 3ß (GSK3ß) phosphorylates Axin2 at two consensus motifs and coupled Axin2 phosphorylation to its ubiquitination (mediated by the E3 ligase ß-Trcp2) and proteasomal degradation. The binding of Axin2 to GSK3ß in CRC cells is faint, which enables most of the Axin2 protein to maintain an unphosphorylated status and thereby permits the cells to preserve high levels of Axin2. Importantly, we identified a small-molecule compound CW85319 that enhances Axin2's interaction with GSK3ß via forming a high affinity for Axin2. Treatment of CRC cells with CW85319 enhanced Axin2 binding with GSK3ß, thereby promoting Axin2 phosphorylation, subsequent ubiquitination, and degradation. Furthermore, we demonstrated that CW85319 efficiently suppressed Axin2-driven CRC growth and metastasis, without eliciting side toxicity. CONCLUSIONS AND IMPLICATIONS: These findings suggest that pharmacological targeting of Axin2 by CW85319 may provide therapeutic benefits against certain human cancers, especially CRC.

Diagnostic value of BinaxNOW antigen card for Severe Acute Respiratory Syndrome Coronavirus 2.

Rapid laboratory detection is remarkably crucial to diagnosing coronavirus disease 2019 (COVID-19) infection, due to whose outbreak causes to the world pandemic. The BinaxNOW antigen card (BinaxNOW) is a simple, effective, and cheap tool to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The meta-analysis in this study was conducted to evaluate the diagnostic performance of BinaxNOW for SARS-CoV-2. The researchers independently retrieved the related databases (PubMed, Embase, Web of Science, Cochrane Library) before May 1st, 2021, and extracted the relevant data based on the early inclusion/exclusion criterion. Quality Assessment of Diagnostic Accuracy Study-2 was used to evaluate the quality of the enrolled studies. Stata 16.0, Meta-DiSc 1.4, and Review Manager 5.3 were used to generate analytical data for the statistical analysis. 59 sets of data were identified from the seven studies included in this meta-analysis. The combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and their 95% confidence intervals were 0.77 (0.76 to 0.79), 0.99 (0.99 to 0.99), 65.72 (48.23 to 89.56), 0.23 (0.19 to 0.28), and 461.10 (281.55 to 755.13), respectively. The area under curve was 0.9910 in the summary receiver operating characteristic curve. BinaxNOW is beneficial for symptomatic patients' onset within 7 days. CT value and testing site may be the heterogeneity source of BinaxNOW accuracy. Moreover, this technology has an efficient performance for diagnosing COVID-19, especially in patients with heavy viral load. BinaxNOW may become a practical tool for large-scale or at-home use for COVID-19 in the post-pandemic era.Highlights● Pooled sensitivity with 0.77 and specificity with 0.99 in the BinaxNOW assay.● CT value and testing site may be the heterogeneity source of BinaxNOW accuracy.● BinaxNOW is beneficial for symptomatic patients' onset within 7 days.● BinaxNOW may become a practical tool for large-scale or at-home use for COVID-19.

Luteolin Attenuates Hypertension via Inhibiting NF-κB-Mediated Inflammation and PI3K/Akt Signaling Pathway in the Hypothalamic Paraventricular Nucleus.

BACKGROUND: Luteolin is widely distributed among a number of vegetal species worldwide. The pharmacological effects of luteolin are diverse and amongst antioxidant, free radical scavenging, and anti-inflammatory activities. Preliminary study showed that luteolin can ameliorate hypertension. However, the precise mechanism needs further investigation. There is no evidence that luteolin affects the paraventricular nucleus of the hypothalamus (PVN), a brain nucleus associated with a critical neural regulator of blood pressure. Our main aim was to explore the effect of luteolin on the PI3K/Akt/NF-κB signaling pathway within the PVN of hypertensive rats. METHODS: spontaneously hypertensive rats (SHRs) and corresponding normotensive control rats, the Wistar Kyoto (WKY) rats were divided into four groups and subsequently treated for 4 weeks with bilateral PVN injections of either luteolin (20 µg/0.11 µL, volume: 0.11 µL/h) or vehicle (artificial cerebrospinal fluid). RESULTS: luteolin infusion to the PVN significantly decreased some hemodynamic parameters including the mean arterial pressure (MAP), heart rate (HR), circulating plasma norepinephrine (NE) and epinephrine (EPI). Additionally, there was a decrease in the expressions of the phosphatidylinositol 3-kinase (p-PI3K) and phosphorylated protein kinase-B (p-AKT), levels of reactive oxygen species (ROS), NAD(P)H oxidase subunit (NOX2, NOX4) in the PVN of SHRs. Meanwhile, the expression of inflammatory cytokines and the activity of nuclear factor κB (NF-κB) p65 in the PVN of SHRs were lowered. Furthermore, immunofluorescence results showed that injection of luteolin in the PVN reduced the expression of tyrosine hydroxylase (TH), and increased that of superoxide dismutase (SOD1) and the 67-kDa isoform of glutamate decarboxylase (GAD67) in the PVN of SHRs. CONCLUSION: Our novel findings revealed that luteolin lowered hypertension via inhibiting NF-κB-mediated inflammation and PI3K/Akt signaling pathway in the PVN.

Metformin use is associated with a reduced risk of cognitive impairment in adults with diabetes mellitus: A systematic review and meta-analysis.

Objective: Controversy exists regarding the impact of metformin and whether it prevents or promotes the incidence of cognitive dysfunction. This systematic review and meta-analysis were conducted to identify the effect of metformin therapy on cognitive function in patients with diabetes. Methods: Electronic databases (PubMed, EMBASE, PsycINFO, the Cochrane Library, and Web of Science) were systematically searched by two investigators from the date of inception until March 1, 2022. The study followed PRISMA guidelines. Inclusion criteria were defined according to the PECOS model. Eligible studies investigated cognitive dysfunction in metformin users compared with non-users in adults with diabetes. Only observational study designs (such as cohort, cross-section, and case-control) were included. Results: A systematic search identified 1,839 articles, of which 28 (17 cohort, 8 case-control, and 3 cross-sectional studies) were included in the meta-analysis. Metformin reduced the occurrence of cognitive impairment in patients with diabetes [unadjusted hazard ratio (HR) = 0.67, 95% CI: 0.62-0.73; adjusted hazard ratio (aHR) = 0.92, 95% CI: 0.85-0.99]. In addition, the use of metformin was associated with a decreased risk of dementia (HR = 0.64, 95% CI: 0.59-0.69; aHR = 0.90, 95% CI: 0.84-0.96), while a random-effects meta-analysis indicated no significant effect of metformin on the risk of Alzheimer's disease (AD) (HR = 0.85, 95% CI: 0.60-1.22; aHR = 1.10, 95% CI: 0.95-1.28). Conclusion: Metformin therapy decreased the occurrence risk of cognitive decline in patients with diabetes mellitus. Moreover, the use of metformin by adults with diabetes for the prevention of dementia, but not AD, is supported by the available evidence.

Early-Onset Pulmonary Events with Combined Brigatinib and Afatinib Treatment of L858/cisT790M/cisC797S NSCLC: A Case Report.

BACKGROUND Brigatinib is used for anaplastic lymphoma kinase (ALK)-positive lung cancer treatment, and some research showed it was useful in treating triple-mutant epidermal growth factor receptor lung cancer. Clinical trials have shown some potential pulmonary toxicities of brigatinib. The early-onset pulmonary events (EOPEs) of brigatinib are associated with high dosage and older age. The successful treatment of EOPEs with steroids was reported. We present the case of a patient with epidermal growth factor receptor L858R/cis-T790M/cis-C797S triple mutations who developed EOPEs after using brigatinib together with afatinib, and the patient was successfully treated with high-dose steroids. CASE REPORT A 54-year-old woman with underlying stage IV lung adenocarcinoma, ECOG score of 0, was treated with brigatinib and afatinib due to disease progression secondary to L858R/cis-T790M/cis-C797S triple mutations. After starting brigatinib and afatinib, she developed dyspnea and dry cough within 2 days and was intubated due to hypercapnic respiratory failure. The chest X-ray showed bilateral interstitial infiltrates while chest computed tomography (CT) showed bilateral ground-glass opacities. EOPEs were suspected and methylprednisolone was prescribed. The oxygenation of the patient improved and her chest CT showed complete resolution after 2 weeks of steroid treatment. CONCLUSIONS This is the first reported case in which brigatinib combined with afatinib induced EOPEs in a patient with triple-mutant epidermal growth factor receptors of lung cancer. Use of doubled tyrosine kinase inhibitors may result in increased risk of pulmonary toxicities that require high alertness, and the respiratory symptoms should be monitored closely after prescription. The early treatment of EOPEs with high-dose steroids resulted in remarkable improvement.

A Novel Insight into Paraptosis-Related Classification and Signature in Lower-Grade Gliomas.

Lower-grade gliomas (LGG) are the most common intracranial malignancies that readily evolve to high-grade gliomas and increase drug resistance. Paraptosis is defined as a nonapoptotic form of programmed cell death, which is gradually focused on patients with gliomas to develop treatment options. However, the specific role of paraptosis in LGG and its correlation is still vague. In this study, we first establish the novel paraptosis-based prognostic model for LGG patients. The relevant data of LGG patients were acquired from The Cancer Genome Atlas database, and we found that LGG patients could be divided into three different clusters based on paraptosis via consensus cluster analysis. Through least absolute shrinkage and selection operator regression analysis and multivariate Cox regression analysis, 10-paraptosis-related gene (PRG) signatures (CDK4, TNK2, DSTYK, CDKN3, CCR4, CASP9, HSPA5, RGR, LPAR1, and PDCD6IP) were identified to separate LGG patients into high- and low-risk subgroups successfully. The Kaplan-Meier analysis and time-dependent receiver-operating characteristic showed that the performances of predicting overall survival (OS) were dramatically high. The parallel results were reappeared and verified by using the Chinese Glioma Genome Atlas and Gene Expression Omnibus databases. Independent prognostic analysis and nomogram construction implied that risk scores could be considered the independent factor to predict OS. Enrichment analysis indicated that immune-related biological processes were generally enriched, and different immune statuses were highly infiltrated in high-risk group. We also confirmed the potential relationship of 10-PRG signatures and drug sensitivity of Food and Drug Administration-approved drugs. In summary, our findings provide a novel knowledge of paraptosis status and crucial direction to further explore the role of PRG signatures in LGG.

Effects of bone morphogenetic proteins on epithelial repair.

Epithelial tissue has important functions such as protection, secretion, and sensation. Epithelial damage is involved in various pathological processes. Bone morphogenetic proteins (BMPs) are a class of growth factors with multiple functions. They play important roles in epithelial cells, including in differentiation, proliferation, and migration during the repair of the epithelium. This article reviews the functions and mechanisms of the most profoundly studied BMPs in the process of epithelial damage repair and their clinical significance.

Positive end-expiratory pressure titration with electrical impedance tomography and pressure-volume curve: a randomized trial in moderate to severe ARDS.

OBJECTIVE: The aim of the study was to compare titration of positive end-expiratory pressure (PEEP) with electrical impedance tomography (EIT) and with ventilator-embedded pressure-volume (PV) loop in moderate to severe acute respiratory distress syndrome (ARDS). APPROACH: Eighty-seven moderate to severe ARDS patients (arterial oxygen partial pressure to fractional inspired oxygen ratio, PaO2/FiO2 ≤ 200 mmHg) were randomized to either EIT group (n = 42) or PV group (n = 45). All patients received identical medical care using the same general support guidelines and protective mechanical ventilation. In the EIT group, the selected PEEP equaled the airway pressure at the intercept between cumulated collapse and overdistension percentages curves and in the PV group, at the pressure where maximal hysteresis was reached. MAIN RESULTS: Baseline characteristics and settings were comparable between the groups. After optimization, PEEP was significantly higher in the PV group (17.4 ± 1.7 versus 16.2 ± 2.6 cmH2O, PV versus EIT groups, p = 0.02). After 48 h, driving pressure was significantly higher in the PV group (12.4 ± 3.6 versus 10.9 ± 2.5 cmH2O, p = 0.04). Lung mechanics and oxygenation were better in the EIT group but did not statistically differ between the groups. The survival rate was lower in the PV group (44.4% versus 69.0%, p = 0.02; hazard ratio 2.1, confidence interval 1·1-3.9). None of the other pre-specified exploratory clinical endpoints were significantly different. SIGNIFICANCE: In moderate to severe ARDS, PEEP titration guided with EIT, compared with PV curve, might be associated with improved driving pressure and survival rate. TRIAL REGISTRATION: NCT03112512, 13 April, 2017.

Network of Interactions Between Gut Microbiome, Host Biomarkers, and Urine Metabolome in Carotid Atherosclerosis.

Comprehensive analyses of multi-omics data may provide insights into interactions between different biological layers concerning distinct clinical features. We integrated data on the gut microbiota, blood parameters and urine metabolites of treatment-naive individuals presenting a wide range of metabolic disease phenotypes to delineate clinically meaningful associations. Trans-omics correlation networks revealed that candidate gut microbial biomarkers and urine metabolite feature were covaried with distinct clinical phenotypes. Integration of the gut microbiome, the urine metabolome and the phenome revealed that variations in one of these three systems correlated with changes in the other two. In a specific note about clinical parameters of liver function, we identified Eubacteriumeligens, Faecalibacteriumprausnitzii and Ruminococcuslactaris to be associated with a healthy liver function, whereas Clostridium bolteae, Tyzzerellanexills, Ruminococcusgnavus, Blautiahansenii, and Atopobiumparvulum were associated with blood biomarkers for liver diseases. Variations in these microbiota features paralleled changes in specific urine metabolites. Network modeling yielded two core clusters including one large gut microbe-urine metabolite close-knit cluster and one triangular cluster composed of a gut microbe-blood-urine network, demonstrating close inter-system crosstalk especially between the gut microbiome and the urine metabolome. Distinct clinical phenotypes are manifested in both the gut microbiome and the urine metabolome, and inter-domain connectivity takes the form of high-dimensional networks. Such networks may further our understanding of complex biological systems, and may provide a basis for identifying biomarkers for diseases. Deciphering the complexity of human physiology and disease requires a holistic and trans-omics approach integrating multi-layer data sets, including the gut microbiome and profiles of biological fluids. By studying the gut microbiome on carotid atherosclerosis, we identified microbial features associated with clinical parameters, and we observed that groups of urine metabolites correlated with groups of clinical parameters. Combining the three data sets, we revealed correlations of entities across the three systems, suggesting that physiological changes are reflected in each of the omics. Our findings provided insights into the interactive network between the gut microbiome, blood clinical parameters and the urine metabolome concerning physiological variations, and showed the promise of trans-omics study for biomarker discovery.

The best optical zone for small-incision lenticule extraction in high myopic patients.

Small-incision lenticule extraction (SMILE) is an effective and safe procedure for the correction of myopia due to minimally invasive and noncorneal flap surgery. However, the SMILE procedure has certain requirements for corneal cap thickness, attempted refractive correction, residual stromal bed thickness, and optical zone diameter, which sometimes make surgeons hesitant to choose SMILE or other refractive surgeries. The requirements limit its use in patients with high myopia. The purpose of this review was to find the optimal parameters of SMILE through discussing the best optical zone for high myopic patients, the visual quality of different optical zones, the choice of corneal cap thickness, and their effects on corneal biomechanical parameters, so surgeons can provide reference recommendations for patients with high myopia in choosing a reasonable and safe procedure.