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As a highly toxic contaminant, heavy metals have been proven to be widely distributed in the water and sediments of the global oceans, rivers, and lakes. Due to the functional differences in urban areas, the extent, characteristics, and hazards of heavy metal pollution in rivers are also different. To monitor and eliminate heavy metal pollution in rivers, indicators and hyperaccumulators perform crucial roles. In this study, heavy metal concentrations in the water, sediment, benthic faunae and aquatic plants of the Jiang'an River (which flows through Chengdu city, Sichuan Province, P.R. China) were investigated, followed by heavy metal correlation analysis of different media to identify potential bioindicator and hyperaccumulator. The results demonstrated that, none of the heavy metals were detected in the water. However, the 6 heavy metals in the surface sediments showed dramatic spatial regional differences, with Ni-As, Ni-Pb, Ni-Cr, Cr-Cu and Cr-Zn being highly significantly correlated. Furthermore, heavy metal contents in surface sediments were highly significantly correlated with the enrichment capacity of Eriocheir sinensis, Polypogon fugax, and Setaria viridis, and significantly correlated with Erigeron acer. Moreover, all plants were poorly enriched with Pb, which may be related to the morphology of Pb in the sediments. Besides, Eriocheir sinensis is a potential indicator of Zn and Cr in the sediments, and Erigeron acer is a possible Zn hyperaccumulator. This research confirms that heavy metals migrated in the water–sediment-benthic-plant system. Therefore, this study can provide a theoretical foundation for river monitoring and administration in Chengdu city and Sichuan Province.

Deoxynivalenol (DON) is universally detected trichothecene in most cereal commodities, which is considered as a major hazardous material for human and animal health. Intestine is the most vulnerable organ with higher concentration of DON than other organs, owing to the first defense barrier function to exogenous substances. However, the underling mechanisms about DON-induced intestinal toxicity remain poorly understood. Here, DON poisoning models of IPEC-J2 cells was established to explore adverse effect and the potential mechanism of DON-induced enterotoxicity. Results showed that DON exposure destroyed IPEC-J2 cells morphology. Results showed that DON exposure destroyed IPEC-J2 cells morphology. Intestinal epithelial barrier injury was caused by DON with increasing LDH release, decreasing cell viability as well decreasing tight junction protein expressions (Occludin, N-Cad, ZO-1, Claudin-1 and Claudin-3). Moreover, DON caused mitochondrial dysfunction by opening mitochondrial permeability transition pore and eliminating mitochondrial membrane potential. DON exposure upregulated protein and mRNA expression of mitochondrial fission factors (Drp1, Fis1, MIEF1 and MFF) and mitophagy factors (PINK1, Parkin and LC3), downregulated mitochondrial fusion factors (Mfn1, Mfn2, except OPA1), resulting in mitochondrial dynamics imbalance and mitophagy. Overall, these findings suggested that DON induced tight junction dysfunction in IPEC-J2 cells was related to mitochondrial dynamics-mediated mitophagy.

Abstract Background The melanocortin receptor accessory proteins (MRAP1 and MRAP2) are well‐known endocrine regulators for the trafficking and signalling of all five melanocortin receptors (MC1R–MC5R). The observation of MRAP2 on regulating several non‐melanocortin G protein‐coupled receptors (GPCRs) has been sporadically reported, whereas other endogenous GPCR partners of the MRAP protein family are largely unknown. Methods Here, we performed single‐cell transcriptome analysis and drew a fine GPCR blueprint and MRAPs‐associated network of two major endocrine organs, the hypothalamus and adrenal gland at single‐cell resolution. We also integrated multiple bulk RNA‐seq profiles and single‐cell datasets of human and mouse tissues, and narrowed down a list of 48 GPCRs with strong endogenous co‐expression correlation with MRAPs. Results 36 and 46 metabolic‐related GPCRs were consequently identified as novel interacting partners of MRAP1 or MRAP2, respectively. MRAPs exhibited protein–protein interactions and varying pharmacological properties on the surface translocation, constitutive activities and ligand‐stimulated downstream signalling of these GPCRs. Knockdown of MRAP2 expression by hypothalamic administration of adeno‐associated virus (AAV) packed shRNA stimulated body weight gain in mouse model. Co‐injection of corticotropinreleasing factor (CRF), the agonist of corticotropin releasing hormone receptor 1 (CRHR1), suppressed feeding behaviour in a MRAP2‐dependent manner. Conclusions Collectively, our study has comprehensively elucidated the complex GPCR networks in two major endocrine organs and redefined the MRAP protein family as broad‐spectrum GPCR modulators. MRAP proteins not only serve as a vital endocrine pivot on the regulation of global GPCR activities in vivo that could explain the composite physiological phenotypes of the MRAP2 null murine model but also provide us with new insights of the phenotyping investigation of GPCR–MRAP functional complexes.

Ultra-high strength martensitic stainless steel plays an essential role in aerospace, nuclear and other fields. This paper addresses laser-based powder bed fusion of martensitic stainless steel, based on thermodynamic software and computer languages for high-throughput calculation in combination with the hot tear sensitivity index criterion, Optimization of the alloy composed of Fe11Cr8Ni5Co3Mo martensitic stainless steel for resistance to hot tearing. The martensitic stainless steel composition with the lowest crack sensitivity was selected from hundreds of millions of data sets, reducing the hot tearing sensitivity index from 6841 to 1861. The alloy with the lowest hot tearing sensitivity was Fe11.3Cr8.18Ni2.0Mo2.8Co0.24Mn0.02V0.02Si0.01C0.17Mg. The hot tearing sensitivity has been experimentally verified in conjunction with additive manufacturing, and a comparative study of the building state organization and mechanical properties has been made.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease, which is caused by severe fever with thrombocytopenia syndrome virus (SFTSV). The disease results in high mortality and increased morbidity and threatens global public health. Rapid detection of SFTSV is crucial for epidemic prevention in low-resource settings. Here we developed deployable, sensitive and rapid detection methods based on CRISPR/Cas12a or Cas13a technologies. The CRISPR/Cas12a-based detection assay could stably detect the SFTSV L or M genes at 10 cp/μl. The Cas13a-based method could detect the L gene as low as 0.75 cp/μl. For point-of-care testing, we combined fluorescence visualization and lateral flow detection with CRISPR/Cas-based assays. Furthermore, using the orthogonal DNA/RNA collateral activity of the Cas12a/Cas13a system, we present the dual-gene detection platform for SFTSV, which can simultaneously detect the L and M genes in a single tube. Based on the dual-gene detection, we designed multiplexed test strips to detect SFTSV. All our methods were initially validated using 52 clinical samples, showing 100% sensitivity and specificity. These new CRISPR/Cas-based detection methods are promising candidates for on-site detection of SFTSV.

Background: Severe pneumonia is one of the common acute diseases caused by pathogenic microorganism infection, especially by pathogenic bacteria, leading to sepsis with a high morbidity and mortality rate. However, the existing bacteria cultivation method cannot satisfy current clinical needs requiring rapid identification of bacteria strain for antibiotic selection. Therefore, developing a sensitive liquid biopsy system demonstrates the enormous value of detecting pathogenic bacterium species in pneumonia patients. Methods: In this study, we developed a tool named Species-Specific Bacterial Detector (SSBD, pronounce as ‘speed’) for detecting selected bacterium. Newly designed diagnostic tools combining specific DNA-tag screened by our algorithm and CRISPR/Cas12a, which were first tested in the lab to confirm the accuracy, followed by validating its specificity and sensitivity via applying on bronchoalveolar lavage fluid (BALF) from pneumonia patients. In the validation I stage, we compared the SSBD results with traditional cultivation results. In the validation II stage, a randomized and controlled clinical trial was completed at the ICU of Nanjing Drum Tower Hospital to evaluate the benefit SSBD brought to the treatment. Results: In the validation stage I, 77 BALF samples were tested, and SSBD could identify designated organisms in 4 hr with almost 100% sensitivity and over 87% specific rate. In validation stage II, the SSBD results were obtained in 4 hr, leading to better APACHE II scores (p=0.0035, ANOVA test). Based on the results acquired by SSBD, cultivation results could deviate from the real pathogenic situation with polymicrobial infections. In addition, nosocomial infections were found widely in ICU, which should deserve more attention. Conclusions: SSBD was confirmed to be a powerful tool for severe pneumonia diagnosis in ICU with high accuracy. Funding: National Natural Science Foundation of China. The National Key Scientific Instrument and Equipment Development Project. Project number: 81927808. Clinical trial number: This study was registered at https://clinicaltrials.gov/ (NCT04178382).

The pharmacokinetic profiles and bioequivalence of two cefpodoxime proxetil tablets were investigated in Beagle dogs. A single-dose, four-way complete replication and crossover design was used in the present study. A total of 28 healthy Beagle dogs (half male and female) with an average body weight of 11.1 kg were randomly allocated to this study. A whole reference or test tablet containing the equivalent of 100 mg of cefpodoxime was administered orally to each dog. Serial plasma samples were collected, and cefpodoxime concentrations were determined by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Then a non-compartmental method was used to calculate the pharmacokinetic parameters of both tablet formulations. The average bioequivalence (ABE) or reference-scaled average bioequivalence (RSABE) methods were used to determine the 90% confidence interval (CI) of AUCINF_obs and Cmax. No significant differences were observed for both parameters between both tablets. The test formulation was bioequivalent to the reference one because the 90% CI ranges of Cmax and AUCINF_obs were all between 80 and 125%.

This study investigated the effect of sodium humate supplementation on changes in the intestinal microbiome, intestinal short-chain fatty acids production, and trace element absorption in older laying hens, with consequent effects on egg performance and shell quality. We used the same hens as their own control; a total of 720 laying hens aged 422 days were randomly divided into three replicates, with the CON group fed a commercial diet at 422–441 days of age and the HANa group fed a commercial diet supplemented with 0.05% sodium humate at 442–461 days of age. Compared with the CON group, in the HANa group, Bacteroidetes and Actinobacteria were significantly increased, whereas, Firmicutes was significantly decreased. Further, Veillonella, Enterococcus, Lactobacillus, and Turricibacter significantly decreased, and Peptoniphilus, Helcococcus, GW-34, Psychrobacter, Anaerococcus, Corynebacterium, Facklamia, Trichococcus, Gallicola, Clostridium, and Oscillospira were significantly increased. The results showed that sodium humate significantly altered the alpha and beta diversity and changed the structure of the intestinal microbiome. Acetic acid, isovaleric acid, and isobutyric acid, among short-chain fatty acids were significantly increased in the HANa group, whereas trace elements such as Mn, Zn, and Fe were significantly reduced. The eggshell strength and ultrastructure were significantly altered. In this study, sodium humate was found to alter the intestinal microbiome structure of aged hens, change the production of short-chain fatty acids, and promote the absorption of trace elements to keep aged hens from experiencing a decrease in egg production performance.

Hexavalent chromium [Cr (VI)] exists environmentally and occupationally. It has been shown to pose a carcinogenic hazard in certain occupations. This study was to investigate the role of high mobility group A2 (HMGA2) in Cr (VI)-induced metabolism reprogramming from oxidative phosphorylation (OXPHOS) to glycolysis in A549 and HELF cells. First, knockdown of HMGA2 by siHMGA2 significantly attenuated Cr (VI)-reduced expression of OXPHOS-related proteins (COX IV and ND1) and mitochondrial mass, indicating that HMGA2 was involved in Cr (VI)-reduced OXPHOS. Overexpression of HMGA2 by transfection of HMGA2-DNA plasmids reduced the expression of COX IV, ND1 and mitochondrial mass, suggesting the negative role of HMGA2 in OXPHOS. Secondly, both CCCP, the inhibitor of mitochondrial function, and the ER stress inhibitor, 4-phenylbutyric acid (4-PBA), decreased the level of HMGA2, indicating that the interaction of mitochondrial dysfunction and ER stress resulted in Cr (VI)-induced HMGA2 expression. Further study demonstrated that ER stress/HMGA2 axis mediated the metabolism rewiring from OXPHOS to aerobic glycolysis. Notably, Cr (VI) induced the accumulation of HMGA2 proteins in mitochondria and ChIP assay demonstrated that HMGA2 proteins could bind to D-loop region of mitochondrial DNA (mtDNA), which provided the proof for HMGA2-modulating OXPHOS. Taken together, our results suggested that the interaction of mitochondria and ER stress-enhanced HMGA2 played an important role in Cr (VI)-induced metabolic reprogramming from OXPHOS to glycolysis by binding directly to D-loop region of mtDNA. This work informs on the potential mode of action for Cr (VI)-induced tumors and builds on growing evidence regarding the contribution of cellular metabolic disruption contributing to carcinogenicity.

Abstract Background Triple-negative breast cancer (TNBC) is a clinically aggressive disease with abundant variants that cause homologous recombination repair deficiency (HRD). Whether TNBC patients with HRD are sensitive to anthracycline, cyclophosphamide and taxane (ACT), and whether the combination of HRD and tumour immunity can improve the recognition of ACT responders are still unknown. Methods Data from 83 TNBC patients in The Cancer Genome Atlas (TCGA) was used as a discovery cohort to analyse the association between HRD and ACT chemotherapy benefits. The combined effects of HRD and immune activation on ACT chemotherapy were explored at both the genome and the transcriptome levels. Independent cohorts from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and Gene Expression Omnibus (GEO) were adopted to validate our findings. Results HRD was associated with a longer ACT chemotherapy failure-free interval (FFI) with a hazard ratio of 0.16 (P = 0.004) and improved patient prognosis (P = 0.0063). By analysing both HRD status and ACT response, we identified patients with a distinct TNBC subtype (ACT-S&HR-P) that showed higher tumour lymphocyte infiltration, IFN-γ activity and NK cell levels. Patients with ACT-S&HR-P had significantly elevated immune inhibitor levels and presented immune activation associated with the increased activities of both innate immune cells and adaptive immune cells, which suggested treatment with immune checkpoint blockade as an option for this subtype. Our analysis revealed that the combination of HRD and immune activation enhanced the efficiency of identifying responders to ACT chemotherapy (AUC = 0.91, P = 1.06e−04) and synergistically contributed to the clinical benefits of TNBC patients. A transcriptional HRD signature of ACT response-related prognostic factors was identified and independently validated to be significantly associated with improved survival in the GEO cohort (P = 0.0038) and the METABRIC dataset (P < 0.0001). Conclusions These findings highlight that HR deficiency prolongs FFI and predicts intensified responses in TNBC patients by combining HRD and immune activation, which provides a molecular basis for identifying ACT responders.

Abstract Polycomb repressive complexes (PRCs) are essential in mouse gastrulation and specify neural ectoderm in human embryonic stem cells (hESCs), but the underlying molecular basis remains unclear. Here in this study, by employing an array of different approaches, such as gene knock-out, RNA-seq, ChIP-seq, et al., we uncover that EZH2, an important PRC factor, specifies the normal neural fate decision through repressing the competing meso/endoderm program. EZH2−/− hESCs show an aberrant re-activation of meso/endoderm genes during neural induction. At the molecular level, EZH2 represses meso/endoderm genes while SOX2 activates the neural genes to coordinately specify the normal neural fate. Moreover, EZH2 also supports the proliferation of human neural progenitor cells (NPCs) through repressing the aberrant expression of meso/endoderm program during culture. Together, our findings uncover the coordination of epigenetic regulators such as EZH2 and lineage factors like SOX2 in normal neural fate decision.

Abstract This work studies the self-interacting dark matter (SIDM) scenario in the general NMSSM and beyond, where the dark matter is a Majorana fermion and the force mediator is a scalar boson. An improved analytical expression for the dark matter (DM) self-interacting cross section which takes into account the Born level effects is proposed. Due to the large couplings and light mediator in SIDM scenario, the DM/mediator will go through multiple branchings if they are produced with high energy. Based on the Monte Carlo simulation of the showers in the DM sector, we obtain the multiplicities and the spectra of the DM/mediator from the Higgsino production and decay at the LHC for our benchmark points.

Abstract Head and neck squamous cell carcinoma (HNSCC) is a common cancer with high mortality. Anilin actin-binding protein (ANLN) has been reported to be associated with carcinogenesis in multiple tumors. However, the expression pattern and functional effects of ANLN in HNSCC remain to be unclear. Clinical data and online databases were used to analyze the expression of ANLN and its relationship with HNSCC patient survival. Expression of two major splice variants of ANLN was assessed in HNSCC tissues and cell lines. The functional effects and related mechanisms of ANLN isoforms were investigated in HNSCC in vitro and in vivo. Our study showed that patients with high expression of ANLN had a poor prognosis. The two primary isoforms of ANLN transcripts ANLN-201 and ANLN-210 were highly expressed in HNSCC tissues and cell lines. Knockout of ANLN restrained cell proliferation, migration, and invasion of SCC-9 cells. Mechanically, ANLN-201 could interact with c-Myc to keep its protein stability, thereby playing a oncogenic role in HNSCC. ANLN-210 could be transferred to macrophages via exosomes by binding to RNA-binding protein hnRNPC. Exosomal ANLN-210 promoted macrophage polarization via PTEN/PI3K/Akt signaling pathway, thus stimulating tumor growth of HNSCC. ANLN was an independent prognostic factor in patients with HNSCC. Alternatively spliced ANLN isoforms collaboratively promote HNSCC tumorigenesis in vitro and in vivo, which might provide the in-depth role and mechanism of ANLN in HNSCC development.

Abstract Background N-hexane, with its metabolite 2,5-hexanedine (HD), is an industrial hazardous material. Chronic hexane exposure causes segmental demyelination in the peripheral nerves, and high-dose intoxication may also affect central nervous system. Demyelinating conditions are difficult to treat and stem cell therapy using bone marrow mesenchymal stem cells (BMSCs) is a promising novel strategy. Our previous study found that BMSCs promoted motor function recovery in rats modeling hexane neurotoxicity. This work aimed to explore the underlying mechanisms and focused on the changes in spinal cord. Methods Sprague Dawley rats were intoxicated with HD (400 mg/kg/day, i.p, for 5 weeks). A bolus of BMSCs (5 × 107 cells/kg) was injected via tail vein. Demyelination and remyelination of the spinal cord before and after BMSC treatment were examined microscopically. Cultured oligodendrocyte progenitor cells (OPCs) were incubated with HD ± BMSC-derived conditional medium (BMSC-CM). OPC differentiation was studied by immunostaining and morphometric analysis. The expressional changes of Hes1, a transcription factor negatively regulating OPC-differentiation, were studied. The upstream Notch1 and TNFα/RelB pathways were studied, and some key signaling molecules were measured. The correlation between neurotrophin NGF and TNFα was also investigated. Statistical significance was evaluated using one-way ANOVA and performed using SPSS 13.0. Results The demyelinating damage by HD and remyelination by BMSCs were evidenced by electron microscopy, LFB staining and NG2/MBP immunohistochemistry. In vitro cultured OPCs showed more differentiation after incubation with BMSC-CM. Hes1 expression was found to be significantly increased by HD and decreased by BMSC or BMSC-CM. The change of Hes1 was found, however, independent of Notch1 activation, but dependent on TNFα/RelB signaling. HD was found to increase TNFα, RelB and Hes1 expression, and BMSCs were found to have the opposite effect. Addition of recombinant TNFα to OPCs or RelB overexpression similarly caused upregulation of Hes1 expression. The secretion of NGF by BMSC and activation of NGF receptor was found important for suppression of TNFα production in OPCs. Conclusions Our findings demonstrated that BMSCs promote remyelination in the spinal cord of HD-exposed rats via TNFα/RelB-Hes1 pathway, providing novel insights for evaluating and further exploring the therapeutical effect of BMSCs on demyelinating neurodegenerative disease.

Abstract Background Neutrophilic asthmatics (NA) have less response to inhaled corticosteroids. We aimed to find out the predictor of treatment response in NA. Methods Asthmatics (n = 115) and healthy controls (n = 28) underwent clinical assessment during 6-month follow-up with standardized therapy. Asthmatics were categorized by sputum differential cell count. The mRNA expressions were measured by RT-qPCR for sputum cytokines (IFN-γ, IL-1β, IL-27, FOXP3, IL-17A, and IL-5). The protein of IL-1β in sputum supernatant was detected by ELISA. Reticular basement membranes (RBM) were measured in the biopsy samples. The role and signaling pathways of IL-1β mediating the epithelial-mesenchymal transition (EMT) process were explored through A549 cells. Results NA had increased baseline sputum cell IL-1β expression compared to eosinophilic asthmatics (EA). After follow-up, NA had less improvement in FEV1 compared to EA. For all asthmatics, sputum IL-1β mRNA was positively correlated with protein expression. Sputum IL-1β mRNA and protein levels were negatively correlated to FEV1 improvement. After subgrouping, the correlation between IL-1β mRNA and FEV1 improvement was significant in NA but not in EA. Thickness of RBM in asthmatics was greater than that of healthy controls and positively correlated with neutrophil percentage in bronchoalveolar lavage fluid. In vitro experiments, the process of IL-1β augmenting TGF-β1-induced EMT cannot be abrogated by glucocorticoid or montelukast sodium, but can be reversed by MAPK inhibitors. Conclusions IL-1β level in baseline sputum predicts the poor lung function improvement in NA. The potential mechanism may be related to IL-1β augmenting TGF-β1-induced steroid-resistant EMT through MAPK signaling pathways. Trial registration: This study was approved by the Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (IRB ID: 20150406).

Massive Multiple-Input-Multiple-Output (MIMO) is a promising technology to meet the demand for the connection of massive devices and high data capacity for mobile networks in the next generation communication system. However, due to the massive connectivity of mobile devices, the pilot contamination problem will severely degrade the communication quality and spectrum efficiency of the massive MIMO system. We propose a deep Monte Carlo Tree Search (MCTS)-based intelligent Pilot-power Allocation Scheme (iPAS) to address this issue. The core of iPAS is a multi-task deep reinforcement learning algorithm that can automatically learn the radio environment and make decisions on the pilot sequence and power allocation to maximize the spectrum efficiency with self-play training. To accelerate the searching convergence, we introduce a Deep Neural Network (DNN) to predict the pilot sequence and power allocation actions. The DNN is trained in a self-supervised learning manner, where the training data is generated from the searching process of the MCTS algorithm. Numerical results show that our proposed iPAS achieves a better Cumulative Distribution Function (CDF) of the ergodic spectral efficiency compared with the previous suboptimal algorithms.

Abstract A new method was used to study the performance of pile across cave. This paper investigated the vertical bearing characteristics of piles cross caves using centrifugal model tests and a theoretical model of sensitivity. Twelve pile scenarios were selected, the first was a conventional pile, 24 cm long and 2.5 cm in diameter, with no karst cave as a control. In the other eleven scenarios the piles passed through karst caves of four different heights, of four different spans, and three different numbers of caves. The results reveal that increasing the height, span, and number of caves all are negative for vertical ultimate bearing capacity of piles. The axial force and unit shaft resistance of piles are great different. According to the ratios of the tip and shaft resistance, caves change the type of piles. The sensitivity of vertical ultimate bearing capacity to these factors from high to low is height, number, and span of caves. Importantly, the bearing characteristics of piles decrease faster once the height of the prototype karst cave is higher than 9 m, but decreases slowly when the cave’s span is greater than 9 m × 9 m.

Abstract To describe the long-term health outcomes of patients with COVID-19 and investigate the potential risk factors. Clinical data during hospitalization and at a mean (SD) day of 249 (15) days after discharge from 40 survivors with confirmed COVID-19 (including 25 severe cases) were collected and analyzed retrospectively. At follow-up, severe cases had higher incidences of persistent symptoms, DLCO impairment, and higher abnormal CT score as compared with mild cases. CT score at follow-up was positively correlated with age, LDH level, cumulative days of oxygen treatment, total dosage of glucocorticoids used, and CT peak score during hospitalization. DLCO% at follow-up was negatively correlated with cumulative days of oxygen treatment during hospitalization. DLCO/VA% at follow-up was positively correlated with BMI, and TNF-α level. Among the three groups categorized as survivors with normal DLCO, abnormal DLCO but normal DLCO/VA, and abnormal DLCO and DLCO/VA, survivors with abnormal DLCO and DLCO/VA had the lowest serum IL-2R, IL-8, and TNF-α level, while the survivors with abnormal DLCO but normal DLCO/VA had the highest levels of inflammatory cytokines during hospitalization. Altogether, COVID-19 had a greater long-term impact on the lung physiology of severe cases. The long-term radiological abnormality maybe relate to old age and the severity of COVID-19. Either absent or excess of inflammation during COVID-19 course would lead to the impairment of pulmonary diffusion function.

Abstract Recent studies suggested that cerebrovascular micro-occlusions, i.e. microstokes, could lead to ischemic tissue infarctions and cognitive deficits. Due to their small size, identifying measurable biomarkers of these microvascular lesions remains a major challenge. This work aims to simulate potential MRI signatures combining arterial spin labeling (ASL) and multi-directional diffusion-weighted imaging (DWI). Driving our hypothesis are recent observations demonstrating a radial reorientation of microvasculature around the micro-infarction locus during recovery in mice. Synthetic capillary beds, randomly- and radially-oriented, and optical coherence tomography (OCT) angiograms, acquired in the barrel cortex of mice (n = 5) before and after inducing targeted photothrombosis, were analyzed. Computational vascular graphs combined with a 3D Monte-Carlo simulator were used to characterize the magnetic resonance (MR) response, encompassing the effects of magnetic field perturbations caused by deoxyhemoglobin, and the advection and diffusion of the nuclear spins. We quantified the minimal intravoxel signal loss ratio when applying multiple gradient directions, at varying sequence parameters with and without ASL. With ASL, our results demonstrate a significant difference (p < 0.05) between the signal-ratios computed at baseline and 3 weeks after photothrombosis. The statistical power further increased (p < 0.005) using angiograms measured at week 4. Without ASL, no reliable signal change was found. We found that higher ratios, and accordingly improved significance, were achieved at lower magnetic field strengths (e.g., B0 = 3T) and shorter echo time TE (< 16 ms). Our simulations suggest that microstrokes might be characterized through ASL-DWI sequence, providing necessary insights for posterior experimental validations, and ultimately, future translational trials.

Abstract The conventional dyeing process requires a substantial amount of auxiliaries and water, which leaches hazardous colored effluents to the environment. Herein, a newly developed sustainable spray dyeing system has been proposed for cotton fabric in the presence of reactive dyes, which has the potential to minimize the textile dyeing industries environmental impact in terms of water consumption and save significant energy. The results suggest that fresh dye solution can be mixed with an alkali solution before spray dyeing to avoid the reactive dye hydrolysis phenomenon. After that, drying at 60–100 °C, wet fixation treating for 1–6 min, and combined treatments (wet fixation + drying) were sequentially investigated and then dye fixation percentages were around 63–65%, 52–70%, and above 80%, respectively. Following this, fixation conditions were optimized using L16 orthogonal designs, including wet fixation time, temperature, dye concentration, and pH with four levels where the “larger-the-better” function was selected to maximize the dye fixation rate. Additionally, the color uniformity and wash and rubbing fastnesses were at an acceptable level when both treatments were applied. Finally, the dyes were hydrolyzed after wet fixation, and the hydrolysis percentages were enhanced after the drying process.

To realize the triple functions of “roadway support, thermal insulation and heat regulation” of pumping wet shotcrete (PWS), the microencapsulated phase change material (MPCM) with poly (lauryl methacrylate) as shell and paraffin wax as core was synthetized by interfacial polymerization. The surface morphology, particle size distributions, core-shell compositions, the performances of the thermal stability and phase change of the MPCM were analyzed. The results show that the synthetized MPCM has excellent performances and can be applied in PWS. To obtain the optimal mixed proportions of the key materials (i.e., ceramsite, sand and MPCM) in PWS, the key performance indices were employed in the orthogonal experimental design to test the multiple performances of the PWS containing MPCMs. The results show that these performances are influenced by the dosages of the key materials and the recommended dosages were: 112.5 kg/m3 of ceramsite, 1250 kg/m3 of sand and 100 kg/m3 of MPCM. This study shows that the application of the MPCMs cannot only further reduce the thermal conductivity of PWS but also endow PWS with the function of heat regulation. A broad prospect of the application of MPCMs in underground cooling engineering can be expected.

BackgroundHashimoto thyroiditis (HT) is the most common autoimmune thyroid disease and is considered an independent risk factor for papillary thyroid carcinoma (PTC), with a higher incidence of PTC in patients with HT.ObjectiveTo build an integrated nomogram using clinical information and ultrasound-based radiomics features in patients with papillary thyroid carcinoma (PTC) with Hashimoto thyroiditis (HT) to predict central lymph node metastasis (CLNM).MethodsIn total, 235 patients with PTC with HT were enrolled in this study, including 101 with CLNM and 134 without CLNM. They were divided randomly into training and validation datasets with a 7:3 ratio for developing and evaluating clinical features plus conventional ultrasound features (Clin-CUS) model and clinical features plus radiomics scores (Clin-RS) model, respectively. In the Clin-RS model, the Pyradiomics package (V1.3.0) was used to extract radiomics variables, and LASSO regression was used to select features and construct radiomics scores (RS). The Clin-CUS and Clin-RS nomogram models were built using logistic regression analysis.ResultsTwenty-seven CLNM-associated radiomics features were selected using univariate analysis and LASSO regression from 1488 radiomics features and were calculated to construct the RS. The integrated model (Clin-RS) had better diagnostic performance than the Clin-CUS model for differentiating CLNM in the training dataset (AUC: 0.845 vs. 0.778) and the validation dataset (AUC: 0.808 vs. 0.751), respectively.ConclusionOur findings suggest that applying an ultrasound-based radiomics approach can effectively predict CLNM in patients with PTC with HT. By incorporating clinical information and RS, the Clin-RS model can achieve a high diagnostic performance in diagnosing CLNM in patients with PTC with HT.

In-situ coal bio-gasification can be defined as one of the coal bio-mining methodology that fully utilizes the methanogenic bacteria in coal to review the current findings, namely anaerobic digestion of organic components. The following experiment has been done in regards, one vertical well and one multi-branch horizontal well were used as experiment wells and two vertical wells were used as control wells, the pilot test was carried out with single well nutrition injection method. By applying the above mentioned method, the concentration of Cl− ion and number altered in Methanogen spp. were used to trace nutrition diffusion. Furthermore, technical implementation results analysis has been made with the observation of CH4 production changes and coal bed biome evolution.Gas production rates in each well were monitored by using the FLLQ gas roots flow mete. The concentration of CH4 and CO2 were evaluated by using the Agilent 7890A gas chromatograph, on the other hand, concentrations of Cl− were determined by the application of ICS-1100 ion chromatography system. The F420 fluorescence method was adopted to test for the presence of methanogenic bacteria. In the interim of the completion stage, the study stated that the bacterial diversity of underground water of Z-7H well has a high pass sequence with the experimental period of 814 days. Gas production data in Z-159 and Z-7H wells showed the gasification of coal lasted 635 and 799 days, yielded 74817 m3 and 251754 m3 coalbed methane, respectively. Furthermore, experimental data presented that one time nutrition injection in anthracite coalbed methane wells achieved an average of 717 days of continuous gas production among all experimental wells. The above fore-said study dedicated the significance of native bacterial fermentation, as it proven the fact that anthracite can be applied to accomplish coal bio-gasification and coalbed methane production stimulation in-situ.

ObjectiveBiliary atresia (BA) presents as a severe infantile cholangiopathy disease, characterized by progressive liver fibrosis and the resulting poor prognosis. Leukocyte cell-derived chemotaxin 2 (LECT2) was proposed as the key gene associated with hepatic fibrosis in BA, but the molecular mechanism is unclear. This study aims to investigate the function of LECT2 in BA.MethodsA total of 53 patients were enrolled in this study; 36 patients with BA, and 17 control patients with cholestasis, including congenital biliary dilations, biliary hypoplasia, and inspissated bile syndrome. The role of LECT2 in BA was analyzed using histological and cytological tests. The correlation between LECT2 and infiltrating immune cells was further analyzed by bioinformatics. The analyses were conducted using correlational analyses and ROC curves.ResultsLECT2 was highly expressed in infants with BA and positively related with fibrosis (0.1644 ± 0.0608 vs. 0.0779 ± 0.0053, p < 0.0001; rs = 0.85, p < 0.0001). Serum levels of LECT2 showed high distinguishing features for patients with BA having an AUC of 0.95 (95% CI: 0.90–1.00). CD163 was highly expressed in the aggravation of fibrosis (0.158 ± 0.062 vs. 0.29 ± 0.078, p < 0.0001), and the expression of LECT2 was positively correlated with the accumulation of CD163+ macrophages (r = 0.48, p = 0.003). The bioinformatic analysis also showed that LECT2 was positively correlated with macrophage M2 (r = 0.34, p = 0.03). TGF-β1 and CD163 colocalized to the portal area in the livers of patients with BA. Moreover, TGF-β1 upregulated the expression of LECT2.ConclusionLECT2 is highly expressed in both BA liver tissue and serum, and serum LECT2 is a potential diagnostic biomarker of BA. Meanwhile, TGF-β1 is secreted by macrophages to regulate LECT2 associated with BA liver fibrosis.

Tetrazine compounds are promising candidates of high performance energetic materials (EMs). For the purpose of exploring high performance asymmetrically substituted teterazine explosives, 3-hydrazino-6-(1H-1,2,3,4-tetrazol-5-ylimino)-s-tetrazine was selected as the precursor and a series of teterazine EMs were prepared based on three synthetic strategies. All the obtained compounds were fully characterized and the crystal structures of seven compounds were further confirmed by single crystal X-ray diffraction. The thermal dynamics and thermal safety parameters, the detonation properties and impact sensitivities were also obtained. The results revealed that compounds 15–17 show excellent energetic properties (detonation velocities > 9000 m·s−1, detonation pressures > 30 GPa) and have impact sensitivities (8–12 J) that comparable or lower than RDX. Compounds 9–13 are insensitive to impact and have detonation velocities range from 8452 to 8775 m·s−1. These compounds can be good candidates of high performance secondary explosives or insensitive EMs.

Background and purposePrevious studies have indicated the protective effects of luteolin against non-alcoholic steatohepatitis (NASH), but the definite underlying mechanism still remains unclear. This study aimed to explore the metabolomic and metagenomic signatures of NASH with luteolin supplementation.Experimental approachMice were fed with a methionine–choline-deficient (MCD) diet containing 0.05% luteolin for 6 weeks. NASH severity was determined based on the liver histological observations, serum and hepatic biochemical measurements. Targeted metabolomics was conducted to identify differential metabolites in mice serum. 16S rRNA sequencing was conducted to assess the gut microbiota composition and function in mice colon.ResultsIn detail, luteolin treatment significantly alleviated MCD diet-induced hepatic lipid deposition, liver function damage, and oxidative stress. Targeted plasma metabolomics revealed that 5-hydroxyindole, LPE (0:0/22:5), indole 3-phosphate, and N-phenylacetylphenylalanine were remarkably elevated, and homogentisic acid, thiamine, KN-93, PC (16:1e/8, 9-EpETE), carnitine C9:1-OH, FFA (18:4) and carnitine C8:1 were significantly decreased in NASH group as compared to normal group, which could be profoundly reversed after luteolin treatment. 16S rRNA sequencing indicated that luteolin supplementation significantly increased Erysipelatoclostridium and Pseudomonas as well as decreased Faecalibaculum at genus level. Most importantly, a negative association between thiamine and Faecalibaculum was observed based on Spearman's correlation analysis, which may play an important role in the preventive effects of luteolin against NASH.ConclusionCollectively, luteolin may alleviate the NASH by modulating serum metabolome and gut microbiome, which supports its use as a dietary supplement for NASH prevention.

We report a machine learning (ML) and Python assisted strategy to accelerate the design and verification of Fe–based amorphous and nanocrystalline alloy with desired properties. Linear Regression (LR), Support Vector Regression (SVR), Decision Tree Regression (DTR), Artificial Neural Network (ANN) and Random Forest Regression (RFR) are employed to build prediction models of soft magnetic properties, such as saturation magnetic flux density (Bs), coercivity force (Hc), magnetization (Ms), Curie temperature (Tc), maximum permeability (µmax) and effective permeability (µe). It is found that ANN has the excellent fitting ability with largest coefficient of determination (R2) to predict the soft magnetic properties of new designed alloys. Then, Python screening is used to find the alloy compositions with best soft magnetic properties of Fe–B–P–C–Nb system. Finally, Fe83B9P3C4Nb1 alloy with good soft magnetic properties has been designed and prepared to verify. It is indicated that the soft magnetic properties of Fe83B9P3C4Nb1 amorphous and nanocrystalline alloy predicted by ML are in agreement with the experimental measured results. These findings indicate that ML and Python assisted approach can accelerate the design of Fe–based alloys with desired properties accurately.

Although, the cecum plays vital roles in absorption of water, electrolytes, and other small molecules, and harbors trillions of commensal bacteria to shape large intestine immune functions, it is unknown the cecum development potentials at single cell level during the very crucial neonatal developmental period. Using singe cell RNA-seq and proteomics, we have characterized six major types of cecal cells: undifferentiated cells; immune cells (Ims); cecumocytes (CCs); goblet, Paneth like cells (PLCs), and enteroendocrine cells (EECs) with specific markers. CCs mature with a gradual decrease in proportion of cells; however, Ims develop with a continuing increase in proportion of cells. Meanwhile, goblet and EEC cells reduced in proportion of cells from do to d14 or d21; PLCs increased in proportion of cells from d0 to d7 then decreased at d14 and d21. The cells exhibit specific development and maturation trends controlled by transcriptional factors, ligand-receptor pairs, and other factors. As piglets grow, cecal content and mucosal microbial diversity increases dramatically with population of beneficial microbiota, such as lactobacillus. Moreover, cecal mucosal-associated and cecal content microbiota are positively correlated and both show significant correlation with different types of cecal cells and plasma metabolites. This is the first presentation of neonatal cecal cell development and maturation naturally at single cell level with transcript, protein, microbiota and metabolism perspectives. Furthermore, this study provides an important tool for the determination of novel interventions in cecal drug delivery and metabolism studies.

BackgroundAsthma patients potentially have impaired adaptive immunity to virus infection. The levels of SARS-CoV-2-specific adaptive immunity between COVID-19 survivors with and without asthma are presently unclear.MethodsCOVID-19 survivors (patients with asthma n=11, with allergies n=8, and COVID-19 only n=17) and non-COVID-19 individuals (asthmatic patients n=10 and healthy controls n=9) were included. The COVID-19 patients were followed up at about 8 months and 16 months after discharge. The clinical characteristics, lymphocyte subsets, memory T cells, and humoral immunity including SARS-CoV-2 specific antibodies, SARS-CoV-2 pseudotyped virus neutralization assay, and memory B cells were analyzed in these subjects.ResultsThe strength of virus-specific T cell response in COVID-19 survivors was positively correlated with the percentage of blood eosinophils and Treg cells (r=0.4007, p=0.0188; and r=0.4435, p=0.0086 respectively) at 8-month follow-up. There were no statistical differences in the levels of SARS-CoV-2-specific T cell response between the COVID-19 survivors with, and without, asthma. Compared to those without asthma, the COVID-19 with asthma survivors had higher levels of SARS-CoV-2-specific neutralizing antibodies (NAbs) at the 8-month follow-up (p

The use of the heavy hammer compaction method can enhance the bearing characteristics of underwater rubble-mound foundations. This is crucial to ensure the safety and stability of port and coastal engineering projects. In the present work, a combination of image-recognition technology, 3D laser scanning technology, a discrete element numerical simulation, and a field test was first utilized to establish riprap particles and reconstruct a discrete element numerical model of a rubble-mound foundation, and then the effects of various influencing factors on the bearing characteristics of the rubble-mound foundation were studied. The main conclusions are as follows. (1) The load–settlement curve of the rubble-mound foundation can be divided into three stages: rapid growth stage, slow growth stage, and failure stage. (2) The ultimate bearing capacity of the rubble-mound foundation is positively correlated with the vibration time and vibration amplitude. The riprap particle size and the foundation thickness have negligible effects on the ultimate bearing capacity of the rubble-mound foundation. (3) When adjusting the vibration time, vibration amplitude, and foundation thickness, the settlement value of the rubble-mound foundation tends to increase as the compactness increases. On the other hand, the effects of factors such as the riprap particle size, riprap particle gradation, and vibration frequency on the compactness and settlement value of the rubble-mound foundation are less significant.

The rampant misuse of drones poses a serious threat to national security and human life. Currently, CNN (Convolutional Neural Networks) are widely used to detect drones. However, small drone targets often reduced amplitude or even lost features in infrared images which traditional CNN cannot overcome. This paper proposes a Progressive Feature Fusion Network (PFFNET) and designs a Pooling Pyramid Fusion (PFM) to provide more effective global contextual priors for the highest downsampling output. Then, the Feature Selection Model (FSM) is designed to improve the use of the output coding graph and enhance the feature representation of the target in the network. Finally, a lightweight segmentation head is designed to achieve progressive feature fusion with multi-layer outputs. Experimental results show that the proposed algorithm has good real-time performance and high accuracy in drone target detection. On the public dataset, the intersection over union (IOU) is improved by 2.5% and the detection time is reduced by 81%.

In organic light-emitting diodes, positive and negative charge carriers mostly migrate at different rates. This could result in excitons formed in the EML often migrating to the vicinity of the hole transport layer and the electron transport layer. To address this, it is important to design high-quality multi-resonance hosts that can balance the migration rate of carriers. Here, we report two newly developed multi-resonance hosts, m-ICzPBI and o-ICzPBI. The hosts contain an indolo[3,2,1-jk]carbazole (ICz) motif, which functionalized as either a donor or an acceptor unit. The hosts exhibit extremely high molecular rigidity and thermal stability. Devices A and B were constructed using FIrpic as a phosphorescent emitter with m-ICzPBI or o-ICzPBI as a host. Device A achieved high maximum values of EQE, PE and CE of 13.4%, 24.8 lm W−1 and 31.6 cd A−1, respectively, and low efficiency roll-off at 5000 cd m−2 of 8.6%, 10.6 lm W−1 and 20.3 cd A−1, respectively.

Background: Our previous research revealed that inflammation plays an important role in the pathophysiology of cerebral ischemia. The function of the NOD-like receptor protein 3 (NLRP3) inflammasome is to activate the inflammatory process. Recent findings suggest that reactive oxygen species (ROS) are essential secondary messengers that activate the NLRP3 inflammasome. Hydrogen-rich saline (HS) has attracted attention for its anti-inflammatory properties. However, the protective effect and possible mechanism of HSin brain ischemia have not been well elucidated. Methods: To test the therapeutic effect of HS, we established a mouse model of distal middle cerebral artery occlusion (dMCAO) and an in vitro model of BV2 cells induced by lipopolysaccharide (LPS). The ROS scavenger N-acetylcysteine (NAC) was used to investigate the underlying mechanisms of HS. Results: HS significantly improved neurological function, reduced infarct volume, and increased cerebral blood flow in a dMCAO mouse model. ROS, NLRP3, Caspase-1, and IL-1β expression increased after cerebral ischemia, and this was reversed by HS treatment. In BV2 cells, the application of NAC further demonstrated that HS could effectively inhibit the expression of the ROS-activated NLRP3 inflammasome. Conclusions: HS, as a novel therapeutic option, could exert protect the brain by inhibiting the activation of the ROS-NLRP3 signaling pathway after cerebral ischemia.

In this study, the preparation of covalent polyoxometalate organic frameworks (CPOFs) is introduced using the idea of polyoxometalate and covalent organic frameworks. Firstly, the prepared polyoxometalate was functionalized with an amine group (NH2-POM-NH2), and then the CPOFs were prepared by a solvothermal Schiff base reaction with NH2-POM-NH2 and 2,4,6-trihydroxybenzene-1,3,5-tricarbaldehyde (Tp) as monomers. After the incorporation of PtNPs and MWCNTs into the CPOFs material, the PtNPs-CPOFs-MWCNTs nanocomposites, which possess excellent catalytic activity and electrical conductivity, were formed and utilized as new electrode materials for the electrochemical thymol sensors. The obtained PtNPs-CPOFs-MWCNTs composite exhibits excellent activity toward thymol, which is attributable to its large special surface area, good conductivity and the synergistic catalysis of each component. Under optimal experimental conditions, the sensor presented a good electrochemical response to thymol. The sensor shows two good linear relationships between the current and thymol concentration in the range of 2–65 μM (R2 = 0.996) and 65–810 μM (R2 = 0.997), with the corresponding sensitivity of 72.7 μA mM−1 and 30.5 μA mM−1, respectively. Additionally, the limit of detection (LOD) was calculated to be 0.2 μM (S/N = 3). At the same time, the prepared thymol electrochemical sensor revealed superior stability and selectivity. The constructed PtNPs-CPOFs-MWCNT electrochemical sensor is the first example of thymol detection.

Deep learning and convolutional neural networks (CNN) have been widely applied in polarimetric synthetic aperture radar (PolSAR) image classification, and satisfactory results have been obtained. However, there is one crucial issue that still has not been solved. These methods require abundant labeled samples and obtaining the labeled samples of PolSAR images is usually time-consuming and labor-intensive. To obtain better classification results with fewer labeled samples, a new attention-based 3D residual relation network (3D-ARRN) is proposed for PolSAR image. Firstly, a multilayer CNN with residual structure is used to extract depth polarimetric features. Secondly, to extract more important feature information and improve the classification results, a spatial weighted attention network (SWANet) is introduced to concentrate the feature information, which is more favorable for a classification task. Then, the features of training and test samples are integrated and CNN is utilized to compute the score of similarity between training and test samples. Finally, the similarity score is used to determine the category of test samples. Studies on four different PolSAR datasets illustrate that the proposed 3D-ARRN model can achieve higher classification results than other comparison methods with few labeled data.

T-2 toxin, the most toxic type A trichothecene mycotoxin, is produced by Fusarium, and is widely found in contaminated feed and stored grains. T-2 toxin is physicochemically stable and is challenging to eradicate from contaminated feed and cereal, resulting in food contamination that is inescapable and poses a major hazard to both human and animal health, according to the World Health Organization. Oxidative stress is the upstream cause of all pathogenic variables, and is the primary mechanism through which T-2 toxin causes poisoning. Nuclear factor E2-related factor 2 (Nrf2) also plays a crucial part in oxidative stress, iron metabolism and mitochondrial homeostasis. The major ideas and emerging trends in future study are comprehensively discussed in this review, along with research progress and the molecular mechanism of Nrf2’s involvement in the toxicity impact brought on by T-2 toxin. This paper could provide a theoretical foundation for elucidating how Nrf2 reduces oxidative damage caused by T-2 toxin, and a theoretical reference for exploring target drugs to alleviate T-2 toxin toxicity with Nrf2 molecules.

Abstract Background Recurrent miscarriage (RM) is a very frustrating problem for both couples and clinicians. To date, the etiology of RM remains poorly understood. Decidualization plays a critical role in implantation and the maintenance of pregnancy, and its deficiency is closely correlated with RM. The F-box protein S-phase kinase associated protein 2 (SKP2) is a key component of the SCF-type E3 ubiquitin ligase complex, which is critically involved in ErbB family-induced Akt ubiquitination, aerobic glycolysis and tumorigenesis. SKP2 is pivotal for reproduction, and SKP2-deficient mice show impaired ovarian development and reduced fertility. Methods Here, we investigated the expression and function of SKP2 in human decidualization and its relation with RM. A total of 40 decidual samples were collected. Quantitative PCR analysis, western blot analysis and immunohistochemistry analysis were performed to analyze the differential expression of SKP2 between RM and control cells. For in vitro induction of decidualization, both HESCs (human endometrial stromal cells) cell line and primary ESCs (endometrial stromal cells) were used to analyze the effects of SKP2 on decidualization via siRNA transfection. Results Compared to normal pregnant women, the expression of SKP2 was reduced in the decidual tissues from individuals with RM. After in vitro induction of decidualization, knockdown of SKP2 apparently attenuated the decidualization of HESCs and resulted in the downregulation of HOXA10 and FOXM1, which are essential for normal human decidualization. Moreover, our experiments demonstrated that SKP2 silencing reduced the expression of its downstream target GLUT1. Conclusions Our study indicates a functional role of SKP2 in RM: downregulation of SKP2 in RM leads to impaired decidualization and downregulation of GLUT1 and consequently predisposes individuals to RM.

Abstract Direct comparison data on spatial patterns of visual field (VF) defects among primary angle-closure glaucoma (PACG), high-tension glaucoma (HTG) and normal-tension glaucoma (NTG) are not available. We aimed to compare the intraocular asymmetry of VF loss among patients with PACG, NTG and HTG across different severity levels. A total of 162 eyes of 114 patients with PACG, 111 eyes of 74 patients with HTG and 148 eyes of 102 patients with NTG were included. VF defects were categorized into 3 stages (early, moderate, and advanced), and each hemifield was divided into 5 regions according to the Glaucoma hemifield test (GHT). The mean total deviation (TD) of each GHT region was calculated. In the early stage, the paracentral, peripheral arcuate 1 and peripheral arcuate 2 regions in the superior hemifield in the NTG group had significantly worse mean TDs than their corresponding regions in the inferior hemifield. In the advanced stage, the central region in the superior hemifield in the PACG group had a significantly worse mean TD than that in the inferior hemifield. There was no significant difference in the mean TD for any of the five regions between hemifields across all severity levels in the in the HTG group. The superior hemifield was affected more severely than the inferior hemifield in all three subtypes of primary glaucoma. This asymmetric tendency was more pronounced in NTG than in PACG and HTG.

Abstract Background Malignant tumor is one of the most serious diseases endangering human health. Circular RNAs play an important role in the tumorigenesis and progression of various malignant tumors. Although various studies have investigated the biological function of circular RNA circSMARCA5 in malignant tumors, the prognostic value of circSMARCA5 in malignant tumor patients has not been systematically analyzed. Methods Relevant studies were obtained from the PubMed and Web of Science database. The quality of the enrolled studies was evaluated using the Newcastle-Ottawa Scale quality assessment system. Survival features and clinicopathological features were assessed using pooled hazard ratios and odds ratios with 95% confidence intervals, respectively. Results Overall, 7 relevant publications were enrolled in the meta-analysis. CircSMARCA5 expression was significantly correlated with better OS (HR = 0.51, 95%CI 0.41–0.65) or DFS/RFS/PFS (HR = 0.56, 95%CI 0.43–0.73) in malignant tumors. In the pooled analyses of clinicopathological characteristics, malignant tumors with higher circSMARCA5 were better differentiated (OR = 0.41, 95%CI 0.19–0.88). CircSMARCA5 expression was correlated with less advanced TNM stage (OR = 0.33, 95%CI 0.19–0.55). Moreover, malignant tumors with higher circSMARCA5 expression have less advanced lymph node metastasis (OR = 0.26, 95%CI 0.08–0.79). Conclusion These results indicated that circSMARCA5 was a promising biomarker in malignant tumors, which may potentially facilitate clinical decisions in the future.

Abstract Aims/Introduction The early pathological changes of diabetic peripheral neuropathy (DPN) are mainly small nerve fiber injuries. Corneal confocal microscopy (CCM) is an easy, rapid, non‐invasive and repeatable technique to detect the damage of small nerve fibers. The purpose of this study was to explore the application of CCM in DPN and other chronic complications of type 2 diabetes mellitus. Materials and Methods A total of 220 individuals (48 normal healthy control participants and 172 patients with type 2 diabetes mellitus) were included in the study. All participants were assessed and scored for neurological symptoms and neurological deficits, quantitative sensory test, neuroelectrophysiological test, and CCM. Results Corneal nerve fiber density, corneal nerve fiber length and corneal nerve branch density were significantly reduced in patients with type 2 diabetes mellitus compared with normal healthy control subjects (P

ObjectivePost-operative biochemical relapse (BCR) continues to occur in a significant percentage of patients with localized prostate cancer (PCa). Current stratification methods are not adequate to identify high-risk patients. The present study exploits the ability of deep learning (DL) algorithms using the H2O package to combine multi-omics data to resolve this problem.MethodsFive-omics data from 417 PCa patients from The Cancer Genome Atlas (TCGA) were used to construct the DL-based, relapse-sensitive model. Among them, 265 (63.5%) individuals experienced BCR. Five additional independent validation sets were applied to assess its predictive robustness. Bioinformatics analyses of two relapse-associated subgroups were then performed for identification of differentially expressed genes (DEGs), enriched pathway analysis, copy number analysis and immune cell infiltration analysis.ResultsThe DL-based model, with a significant difference (P = 6e-9) between two subgroups and good concordance index (C-index = 0.767), were proven to be robust by external validation. 1530 DEGs including 678 up- and 852 down-regulated genes were identified in the high-risk subgroup S2 compared with the low-risk subgroup S1. Enrichment analyses found five hallmark gene sets were up-regulated while 13 were down-regulated. Then, we found that DNA damage repair pathways were significantly enriched in the S2 subgroup. CNV analysis showed that 30.18% of genes were significantly up-regulated and gene amplification on chromosomes 7 and 8 was significantly elevated in the S2 subgroup. Moreover, enrichment analysis revealed that some DEGs and pathways were associated with immunity. Three tumor-infiltrating immune cell (TIIC) groups with a higher proportion in the S2 subgroup (p = 1e-05, p = 8.7e-06, p = 0.00014) and one TIIC group with a higher proportion in the S1 subgroup (P = 1.3e-06) were identified.ConclusionWe developed a novel, robust classification for understanding PCa relapse. This study validated the effectiveness of deep learning technique in prognosis prediction, and the method may benefit patients and prevent relapse by improving early detection and advancing early intervention.

Urolithin A (UroA) is one of the primary intestinal metabolites of ellagitannins, showing translational potential as a nutritional intervention in humans. Mounting evidence suggests that fructose consumption contributes to the progression of chronic kidney disease (CKD) that manifests in hyperuricemic nephropathy, renal inflammation, and tubulointerstitial injury. Here, we investigated the efficacy of UroA in alleviating fructose-induced hyperuricemic nephropathy in mice. Uric acid-exposed human kidney-2 (HK-2) cells were utilized for in vitro mechanism validation. Histopathological staining, immunoblotting, and transmission electron microscope were performed for the mechanistic investigations. Our results revealed that UroA ameliorated fructose-induced hyperuricemic nephropathy in mice. The histopathologic assessment showed that UroA attenuated tubular hypertrophy and dilation, glomerular basement membrane thickening, and collagen deposition in the kidney of fructose-fed mice. Mechanistically, UroA treatment impaired STING-NLRP3 activation, resulting in reduced production of proinflammatory cytokines IL-1β, IL-6, and TNF-α. Notably, UroA exhibited a scavenging effect against reactive oxygen species (ROS) and restored fructose-impaired PINK1/Parkin-mediated mitophagy in nephropathic mice. Furthermore, the inhibitory effect of UroA in STING-NLRP3 activation was impaired after Parkin gene silencing in HK-2 cells. Together, this study suggests that UroA alleviates fructose-induced hyperuricemic nephropathy by promoting Parkin-dependent mitophagy, thereby suppressing STING-NLRP3 axis-mediated inflammatory response. Thus, dietary supplementation with UroA or ellagitannins-rich foods may serve as a promising intervention to prevent CKD progression.

ABSTRACT The World Health Organization has recommended prevaccination screening for prior dengue infection as the preferred approach prior to vaccination with the dengue vaccine CYD-TDV. These screening tests need to be highly specific and sensitive, and deliverable at the point-of-care. We evaluate here the sensitivity and specificity of the newly developed OnSite Dengue IgG rapid diagnostic test (RDT). A retrospective double-blind study of the sensitivity and specificity of the OnSite Dengue IgG RDT was performed using a sample panel consisting of archived serum specimens collected during CYD-TDV clinical trials in Latin American and Asia, with the reference serostatus for each sample determined by an algorithm using measured dengue PRNT90, PRNT50, and NS1 IgG ELISA. An additional panel of dengue seronegative samples positive for other flaviviruses and infections was used to assess cross-reactivity. Samples were included from 579 participants; 346 in the specificity panel and 233 in the sensitivity panel. The OnSite dengue IgG RDT exhibited a specificity of 98.0% (95% CI = 95.9 to 99.2) and sensitivity of 95.3% (95% CI = 91.7 to 97.6). The sensitivity for samples exhibiting a multitypic immune profile (PRNT90-positive to >1 dengue serotype) was 98.8% while for monotypic immune samples (PRNT90-positive to a single dengue serotype) it was 88.1%. The OnSite dengue IgG RDT showed minimal to no cross-reactivity to related flaviviruses. These findings support the use of the OnSite dengue IgG RDT to determine dengue serostatus in CYD-TDV prevaccination screening. IMPORTANCE Dengue remains a significant public health issue, with over 5.2 million cases reported to the World Health Organization (WHO) in 2019. The tetravalent dengue vaccine (CYD-TDV) is currently licensed for use in those aged ≥9 years; however, vaccinees with no previous exposure to dengue experience an increased risk of hospitalized and severe dengue upon subsequent heterotypic infection. Consequently, WHO recommends screening for prior dengue infection before vaccination. Screening tests for previous infection need to be highly specific and sensitive, and deliverable at the point-of-care. High sensitivity ensures that the largest number of individuals with previous infection can be identified and vaccinated, while high specificity prevents the inadvertent vaccination of those without previous infection. This study of the OnSite Dengue IgG Rapid Test, which was explicitly developed to meet this need, found that it had both high specificity (98.0% [95% CI = 95.9 to 99.2]) and sensitivity (95.3% [95% CI = 91.7 to 97.6]).

ObjectivesThis study compared results of non-surgical treatment (compression and ultrasound guided thrombin injection (UGTI)) and surgery to treat iatrogenic femoral artery pseudoaneurysms.MethodsPubMed and Embase databases were searched up to October 2021. Primary outcome measure was success rate, and other outcomes examined were complication rate, reintervention rate. Two authors independently reviewed and extracted data. Data were presented as the odds ratios (ORs) with 95% confidence intervals (CIs). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to appraise the quality of the body of evidence.ResultsEight studies were included. A total of 623 patients with pseudoaneurysm undergoing treatment were included, of which 163 subjects underwent surgery, 397 subjects underwent compression, and 63 subjects underwent UGTI. The success rate was significantly lower in the non-surgery group (OR 0.24, 95% CI, 0.08–0.69, I2 = 0%). The complication rate was significantly lower in the non-surgery group (OR 0.10, 95% CI, 0.03 –0.29, I2 = 0%). Patients in the non-surgery group tended to have a lower, but statistically insignificant, reintervention rate (OR 0.11, 95% CI, 0.01–1.06, I2 = 35%). Further, the GRADE assessment showed that these results (success rate, complication rate, and reintervention rate) were of very low quality.ConclusionsAvailable evidence shows that it is reasonable to regard non-surgical treatment as the primary treatment for iatrogenic femoral artery pseudoaneurysms, and surgery as a remedy after failure of non-surgical treatment in some cases.

Energy efficiency (EE) has long been recognized as a source of value to the electricity grid. Especially with increasing penetration of variable renewable generation, demand response (DR) can also provide system value and support the evolving needs of the grid. Yet there has been little study to date of interactions between EE and DR that may complicate their grid impacts. In this study we perform bottom-up modelling of the interactive effects between EE and DR in buildings for three representative regions of the United States electricity grid. Leveraging new simulation tools that enable detailed modelling of the building stock, we synthesize system-level demand profiles for several scenarios representing different portfolios of EE measures. In each scenario, we couple the underlying building models with a database of DR-enabling technologies to estimate building-level DR capabilities and compute a system-level supply curve for DR. We assess the resulting EE and DR interactive effects based on an existing conceptual framework. The results show a complex relationship between EE and DR, with interactive effects whose size and direction can vary widely depending on the grid system, type of DR, and the framework level being considered. Most often, the overall effect is competition between EE and DR, but significant complementarity can also occur, especially when the EE portfolio includes controls measures. Our results suggest that EE and DR programs developed without considering interactive effects may erode the benefits of both resources, whereas a more integrated approach may yield increased benefits.

Abstract Biodegradable organic field‐effect transistors (OFETs) have drawn tremendous attention for potential applications such as green electronic skins, degradable flexible displays, and novel implantable devices. However, it remains a huge challenge to simultaneously achieve high mobility, stable operation and controllable biodegradation of OFETs, because most of the widely used biodegradable insulating materials contain large amounts of hydrophilic groups. Herein, it is firstly proposed fungal‐degradation ultraflexible OFETs based on the crosslinked dextran (C‐dextran) as dielectric layer. The crosslinking strategy effectively eliminates polar hydrophilic groups and improves water and solvent resistance of dextran dielectric layer. The device with spin‐coated 2,7‐dioctyl[1]benzothieno[3,2‐b][1]benzothiophene (C8‐BTBT) semiconductor and C‐dextran dielectric exhibits the highest mobility up to 7.72 cm2 V−1 s−1, which is higher than all the reported degradable OFETs. Additionally, the device still maintains high performance regardless of in an environment humidity up to 80% or under the extreme bending radius of 0.0125 mm. After completion of their mission, the device can be controllably biodegraded by fungi without any adverse environmental effects, promoting the natural ecological cycles with the concepts of “From nature, for nature”. This work opens up a new avenue for realizing high‐performance biodegradable OFETs, and advances the process of the “green” electrical devices in practical applications.

Lung ultrasound (LUS) is useful for diagnosis of respiratory distress syndrome in neonates. Recently, it has been proved to play an important role in the management of neonatal respiratory distress syndrome (RDS). It is feasible to grade RDS and select therapeutic modalities accordingly by LUS. The treatment also should be adjusted with the change in ultrasound images. In conclusion, LUS is valuable for the diagnosis and management of neonatal respiratory distress syndrome.

BackgroundWith the development of the Internet, more and more patients search for disease-related information on video platforms during the treatment process, and physicians also look for learning materials through these video platforms. Bilibili is one of the most popular video platforms in China. This study evaluated information on various interesting topics, and related surgical procedures searched through Bilibili.MethodThe Bilibili platform was independently queried for 12 common vascular diseases or related surgical procedures between October and November 2021 by two independent authors using the Baidu search engine. Information about the video and uploader was collected, and descriptive analyses of the overall and first-page results were performed.ResultsA total of 3,998 search results were retrieved by searching 12 vascular-related topics, of which 2,225 actual videos (55.7%) were finally confirmed to be related to medicine. Videos for the public accounted for 84.8% of these 2,225 videos. In addition, 50.5% of the video results were uploaded by vascular surgeons, 12.4% by other specialties, 17.7% by organizations, and 19.4% by other individuals. The total number of videos searched for varicose vein and peripheral vascular diseases was the largest, and the total number of leg amputation videos was the smallest. The largest number of videos for medical professionals was about pulmonary embolism, and the smallest was about leg amputation. On the first pages, 168 results (70.0%) were actually medically relevant, and only 7.7% of the videos were uploaded by vascular surgeons.ConclusionOn the Bilibili platform, videos about vascular diseases are extensive but not comprehensive. The videos uploaded by vascular surgeons are rare, and the results searched are not precise. The online presence of vascular surgeons needs to be improved, which may partially solve the problem of low-quality videos due to the lack of strict management and censorship.