Therapeutic Implications of Phenolic Acids for Ameliorating Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disorder, and its complex etiology makes prevention and treatment challenging. Research on new drugs and treatment strategies is currently a focal point. Phenolic acids are widely present in plant-based diets and have demonstrated the potential to alleviate colitis due to their powerful antioxidant and anti-inflammatory properties. In this review, we provide an overview of the structures and main dietary sources of phenolic acids, encompassing benzoic acid and cinnamic acid. Additionally, we explore the potential of phenolic acids as a nutritional therapy for preventing and treating IBD. In animal and cell experiments, phenolic acids effectively alleviate IBD induced by drug exposure or genetic defects. The mechanisms include improving intestinal mucosal barrier function, reducing oxidative stress, inhibiting excessive activation of the immune response, and regulating the balance of the intestinal microbiota. Our observation points towards the need for additional basic and clinical investigations on phenolic acids and their derivatives as potential novel therapeutic agents for IBD.

Analysis of tissue tropism of GCRV-II infection in grass carp using a VP35 monoclonal antibody.

Grass carp, one of the major freshwater aquaculture species in China, is susceptible to grass carp reovirus (GCRV). GCRV is a non-enveloped RNA virus and has a double-layered capsid, causing hemorrhagic disease and high mortalities in infected fish. However, the tropism of GCRV infection has not been investigated. In this study, monoclonal antibodies against recombinant VP35 protein were generated in mice and characterized. The antibodies exhibited specific binding to the N terminal region (1-155 aa) of the recombinant VP35 protein expressed in the HEK293 cells, and native VP35 protein in the GCRV-II infected CIK cells. Immunofluorescent staining revealed that viruses aggregated in the cytoplasm of infected cells. In vivo challenge experiments showed that high levels of GCRV-II viruses were present in the gills, intestine, spleen and liver, indicating that they are the major sites for virus infection. Our study showed that the VP35 antibodies generated in this study exhibited high specificity, and are valuable for the development of diagnostic tools for GCRV-II infection.

Redefining left bundle branch block from high-density electroanatomical mapping.

BACKGROUND: The existing ECG criteria for diagnosing left bundle branch block (LBBB) are insufficient to distinguish between true and false blocks accurately. METHODS: We hypothesized that the notch width of the QRS complex in the lateral leads (I, avL, V5, V6) on the LBBB-like ECG could further confirm the diagnosis of true complete left bundle branch block (t-LBBB). We conducted high-density, three-dimensional electroanatomical mapping in the cardiac chambers of 37 patients scheduled to undergo CRT. These patients' preoperative electrocardiograms met the ACC/AHA/HRS guidelines for the diagnosis of complete LBBB. If the left bundle branch potential could be mapped from the base of the heart to the apex on the left ventricular septum, it was defined as a false complete left bundle branch block (f-LBBB). Otherwise, it was categorized as a t-LBBB. We conducted a comparative analysis between the two groups, considering the clinical characteristics, real-time correspondence between the spread of ventricular electrical excitation and the QRS wave, QRS notch width of the lateral leads (I, avL, V5, V6), and the notch width/left ventricular end-diastolic diameter (Nw/LVd) ratio. We performed the ROC correlation analysis of Nw/LVd and t-LBBB to determine the sensitivity and specificity for diagnostic authenticity. RESULTS: Twenty-five patients were included in the t-LBBB group, while 12 patients were assigned to the f-LBBB group. Within the t-LBBB group, the first peak of the QRS notch correlated with the depolarization of the right ventricle and septum, the trough corresponded to the depolarization of the left ventricle across the left ventricle, and the second peak aligned with the depolarization of the left ventricular free wall. In contrast, within the f-LBBB group, the first peak coincided with the depolarization of the right ventricle and a majority of the left ventricle, the second peak occurred due to the depolarization of the latest, locally-activated myocardium in the left ventricle, and the trough was a result of delayed activation of the left ventricle that did not align with the usual peak timing. The QRS notch width (45.2 ± 12.3 ms vs. 52.5 ± 9.2 ms, P < 0.05) and the Nw/LVd ratio (0.65 ± 0.19 ms/mm vs. 0.81 ± 0.17 ms/mm, P < 0.05) were compared between the two groups. After conducting the ROC correlation analysis, a sensitivity of 56% and a specificity of 91.7% for diagnosing t-LBBB using Nw/LVd were obtained. CONCLUSION: By utilizing the current diagnostic criteria for LBBB, an increased Nw/LVd value can enhance the effectiveness of diagnosing LBBB.

Agronomic, physiological and transcriptional characteristics provide insights into fatty acid biosynthesis in yellowhorn (Xanthoceras sorbifolium Bunge) during fruit ripening.

Yellowhorn (Xanthoceras sorbifolium Bunge) is an oil-bearing tree species in northern China. In this study, we used yellowhorn from Heilongjiang to analyze the morphological and physiological changes of fruit development and conducted transcriptome sequencing. The results showed that the fruit experienced relatively slow growth from fertilization to DAF20 (20 days after flowering). From DAF40 to DAF60, the fruit entered an accelerated development stage, with a rapid increase in both transverse and longitudinal diameters, and the kernel contour developed completely at DAF40. From DAF60 to DAF80, the transverse and vertical diameters of the fruit developed slowly, and the overall measures remained stable until maturity. The soluble sugar, starch, and anthocyanin content gradually accumulated until reaching a peak at DAF80 and then rapidly decreased. RNA-seq analysis revealed differentially expressed genes (DEGs) in the seed coat and kernel, implying that seed components have different metabolite accumulation mechanisms. During the stages of seed kernel development, k-means clustering separated the DEGs into eight sub-classes, indicating gene expression shifts during the fruit ripening process. In subclass 8, the fatty acid biosynthesis pathway was enriched, suggesting that this class was responsible for lipid accumulation in the kernel. WGCNA revealed ten tissue-specific modules for the 12 samples among 20 modules. We identified 54 fatty acid biosynthesis pathway genes across the genome, of which 14 was quantified and confirmed by RT-qPCR. Most genes in the plastid synthesis stage showed high expression during the DAF40-DAF60 period, while genes in the endoplasmic reticulum synthesis stage showed diverse expression patterns. EVM0012847 (KCS) and EVM0002968 (HCD) showed similar high expression in the early stages and low expression in the late stages. EVM0022385 (HCD) exhibited decreased expression from DAF40 to DAF60 and then increased from DAF60 to DAF100. EVM0000575 (KCS) was increasingly expressed from DAF40 to DAF60 and then decreased from DAF60 to DAF100. Finally, we identified transcription factors (TFs) (HB-other, bHLH and ARF) that were predicted to bind to fatty acid biosynthesis pathway genes with significant correlations. These results are conducive to promoting the transcriptional regulation of lipid metabolism and the genetic improvement in terms of high lipid content of yellowhorn.

Predictors and prognosis of early neurological outcomes on patients with Vertebrobasilar artery occlusion undergoing endovascular treatment.

BACKGROUND: This research explored the factors influencing early neurological outcomes (ENO) in patients who had vertebrobasilar artery occlusion (VBAO) and received endovascular treatment (EVT), as well as examining the causal influence of ENO on the prognosis of VBAO patients. METHODS: A retrospective review was carried out on patients from 65 Chinese stroke centers, all within 24 hours of the estimated occlusion time. ENO includes early neurological improvement (ENI) and early neurological deterioration (END), defined as a decrease or an increase of at least 4 points in NIHSS score between baseline and 24 hours after EVT. Death within 24 hours after EVT also consider as END. END was further divided into explainable END and unexplainable END (unEND). Independent predictors of ENO and the association between ENO and outcomes in patients with VBAO were determined using center-adjusted analyses. The study developed a multivariate logistic regression model to examine the comparative risk of unEND versus explainable END on the clinical outcomes in VBAO patients. RESULTS: A total of 2257 patients were included. Glasgow Coma Scale (GCS) (OR 1.16, 95% CI 1.03-1.30) and successful reperfusion (OR 1.15, 95% CI 1.02-1.30) were associated with ENI. Baseline NIHSS (OR 0.60, 95% CI 0.53-0.68), successful reperfusion (OR 0.79, 95% CI 0.71-0.89) and puncture to reperfusion time (OR 1.17, 95% CI 1.03-1.33) were associated with END. When examining three-month prognostic indexes, both END and ENI were found to be linked to the three-month outcomes, but in opposite directions. A subgroup analysis of END suggested that unexplained END typically demonstrated a more favorable prognosis compared to explained END, although the prognosis remained generally unfavorable. CONCLUSIONS: ENO, whether they manifested as early improvement or deterioration, were linked to the prognosis of VBAO patients undergoing EVT. The outcomes after unEND were more favorable than those following explained END.

Rescue stenting after failure of endovascular thrombectomy for acute vertebrobasilar artery occlusion: data from the PERSIST registry.

BACKGROUND: Among acute vertebrobasilar artery occlusion (VBAO) patients, successful reperfusion is a strong predictor of favorable outcomes. However, failed reperfusion (FR) with endovascular thrombectomy (EVT) in VBAO was observed to occur in 18-50% of cases. We aim to evaluate the safety and efficacy of rescue stenting (RS) for VBAO after failed EVT. METHODS: Patients with VBAO who received EVT were enrolled retrospectively. Propensity score matching was performed as the primary analysis to compare the outcomes between patients with RS and FR. Furthermore, a comparison between using the self-expanding stent (SES) and balloon-mounted stent (BMS) in the RS group was also conducted. The primary and secondary outcomes were defined as a 90-day modified Rankin Scale (mRS) score 0-3, and a 90-day mRS score 0-2, respectively. Safety outcomes included all-cause mortality at 90 days and symptomatic intracranial hemorrhage (sICH). RESULTS: The RS group showed a significantly higher rate of 90-day mRS score 0-3 (46.6% vs 20.7%; adjusted OR (aOR) 5.06, 95% CI 1.88 to 13.59, P=0.001) and a lower rate of 90-day mortality (34.5% vs 55.2%; aOR 0.42, 95% CI 0.23 to 0.90, P=0.026) than the FR group. The rates of 90-day mRS score 0-2 and sICH were not significantly different between the RS group and FR group. There were no differences in all outcomes between SES and BMS groups. CONCLUSIONS: RS appeared to be a safe and effective rescue approach in patients with VBAO who failed EVT, and there was no difference between using SES and BMS.

Efficient Flexible Fabric-Based Top-Emitting Polymer Light-Emitting Devices for Wearable Electronics.

Low-cost fabric-based top-emitting polymer light-emitting devices (Fa-TPLEDs) have aroused increasing attention due to their remarkable potential applications in wearable displays. However, it is still challenging to realize efficient all-solution-processed devices from bottom electrodes to top electrodes with large-scale fabrication. Here, a smooth reflective Ag cathode integrated on fabric by one-step silver mirror reaction and a composite transparent anode of polydimethylsiloxane/silver nanowires/poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) via a water-assisted peeling method are presented, both of which possess excellent optoelectrical properties and robust mechanical flexibility. The Fa-TPLEDs are constructed by spin-coating functional layers on the bottom reflective cathodes and laminating the top transparent anodes. The Fa-TPLEDs show a current efficiency of 16.3 cd A-1 , an external quantum efficiency of 4.9% and angle-independent electroluminescence spectra. In addition, the Fa-TPLEDs possess excellent mechanical stability, maintaining a current efficiency of 14.3 cd A-1 after 200 bending cycles at a radius of 4 mm. The results demonstrate that the integration of solution-processed reflective cathodes and transparent anodes sheds light on a new avenue to construct low-cost and efficient fabric-based devices, showing great potential applications in emerging smart flexible/wearable electronics.

The MRI radiomics signature can predict the pathologic response to neoadjuvant chemotherapy in locally advanced esophageal squamous cell carcinoma.

OBJECTIVES: To investigate the MRI radiomics signatures in predicting pathologic response among patients with locally advanced esophageal squamous cell carcinoma (ESCC), who received neoadjuvant chemotherapy (NACT). METHODS: Patients who underwent NACT from March 2015 to October 2019 were prospectively included. Each patient underwent esophageal MR scanning within one week before NACT and within 2-3 weeks after completion of NACT, prior to surgery. Radiomics features extracted from T2-TSE-BLADE were randomly split into the training and validation sets at a ratio of 7:3. According to the progressive tumor regression grade (TRG), patients were stratified into two groups: good responders (GR, TRG 0 + 1) and poor responders (non-GR, TRG 2 + 3). We constructed the Pre/Post-NACT model (Pre/Post-model) and the Delta-NACT model (Delta-model). Kruskal-Wallis was used to select features, logistic regression was used to develop the final model. RESULTS: A total of 108 ESCC patients were included, and 3/2/4 out of 107 radiomics features were selected for constructing the Pre/Post/Delta-model, respectively. The selected radiomics features were statistically different between GR and non-GR groups. The highest area under the curve (AUC) was for the Delta-model, which reached 0.851 in the training set and 0.831 in the validation set. Among the three models, Pre-model showed the poorest performance in the training and validation sets (AUC, 0.466 and 0.596), and the Post-model showed better performance than the Pre-model in the training and validation sets (AUC, 0.753 and 0.781). CONCLUSIONS: MRI-based radiomics models can predict the pathological response after NACT in ESCC patients, with the Delta-model exhibiting optimal predictive efficacy. CLINICAL RELEVANCE STATEMENT: MRI radiomics features could be used as a useful tool for predicting the efficacy of neoadjuvant chemotherapy in esophageal carcinoma patients, especially in selecting responders among those patients who may be candidates to benefit from neoadjuvant chemotherapy. KEY POINTS: • The MRI radiomics features based on T2WI-TSE-BLADE could potentially predict the pathologic response to NACT among ESCC patients. • The Delta-model exhibited the best predictive ability for pathologic response, followed by the Post-model, which similarly had better predictive ability, while the Pre-model performed less well in predicting TRG.

T-cell lymphopenia is associated with an increased infecting risk in children after cardiopulmonary bypass.

BACKGROUND: children who undergo CPB operations are at an elevated risk of infection due to immunosuppression. This study aims to investigate the association between lymphopenia following CPB and early postoperative infection in children. METHODS: A retrospective analysis including 41 children under 2 years old underwent CPB. Among them, 9 subjects had an early postoperative infection, and 32 subjects were period-matched without infection. Inflammatory cytokines, serum CRP and PCT values were measured in plasma, additionally, circulating total leucocyte and lymphocyte subpopulations were counted. RESULTS: Infected subjects exhibited significantly higher levels of inflammatory cytokines, including IL-6, IL-8, IL-10, IL-1ß and TNF-α, than non-infected subjects after CPB. Additionally, lower absolute number of lymphocyte and their subpopulations CD3+ T cells, CD4+ T-helper cells and CD8+cytotoxic T-cells, were observed in infected subjects. The impairment of T-cells Immune was found to be associated with higher levels of inflammatory cytokines IL-10. The ROC demonstrated that the absolute number of CD3+ T-cells <1934/ul, CD4+ T helper cells <1203/ul and CD8+cytotoxic T-cells <327/ul were associated with early postoperative infection. CONCLUSION: Higher levels of inflammatory cytokines resulted in T-cells lymphopenia after CPB, which significantly increasing the risk of postoperative infection in infants and young children. IMPACT: Infection complications after cardiopulmonary bypass (CPB) in pediatric CHD patients are serious issues, identifing the infection from after CPB remains a challenging. CPB can release numerous inflammatory cytokines associated with T cells lymphopenia, which increases the risk of postoperative infection after surgery. Monitoring T cells lymphopenia maybe more beneficial to predict early postoperative infection than C-reactive protein and procalcitonin.

Tumour-associated macrophages and Schwann cells promote perineural invasion via paracrine loop in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is frequently accompanied by perineural invasion (PNI), which is associated with excruciating neuropathic pain and malignant progression. However, the relationship between PNI and tumour stromal cells has not been clarified. METHODS: The dorsal root ganglia or sciatic nerves nerve model was used to observe the paracrine interaction and the activation effect among Schwann cells, tumour-associated macrophages (TAMs), and pancreatic cancer cells in vitro. Next generation sequencing, enzyme-linked immunosorbent assay and chromatin immunoprecipitation were used to explore the specific paracrine signalling between TAMs and Schwann cells. RESULTS: We demonstrated that more macrophages were expressed around nerves that have been infiltrated by pancreatic cancer cells compared with normal nerves in murine and human PNI specimens. In addition, high expression of CD68 or GFAP is associated with an increased incidence of PNI and indicates a poor 5-year survival rate in patients with PDAC. Mechanistically, tumour-associated macrophages (TAMs) activate Schwann cells via the bFGF/PI3K/Akt/c-myc/GFAP pathway. Schwann cells secrete IL-33 to recruit macrophages into the perineural milieu and facilitate the M2 pro-tumourigenic polarisation of macrophages. CONCLUSIONS: Our study demonstrates that the bFGF/IL-33 positive feedback loop between Schwann cells and TAMs is essential in the process of PNI of PDAC. The bFGF/PI3K/Akt/c-myc/GFAP pathway would open potential avenues for targeted therapy of PDAC.

Domain nucleation kinetics and polarization-texture-dependent electronic properties in two-dimensional α-In2Se3 ferroelectrics.

Two-dimensional (2D) ferroelectric semiconductors, such as α-In2Se3 with switchable spontaneous polarization and superior optoelectronic properties, exhibit large potential for functional device applications. The electric transport properties and device performance of 2D α-In2Se3 are strongly sensitive to the ferroelectric domain structures and polarization textures, but they are rarely explored at the atomic scale. Herein, by a combination of first-principles calculations and a developed domain switching theory, we report the domain nucleation kinetics and polarization-texture dependent electronic properties in α-In2Se3 ferroelectrics. Our calculated results reveal that the reversed domains characterized by armchair boundaries tend to form triangular or stripped shape. The energy barrier for propagating domain boundaries is ∼1.42 eV and can be reduced by loading external electric field, which is responsible for driving the evolution of domain structures. Moreover, the domain switching leads to notable changes in the band gap and carrier spatial distribution of α-In2Se3 monolayer, resulting in higher electric resistance of multi-polarization domain structures than that of single-polarization state. The domain structures of multilayer α-In2Se3 follow a layer-by-layer switching mechanism, which causes the transition of electronic structures from self-doped p-n junctions to type-II semiconductor homojunctions. This study not only provides an in-depth insight into the domain switching mechanisms of α-In2Se3 but also opens up the possibility to tailor their electronic and transport properties.

Vav2 promotes ductus arteriosus anatomic closure via the remodeling of smooth muscle cells by Rac1 activation.

The ductus arteriosus (DA), bridging the aorta and pulmonary artery, immediately starts closing after birth. Remodeling of DA leads to anatomic obstruction to prevent repatency. Several histological changes, especially extracellular matrices (ECMs) deposition and smooth muscle cells (SMCs) migration bring to anatomic closure. The genetic etiology and mechanism of DA closure remain elusive. We have previously reported a novel copy number variant containing Vav2 in patent ductus arteriosus (PDA) patients, but its specific role in DA closure remains unknown. The present study revealed that the expression of Vav2 was reduced in human patent DA, and it was less enrichment in the adjacent aorta. Matrigel experiments demonstrated that Vav2 could promote SMC migration from PDA patient explants. Smooth muscle cells with Vav2 overexpression also presented an increased capacity in migration and downregulated contractile-related proteins. Meanwhile, SMCs with Vav2 overexpression exhibited higher expression of collagen III and lessened protein abundance of lysyl oxidase, and both changes are beneficial to DA remodeling. Overexpression of Vav2 resulted in increased activity of Rac1, Cdc42, and RhoA in SMCs. Further investigation noteworthily found that the above alterations caused by Vav2 overexpression were particularly reversed by Rac1 inhibitor. A heterozygous, rare Vav2 variant was identified in PDA patients. Compared with the wild type, this variant attenuated Vav2 protein expression and weakened the activation of downstream Rac1, further impairing its functions in SMCs. In conclusion, Vav2 functions as an activator for Rac1 in SMCs to promote SMCs migration, dedifferentiation, and ECMs production. Deleterious variant potentially induces Vav2 loss of function, further providing possible molecular mechanisms about Vav2 in PDA pathogenesis. These findings enriched the current genetic etiology of PDA, which may provide a novel target for prenatal diagnosis and treatment. KEY MESSAGES: Although we have proposed the potential association between Vav2 and PDA incidence through whole exome sequencing, the molecular mechanisms underlying Vav2 in PDA have never been reported. This work, for the first time, demonstrated that Vav2 was exclusively expressed in closed DAs. Moreover, we found that Vav2 participated in the process of anatomic closure by mediating SMCs migration, dedifferentiation, and ECMs deposition through Rac1 activation. Our findings first identified a deleterious Vav2 c.701C>T variant that affected its function in SMCs by impairing Rac1 activation, which may lead to PDA defect. Vav2 may become an early diagnosis and an effective intervention target for PDA clinical therapy.

Preparation and Molecular Structural Characterization of Fulvic Acid Extracted from Different Types of Peat.

Humic acid is a type of polymeric, organic weak acid mixture with a core aromatic structure and main-component oxygen-containing functional group. Fulvic acid is a type of humic substance that can be dissolved in acid, alkali, or water. This study discusses the influence of different peptides on the molecular structure of fulvic acid, which was extracted from herbaceous, woody, and mossy peats using alkaline dissolution and acid precipitation methods. Analyses using infrared, UV-Vis, 13C-NMR, and X-ray photoelectron spectroscopies, as well as X-ray diffraction (XRD), were conducted to compare the effects of different peat types on the content and molecular structure of fulvic acid. The woody peat fulvic acid content was the highest among all peat fulvic acids (0.38%). However, the yield of fulvic acid from herbaceous peat was the highest (2.53%). Herbaceous peat fulvic acid contains significant quantities of carbonyl, amino, methylene, carboxyl, and phenolic hydroxyl groups and ether bonds. Woody peat fulvic acid contains carbonyl and methoxy groups, benzenes, aromatic carbons, aromatic ethers, and phenols. The degree of aromatization of woody peat fulvic acid was the highest. Mossy peat fulvic acid contains high levels of hydroxy, methyl, methylene, and phenol groups and aromatic ethers. The structural differences in fulvic acids in the different types of peat were primarily manifested in the content of functional groups, with little influence from the types of functional groups. XRD analysis of the different peats revealed that their structures all comprised benzene rings. However, mossy peat contained more C=O and -COOH groups, whereas herbaceous peat contained more C-O groups.

CT-based and CTA-based posterior circulation ASPECTS in acute basilar artery occlusion: An Agreement Study.

BACKGROUND AND PURPOSE: The purpose of the present study was to evaluate the agreement on pc-ASPECTS (posterior circulation Acute Stroke Prognosis Early Computed Tomography Scores) based on non-contrast CT (NCCT) and CT angiography (CTA) source images in patients with acute basilar artery occlusion (BAO). METHODS: We prospectively enrolled consecutive patients with acute BAO from January 2022 to August 2022 at The First Affiliated Hospital of University of Science and Technology of China. The NCCT and CTA were scored independently by 15 raters during 2 different reading sessions at least 3 weeks apart. The pc-ASPECTS based on NCCT and CTA were analyzed on the full scale or were dichotomized (0-6 versus 7-10, 0-7 versus 8-10 and 0-8 versus 9-10). The level of agreement was measured using Fleiss κ Statistics. RESULTS: The median (IQR) CT-based pc-ASPECTS was 8 (6.75-9). The interrater agreement for CT-based pc-ASPECTS (κ=0.133 [0.132-0.133]) and CTA-based pc-ASPECTS (κ=0.204 [0.203-0.204]) was slight for all raters. Dichotomizations obtaining the highest concordance for the CT-based pc-ASPECTS (0-6 versus 7-10) and the CTA-based pc-ASPECTS (0-8 versus 9-10) failed to increase the interrater agreement to a substantial level (κ=0.350 [0.348-0.351] and 0.396 [0.395-0.398], respectively). Intrarater agreement for global CT-based pc-ASPECTS was less than substantial for the 14/15 raters and reached the level of substantial for the 3/15 raters with dichotomization. CONCLUSIONS: Agreement between clinicians assessing CT-based and CTA-based pc-ASPECTS cannot be sufficient to make reproducible clinical decisions and assessments. The dichotomization failed to improve interrater and intrarater agreement to the level of substantial.

Multistation collaborative prediction of air pollutants based on the CNN-BiLSTM model.

The development of industry has led to serious air pollution problems. It is very important to establish high-precision and high-performance air quality prediction models and take corresponding control measures. In this paper, based on 4 years of air quality and meteorological data from Tianjin, China, the relationships between various meteorological factors and air pollutant concentrations are analyzed. A hybrid deep learning model consisting of a convolutional neural network (CNN) and bidirectional long short-term memory (BiLSTM) is proposed to predict pollutant concentrations. In addition, a Bayesian optimization algorithm is applied to obtain the optimal combination of hyperparameters for the proposed deep learning model, which enhances the generalization ability of the model. Furthermore, based on air quality data from multiple stations in the region, a multistation collaborative prediction method is designed, and the concept of a strongly correlated station (SCS) is defined. The predictive model is modified using the idea of SCS and is used to predict the pollutant concentration in Tianjin. The coefficient of determination R2 of PM2.5, PM10, SO2, NO2, CO, and O3 are 0.89, 0.84, 0.69, 0.83, 0.92, and 0.84, respectively. The results show that our model is capable of dealing with air pollutant prediction with satisfactory accuracy.

GLP­1 receptor agonist protects palmitate-induced insulin resistance in skeletal muscle cells by up-regulating sestrin2 to promote autophagy.

In this study, we aimed to determine whether liraglutide could effectively reduce insulin resistance (IR) by regulating Sestrin2 (SESN2) expression in L6 rat skeletal muscle cells by examining its interactions with SESN2, autophagy, and IR. L6 cells were incubated with liraglutide (10-1000 nM) in the presence of palmitate (PA; 0.6 mM), and cell viability was detected using the cell counting kit-8 (CCK-8) assay. IR-related and autophagy-related proteins were detected using western blotting, and IR and autophagy-related genes were analyzed using quantitative real-time polymerase chain reaction. Silencing SESN2 was used to inhibit the activities of SESN2. A reduction in insulin-stimulated glucose uptake was observed in PA-treated L6 cells, confirming IR. Meanwhile, PA decreased the levels of GLUT4 and phosphorylation of Akt and affected SESN2 expression. Further investigation revealed that autophagic activity decreased following PA treatment, but that liraglutide reversed this PA-induced reduction in autophagic activity. Additionally, silencing SESN2 inhibited the ability of liraglutide to up-regulate the expression of IR-related proteins and activate autophagy signals. In summary, the data showed that liraglutide improved PA-induced IR in L6 myotubes by increasing autophagy mediated by SESN2.

Recent advances in polygalacturonase: Industrial applications and challenges.

This review focuses on the applications of polygalacturonase (PG), one of the most commercially produced enzymes on the biocatalyst market, in the food, beverage, feed, textile, and paper industries. Most PGs are acidic mesophilic enzymes, as shown by a summary of their biochemical properties. However, the acidic PGs discovered to date are insufficiently effective for industrial applications. The sequence and structural characteristics of thermophilic PGs are analyzed based on the results of extensive discussions regarding the catalytic mechanism and structural characteristics of PGs with shared right-handed parallel ß-helical structures. In addition, the molecular modification methods for obtaining thermostable PGs are systematically presented. Notably, the demand for alkaline heat-resistant PGs has increased significantly concurrent with the biomanufacturing industry development. Therefore, this review also provides a theoretical guideline for mining heat-resistant PG gene resources and modifying PG thermostability.

Correlation of asprosin and Nrg-4 with type 2 diabetes Mellitus Complicated with Coronary Heart Disease and the Diagnostic Value.

PURPOSE: Asprosin is a newly discovered adipose factor secreted by white fat, which is involved in glucose metabolism and inflammation. Neuregulin-4 (Nrg-4) is a new adipose factor released from brown adipose tissue and is considered to play an important role in metabolism. This study aims to explore the association between serum Asprosin, Nrg-4 level and coronary heart disease(CHD) in patients with type 2 diabetes mellitus(T2DM) and the diagnostic value. PATIENTS AND METHODS: 157 patients with T2DM were enrolled from Affiliated Hospital of Chengde Medical University between December 2020 to July 2021. These patients were divided into T2DM without CHD group (T2DM-0, n = 80) and T2DM with CHD (T2DM-CHD, n = 77). Serum Asprosin and Nrg-4 expression was detected by enzyme-linked immunosorbent assay, and the correlations between Asprosin or Nrg-4 and clinical and biochemical indicators were analyzed. A receiver operating characteristics curve analysis and area under the curve (AUC) were used to evaluate diagnostic accuracy. RESULTS: Serum Asprosin level of the T2DM-CHD group were significantly higher and Nrg-4 level significantly lower than those of the T2DM-0 group.Spearman correlation analysis showed that serum Asprosin levels were significantly positively correlated with diabetes course,history of hypertension, fasting plasma glucose(FPG), glycosylated hemoglobin A1c(HbA1C), triglycerides(TG),triglyceride glucose index(TyG index) and urea, and negatively correlated with ALT (all p < 0.05). Nrg-4 was negatively correlated with history of hypertension, body mass index(BMI), FPG, HbA1C, TG, and TyG indexes (all p < 0.05), and positively correlated with high-density lipoprotein cholesterol(HDL-C)(p < 0.05).Logistic regression analysis showed that after adjusting potential confounders, Asprosin was a risk factor for diabetes mellitus, Nrg-4 was a protective factor.The AUC of Asprosin for diagnosing T2DM-CHD was 0.671 (95% confidence interval [CI] 0.584-0.759), and the AUC of the Nrg4 index for diagnosing T2DM-CHD was 0.772 (95% CI 0.700-0.844). The AUC of Asprosin and Nrg-4 for the combined diagnosis of T2DM-CHD was 0.796 (95% CI 0.726-0.864). CONCLUSION: Asprosin and Nrg-4 may be novel diagnostic biomarkers for T2DM with CHD, as they effectively improved the diagnostic accuracy for T2DM-CHD.

Artificial intelligence-based computer-aided diagnosis system supports diagnosis of lymph node metastasis in esophageal squamous cell carcinoma: A multicenter study.

Background: This study aimed to develop an artificial intelligence-based computer-aided diagnosis system (AI-CAD) emulating the diagnostic logic of radiologists for lymph node metastasis (LNM) in esophageal squamous cell carcinoma (ESCC) patients, which contributed to clinical treatment decision-making. Methods: A total of 689 ESCC patients with PET/CT images were enrolled from three hospitals and divided into a training cohort and two external validation cohorts. 452 CT images from three publicly available datasets were also included for pretraining the model. Anatomic information from CT images was first obtained automatically using a U-Net-based multi-organ segmentation model, and metabolic information from PET images was subsequently extracted using a gradient-based approach. AI-CAD was developed in the training cohort and externally validated in two validation cohorts. Results: The AI-CAD achieved an accuracy of 0.744 for predicting pathological LNM in the external cohort and a good agreement with a human expert in two external validation cohorts (kappa = 0.674 and 0.587, p < 0.001). With the aid of AI-CAD, the human expert's diagnostic performance for LNM was significantly improved (accuracy [95% confidence interval]: 0.712 [0.669-0.758] vs. 0.833 [0.797-0.865], specificity [95% confidence interval]: 0.697 [0.636-0.753] vs. 0.891 [0.851-0.928]; p < 0.001) among patients underwent lymphadenectomy in the external validation cohorts. Conclusions: The AI-CAD could aid in preoperative diagnosis of LNM in ESCC patients and thereby support clinical treatment decision-making.