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Abstract Organic light-emitting diodes (OLEDs) offer the advantage of flexibility; however, the use of traditional transparent anode ITO limits further extension of their flexible characteristics. In this study, we propose employing an polymer polybenzodifuranedione (PBFDO) as a flexible transparent anode instead of the rigid ITO. To address the issue encountered during the PBFDO solution spin-coating process, we introduced n-butanol into the PBFDO conductive solution to reduce its viscosity and freezing point by modulating intermolecular hydrogen bonding interactions. Consequently, high-quality PBFDO films with high conductivity, superior transmittance, and low surface roughness were successfully obtained via spin-coating. Moreover, due to its proper work function, regular molecular stacking, and low refractive index properties, PBFDO electrode facilitate efficient carrier injection and transport as well as photon extraction. The resulting device utilizing a PBFDO anode combined with Super Yellow as the light-emitting layer exhibited excellent performance characteristics including a normal threshold voltage of 2.6 V and a maximum luminous efficiency of 12.8 cd A−1 comparable to that device based on the ITO electrode. Furthermore, flexible device also achieved satisfactory performance (7.7 cd A−1) when using the PEN substrate.

Abstract Outdoor air pollution, particularly volatile organic compounds (VOCs), significantly contributes to the global health burden. Previous analyses of VOC exposure have typically focused on regional and national scales, thereby limiting global health burden assessments. In this study, we utilized a global chemistry-climate model to simulate VOC distributions and estimate related cancer risks from 2000 to 2019. Our findings indicated a 10.2% rise in global VOC emissions during this period, with substantial increases in Sub-Saharan Africa, the Rest of Asia, and China, but decreases in the U.S. and Europe due to reductions in the transportation and residential sectors. Carcinogenic VOCs such as benzene, formaldehyde, and acetaldehyde contributed to a lifetime cancer burden affecting 0.60 [95% confidence interval (95CI): 0.40–0.81] to 0.85 [95CI: 0.56–1.14] million individuals globally. We projected that between 36.4% and 39.7% of the global population was exposed to harmful VOC levels, with the highest exposure rates found in China (82.8–84.3%) and considerably lower exposure in Europe (1.7–5.8%). Open agricultural burning in less-developed regions amplified VOC-induced cancer burdens. Significant disparities in cancer burdens between high-income and low-to-middle-income countries were identified throughout the study period, primarily due to unequal population growth and VOC emissions. These findings underscore health disparities among different income nations and emphasize the persistent need to address the environmental injustice related to air pollution exposure.

Abstract The microenvironment mediated by the microglia (MG) M1/M2 phenotypic switch plays a decisive role in the neuronal fate and cognitive function of Alzheimer's disease (AD). However, the impact of metabolic reprogramming on microglial polarization and its underlying mechanism remains elusive. This study reveals that cordycepin improved cognitive function and memory in APP/PS1 mice, as well as attenuated neuronal damage by triggering MG‐M2 polarization and metabolic reprogramming characterized by increased OXPHOS and glycolysis, rather than directly protecting neurons. Simultaneously, cordycepin partially alleviates mitochondrial damage in microglia induced by inhibitors of OXPHOS and glycolysis, further promoting MG‐M2 transformation and increasing neuronal survival. Through confirmation of cordycepin distribution in the microglial mitochondria via mitochondrial isolation followed by HPLC‐MS/MS techniques, HKII and PDK2 are further identified as potential targets of cordycepin. By investigating the effects of HKII and PDK2 inhibitors, the mechanism through which cordycepin targeted HKII to elevate ECAR levels in the glycolysis pathway while targeting PDK2 to enhance OCR levels in PDH‐mediated OXPHOS pathway, thereby inducing MG‐M2 polarization, promoting neuronal survival and exerting an anti‐AD role is elucidated.

Summary: Hydrodesulfurization (HDS) is a commonly used route for producing clean fuels in modern refinery. Herein, ammonium/amine-intercalated MoS2 catalysts with various content of 1T phase and S vacancies have been successfully synthesized. Along with the increment of 1T phase and S vacancies of MoS2, the initial reaction rate of the HDS of dibenzothiophene (DBT) can be improved from 0.09 to 0.55 μmol·gcat−1·s−1, accounting for a remarkable activity compared to the-state-of-the-art catalysts. In a combinatory study via the activity evaluation and catalysts characterization, we found that the intercalation species of MoS2 played a key role in generating more 1T phase and S vacancies through the ‘intercalation-deintercalation’ processes, and the hydrogenation and desulfurization of HDS can be significantly promoted by 1T phase and S vacancies on MoS2, respectively. This study provides a practically meaningful guidance for developing more advanced HDS catalysts by the intercalated MoS2-derived materials with an in-depth understanding of structure-function relationships.

Because of its enhanced antitumor efficacy, lapatinib (LAP) is commonly used clinically in combination with the anthracycline drug doxorubicin (DOX) to treat metastatic breast cancer. While it is well recognized that this combination chemotherapy can lead to an increased risk of cardiotoxicity in adult women, its potential cardiotoxicity in the fetus during pregnancy remains understudied. Here, we aimed to examine the combination of LAP chemotherapy and DOX-induced cardiotoxicity in the fetus using a zebrafish embryonic system and investigate the underlying pathologic mechanisms. First, we examined the dose-dependent cardiotoxicity of combined LAP and DOX exposure in zebrafish embryos, which mostly manifested as pericardial edema, bradycardia, cardiac function decline and reduced survival. Second, we revealed that a significant increase in oxidative stress concurrent with activated MAPK signaling, as indicated by increased protein expression of phosphorylated p38 and Jnk, was a notable pathophysiological event after combined LAP and DOX exposure. Third, we showed that inhibiting MAPK signaling by pharmacological treatment with the p38MAPK inhibitor SB203580 or genetic ablation of the map2k6 gene could significantly alleviate combined LAP and DOX exposure-induced cardiotoxicity. Thus, we provided both pharmacologic and genetic evidence to suggest that inhibiting MAPK signaling could exert cardioprotective effects. These findings have implications for understanding the potential cardiotoxicity induced by LAP and DOX combinational chemotherapy in the fetus during pregnancy, which could be leveraged for the development of new therapeutic strategies.

Gynostemma pentaphyllum (Thunb.) Makino is an important producer of dammarene-type triterpenoid saponins. These saponins (gypenosides) exhibit diverse pharmacological benefits such as anticancer, antidiabetic, and immunomodulatory effects, and have major potential in the pharmaceutical and health care industries. Here, we employed single-cell RNA sequencing (scRNA-seq) to profile the transcriptomes of more than 50,000 cells derived from G. pentaphyllum shoot apexes and leaves. Following cell clustering and annotation, we identified five major cell types in shoot apexes and four in leaves. Each cell type displayed substantial transcriptomic heterogeneity both within and between tissues. Examining gene expression patterns across various cell types revealed that gypenoside biosynthesis predominantly occurred in mesophyll cells, with heightened activity observed in shoot apexes compared to leaves. Furthermore, we explored the impact of transposable elements (TEs) on G. pentaphyllum transcriptomic landscapes. Our findings the highlighted the unbalanced expression of certain TE families across different cell types in shoot apexes and leaves, marking the first investigation of TE expression at the single-cell level in plants. Additionally, we observed dynamic expression of genes involved in gypenoside biosynthesis and specific TE families during epidermal and vascular cell development. The involvement of TE expression in regulating cell differentiation and gypenoside biosynthesis warrant further exploration. Overall, this study not only provides new insights into the spatiotemporal organization of gypenoside biosynthesis and TE activity in G. pentaphyllum shoot apexes and leaves but also offers valuable cellular and genetic resources for a deeper understanding of developmental and physiological processes at single-cell resolution in this species.

Abstract Background Rehabilitation post-knee arthroplasty is integral to regaining knee function and ensuring patients’ overall well-being. The debate over the relative effectiveness and safety of outpatient versus home-based rehabilitation persists. Methods A thorough literature review was conducted adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines across four databases. Two researchers independently identified eligible studies centering on knee arthroplasty patients undergoing either outpatient or home-based rehabilitation. Study quality was assessed using the Cochrane Collaboration’s risk of bias tool, while continuous outcomes were subject to meta-analyses using Stata 17 software. Results Our analysis identified no significant differences in primary outcomes, including Range of Motion, Western Ontario and McMaster Universities Arthritis Index, Knee Injury and Osteoarthritis Outcome Score, Oxford Knee Score, and the Knee Society Score, between home-based and outpatient rehabilitation across different follow-up points. Adverse reactions, readmission rates, the need for manipulation under anesthesia, reoperation rate, and post-surgery complications were also similar between both groups. Home-based rehabilitation demonstrated cost-effectiveness, resulting in substantial annual savings. Furthermore, quality of life and patient satisfaction were found to be comparable in both rehabilitation methods. Conclusions Home-based rehabilitation post-knee arthroplasty appears as an effective, safe, and cost-efficient alternative to outpatient rehabilitation. Despite these findings, further multicenter, long-term randomized controlled trials are required to validate these findings and provide robust evidence to inform early rehabilitation choices post-knee arthroplasty.

Food-borne Campylobacter jejuni infections constitute serious threats to human health worldwide. Since antibiotic treatment is usually not indicated in infected immune-competent patients, antibiotic-independent treatment approaches are needed to tackle campylobacteriosis. To address this, we orally applied carvacrol, deferoxamine, deoxycholate, and 2-fucosyl-lactose either alone or all in combination to human microbiota-associated IL-10−/− mice from day 2 until day 6 following oral C. jejuni infection. Neither treatment regimen affected C. jejuni loads in the colon, whereas carvacrol lowered the pathogen numbers in the ileum on day 6 post-infection (p.i.). The carvacrol and combination treatment regimens resulted in alleviated diarrheal symptoms, less distinct histopathological and apoptotic epithelial cell responses in the colon, as well as diminished numbers of colonic neutrophils and T lymphocytes on day 6 p.i., whereas the latter cells were also decreased upon deferoxamine, deoxycholate, or 2-fucosyl-lactose application. Remarkably, the carvacrol, deferoxamine, and combination treatment regimens dampened ex-vivo IFN-γ secretion in the colon, the kidneys, and even in the serum to basal concentrations on day 6 p.i. In conclusion, carvacrol alone and its combination with deferoxamine, deoxycholate, and 2-fucosyl-lactose constitute promising antibiotics-independent treatment options to fight acute campylobacteriosis.

Abstract Light-absorbing Brown Carbon (BrC) aerosols partially offset the overall climate-cooling of aerosols. However, the evolution of BrC light-absorption during atmospheric transport is poorly constrained. Here, we utilize optical properties, ageing-diagnostic δ13C-BrC and transport time to deduce that the mass absorption cross-section (MACWS-BrC) is decreasing by ~50% during long-range oversea transport, resulting in a first-order bleaching rate of 0.24 day‒1 during the 3-day transit from continental East Asia to a south-east Yellow Sea receptor. A modern 14C signal points to a strong inverse correlation between BrC light-absorption and age of the source material. Combining this with results for South Asia reveals a striking agreement between these two major-emission regions of rapid photobleaching of BrC with a higher intrinsic absorptivity for BrC stemming from biomass burning. The consistency of bleaching parameters constrained independently for the outflows of both East and South Asia indicates that the weakening of BrC light absorption, thus primarily related to photochemical processes rather than sources, is likely a ubiquitous phenomenon.

Abstract The occlusion of dentinal tubules has become a rapid and effective method for treating dentin hypersensitivity. Accurate evaluation of dentin occlusion is critical to illustrate the efficacy of oral care products and to optimize dental therapy in the clinics, which is limited by the conventional two-dimensional (2-D) characterization methods. Here, we demonstrate the visualization of the dentin occlusion via three-dimensional (3-D) characterization using a focused ion beam-scanning electron microscopy (FIB-SEM) tomography. Using the “Slice and View” approach, the material used for occluding dentin tubules is imaged with a very high-resolution voxel (10 nm × 10 nm × 20 nm) from 2-D SEM images and then reconstructed into a 3-D volume, which presents the mode of action of toothpaste for treating dentin hypersensitivity. Meanwhile, quantitative analysis of the depth of occlusion is successfully obtained. This work validates the feasibility of FIB-SEM tomography in the analysis of dentin occlusion within the complicated networks of dentine tubules at the nanoscale, and provides a novel approach to facilitate the research and development of oral care products.

In recent years, the incidence and mortality rate of cancer is raising worldwide. Traditional approaches for cancer patient management including surgery, chemotherapy, radiotherapy, and targeted therapies provide unsatisfactory results and are often associated with adverse reactions. Over the last few decades, nanotechnology has been a rapidly emerging area of theragnostic in clinical research. It plays a vital role as a bridge between the science and technology of miscellaneous nanoparticles (NPs) and nanomedicine. In general, NPs with a range of sizes of 1–100 nm are thought to be acceptable for cancer medications. NPs may enhance the consistency and solubility of therapeutic drugs to obtain site-specific targeting, controlled release, and safe for healthy organs. NPs have the benefit of pathophysiological properties, enhanced permeability and retention (EPR) effects, and an advantage in cancer targeting. Furthermore, theranostic nanoparticles have been established having incorporated diagnostics and therapy in a single system that might provide more personalized treatment with optimal doses and monitoring the distribution, targeting, and response to therapy by using imaging tools. In this review, we have discussed the classes of nanoparticles, targeting approaches, and implications of NPs for cancer theranostics with recent examples.

N6-methyladenosine (m6A) is a ubiquitous mRNA modification in eukaryotes. m6A occurs through the action of methyltransferases, demethylases, and methylation-binding proteins. m6A methylation of RNA is associated with various neurological disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), depression, cerebral apoplexy, brain injury, epilepsy, cerebral arteriovenous malformations, and glioma. Furthermore, recent studies report that m6A-related drugs have attracted considerable concerns in the therapeutic areas of neurological disorders. Here, we mainly summarized the role of m6A modification in neurological diseases and the therapeutic potential of m6A-related drugs. The aim of this review is expected to be useful to systematically assess m6A as a new potential biomarker and develop innovative modulators of m6A for the amelioration and treatment of neurological disorders.

Abstract A deformable microfluidic system and a fluidic dynamic model have been successfully coupled to understand the dynamic fluid–structure interaction in transient flow, designed to understand the dentine hypersensitivity caused by hydrodynamic theory. The Polydimethylsiloxane thin sidewalls of the microfluidic chip are deformed with air pressure ranging from 50 to 500 mbar to move the liquid meniscus in the central liquid channel. The experiments show that the meniscus sharply increased in the first 10th of second and the increase is nonlinearly proportional to the applied pressure. A theoretical model is developed based on the unsteady Bernoulli equation and can well predict the ending point of the liquid displacement as well as the dynamics process, regardless of the wall thickness. Moreover, an overshooting and oscillation phenomenon is observed by reducing the head loss coefficient by a few orders which could be the key to explain the dentine hypersensitivity caused by the liquid movement in the dentine tubules.

Catalysed oxidative C-C bond formation reactions are important in the synthesis of natural products, but poorly tolerated by polyphenolic flavones. Here the authors report the reactivity of molecular oxygen in alkaline water without added catalyst for the synthesis of a collection of flavone dimers and trimers.

Xylooligosaccharides (XOS) are mainly derived from lignocellulosic materials, such as rice husk, corn cobs, straw, wheat bran, wheat straw and other grain by-products. XOS have become one of the functional oligosaccharides of great concern at home and abroad due to their beneficial functional properties, such as low calorie, high stability, poor digestibility and high performance in proliferating probiotics. At present, the XOS extraction methods from grain byproducts mainly include autohydrolysis, acidolysis and enzymolysis. Among them, autohydrolysis has high requirements for equipment for achieving higher extraction rate and higher purity of products; and acidolysis can cause environmental pollution due to the usage of harmful reagents. Enzymolysis is the most common method for the production of XOS because of its high convenience, high efficiency and no pollution; and the widely used enzyme is the xylanase from Aspergillus niger. Current researches have showed that XOS can be utilized by probiotics such as Bifidobacteria and Lactobacillus to exert prebiotic effects, such as optimizing intestinal flora, promoting intestinal health, improving intestinal barrier, enhancing immune function, improving antioxidant capacity and so on. However, XOS extracted from the grain by-products contain a large amount of impurities, which limits their industrial application and makes it difficult to control the product quality. Therefore, XOS refining, separation and purification has become the key to their subsequent industrial application. This paper reviewed the current status of XOS extraction technologies from various grain by-products, and also summarized the prebiotic effect of XOS to provide reference for industrial production of XOS and its wide application in prebiotics market, thereby facilitating utilization and development of grain byproducts.

Iron widely exists in minerals and food, and has an essential role in human health. A major iron-regulating peptide hormone, hepcidin, maintains the balance of iron metabolism. The association between serum iron, hepcidin levels, and stroke risk is still under ongoing research. In this meta-analysis, Random‐effects meta‐analysis revealed that stroke patients had significantly higher serum iron and hepcidin levels compared with HC subjects. Further analysis of serum hepcidin levels in different degrees of stroke and its relation to prognosis revealed that hepcidin level is also associated with the degrees and prognosis of stroke. Finally, the role of iron overload in the mechanism of stroke development and the effect and mechanism of iron chelator intervention in stroke were also reviewed. Overall, the findings indicate that stroke patients had higher serum iron and hepcidin levels compared with healthy subjects, and their changes were associated with the severity and prognosis of stroke.

Ischemic stroke (IS) is the second leading cause of death and disability in the world. Pyroptosis, a form of programmed cell death initiated by caspases, participates in the occurrence and development of IS. Because it can increase cell membrane permeability, mediate the release of inflammatory factors, and aggravate inflammation, inhibiting this process can significantly reduce the pathological injury of IS. The nucleotide binding oligomerization domain-like receptor family pyrin domain protein 3 (NLRP3) is a multiprotein complex whose activation is the core link of pyroptosis. In recent years, studies have reported that traditional Chinese medicine (TCM) could regulate pyroptosis mediated by NLRP3 inflammasome through multi-channel and multi-target networks and thus exert the effect against IS. This article reviews 107 papers published in recent years in PubMed, Chinese National Knowledge Infrastructure (CNKI), and WanFang Data in recent years. It has found that the activation factors of NLRP3 inflammasome include ROS, mitochondrial dysfunction, K+, Ca2+, lysosome rupture, and trans-Golgi breakdown. TLR4/NF-κB/NLRP3, ROS/TXNIP/NLRP3, AMPK/Nrf2/NLRP3, DRP1/NLRP3, TAK1/JNK/NLRP3 signaling pathways regulate the initiation and assembly of the NLRP3 inflammasome, subsequently induce pyroptosis, affecting the occurrence and development of IS. TCM can affect the above signaling pathways and regulate the pyroptosis mediated by NLRP3 inflammasome, so as to play a protective role against IS, which provides a new entry point for discussing the pathological mechanism of IS and a theoretical basis for developing TCM treasure house.

IntroductionThe food-borne Gram-negative bacterial pathogen Campylobacter jejuni may cause the acute enterocolitis syndrome campylobacteriosis in infected humans. Given that human C. jejuni infections are rising globally which hold also true for resistance rates against antibiotic compounds such as macrolides and fluoroquinolones frequently prescribed for the treatment of severe infectious enteritis, novel antibiotics-independent therapeutic strategies are needed. Distinct organic acids are well known for their health-beneficial including anti-microbial and immunomodulatory properties. In our present study, we investigated potential pathogen-lowering and anti-inflammatory effects of benzoic acid, butyric acid, caprylic acid, and sorbic acid either alone or in combination during acute murine campylobacteriosis.MethodsTherefore, secondary abiotic IL-10–/– mice were perorally infected with C. jejuni strain 81–176 and subjected to a 4-day-course of respective organic acid treatment.Results and discussionOn day 6 post-infection, mice from the combination cohort displayed slightly lower pathogen loads in the duodenum, but neither in the stomach, ileum nor large intestine. Remarkably, the clinical outcome of C. jejuni induced acute enterocolitis was significantly improved after combined organic acid treatment when compared to the placebo control group. In support, the combinatory organic acid treatment dampened both, macroscopic and microscopic inflammatory sequelae of C. jejuni infection as indicated by less colonic shrinkage and less pronounced histopathological including apoptotic epithelial cell changes in the colon on day 6 post-infection. Furthermore, mice from the combination as compared to placebo cohort exhibited lower numbers of innate and adaptive immune cells such as neutrophilic granulocytes, macrophages, monocytes, and T lymphocytes in their colonic mucosa and lamina propria, respectively, which also held true for pro-inflammatory cytokine secretion in the large intestines and mesenteric lymph nodes. Notably, the anti-inflammatory effects were not restricted to the intestinal tract, but could also be observed systemically given pro-inflammatory mediator concentrations in C. jejuni infected mice from the combination organic acid treatment that were comparable to basal values. In conclusion, our in vivo study provides first evidence that an oral application of distinct organic acids in combination exhibits pronounced anti-inflammatory effects and hence, constitutes a promising novel antibiotics-independent therapeutic strategy in the combat of acute campylobacteriosis.

A recombinant inbred line population including 371 lines was developed by a high kernel number per spike (KNPS) genotype T1208 and a low KNPS genotype Chuannong18 (CN18). A genetic linkage map consisting of 11,583 markers was constructed by the Wheat55K SNP Array. The quantitative trait loci (QTLs) related to KNPS were detected in three years. Eight, twenty-seven, and four QTLs were identified using the ICIM-BIP, ICIM-MET, and ICIM-EPI methods, respectively. One QTL, QKnps.sau-2D.1, which was mapped on chromosome 2D, can explain 18.10% of the phenotypic variation (PVE) on average and be considered a major and stable QTL for KNPS. This QTL was located in a 0.89 Mb interval on chromosome 2D and flanked by the markers AX-109283238 and AX-111606890. Moreover, KASP-AX-111462389, a Kompetitive Allele-Specific PCR (KASP) marker which closely linked to QKnps.sau-2D.1, was designed. The genetic effect of QKnps.sau-2D.1 on KNPS was successfully confirmed in two RIL populations. The results also showed that the significant increase of KNPS and 1000-kernel weight (TKW) was caused by QKnps.sau-2D.1 overcoming the disadvantage due to the decrease of spike number (SN) and finally lead to a significant increase of grain yield. In addition, within the interval in which QKnps.sau-2D.1 is located in Chinese Spring reference genomes, only fifteen genes were found, and two genes that might associate with KNPS were identified. QKnps.sau-2D.1 may provide a new resource for the high-yield breeding of wheat in the future.

Introduction: Hyperlipidemia is a common metabolic disorder with presence of excess fat or lipids in the blood, may induce liver injury, oxidative stress and inflammatory. Xuezhiping capsule (XZP) is a famous Chinese patent medicine clinically used for anti-hyperlipidemia. However, the regulation mechanism of XZP on hyperlipidemia has not been elucidated so far.Methods: This study aimed to explore the effects of XZP on hypolipidemic, antioxidant and anti-inflammatory effects, and the potential mechanism by a combination of untargeted metabolomics and 16S rRNA sequencing.Results: The results indicated that XZP reduced the level of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), increased the level of high density liptein cholesterol (HDL-C), alleviated excessive accumulation of lipid droplets in liver. Biochemical indexes of liver function including gamma glutamyl transferase (GGT) and glutamic oxaloacetic transaminase (GOT) in liver were remarkably decreased. Meanwhile, XZP increased the level of oxidative stress biochemical indexes including superoxide dismutase (SOD) and glutathione (GSH). In addition, XZP increased the level of peroxisome proliferators-activated receptors α (PPARα), acetyl CoA carboxylase 1 (ACOX1) and cholesterol 7-alpha hydroxylase (CYP7A1) in liver, and improved lipid metabolism in serum, liver and fecal lipid metabolism. XZP increased diversity index and the ratio of Firmicutes and Bacteroidetes, regulated seventeen genera, and illustrated strong correlations with liver lipid metabolism and phenotypic indicators.Discussion: These findings suggest that XZP reduced blood lipid and liver lipid, protected liver function, anti inflammation and anti-oxidation, ameliorate lipid metabolic disorders by modulating alpha linolenic acid and linoleic acid metabolism, bile acid metabolism, arachidonic acid metabolism, and regulated gut microbiota composition of high-fat diet (HFD) hamsters.

Abstract A novel localized surface plasmon resonance (LSPR) system based on the coupling of gold nanomushrooms (AuNMs) and gold nanoparticles (AuNPs) is developed to enable a significant plasmonic resonant shift. The AuNP size, surface chemistry, and concentration are characterized to maximize the LSPR effect. A 31 nm redshift is achieved when the AuNMs are saturated by the AuNPs. This giant redshift also increases the full width of the spectrum and is explained by the 3D finite‐difference time‐domain (FDTD) calculation. In addition, this LSPR substrate is packaged in a microfluidic cell and integrated with a CRISPR‐Cas13a RNA detection assay for the detection of the SARS‐CoV‐2 RNA targets. Once activated by the target, the AuNPs are cleaved from linker probes and randomly deposited on the AuNM substrate, demonstrating a large redshift. The novel LSPR chip using AuNP as an indicator is simple, specific, isothermal, and label‐free; and thus, provides a new opportunity to achieve the next generation multiplexing and sensitive molecular diagnostic system.

Purpose: Microglia-neuron crosstalk is critically involved in synaptic plasticity and degeneration by releasing diverse mediators in Alzheimer’s disease (AD). Therefore, determining contributors that modulate the systemic microenvironment is essential. Cordycepin (CCS) is a novel neuroprotective compound obtained from Cordyceps militaris. However, the anti-AD efficacy and potential mechanism of CCS treatment remain unclear. This study aimed to elucidate the microglia-neuron symphony in AD after CCS treatment and to explore the possible mechanisms of its neuroprotective efficacy. Methods and results: CCS treatment improved learning and memory impairment in 9-month-old APP/PS1 mice by behavioral tests. CCS polarized the microglia from M1 to M2, inhibited neuronal apoptosis and promoted synaptic remodeling accompanied by in vivo and in vitro upregulation of NGF. The cAMP-response element-binding protein (CREB) was also activated after MG-M2 polarization. Further, we verified that the sg3 promoter region of NGF (–1018 to –1011) is the key binding site for CREB-induced NGF transcription, which increased NGF expression and secretion. Finally, microglia-derived NGF was confirmed as an important mediator in microglia-neuron symphony to improve the neuronal microenvironment after CCS treatment. Conclusions: CCS improved the neuronal synaptic plasticity and senescence by promoting MG-M2 activation driven by CREB-induced NGF upregulation and facilitated symphony communication between the microglia and neuron in AD. This study provides a new perspective on the development of a novel strategy for anti-AD therapy and offers new targets for anti-AD drug development.

Abstract Scanning Electron Microscope/Focused Ion Beam (SEM/FIB) system has become valuable and popular tool for the analysis of biological materials such as dentine structures. According to physiological and anatomical studies, dentine structures are a complicated system containing collagen fibers, nanocrystalline hydroxyapatite, and numerous networks of tubular pores. During a routine FIB milling process, collagen fibers and other organic structures are vaporized, which increases the number of pores on the milled surface of the dentine. This causes the final cross-section to be more porous than the pristine sample. Unfortunately, little attention has been paid to the collagen fiber loss and how to preserve them during a FIB milling process. In this work, we present a novel and simple approach to preserve the organic portions of the dentine structure through metal staining. By using this method, the porosity of the dentine structure after the FIB milling process is significantly reduced similar to the pristine sample. This indicates that the organic portion of the dentine structure is well protected by the metal staining. This approach enables the SEM/FIB system to generate super-high quality SEM images with less ion beam damage; and the SEM images can better reflect the original condition of the dentine structure. Further, serial energy-dispersive X-ray spectroscopy (EDS) mapping of the stained dentine structure is achieved without an additional metal coating; and three-dimensional (3-D) elemental mapping of an occluded dentine is achieved with a significantly reduced data acquisition time.

The copper/graphene (Cu/Gr) composites made of Gr/Cu/Gr foils with a thickness of 25 μm were prepared using spark plasma sintering diffusion bonding (SPS) and hot press diffusion bonding (HP) in an Ar atmosphere at 900 °C for 20 min under a pressure of 50 MPa. The electrical conductivity of the prepared Cu/Gr composites was measured by the van der Pauw method, the microstructure was characterized using Raman spectroscopy, scanning electron microscope and transmission electron microscope, and the corresponding mechanism was analyzed by employing the first-principles calculations. The result indicates that, SPS process reduces the interfacial impurities of Cu/Gr composites, rendering a much higher electrical conductivity (108.6% IACS) than that prepared by using HP (98.8% IACS). This finding is correlated to the reduced oxygen (O) impurities on Gr/Gr interface, which is attributed to the high temperature plasma sputtering effect of SPS. In the prepared Cu/Gr composites, the impurity-free Gr/Gr interface has an ideal spacing of ∼3.3 Å wherein carbon (C) across the interface do not bond. Despite the generated C–C covalent bonding within the same Gr layer bounds some of the electrons, the remaining electrons of the p orbital on each C atom are free electrons, leading to the excellent electrical conductivity. In contrast, absorption of O impurities on the Gr/Gr interface increases the spacing between the Gr layers to ∼3.8 Å, and generates covalent C–O–C bonding across the interface due to p orbital hybridization. This reduces the free electron concentration and the corresponding electrical conductivity.

Traditional Chinese medicine (TCM) has attracted a great deal of attention in the treatment of cerebral ischemia is credited with the remarkable neuroprotective effects. However, the imperfect functional mechanism of TCM is a major obstacle to their application. Many studies have been conducted to illustrate the pathophysiology of post-ischemic cerebral ischemia by elucidating the neuronal cell death pathway. Meanwhile, a new type of cell death, ferroptosis, is gradually being recognized in various diseases and is becoming a new pathway of therapeutic intervention strategy to solve many health problems. Especially since ferroptosis has been found to be closely involved into the pathogenesis of cerebral ischemia, it has been considered as a key target in the treatment of cerebral ischemia. Therefore, this paper reviews the latest research findings about the treatment of cerebral ischemia with TCM focused on ferroptosis as a target. Also, in order to explores the possibility of a new approach to treat cerebral ischemia with TCM, we discusses the correlation between ferroptosis and other cell death pathways such as apoptosis and autophagy, which would provide references for the following researches.

Xylooligosaccharide (XOS) are functional oligosaccharides with prebiotic activities, which originate from lignocellulosic biomass and have attracted extensive attention from scholars in recent years. This paper summarizes the strategies used in the production of XOS, and introduces the raw materials, preparation methods, and purification technology of XOS. In addition, the biological characteristics and applications of XOS are also presented. The most commonly recommended XOS production strategy is the two-stage method of alkaline pre-treatment and enzymatic hydrolysis; and further purification by membrane filtration to achieve the high yield of XOS is required for prebiotic function. At the same time, new strategies and technologies such as the hydrothermal and steam explosion have been used as pre-treatment methods combined with enzymatic hydrolysis to prepare XOS. XOS have many critical physiological activities, especially in regulating blood glucose, reducing blood lipid, and improving the structure of host intestinal flora.

Fowl adenovirus serotype 4 (FAdV-4) is recognized as a pathogen that causes hydropericardium syndrome. Irrespective of the pathway used by the virus to invade the chicken, the pathological characteristics of the disease include degeneration and necrosis of hepatocytes, formation of intranuclear inclusions, as well as inflammatory cell infiltration. Liver dysfunction constitutes one of the critical factors leading to death. Therefore, it is vital to investigate the virus-mediated severe pathological liver damage to further understand the pathogenesis of FAdV-4. Here, proteomics, a tandem mass tag (TMT)-based approach to directly analyze protein expression, was used to determine the protein expression during FAdV-4 proliferation in leghorn male hepatoma (LMH) cells. We identified 177 differentially expressed proteins associated with various biological processes and pathways. The functional enrichment analysis revealed that FAdV-4 could downregulate some signaling pathways in LMH cells, including NOD-like receptor signaling, RIG-I-like receptor signaling, NF-κB signaling, TNF signaling pathway, and Notch signaling, FoxO signaling, PI3K-Akt signaling, and autophagy. The results of proteomics screening suggested an association between FAdV-4 infection and Notch signaling in LMH in vitro, indicating that Notch signaling regulated the expression of inflammatory cytokines and interferons but not viral replication in LMH cells. These data contributed to the understanding of the immunopathogenesis and inflammopathogenesis of FAdV-4 infection and also provided valuable information for the further analysis of the molecular mechanisms underlying viral pathogenesis.

Wheat germ, a byproduct of wheat industrial processing, contains 30% protein and is a comprehensive source of plant-based protein. But a large amount of wheat germs are disposed of as waste every year. Wheat germ protein can be hydrolyzed into polypeptides with antioxidant, antihypertensive, anti-tumor, bacteriostatic and other activities. At present, researches on the hydrolysis of wheat germ protein and the preparation of bioactive peptides from wheat germ protein have attracted increasing attentions. However, the traditional protein hydrolysis method, protease hydrolysis, can no longer meet the market's needs for efficient production. Various auxiliary means, such as ultrasound, microwave and membrane separation, were applied to boost the yield and biological activity of wheat germ peptides by enzymatic hydrolysis. Under ultrasound and microwave, the protein structure may expand to increase the binding sites between enzyme and substrate and promote hydrolysis efficiency. Membrane separation is applied to separate products from enzymatic hydrolysate to reduce the inhibitory effect of the product on the hydrolysis reaction. The paper reviewed the hydrolysis methods of wheat germ protein and summarized the biological activity of wheat germ peptides to provide references for further study of wheat germ peptides.

Cognitive dysfunction is a frequent complication of type 2 diabetes mellitus (T2DM), usually accompanied by metabolic disorders. However, the metabolic changes in diabetic cognitive dysfunction (DCD) patients, especially compared to T2DM groups, are not fully understood. Due to the subtle differences in metabolic alterations between DCD groups and T2DM groups, the comprehensive detection of the untargeted metabolic profiles of hippocampus and urine samples of rats was conducted by LC–MS, considering the different ionization modes and polarities of the examined compounds, and feature-based molecular networking (FBMN) was performed to help identify differential metabolites from a comprehensive perspective in this study. In addition, an association analysis of the differential metabolites in hippocampus and urine was conducted by the O2PLS model. Finally, a total of 71 hippocampal tissue differential metabolites and 179 urine differential metabolites were identified. The pathway enrichment results showed that glutamine and glutamate metabolism, alanine, aspartate, and glutamate metabolism, glycerol phospholipid metabolism, TCA cycle, and arginine biosynthesis in the hippocampus of DCD animals were changed. Seven metabolites (AUC > 0.9) in urine appeared as key differential metabolites that might reflect metabolic changes in the target tissue of DCD rats. This study showed that FBMN facilitated the comprehensive identification of differential metabolites in DCD rats. The differential metabolites may suggest an underlying DCD and be considered as potential biomarkers for DCD. Large samples and clinical experiments are needed for the subsequent elucidation of the possible mechanisms leading to these alterations and the verification of potential biomarkers.

The most severe form of epilepsy, status epilepticus (SE), causes brain damage and results in the development of recurring seizures. Currently, the management of SE remains a clinical challenge because patients do not respond adequately to conventional treatments. Evidence suggests that neural cell death worsens the occurrence and progression of SE. The main forms of cell death are apoptosis, necroptosis, pyroptosis, and ferroptosis. Herein, these mechanisms of neuronal death in relation to SE and the alleviation of SE by potential modulators that target neuronal death have been reviewed. An understanding of these pathways and their possible roles in SE may assist in the development of SE therapies and in the discovery of new agents.

BackgroundEarly diagnosis and effective intervention are the keys to delaying the progression of Alzheimer’s Disease (AD). Therefore, we aimed to identify new biomarkers for the early diagnosis of AD through bioinformatic analysis and elucidate the possible underlying mechanisms.Methods and ResultsGSE1297, GSE63063, and GSE110226 datasets from the GEO database were used to screen the highly differentially expressed genes. We identified a potential biomarker, Platelet activating factor receptor (PTAFR), significantly upregulated in the brain tissue, peripheral blood, and cerebrospinal fluid of AD patients. Furthermore, PTAFR levels in the plasma and brain tissues of APP/PS1 mice were significantly elevated. Simultaneously, PTAFR could mediate the inflammatory responses to exaggerate the microenvironment, particularly mediated by the microglia through the IL10-STAT3 pathway. In addition, PTAFR was a putative target of anti-AD compounds, including EGCG, donepezil, curcumin, memantine, and Huperzine A.ConclusionPTAFR was a potential biomarker for early AD diagnosis and treatment which correlated with the microglia-mediated microenvironment. It is an important putative target for the development of a novel strategy for clinical treatment and drug discovery for AD.

Arrhythmogenic cardiomyopathy (ACM) is largely an autosomal dominant genetic disorder manifesting fibrofatty infiltration and ventricular arrhythmia with predominantly right ventricular involvement. ACM is one of the major conditions associated with an increased risk of sudden cardiac death, most notably in young individuals and athletes. ACM has strong genetic determinants, and genetic variants in more than 25 genes have been identified to be associated with ACM, accounting for approximately 60% of ACM cases. Genetic studies of ACM in vertebrate animal models such as zebrafish (Danio rerio), which are highly amenable to large-scale genetic and drug screenings, offer unique opportunities to identify and functionally assess new genetic variants associated with ACM and to dissect the underlying molecular and cellular mechanisms at the whole-organism level. Here, we summarize key genes implicated in ACM. We discuss the use of zebrafish models, categorized according to gene manipulation approaches, such as gene knockdown, gene knock-out, transgenic overexpression, and CRISPR/Cas9-mediated knock-in, to study the genetic underpinning and mechanism of ACM. Information gained from genetic and pharmacogenomic studies in such animal models can not only increase our understanding of the pathophysiology of disease progression, but also guide disease diagnosis, prognosis, and the development of innovative therapeutic strategies.

Reducing methane (CH4) emissions from anthropogenic activities is critical to climate change mitigation efforts. However, there is still considerable uncertainty over the amount of fugitive CH4 emissions due to large-scale area sources and heterogeneous emission distributions. To reduce the uncertainty and improve the spatial and temporal resolutions, a new hybrid method was developed combining optical remote sensing (ORS), computed tomography (CT), and inverse-dispersion modeling techniques on the basis of which a multi-path scanning system was developed. It uses a horizontal radial plume mapping path configuration and adapts a Lagrangian stochastic dispersion mode into CT reconstruction. The emission map is finally calculated by using a minimal curvature tomographic reconstruction algorithm, which introduces smooth constraints at each pixel. Two controlled-release experiments of CH4 were conducted with different configurations, showing relative errors of only 2% and 3%. Compared with results from the single-path inverse-dispersion method (5–175%), the new method can not only derive the emission distribution but also obtain a more accurate emission rate. The outcome of this research would bring broad application of the ORS-CT and inverse-dispersion techniques to other gases and sources.

Value chain collaboration management is an effective means for enterprises to reduce costs and increase efficiency to enhance competitiveness. Vertical and horizontal collaboration have received much attention, but the current collaboration model combining the two is weak in terms of task assignment and node collaboration constraints in the whole production-distribution process. Therefore, in the enterprise dynamic alliance, this paper models the MVC (multi-value-chain) collaboration process for the optimization needs of the MVC collaboration network in production-distribution and other aspects. Then a MVC collaboration network optimization model is constructed with the lowest total production-distribution cost as the optimization objective and with the delivery cycle and task quantity as the constraints. For the high-dimensional characteristics of the decision space in the multi-task, multi-production end, multi-distribution end, and multi-level inventory production-distribution scenario, a genetic algorithm is used to solve the MVC collaboration network optimization model and solve the problem of difficult collaboration of MVC collaboration network nodes by adjusting the constraints among genes. In view of the multi-level characteristics of the production-distribution scenario, two chromosome coding methods are proposed: staged coding and integrated coding. Moreover, an algorithm ERGA (enhanced roulette genetic algorithm) is proposed with enhanced elite retention based on a SGA (simple genetic algorithm). The comparative experiment results of SGA, SEGA (strengthen elitist genetic algorithm), ERGA, and the analysis of the population evolution process show that ERGA is superior to SGA and SEGA in terms of time cost and optimization results through the reasonable combination of coding methods and selection operators. Furthermore, ERGA has higher generality and can be adapted to solve MVC collaboration network optimization models in different production-distribution environments.

Human Campylobacter jejuni infections are rising globally. Since antibiotics are usually not indicated in acute campylobacteriosis, antibiotic-independent intervention measures are desirable. The phenolic compound carvacrol constitutes a promising candidate molecule given its antimicrobial and immune-modulatory features. To test the disease-alleviating effects of oral carvacrol treatment in acute murine campylobacteriosis, IL-10−/− mice harboring a human gut microbiota were perorally infected with C. jejuni and treated with carvacrol via the drinking water. Whereas C. jejuni stably established in the gastrointestinal tract of mice from the placebo cohort, carvacrol treatment resulted in lower pathogen loads in the small intestines on day 6 post infection. When compared to placebo, carvacrol ameliorated pathogen-induced symptoms including bloody diarrhea that was accompanied by less distinct histopathological and apoptotic cell responses in the colon. Furthermore, innate and adaptive immune cell numbers were lower in the colon of carvacrol- versus placebo-treated mice. Notably, carvacrol application dampened C. jejuni-induced secretion of pro-inflammatory mediators in intestinal, extra-intestinal and systemic organs to naive levels and furthermore, resulted in distinct shifts in the fecal microbiota composition. In conclusion, our preclinical placebo-controlled intervention study provides evidence that therapeutic carvacrol application constitutes a promising option to alleviate campylobacteriosis in the infected vertebrate host.

Cordycepin (Cor) is a potent bioactive constituent of Cordyceps militaris, which has been used as a daily tonic food and herbal medicine in Asia. Cadmium (Cd) is a widespread neurotoxic environmental contaminant, and it has been detected as a pollutant in Cordyceps militaris. However, the potential effects of Cor on Cd neurotoxicity remains unknown. This study aimed to investigate the effects and possible mechanisms of Cor on neurotoxicity in Cd-induced cell and preclinical models. It was observed that Cor administration aggravated Cd-induced cognitive impairment and neurotoxicity in mice, exerted synergistic growth inhibition, and promoted apoptosis of SH-SY5Y cells. These effects were found to be mediated through the activation of endoplasmic reticulum (ER) stress. Overall, our findings suggest that Cor can increase Cd-induced neurotoxicity via promoting ER stress-associated apoptosis. These observations may support the implementation of stricter criterion for the detection of Cd in Cordyceps militaris, to keep the consumers safe.

Alzheimer's disease (AD) remains a medical and social challenge worldwide. Magnesium (Mg) is one of the most frequently evaluated essential minerals with diverse biological functions in human body. However, the association between circulating Mg levels and AD remains controversial. We conducted a meta-analysis of 21 studies published between 1991 and 2021 to determine whether the Mg levels in the blood and cerebrospinal fluid (CSF) are abnormal in AD. Literatures were searched in PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Data without language limitations. A pooled subject sample including 1,112 AD patients and 1,001 healthy controls (HCs) was available to assess Mg levels in serum and plasma; 284 AD patients and 117 HCs were included for Mg levels in CSF. It was found that serum and plasma levels of Mg were significantly reduced in AD patients compared with HCs (standardized mean difference [SMD] = −0.89; 95% confidence interval [CI] [−1.36, −0.43]; P = 0.000). There was statistically non-significant for Mg level in CSF between AD and HCs, whereas a decreased tendency were detected (SMD = −0.16; 95% CI [−0.50, 0.18]; P = 0.364). .In addition, when we analyzed the Mg levels of serum, plasma and CSF together, the circulating Mg levels in AD patients was significantly lower (SMD = −0.74, 95% CI [−1.13; −0.35]; P = 0.000). These results indicate that Mg deficiency may be a risk factor of AD and Mg supplementation may be a potentially valuable adjunctive treatment for AD.Systematic Review Registration:www.crd.york.ac.uk/PROSPERO/, registration number CRD42021254557.

Background: The anesthetic characteristics of ultrasound-guided bi-level erector spinae plane block (ESPB) plus dexmedetomidine (Dex) remain unclear. We compared the efficacy and safety of ultrasound-guided bi-level ESPB plus different doses of Dex in patients undergoing video-assisted thoracic surgery (VATS).Methods: One-hundred eight patients undergoing VATS were randomized into three groups: R group (n = 38, 15 ml of 0.375% ropivacaine with 0.1 mg/kg dexamethasone), RD1 group (n = 38, 15 ml of 0.375% ropivacaine plus 0.5 μg/kg DEX with 0.1 mg/kg dexamethasone) and RD2 group (n = 38, 15 ml of 0.375% ropivacaine plus 1.0 μg/kg DEX with 0.1 mg/kg dexamethasone). The primary outcome was the pain 12 h after surgery. Secondary outcomes included the Prince Henry Hospital Pain Score; hemodynamics; consumption of sufentanil; anesthetized dermatomal distribution; recovery time; rescue analgesia; satisfaction scores of patients and surgeon; quick recovery index; adverse effects; the prevalence of chronic pain and quality of recovery.Results: The visual analog scale (VAS) and the Prince Henry pain score were significantly lower in both the RD1 and RD2 groups during the first 24 h after surgery (P < 0.05). Both VAS with coughing and the Prince Henry pain score were significantly lower in the RD2 group than in the RD1 group 8–24 h after surgery (P < 0.05). Both heart rate and mean arterial pressure were significantly different from T2 to T6 in the RD1 and RD2 groups (P < 0.05). The receipt of remifentanil, propofol, Dex, and recovery time was significantly reduced in the RD2 group (P < 0.05). The requirement for sufentanil during the 8–72 h after surgery, less rescue medication, and total press times were significantly lower in the RD2 group (P < 0.05). The time to the first dose of rescue ketorolac was significantly longer in the RD2 group (P < 0.05). Further, anal exhaust, removal of chest tubes, and ambulation were significantly shorter in the RD2 group (P < 0.05). The incidence of tachycardia, post-operative nausea and vomiting, and chronic pain was significantly reduced in the RD2 group, while the QoR-40 score was significantly higher in the RD2 group (P < 0.05).Conclusions: Pre-operative bi-level, single-injection ESPB plus 1 μg/kg DEX provided superior pain relief and long-term post-operative recovery for patients undergoing VATS.Clinical Trial Registration:http://www.chictr.org.cn/searchproj.aspx.

The mitochondria play a significant role in many cellular processes and are recognized as one of the most important therapeutic targets in cancer. Direct long-term imaging of the mitochondria is very crucial for treating cancer. However, the development of a red-emitting mitochondrial probe with a large Stokes shift and photostability remains highly challenging. Fluorescent metal complexes with superior physicochemical property have emerged as new fluorescent nanomaterials due to their increasing advantages in bioimaging. Herein, a luminescent pitaya-type nanostructure based on rhein-magnesium(II) (Rh-Mg) coordination polymer nanodots was used as a fluorescent nanoprobe to selectively image the mitochondria benefiting from the introduction of triphenylphosphine. The as-prepared Rh-Mg nanodot-based nanoprobe showed red emission peaking at 620 nm, a large Stokes shift (100 nm), and excellent photostability as compared with commercial mitochondrial probes. Due to these extraordinary features, this fluorescent nanoprobe was successfully used for mitochondrial targeting imaging of live cancer cell line Neuro-2a (mouse neuroblastoma) and BV2 microglial cells. Therefore, our results pave a new way for the design of fluorescent nanoprobes for imaging mitochondria in cancer cell.

The outbreak of the monkeypox virus (MPXV) in non-endemic countries is an emerging global health threat and may have an economic impact if proactive actions are not taken. As shown by the COVID-19 pandemic, rapid, accurate, and cost-effective virus detection techniques play a pivotal role in disease diagnosis and control. Considering the sudden multicountry MPXV outbreak, a critical evaluation of the MPXV detection approaches would be a timely addition to the endeavors in progress for MPXV control and prevention. Herein, we evaluate the current MPXV detection methods, discuss their pros and cons, and provide recommended solutions to the problems. We review the traditional and emerging nucleic acid detection approaches, immunodiagnostics, whole-particle detection, and imaging-based MPXV detection techniques. The insights provided in this article will help researchers to develop novel techniques for the diagnosis of MPXV.

Given that human Campylobacter jejuni infections are rising globally and antibiotic treatment is not recommended, infected patients would substantially benefit from alternative therapeutic strategies. Short-chain fatty acids such as butyrate are known for their health benefits, including anti-microbial and anti-inflammatory effects. This prompted us to investigate potential disease-alleviating properties of butyrate treatment during acute murine C. jejuni-induced enterocolitis. Therefore, following gut microbiota depletion IL-10−/− mice were challenged with 109 viable C. jejuni cells by oral gavage and treated with butyrate via the drinking water (22 g/L) starting on day 2 post-infection. As early as day 3 post-infection, butyrate reduced diarrheal severity and frequency in treated mice, whereas on day 6 post-infection, gastrointestinal C. jejuni burdens and the overall clinical outcomes were comparable in butyrate- and placebo-treated cohorts. Most importantly, butyrate treatment dampened intestinal pro-inflammatory immune responses given lower colonic numbers of apoptotic cells and neutrophils, less distinct TNF-α secretion in mesenteric lymph nodes and lower IL-6 and MCP-1 concentrations in the ileum. In conclusion, results of our preclinical intervention study provide evidence that butyrate represents a promising candidate molecule for the treatment of acute campylobacteriosis.

Necroptosis is a kind of programmed necrosis, which is different from apoptosis and pyroptosis. Its molecular mechanism has been described in inflammatory diseases. Gastric cancer (GC) is one of the most common malignancies worldwide with the third highest mortality. However, the role of necroptosis in the occurrence and progression of GC remains largely unexplored. Therefore, we investigated necroptosis-related genes (NRGs) by analyzing public transcriptomic data from GC samples. Our results indicate that 83 of 740 NRGs are dysregulated in GC tissues. Next, we identified necroptosis-associated early diagnosis and prognostic gene signatures for GC using machine learning. 2-NRGs (CCT6A and FAP) and 4-NRGs (ZFP36, TP53I3, FAP, and CCT6A), respectively, can effectively assess the risk of early GC (AUC = 0.943) and the prognosis of GC patients (AUC = 0.866). Through in-depth analysis, we were pleasantly surprised to find that there was a significant correlation between the 4-NRGs and GC immunotherapy effect and immune checkpoint inhibitors (ICIs), which could be used for the evaluation of immunosuppressants. Finally, we identified the core gene FAP, and established the relationship between FAP and ICIs in GC. These findings could provide a new target for immunotherapy for GC and a more effective treatment scheme for GC patients.

Using a catalyst to mineralize volatile organic compounds (VOCs) in a Non-thermal Plasma (NTP) reactor is an effective method. In many kinds of catalysts for VOCs degradation, oxygen defect is a crucial factor affecting the catalytic activity. Three different methods (steaming, doping, plasma) were used to introduce possible oxygen defects into the Mn/ZSM-5 to prepare modified catalysts, which were evaluated in VOCs degradation activity using a Double Dielectric Barrier Discharge (DDBD) plasma device. Additionally, a novel Y-type ZSM-5 model was employed in the DFT simulation. The new Y-type ZSM-5 model used in this paper is a more realistic aperiodic model. It showed that introducing possible oxygen defects can substantially enhance degradation efficiency. Taking the catalyst with oxygen defects introduced by plasma as an example, the conversion (CO2 selectivity) of the methanol, acetone, and toluene could reach 100% (100%), 97.7% (99.1%), 91.2% (93.9%), respectively, at an initial concentration of 2000 ppm and specific input energy of 9 kJ/L. The results demonstrated that modification could significantly enhance the activity of the catalyst in decomposing VOCs at room temperature using non-thermal plasma catalysis. Theoretical simulation of density functional theory (DFT) revealed that the adsorption of adsorbate on the catalyst becomes easier after possible oxygen defects are introduced.

Abstract Reinforced concrete (RC) coupled wall systems, compared with RC shear wall without opening, have more complex nonlinear behavior under the extreme earthquake loads due to the existence of coupling beams. The behavior characteristics induced by nonlinear shear deformation such as shear–flexure interaction, pinching effect, strength and stiffness deterioration are clearly observed in numerous cyclic tests of RC coupling beams and shear walls. To develop an analytical model capable of accurately and efficiently assessing the expected seismic performance of RC coupled wall systems, it is critical to define the appropriate key components models (i.e., nonlinear models of RC wall piers/shear walls and coupling beams). Classic fiber beam element based on the theory of Euler–Bernoulli beam is frequently adopted to simulate the nonlinear responses of slender RC wall piers and coupling beams in the literature because it is able to accurately model the response characters from interaction of axial–bending moment at the section level. However, classic fiber beam element cannot capture the nonlinear behaviors of non-slender structures mainly controlled by nonlinear shear deformation. To overcome this shortcoming, a modified force-based fiber element (MFBFE) including shear effect is introduced and used as the analysis element of non-slender RC coupling beams and shear walls. At the section level, a novel shear model for RC coupling beams and an existed shear model for RC shear walls are respectively added to this fiber element to simulate nonlinear responses of these two key components. The analytical model for RC coupled walls hence is formed through integrating the proposed models of these two key components. The validations with different experimental results of cyclic tests including key components and structural system reported in the literature using these proposed models are performed. Good agreements are achieved for all of these proposed models via comparisons between predicted results and experimental data.

The study provides an overview of Predictive Emissions Monitoring System's (PEMS) research, application, installation, and regulatory framework as well as develops predictive models for NOx emissions from a natural gas fired cogeneration unit using an open source machine learning library, Keras, and open source programming languages, Python and R. Nine neural network based predictive models were trained with 12 086 examples and tested with 3020 examples. The neural network-based models use eight process parameters as inputs to predict NOx emissions. All models meet the regulatory requirements for precision. The best model (32-64-64-64) has four hidden layers and uses the Nadam method for optimization. The best model has a mean absolute error of 0.5982, r-value of 0.9451, and a difference of 0.14% between the measured and predicted emission values using the test dataset. The study demonstrated the feasibility of using open source machine learning library in PEMS development. It also provides guidance to facility operators to develop their own PEMS models for monitoring emissions.