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Background: Respiratory diseases seriously threaten human health worldwide, and lung injury is an important component of respiratory disease. Complement activation is an important function of the innate immune system. Complement activation helps the body defend against invasion by external microorganisms, whereas excessive complement activation can exacerbate tissue damage or lead to unwanted side effects. Ficolins are a class of immune-related proteins in the lectin pathway that play important roles in the body’s immune defense. Although individual ficolins are not well understood, current information suggests that ficolins may play an important regulatory role in lung injury. Summary: Several studies have shown that ficolins are involved in the immune response in the lung, particularly in the response to infectious and inflammatory processes. Key Messages: This review summarizes the role of ficolins in lung injury. Ficolins may influence the development and repair of lung injury by recognizing and binding pathogenic microorganisms, modulating the inflammatory response, and promoting the clearance of immune cells. In addition, ficolins are associated with the development and progression of lung diseases (such as pneumonia and ARDS) and may have an important impact on the pathophysiological processes of inflammatory diseases.

Abstract Circular RNA (circRNA) is thought to mediate the occurrence and development of human cancer and usually acts as a tiny RNA (miRNA) sponge to regulate downstream gene expression. However, it is not clear whether and how circACVR2A (hsa_circ_0001073) is involved in the progression of HCC. The purpose of this study is to clarify the potential role and molecular mechanism of circACVR2A in regulating the progression of hepatocellular carcinoma cells (HCC). The abundance of related proteins in circACVR2A, microRNA (miR511-5p) and PI3K-Akt signaling pathway was determined by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) or Western blotting. Cell viability, invasion and apoptosis were analyzed by CCK-8, Transwell analysis and Tunel staining, respectively. The interaction between circACVR2A and microRNA was evaluated by double luciferase reporter gene assay. The results showed that circACVR2A was highly expressed in hepatocellular carcinoma cell lines. Our in vivo and in vitro data showed that circACVR2A promoted the proliferation, migration and invasion of HCC. In terms of mechanism, we found that circACVR2A can directly interact with miR511-5p and act as a miRNA sponge to regulate the expression of related proteins in PI3K-Akt signaling pathway. In HCC, circACVR2A can mediate miR-511-5p/mRNA network to activate PI3K signal pathway. This shows that the molecular regulatory network with circACVR2A as the core is a new potential target for diagnosis and treatment of hepatocellular carcinoma.

The correlations between the mechanical properties of HPCs and their mixture compositions are complex, non-linear, and complex to characterize employing standard statistical methods. This paper aimed to estimate HPC’s compressive strength using a machine learning algorithm including Multi-layer Perceptron (MLP) with an HPC mixed collection of 168 samples via eight input variables. In addition, three meta-heuristic optimizers have been used for improving the efficiency and accuracy of MLP, which are included Dandelion Optimization (DO), Aquila Optimizer (AO), and Sooty Tern Optimization Algorithm (STOA). After fitting the presented models, the developed models’ predictive generalization and efficiency ability is evaluated against a set of performance parameters. All models used were found to perform as suitable in predicting outcomes, which can be employed for saving time and energy. As a result, Aquila’s optimization had the most accurate by MLP compared to other hybrid models. MLAO3 obtained R 2 = 0.994 and RMSE = 1.27(MPa), which are the most suitable result compared to other models.

Abstract The presence of cancer stem cells (CSCs) contributes significantly to treatment resistance in various cancers, including head and neck squamous cell carcinoma (HNSCC). Despite this, the relationship between cancer stemness and immunity remains poorly understood. In this study, we aimed to identify potential immunotherapeutic targets and sensitive drugs for CSCs in HNSCC. Using data from public databases, we analyzed expression patterns and prognostic values in HNSCC. The stemness index was calculated using the single-sample gene set enrichment analysis (ssgsea) algorithm, and weighted gene co-expression network analysis (WGCNA) was employed to screen for key stemness-related modules. Consensus clustering was then used to group samples for further analysis, and prognosis-related key genes were identified through regression analysis. Our results showed that tumor samples from HNSCC exhibited higher stemness indices compared to normal samples. WGCNA identified a module highly correlated with stemness, comprising 187 genes, which were significantly enriched in protein digestion and absorption pathways. Furthermore, we identified sensitive drugs targeting prognostic genes associated with tumor stemness. Notably, two genes, HLF and CCL11, were found to be highly associated with both stemness and immunity. In conclusion, our study identifies a stemness-related gene signature and promising drug candidates for CSCs of HNSCC. Additionally, HLF and CCL11, which are associated with both stemness and immunity, represent potential targets for immunotherapy in HNSCC.

Abstract Multiple sevoflurane exposures may damage the developing brain. The neuroprotective function of dexmedetomidine has been widely confirmed in animal experiments and human studies. However, the effect of dexmedetomidine on the glymphatic system has not been clearly studied. We hypothesized that dexmedetomidine could alleviate sevoflurane-induced circulatory dysfunction of the glymphatic system in young mice. Six-day-old C57BL/6 mice were exposed to 3% sevoflurane for 2 h daily, continuously for 3 days. Intraperitoneal injection of either normal saline or dexmedetomidine was administered before every anaesthesia. Meanwhile the circulatory function of glymphatic system was detected by tracer injection at P8 and P32. On P30-P32, behavior tests including open field test, novel object recognition test, and Y-maze test were conducted. Primary astrocyte cultures were established and treated with the PI3K activator 740Y-P, dexmedetomidine, and small interfering RNA (siRNA) to silence ΔFosB. We propose for the first time that multiple exposure to sevoflurane induces circulatory dysfunction of the glymphatic system in young mice. Dexmedetomidine improves the circulatory capacity of the glymphatic system in young mice following repeated exposure to sevoflurane through the PI3K/AKT/ΔFosB/AQP4 signaling pathway, and enhances their long-term learning and working memory abilities.

Abstract Background Benefit finding is the search for positive meaning from traumatic events, such as cancer. It can help caregivers have a positive experience in the caregiving process, relieve negative emotions, and reduce caregiving stress. The aim of this study was to explore benefit finding among caregivers of patients with advanced cancer in their palliative caregiving journey. Methods An exploratory qualitative design of phenomenology was used. Semistructured interviews were conducted with 19 caregivers of palliative care patients with advanced cancer. The Colaizzi 7-step analysis was used to analyse, summarize, and extract themes from the interview data. Results The study identified five themes of caregiver benefit finding in the caregiving process: personal growth, strengthened relationships with patients, adjustment and adaptation, perceived social support, and perceived meaning in life. Most caregivers reported a closer, more dependent relationship with the patient, and only one caregiver did not report any positive changes. Conclusions Caregivers of palliative care patients with advanced cancer can have positive experiences in their care. Healthcare professionals should focus on supporting caregivers and helping them find positive experiences to cope with the challenges of caregiving and improve their quality of life.

Keyhole instability and high porosity are prone to occur in laser-arc hybrid welding (LAHW) with an increase in aluminum alloy thickness. In this study, a high-power laser up to 8.0 kW at different oscillating frequencies (f) was used to achieve acceptable hybrid welding of a 10-mm-thick 6082 aluminum alloy. According to the observations of the laser keyhole from a high-speed camera, increasing f from 0 to 100 Hz increased the opening diameter from 1.3 to 1.6 mm and decreased the collapse frequency from 642 to 353 Hz. With the improved keyhole stability, the weld porosity decreased from 4.5% to 1.8%. In addition, beam oscillation refined the weld microstructure by 15% and transferred the tensile fracture from the weld center to the heat-affected zone (HAZ). Although the change in the ultimate tensile strength (UTS) was not obvious, the elongation increased by 25%. Beam oscillation promoted the formation of turbulent flow inside the molten pool, homogenized the melt flow, and reduced the necking tendency of the keyhole caused by the melt flow, thus greatly improving the keyhole stability.

Abstract Background Comparisons between endurance training (ET) and resistance training (RT) have produced equivocal findings in chronic obstructive pulmonary disease (COPD) patients. The purpose of our study is to investigate the effectiveness and long-term outcomes of adding ET and RT to conventional medical treatment in patients with COPD. A secondary objective is to investigate the clinical improvements resulting from exercise training in patients with different disease severities. Methods The study was a multicenter, prospective trial in people with stable COPD. The cohort was randomized to three groups: individualized medical treatment group (MT), MT + endurance training group (MT + ET) and MT + resistance training group (MT + RT). Exercise was performed 3 times weekly over a 12-week period. The endpoints of exercise capacity, health-related quality of life, COPD symptoms, lung function, and anxiety and depression questionnaires were re-evaluated at baseline, at the completion of the intervention and at 6 and 12-month follow-up. According to the COPD assessment tool offered by GOLD guidelines, patients were stratified into GOLD A and B groups and GOLD C and D groups for further subgroup analysis. Results The intention-to-treat (ITT) population included 366 patients, 328 of them completed the study protocol over 12 months (the PP-population). There were no significant differences in the primary outcome, quality of life, between patients who underwent medical treatment (MT) alone, MT + endurance training (MT + ET), or MT + resistance training (MT + RT) at the completion of the intervention, 6-, or 12-month follow-up. Additionally, no significant differences were observed between MT, MT + RT, or MT + ET groups concerning the primary outcome, exercise capacity (3MWD), after initial 3 months of intervention. However, a small statistically significant difference was noted in favor of MT + ET compared to MT + RT at 12 months (ITT: Δ3MWD in ET vs RT = 5.53 m, 95% confidence interval: 0.87 to 13.84 m, P = 0.03) (PP: Δ3MWD in ET vs RT = 7.67 m, 95% confidence interval: 0.93 to 16.27 m, P = 0.04). For patients in the GOLD C and D groups, improvement in quality of life following ET or RT was significantly superior to medical intervention alone. Furthermore, upon completion of the exercise regimen, RT exhibited a greater improvement in anxiety compared to ET in these patients (ITT: ΔHAD-A at 3-month: RT = -1.63 ± 0.31 vs ET = -0.61 ± 0.33, p

Mobile Crowd Sensing (MCS) has become a promising new data perception paradigm. It is to be able to easily submit the wrong or untrusted data for the malicious attackers in such an environment. This greatly affects the normal operation of the MCS system and the authenticity of task results. Therefore, ensuring the reliability of data is becoming a key research direction in MCS, especially for real-time application scenarios. For this purpose, we propose a multi-dimensional framework for improving data reliability, named MDF. It integrates three dimensions of temporal, spatial context and sensing measurement. Through a series of experiments, it is demonstrated that MDF outperforms existing methods.

Due to rapid industrial development, numerous dye pollutants and heavy metals, such as arsenic (As), have contaminated water sources, causing complex pollution that threatens both the ecological environment and human health. Therefore, there is an urgent need to design an effective strategy for treating complex dye wastewater. Herein, we have constructed high-purity pyrite FeS2 nanoplates as bifunctional catalysts for the simultaneous removal of dyes and arsenite (As(III)). We have developed a visible light-assisted peroxymonosulfate (PMS) activation method to remove typical organic dye pollutants (e.g., rhodamine B, malachite green, methyl orange, methylene blue) and toxic As(III). The FeS2/Light/PMS system can remove 100 % of all dye pollutants and more than 85 % of As(III) within 18 min simultaneously with high cyclic stability, which is believed to be effective in complex pollution control. It is confirmed that the multivalent Fe ions and S22− are the main active centers, and the free radical and non-free radical pathways synergistically enhance the oxidation of dye pollutants, in which SO4·- and 1O2 are the main reactive oxygen species. This work presents a facile strategy for developing a metal sulfide-based Fenton-like system for treating complex dye wastewater.

BackgroundErectile dysfunction (ED) is a very common condition among adult men and its prevalence increases with age. The ankle-brachial blood pressure index (ABPI) is a noninvasive tool used to assess peripheral vascular disease (PAD) and vascular stiffness. However, the association between ABPI and ED is unclear. We aimed to explore the association between ABPI and ED in the US population.MethodsOur study used data from two separate National Health and Nutrition Examination Survey (NHANES) datasets (2001-2002 and 2003-2004). Survey-weighted logistic regression models were used to explore the association between ABPI as a continuous variable and quartiles with ED. We further assessed the association between ABPI and ED using restricted cubic regression while selecting ABPI thresholds using two-piecewise Cox regression models. In addition, we performed subgroup analyses stratified by BMI, race, marital status, diabetes, and hypertension.Main outcome measureABPI was calculated by dividing the mean systolic blood pressure at the ankle by the mean systolic blood pressure at the arm.ResultsFinally, 2089 participants were enrolled in this study, including 750 (35.90%) ED patients and 1339 (64.10%) participants without ED. After adjusting for all confounding covariates, logistic regression analyses showed a significant association between ABPI and ED (OR=0.19; 95% CI, 0.06-0.56, P=0.01); with ABPI as a categorical variable, compared with the lowest quartile, the OR and 95% CI for the second quartile were 0.58 (0.34-0.97; P = 0.04).Besides, splines indicated that there was an L-shaped relationship between ABPI levels and the risk of ED. Piecewise Cox regression demonstrated the inflection point at 1.14, below which the OR for ED was 0.06 (0.02-0.20; P < 0.001), and above which the OR was 2.79 (0.17-4.53; P = 0.469).ConclusionIn our study, lower ABPI was independently associated with ED risk. In addition, the lowest ABPI level associated with ED risk was 1.14, below this level, lower ABPI was associated with higher ED risk.

Oncolytic viruses (OVs) have emerged as a potential strategy for tumor treatment due to their ability to selectively replicate in tumor cells, induce apoptosis, and stimulate immune responses. However, the therapeutic efficacy of single OVs is limited by the complexity and immunosuppressive nature of the tumor microenvironment (TME). To overcome these challenges, engineering OVs has become an important research direction. This review focuses on engineering methods and multi-modal combination therapies for OVs aimed at addressing delivery barriers, viral phagocytosis, and antiviral immunity in tumor therapy. The engineering approaches discussed include enhancing in vivo immune response, improving replication efficiency within the tumor cells, enhancing safety profiles, and improving targeting capabilities. In addition, this review describes the potential mechanisms of OVs combined with radiotherapy, chemotherapy, cell therapy and immune checkpoint inhibitors (ICIs), and summarizes the data of ongoing clinical trials. By continuously optimizing engineering strategies and combination therapy programs, we can achieve improved treatment outcomes and quality of life for cancer patients.

IntroductionLiuweizhiji Gegen-Sangshen beverage (LGS) is popular in China, which has been used for alleviating alcohol-mediated discomfort and preventing alcoholic liver disease (ALD). This beverage is consisted of six herbal components that are known as functional foods and fruits. LGS is rich in polysaccharides, however, the activity and quality evaluation of LGS-derived polysaccharides remain unexplored. The purpose of this study is thus to establish a comprehensive quality control methodology for the assessment of LGS polysaccharides (LGSP) and to further explore the anti-oxidant, anti-inflammatory as well as prebiotic effect of LGSP.MethodsLGSP was extracted, followed by analysis of molecular weight distribution, monosaccharide content and structural characterization via integrating the application of high-performance size exclusion chromatography (HPSEC), 1-phenyl-3-methyl-5-pyrazolone-HPLC (PMP-HPLC), fourier transform infrared spectroscopy (FT-IR) as well as nuclear magnetic resonance spectroscopy (NMR) techniques. The anti-oxidation activity of LGSP was determined by DPPH, ABTS, hydroxyl radical scavenging capacity and total antioxidant capacity. The anti-inflammation of LGSP were assessed on the RAW 264.7 cells. The effect of LGSP on growth of Lactobacillus, Bifidobacterium bifidum and Bifidobacterium adolescentis was evaluated.ResultsThe results demonstrated that LGSP had two molecular weight distribution peaks, with the average molecular weights of (6.569 ± 0.12) × 104 Da and (4.641 ± 0.30) × 104 Da. LGSP was composed of 8 monosaccharides, with galacturonic acid, glucose rhamnose and galactose representing the highest molar ratios. Homogalacturonic acid (HG) type and rhamnosegalacturonic acid glycans I (RG-I) type and α-1,4-glucan were present in LGSP. LGSP concentration in LGS was 17.94 ± 0.28 mg/mL. Furthermore, fingerprint analysis combined with composition quantification of 10 batches of LGSP demonstrated that there was a high similarity among batches. Notably, LGSP exhibited anti-oxidant effect and inhibited expressions of pro-inflammatory factors (TNF-α and IL-6) in LPS-stimulated RAW 264.7 cells. In addition, LGSP remarkably promoted the proliferation of probiotics Lactobacillus, Bifidobacterium bifidum and Bifidobacterium adolescentis, showing good prebiotic activity.DiscussionThe results of present study would be of help to gain the understanding of structure–activity relationship of LGSP, provide a reference for quality evaluation of bioactive LGSP, and facilitate development of unique health and functional products in the future.

Steel slag, as an industrial byproduct obtained from the steel manufacturing industry, may cause land occupation, resource waste, and environmental pollution. The application of steel slag as a material for soil reinforcement in road engineering is very popular due to its potential hydration activity. The unconfined compression strength, microstructure, and transport properties of loess soil with cement, lime and steel slag were investigated. The results show that the loess soil can be reinforced by cement, lime, and steel slag to varying degrees. The reinforcement mechanism of cement for loess soil is realized by pore filling by cement hydration products such as CH, C-S-H and AFt, and their unconfined compression strength is improved by reducing the porosity. The reinforcement mechanism of lime for loess soil is achieved by pore filling by hydration products such as CH and CaCO3, and their strength is improved by a refined pore structure where the porosity has not been significantly reduced. The reinforcement mechanism of steel slag for loess soil is a combined mechanism of cement and lime, including pore filling and refined pores. The pore structure of reinforced soil can be studied at different scales by the MIP, LF NMR, and X-CT test methods. The transport properties including diffusivity and permeability of reinforcing soil can be well explored by Avizo software based on the microstructure obtained from X-CT.

In China, steel slag as a solid waste caused land occupation and environmental pollution, and its utilization ratio is relatively low. To increase the utilization field and ratio of steel slag, hydration behavior and cementitious properties of three types of steel slag were investigated and compared based on test results from an early age to a long-term via multiple techniques. Experimental results suggested that steel slag showed a strong latent hydraulic activity at a later age, and the mechanical strength of steel slag paste specimens (w/b=0.3) could reach 15 MPa at 360 days. Cementitious properties of steel slag were primally depended on the hydration of calcium silicate (C3S and C2S), calcium aluminate (ferrite), glassy phase in steel slag, especially for calcium silicate. The sum amount of calcium silicate in used steel slag was approximately from 21% to 28%, and the amount of C2S was significantly greater than that of C3S. The hydration of C2S and glassy phase resulted in the continuous increase in bound water content of steel slag, and a certain content of C2S still existed in pastes at 360 days. The mechanical strength of steel slag pastes markedly increased at a later age due to more hydrates formed in the microstructure.

Abstract Background Cervicovaginal microbiome plays an important role in the persistence of HPV infection and subsequent disease development. However, cervicovaginal microbiota varied cross populations with different habits and regions. Identification of population-specific biomarkers from cervicovaginal microbiota and host metabolome axis may support early detection or surveillance of HPV-induced cervical disease at all sites. Therefore, in the present study, to identify HPV-specific biomarkers, cervicovaginal secretion and serum samples from HPV-infected patients (HPV group, n = 25) and normal controls (normal group, n = 17) in Xichang, China were collected for microbiome (16S rRNA gene sequencing) and metabolome (UHPLC-MS/MS) analysis, respectively. Results The results showed that key altered metabolites of 9,10-DiHOME, α-linolenic acid, ethylparaben, glycocholic acid, pipecolic acid, and 9,12,13-trihydroxy-10(E),15(Z)-octadecadienoic acid, correlating with Sneathia (Sneathia_amnii), Lactobacillus (Lactobacillus_iners), Atopobium, Mycoplasma, and Gardnerella, may be potential biomarkers of HPV infection. Conclusion The results of current study would help to reveal the association of changes in cervicovaginal microbiota and serum metabolome with HPV infections.

Abstract While Phorbol-12-myristate-13-acetate-induced protein 1 (Noxa/PMAIP1) assumes a pivotal role in numerous tumors, its clinical implications and underlying mechanisms of gastric cancer (GC) are yet enigmatic. In this investigation, our primary objective was to scrutinize the clinical relevance and potential mechanisms of Noxa in gastric cancer. Immunohistochemical analysis was conducted on tissue microarrays comprising samples from a meticulously characterized cohort of 84 gastric cancer patients, accompanied by follow-up data, to assess the expression of Noxa. Additionally, Noxa expression levels in gastric cancer clinical samples and cell lines were measured through quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. The effect of Noxa expression on the prognosis of patients with gastric cancer was evaluated using Kaplan–Meier survival. Further insight into the role of Noxa in driving gastric cancer progression was gained through an array of experimental techniques, including cell viability assays (CCK8), plate cloning assays, transwell assays, scratch assays, and real-time cell analysis (RTCA). Potential upstream microRNAs (miRNAs) that might modulate Noxa were identified through rigorous bioinformatics analysis, substantiated by luciferase reporter assays and Western blot experiments. Additionally, we utilized RNA sequencing, qRT-PCR, and Western blot to identify proteins binding to Noxa and potential downstream target. Finally, we utilized BALB/c nude mice to explore the role of Noxa in vivo. Our investigation unveiled a marked downregulation of Noxa expression in gastric cancer and underscored its significance as a pivotal prognostic factor influencing overall survival (OS). Noxa overexpression exerted a substantial inhibitory effect on the proliferation, migration and invasion of GC cells. Bioinformatic analysis and dual luciferase reporter assays unveiled the capacity of hsa-miR-200b-3p to interact with the 3′-UTR of Noxa mRNA, thereby orchestrating a downregulation of Noxa expression in vitro, consequently promoting tumor progression in GC. Our transcriptome analysis, coupled with mechanistic validation, elucidated a role for Noxa in modulating the expression of ZNF519 in the Mitophagy-animal pathway. The depletion of ZNF519 effectively reversed the oncogenic attributes induced by Noxa. Upregulation of Noxa expression suppressed the tumorigenesis of GC in vivo. The current investigation sheds light on the pivotal role of the hsa-miR-200b-3p/Noxa/ZNF519 axis in elucidating the pathogenesis of gastric cancer, offering a promising avenue for targeted therapeutic interventions in the management of this challenging malignancy.

The identification and categorization of pills constitute critical tasks within a contemporary hospital, particularly for avoiding medication errors. Conventional approaches to visual recognition and classification predominantly rely on visible light imagery, proving inadequate for discerning white pills with similar visual characteristics. However, white pills exhibit distinctive infrared properties across various spectral bands. Building upon these observations, this paper introduces the MCIR-YOLO algorithm, a multi-band infrared image object detection system, which enhances the YOLOv5s model through multimodal fusion techniques. This study presents a novel dataset comprising IR images of white round pills captured across six channels, with peak wavelengths ranging from approximately 1400 nm to 1650 nm. Furthermore, a multimodal fusion strategy is proposed, facilitating multi-level feature integration across the six IR channels. This fusion technique exploits the scale features inherent to each IR modality, thereby enabling comprehensive information fusion across multiple modalities. Additionally, the model incorporates an auxiliary detection branch, independent of the backbone, which utilizes fused feature information to calculate a distinct loss, effectively mitigating overall loss. Attention mechanism modules are integrated after two distinct fusion points to enhance feature precision. Leveraging mean and scaling of IR features, these attention mechanisms significantly boost detection accuracy. Experimental results demonstrate that the improved model outperforms the baseline YOLOv5s model, particularly evident in a self-constructed dataset of white round pill IR images, where mAP0.5 increased by 5.47% and 7.96% for single-channel (peak at 1650 nm) and six-channel configurations, respectively. Notably, the utilization of the MCIR-YOLO model for six-channel recognition yields a substantial advantage of 12.05% over the best-performing single-channel IR image recognition.

Background: Ketamine, as a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, was originally used in general anesthesia. Epidemiological data show that ketamine has become one of the most commonly abused drugs in China. Ketamine administration might cause cognitive impairment; however, its molecular mechanism remains unclear. The glymphatic system is a lymphoid system that plays a key role in metabolic waste removal and cognitive regulation in the central nervous system. Methods: Focusing on the glymphatic system, this study evaluated the behavioral performance and circulatory function of the glymphatic system by building a short-term ketamine administration model in mice, and detected the expression levels of the 5-HT2c receptor, ΔFosb, Pten, Akt, and Aqp4 in the hippocampus. Primary astrocytes were cultured to verify the regulatory relationships among related indexes using a 5-HT2c receptor antagonist, a 5-HT2c receptor short interfering RNA (siRNA), and a ΔFosb siRNA. Results: Ketamine administration induced ΔFosb accumulation by increasing 5-HT2c receptor expression in mouse hippocampal astrocytes and primary astrocytes. ΔFosb acted as a transcription factor to recognize the AATGATTAAT bases in the 5′ regulatory region of the Aqp4 gene (−1096 bp to −1087 bp), which inhibited Aqp4 expression, thus causing the circulatory dysfunction of the glymphatic system, leading to cognitive impairment. Conclusions: Although this regulatory mechanism does not involve the Pten/Akt pathway, this study revealed a new mechanism of ketamine-induced cognitive impairment in non-neuronal systems, and provided a theoretical basis for the safety of clinical treatment and the effectiveness of withdrawal.

Objective: Protein disulfide isomerase A3 (PDIA3) promotes the correct folding of newly synthesized glycoproteins in the endoplasmic reticulum. PDIA3 is overexpressed in most tumors, and it may become a biomarker of cancer prognosis and immunotherapy. Our study aims to detect the expression level of PDIA3 in gastric cancer (GC) and its association with GC development as wells as the underlying mechanisms. Methods: GC cell lines with PDIA3 knockdown by siRNA, CRISPR-cas9 sgRNAs or a pharmacological inhibitor of LOC14 were prepared and used. PDIA3 knockout GC cells were established by CRISPR-cas9-PDIA3 system. The proliferation, migration, invasion and cell cycle of GC cells were analyzed by cell counting kit-8 assay, wound healing assay, transwell assay and flow cytometry, respectively. Immunodeficient nude mice was used to evaluate the role of PDIA3 in tumor formation. Quantitative PCR and western blot were used for examining gene and protein expressions. RNA sequencing was performed to see the altered gene expression. Results: The expressions of PDIA3 in GC tissues and cells were increased significantly, and its expression was negatively correlated with the three-year survival rate of GC patients. Down-regulation of PDIA3 by siRNA, LOC14 or CRISPR-cas9 significantly inhibited proliferation, invasion and migration of GC cells TMK1 and AGS, with cell cycle arrested at G2/M phase. Meanwhile, decreased PDIA3 significantly inhibited growth of tumor xenograft in vivo. It was found that cyclin G1 (encoded by CCNG1 gene) expression was decreased by downregulation of PDIA3 in GC cells both in vitro and in vivo. In addition, protein levels of other cell cycle related factors including cyclin D1, CDK2, and CDK6 were also significantly decreased. Further study showed that STAT3 was associated with PDIA3-mediated cyclin G1 regulation. Conclusion: PDIA3 plays an oncogenic role in GC. Our findings unfolded the functional role of PDIA3 in GC development and highlighted a novel target for cancer therapeutic strategy.

Abstract Thermochemical conversion of fossil resources into fuels, chemicals, and materials has rapidly increased atmospheric CO2 levels, hindering global efforts toward achieving carbon neutrality. With the increasing push for sustainability, utilizing electrochemical technology to transform CO2 or biomass into value‐added chemicals and to close the carbon cycle with sustainable energy sources represents a promising strategy. Expanding the scope of electrosynthesis technology is a prerequisite for the electrification of chemical manufacturing. To this end, constructing the C─N bond is considered a priority. However, a systematic review of electrocatalytic processes toward building C─N bonds using CO2 and biomass as carbon sources is not available. Accordingly, this review highlights the research progress in the electrosynthesis of organic nitrogen compounds from CO2 and biomass by C─N coupling reactions in view of catalytic materials, focusing on the enlightenment of traditional catalysis on C─N coupling and the understanding of the basis of electrochemical C─N coupling. The possibility of C─N bond in electrocatalysis is also examined from the standpoints of activation of substrates, coupling site, mechanism, and inhibition of hydrogen evolution reaction (HER). Finally, the challenges and prospects of electrocatalytic C─N coupling reactions with improved efficiency and selectivity for future development are discussed.

Abstract The combination of low-temperature scanning tunnelling microscopy with a mass-selective electro-spray ion-beam deposition established the investigation of large biomolecules at nanometer and sub-nanometer scale. Due to complex architecture and conformational freedom, however, the chemical identification of building blocks of these biopolymers often relies on the presence of markers, extensive simulations, or is not possible at all. Here, we present a molecular probe-sensitisation approach addressing the identification of a specific amino acid within different peptides. A selective intermolecular interaction between the sensitiser attached at the tip-apex and the target amino acid on the surface induces an enhanced tunnelling conductance of one specific spectral feature, which can be mapped in spectroscopic imaging. Density functional theory calculations suggest a mechanism that relies on conformational changes of the sensitiser that are accompanied by local charge redistributions in the tunnelling junction, which, in turn, lower the tunnelling barrier at that specific part of the peptide.

There is currently great interest in developing an environment-friendly, low-cost, and scalable approach for producing stimuli-responsive fluorescent hydrogels (FHs) with excellent mechanical property, rewritable fluorescence, and dual anti-counterfeiting capabilities. Herein, by applying natural, environment-friendly, and sustainable curcumin as a responsive agent, tough pH-responsive FHs (pH-FHs) are fabricated via a facile preparation strategy. These materials have outstanding mechanical performances: ultimate stress of 180 kPa, an ultimate strain of ∼2500%, and good anti-fatigue performances against compression. These pH-FHs are able to sense ammonia and formaldehyde gas, resulting in both a color change and fluorescence for dual anti-counterfeiting functionality. This sensing information is stored individually by the pH-FHs and could be externally removed using formaldehyde gas to achieve a rewritable system. Our study provides valuable insights that are expected to facilitate the development of smart FHs for information encryption and anti-counterfeiting applications.

Abstract Background Few studies were conducted to explore the association between sleep quality and nocturnal erection. Here, we intended to explore the association between sleep quality and nocturnal erection monitor when conducting nocturnal erection monitor. All erectile dysfunction (ED) patients underwent sleep monitors using Fitbit Charge 2™ (Fitbit Inc.) and nocturnal penile tumescence and rigidity (NPTR) monitors using RigiScan® (GOTOP medical, Inc., USA) for two nights. Subsequently, the patients were divided into two groups: Group A included patients who experienced effective erections only on the second night, while Group B included patients who had effective erections on both nights. To explore the associations between NPTR parameters and sleep parameters, a comparative analysis was performed between Group A and Group B for both nights. Results Finally, our study included 103 participants, with 47 patients in Group A and 56 patients in Group B. Notably, the Group A patients showed significant improvements in NPTR parameters on the second night compared to the first night. Conversely, the NPTR parameters on Group B of the second night did not demonstrate a superior outcome when compared to the second night of Group A. Interestingly, it was found that only the disparities in sleep parameters accounted for the variation in NPTR parameters between the two groups on the first night. After correlation and ROC analysis, we identified the rapid eye movement (REM) sleep time and wake after sleep onset (WASO) time monitoring by the Fitbit Charge 2 as the primary parameters for predicting abnormal NPTR results in the first night. Conclusions Therefore, our study strongly suggests a close association between sleep parameters and NPTR parameters. It emphasizes the importance of incorporating sleep monitoring alongside nocturnal erection monitoring to enhance the reliability of the NPTR results.

Abstract Osteosarcoma (OS) commonly metastasizes to the lung, yet the underlying molecular mechanisms remain poorly understood. Exosomes play a crucial role in tumor migration, including OS lung migration. However, the underlying mechanism by which exosome-derived long non-coding RNAs (lncRNAs) contribute to lung migration in osteosarcoma (OS) remains unclear. This study presents a newly discovered lncRNA, linc00881, derived from OS exosomes. Our study shows that linc00881 promotes the migration of OS cells to the lung and induces the conversion of normal lung fibroblasts into cancer-associated fibroblasts (CAFs). Subsequently, we found that exosomal linc00881 secreted by OS cells can regulate the expression of matrix metalloproteinase 2 (MMP2) in HFL-1 cells by sponging miR-29c-3p, thereby activating the NF-κB signaling in lung fibroblasts. Finally, we discovered that pro-inflammatory cytokines, namely IL-1β, IL-6, and IL-8, were secreted through the linc00881/miR-29c-3p/MMP2 axis. These results suggest that OS-derived exosomes can mediate the intercellular crosstalk between OS cells and lung fibroblasts, ultimately impacting OS lung migration. Our study provides a potential target for the treatment of OS lung migration. Graphical Abstract

Trust systems have been widely studied in Internet of Things (IoT). However, there is a little work done on trust management in cross-domain Industrial Internet of Things (IIoT). Many of these models focus mainly or only on trust management in a single administrative domain where trust is evaluated based on the same criteria. In general, different administrative domains adopt different trust models and trust evaluation standards. Due to different trust evaluation standards, trust values from different administrative domain cannot be compared, directly. Therefore, there is a need for a well-defined trust computing scheme for such multi-domain IIoT environment. This paper focuses on the research of cross-domain trust and proposes a cross-domain trust computing scheme “CDTCS”, where trust recommendation value for an IIoT device in a domain can be transferred to a corresponding value in another domain. We analyze CDTCS performance in terms of trust accuracy and resiliency against attacks.

Deep-sea minerals are regarded as the most economically viable and promising mineral resource. Vertical hydraulic lifting represents one of the most promising methods for deep-sea mining lifting systems. To mitigate the potential for clogging due to the aggregation of particles in vertical pipe transport during deep-sea mining operations, this paper employs numerical simulations utilizing the computational fluid dynamics and discrete element method (CFD-DEM) model to investigate the swirling flow transportation of mineral particles. The characteristics of the swirling flow field and the motion law of double-size particles at different swirling ratios are investigated. The findings demonstrate that, in comparison to axial transport within the pipeline, the particle movement observed in swirling flow transport exhibits an upward spiral trajectory. This phenomenon facilitates the orderly movement of particles, thereby enhancing the fluidization of particles within the pipeline. An increase in the swirling ratio (SR) has a considerable impact on the velocity within the pipe. The tangential velocity distribution undergoes a gradual transition from centrosymmetric to non-centrosymmetric as the distance from the inlet increases. An increase in the SR results in an enhanced aggregation of particles at the wall, accompanied by a notable rise in the local particle concentration. The value of SR = 0.3 represents a critical threshold. When SR exceeds this value, the distribution of particles in the cross-section reaches a relatively stable state, rendering it challenging to further alter the distribution and concentration of particles, even if the SR is augmented. Furthermore, the maximum local particle concentration in the vicinity of the wall tends to be stable. These results provide valuable insights into vertical pipe swirling flow transport for deep-sea mining.

Mixed forests created by incorporating nitrogen-fixing tree species offer enhanced ecological advantages compared with forests consisting of only one type of tree species. These benefits include habitat rehabilitation and the promotion of biodiversity. Nevertheless, the impact of introducing nitrogen-fixing tree species on ecosystem carbon (C), nitrogen (N), and phosphorus (P) sequestration and storage capacity in the Loess Plateau of China remains inadequately explored. To examine changes in the sequestration and storage capacity of ecosystem C, N, and P, the mixed plantations of P. tabulaeformis and H. rhamnoides (HrPt) were selected as the research object, and the pure plantations of H. rhamnoides (Hr) and P. tabulaeformis (Pt) were selected as the control. The results indicated that in comparison to the pure forest, the ecosystem in HrPt significantly increased C and N stocks but decreased P stocks. In addition, C, N, and P stocks in the soil layer accounted for more than 60% of the C, N, and P stocks in the pure and mixed forest ecosystems compared with the vegetation layer. Moreover, HrPt significantly improved ecosystem C and N sequestration rates relative to the pure forest but decreased P sequestration rates. Furthermore, the soil physicochemical properties can be inferred from the redundancy analysis showing 66.79% and 0.06% in Hr, 44.84% and 0.06% in Pt, as well as 44.28% and 0.04% in HrPt, respectively. In conclusion, compared with the pure forest, the introduction of N-fixing tree species was more conducive to the accumulation of C and N. The results offer substantial significance for the scientific guidance of vegetation restoration in degraded landscapes and the stewardship of mixed forests in the Loess Hilly Region, providing essential data for nutrient storage in ecosystems.

The water quality of urban rivers is subject to fluctuation caused by rainstorm flood. The uncertainty of flooding in a dynamic environment brings about changes in river quality, presenting a significant challenge. Water samples were collected at 7 sampling sites in Handan City of China from January 2020 to August 2023, and 9 water quality parameters (WT, pH, Cond, Do, COD, BOD, NH3-N, TP, and TP) were analyzed. Specifically, the spatial and temporal variation of water quality in the Qingzhang River was analyzed. In terms of season, the concentration of water quality parameters in spring and winter was found to be significantly higher than that in summer and autumn. Spatially, the concentration of water quality parameters was lower in the upstream compared to the downstream. Furthermore, it was discovered that the reservoir had a purifying effect on the water quality of the river. Additionally, a comparison of water quality during flood and non-flood periods revealed that the concentration of water quality parameters in the upstream, midstream, and downstream of the Qingzhang River were higher during non-flood periods. These findings indicated that, in comparison to the urbanization factor, the hydrological factor, which results in the runoff carrying nutrients into the Qingzhang River, plays a crucial role in the change of its water quality. Moreover, the autoregressive integrated moving average (ARIMA) method was employed to create a water pollution emergency prediction model for the different sections of the Qingzhang River, and an adaptive urban river water purification strategy was formulated based on its variation patterns. The research results contribute to the theoretical basis for the management of urban rivers and water resources.

The Internet of Things (IOT) is based on the computer Internet, using RFID, wireless data communication and other technologies to construct a network covering everything in the world. It contains numerous entities such as sensors, processors, transmitters and actuators, meanwhile the interactions of which are complicated. These characteristics of IOT are consistent with those of the complex network. Motivated by this, this paper comprehends the security issue of IOT from the sight of the observability of complex network and regards the ability of reconstruction as a security threat to IOT network. We try to identify the minimum vertices whose data could reconstruct the whole data of network, in other words, we need to implement additional protective measures on these vertices to enhance the security of IOT network. By analyzing the topology of IOT network, an identification strategy is adopted and the corresponding algorithm is proposed to identify the minimum protection vertices.

The incidence of hepatocellular carcinoma (HCC) ranks first among primary liver cancers, and its mortality rate exhibits a consistent annual increase. The treatment of HCC has witnessed a significant surge in recent years, with the emergence of targeted immune therapy as an adjunct to early surgical resection. Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) has shown promising results in other types of solid tumors. This article aims to provide a comprehensive overview of the intricate interactions between different types of TILs and their impact on HCC, elucidate strategies for targeting neoantigens through TILs, and address the challenges encountered in TIL therapies along with potential solutions. Furthermore, this article specifically examines the impact of oncogenic signaling pathways activation within the HCC tumor microenvironment on the infiltration dynamics of TILs. Additionally, a concise overview is provided regarding TIL preparation techniques and an update on clinical trials investigating TIL-based immunotherapy in solid tumors.

We present an effective approach to realize a highly efficient, high-power and chirped pulse amplification-free ultrafast ytterbium-doped yttrium aluminum garnet thin-disk regenerative amplifier pumped by a zero-phonon line 969 nm laser diode. The amplifier delivers an output power exceeding 154 W at a pulse repetition rate of 1 MHz with custom-designed 48 pump passes. The exceptional thermal management on the thin disk through high-quality bonding, efficient heat dissipation and a fully locked spectrum collectively contributes to achieving a remarkable optical-to-optical efficiency of 61% and a near-diffraction-limit beam quality with an M2 factor of 1.06. To the best of our knowledge, this represents the highest conversion efficiency reported in ultrafast thin-disk regenerative amplifiers. Furthermore, the amplifier operates at room temperature and exhibits exceptional stability, with root mean square stability of less than 0.33%. This study significantly represents advances in the field of laser amplification systems, particularly in terms of efficiency and average power. This advantageous combination of high efficiency and diffraction limitation positions the thin-disk regenerative amplifier as a promising solution for a wide range of scientific and industrial applications.

Zinc (Zn) is a potential bioresorbable metal material (BMM) with a degradation rate lower than magnesium and higher than iron. However, clinical applications of pure Zn are limited due to its poor mechanical properties and localized degrading tendency. Overcoming these drawbacks is made possible by the process of alloying. The Zn-0.6Li-0.5Mg alloy samples were prepared using the laser powder bed fusion (LPBF) process in this work. The innovative technique combining fast solidification produced by LPBF and alloying with Li and Mg was presented to enhance the mechanical properties of Zn in this work. The relative density, microstructure, mechanical properties, and corrosion resistance of LPBF-built Zn-0.6Li-0.5Mg alloy were investigated. According to the results, the LPBF fabricated Zn-0.6Li-0.5Mg alloy with fine equiaxed α-Zn grains were uniformly distributed with precipitated Mg2Zn11 and LiZn4 at grain boundaries. More interestingly, the average grain size of α-Zn was recorded at 7.2 ± 3.2 μm with Li and Mg. Due to the rapid solidification process, Mg dissolved primarily in the Zn matrix and developed a supersaturated solid solution. As a result, with the addition of Li and Mg, the mechanical properties of the Zn matrix increased considerably. When combined, Zn-0.6Li-0.5Mg alloy can be an attractive candidate for bioresorbable medical implants in orthopedic applications.

Abstract Pathogenesis exploration and timely intervention of lung injury is quite necessary as it has harmed human health worldwide for years. Ficolin B (Fcn B) is a recognition molecule that can recognize a variety of ligands and play an important role in mediating the cell cycle, immune response, and tissue homeostasis in the lung. However, the role of Fcn B in bleomycin (BLM)-induced lung injury is obscure. This study aims to investigate the sources of Fcn B and its mechanism in BLM-induced lung injury. WT, Fcna -/- , and Fcnb -/- mice were selected to construct the BLM-induced lung injury model. Lung epithelial cells were utilized to construct the BLM-induced cell model. Exosomes that were secreted from alveolar macrophages (AMs) were applied for intervention by transporting Fcn B. Clinical data suggested M-ficolin (homologous of Fcn B) was raised in plasma of interstitial lung disease (ILD) patients. In the mouse model, macrophage-derived Fcn B aggravated BLM-induced lung injury and fibrosis. Fcn B further promoted the development of autophagy and ferroptosis. Remarkably, cell experiment results revealed that Fcn B transported by BLM-induced AMs exosomes accelerated autophagy and ferroptosis in lung epithelial cells through the activation of the cGAS-STING pathway. In contrast, the application of 3-Methyladenine (3-MA) reversed the promotion effect of Fcn B from BLM-induced AMs exosomes on lung epithelial cell damage by inhibiting autophagy-dependent ferroptosis. Meanwhile, in the BLM-induced mice model, the intervention of Fcn B secreted from BLM-induced AMs exosomes facilitated lung injury and fibrosis via ferroptosis. In summary, this study demonstrated that Fcn B transported by exosomes from AMs exacerbated BLM-induced lung injury by promoting lung epithelial cells ferroptosis through the cGAS-STING signaling pathway.

Abstract Imaging biomolecules in real space is crucial for gaining a comprehensive understanding of the properties and functions of biological systems at the most fundamental level. Among the various imaging techniques available for biomolecules and their assembled nanostructures, scanning probe microscopy (SPM) provides a powerful and nondestructive imaging option. SPM is unique in visualizing intrinsically disordered biomolecules at the nanometer scale (e.g., glycans). This review highlights recent achievements in studying biomolecules using SPM technique, focusing on DNA bases, amino acids, proteins, and glycans. The atomic‐level analysis of biomolecules made possible by SPM allows for a more accurate definition of the local structure–property relationship. High‐resolution SPM imaging of single biomolecules offers a new way to study basic processes of life at the molecular level.

Purpose: The aim of the present study was to test the hypothesis that recovery sleep could counteract the detrimental effects of sleep deprivation (SD) on male rats’ fertility. Materials and Methods: Twenty-two rats were housed in groups of six per cage with unrestricted access to food and water in a room. The modified multiple platform method was used to induce SD in rats over a 96-hour period. We examined the effect of SD on semen quality, reproductive hormones, and testicular histology in adult male rats. Then, we investigated the effect of 7 days recovery sleep on impaired reproductive function induced by SD. Results: After the acclimation period, 22 rats were randomly separated into three experimental groups (SD, recovery sleep, and the control groups). Ninety-six hours of SD resulted in a significant decrease in sperm motility (24.33±10.93 vs . 48.20±8.55, p

Trust-based service management in IoT systems, a promising research direction provides an intelligent solution for the identification of appropriate and trustworthy service providers from a huge of number smart nodes providing similar services. An efficient trust-based service ranking scheme (TBSRS) is proposed. The novelty of our design lies in providing accurate trust evaluation and service ranking in the absence of assessment data or presence of untrustworthiness recommendations. TBSRS also addresses the issue about the trustworthiness evaluation of a new service. Service providers are ranking based on the binary fruit fly optimization algorithm in TBSRS. The experimental results demonstrate desirable convergence, accuracy, and resiliency properties of TBSRS, and also demonstrate that TBSRS outperforms Adaptive IoT Trust and IoT-HiTrust in terms of the precision of service selection and other a few performance metrics.

In order to fulfill the practical application demands of precisely localizing underwater vehicles using passive electric field localization technology, we propose a scalar-potential-based method for the passive electric field localization of underwater vehicles. This method is grounded on an intelligent differential evolution algorithm and is particularly suited for use in three-layer and stratified oceanic environments. Firstly, based on the potential distribution law of constant current elements in a three-layer parallel stratified ocean environment, the mathematical positioning model is established using the mirror method. Secondly, the differential evolution (DE) algorithm is enhanced with a parameter-adaptive strategy and a boundary mutation processing mechanism to optimize the key objective function in the positioning problem. Additionally, the simulation experiments of the current element in the layered model prove the effectiveness of the proposed positioning method and show that it has no special requirements for the sensor measurement array, but the large range and moderate number of sensors are beneficial to improve the positioning effect. Finally, the laboratory experiments on the positioning method proposed in this paper, involving underwater simulated current elements and underwater vehicle tracks, were carried out successfully. The results indicate that the positioning method proposed in this paper can achieve the performance requirements of independent initial value, strong anti-noise capabilities, rapid positioning speed, easy implementation, and suitability in shallow sea environments. These findings suggest a promising practical application potential for the proposed method.

Metal-containing nanoparticles are now common in applications ranging from catalysts to biomarkers. However, little research has focused on per-particle metal content in multicomponent nanoparticles. In this work, we used single-particle inductively coupled plasma mass spectrometry (ICP-MS) to determine the per-particle metal content of silica nanoparticles doped with tris(2,2′-bipyridyl)ruthenium(II). Monodispersed silica nanoparticles with varied Ru doping levels were prepared using a water-in-oil microemulsion method. These nanoparticles were characterized using common bulk-sample methods such as absorbance spectroscopy and conventional ICP-MS, and also with single-particle ICP-MS. The results showed that averaged concentrations of metal dopant measured per-particle by single-particle ICP-MS were consistent with the bulk-sample methods over a wide range of dopant levels. However, the per-particle amount of metal varied greatly and did not adhere to the usual Gaussian distribution encountered with one-component nanoparticles, such as gold or silver. Instead, the amount of metal dopant per silica particle showed an unexpected geometric distribution regardless of the prepared doping levels. The results indicate that an unusual metal dispersal mechanism is taking place during the microemulsion synthesis, and they challenge a common assumption that doped silica nanoparticles have the same metal content as the average measured by bulk-sample methods.

As a ligand-dependent transcription factor, retinoid-associated orphan receptor γt (RORγt) that controls T helper (Th) 17 cell differentiation and interleukin (IL)-17 expression plays a critical role in the progression of several inflammatory and autoimmune conditions. An emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORγt to decrease Th17 cell development and IL-17 production. Several RORγt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORγt by binding to orthosteric- or allosteric-binding sites in the ligand-binding domain. Some of small-molecule inhibitors have entered clinical evaluations. Therefore, in current review, the role of RORγt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was highlighted. Notably, the recently developed RORγt inhibitors were summarized, with an emphasis on their optimization from lead compounds, efficacy, toxicity, mechanisms of action, and clinical trials. The limitations of current development in this area were also discussed to facilitate future research.

Abstract Introduction Currently, electroencephalogram (EEG)/electromyogram (EMG) system is widely regarded as the “golden standard” for sleep monitoring. Imperfectly, its invasive monitoring may somehow interfere with the natural state of sleep. Up to now, noninvasive methods for sleep monitoring have developed, which could preserve the undisturbed and naïve sleep state of mice to the greatest extent, but the feasibility of their application under different conditions should be extensive validated. Methods Based on existing research, we verified the feasibility of a sleep monitoring system based on mouse behaviors under different conditions. The experimental mice were exposed to various stresses and placed into a combined device comprising noninvasive sleep monitoring equipment and an EEG/EMG system, and the sleep status was recorded under different physiological, pharmacological, and pathophysiological conditions. The consistency of the parameters obtained from the different systems was calculated using the Bland–Altman statistical method. Results The results demonstrated that the physiological sleep times determined by noninvasive sleep monitoring system were highly consistent with those obtained from the EEG/EMG system, and the coefficients were 94.4% and 95.1% in C57BL/6J and CD‐1 mice, respectively. The noninvasive sleep monitoring system exhibited high sensitivity under the sleep‐promoting effect of diazepam and caffeine‐induced wakefulness, which was indicated by its ability to detect the effect of dosage on sleep times, and accurate determination of the sleep/wakeful status of mice under different pathophysiological conditions. After combining the data obtained from all the mice, the coefficient between the sleep times detected by behavior‐based sleep monitoring system and those obtained from the EEG/EMG equipment was determined to .94. Conclusion The results suggested that behavior‐based sleep monitoring system could accurately evaluate the sleep/wakeful states of mice under different conditions.

Negative Poisson's ratio as the anomalous characteristic generally exists in artificial architectures, such as re‐entrant and honeycomb structures. The structures with negative Poisson's ratio have attracted intensive attention due to their unique auxetic effect and many promising applications in shear‐resistant and energy absorption fields. However, experimental observation of negative Poisson's ratio in natural materials barely happens, although various 2D layered materials are predicted in theory. Herein, the anisotropic Raman response and the intrinsic intralayer negative Poisson's ratio of 2D natural black arsenic (b‐As) via strain engineering strategy are reported. The results are evident by the detailed Raman spectrum of b‐As under uniaxial strain together with density functional theory calculations. It is found that b‐As is softer along the armchair than zigzag direction. The anisotropic mechanical features and van der Waals interactions play essential roles in strain‐dependent Raman shifts and negative Poisson's ratio in the natural b‐As along zigzag direction. This work may shed a light on the mechanical properties and potential applications of 2D puckered materials.

Ethnopharmacological relevance: Pinellia ternata (Thunb.) Breit. is a well-known perennial herb that is used in traditional medicine in China, Japan and Korea. It's drawing worldwide interests in medicinal applications owing such as anti-diarrhea, lipid-lowering, anti-tumor, anti-cough, expectorant, anti-gastric ulcer, etc. Aim of the study: This review aims to provide useful information on the botany, traditional uses, phytochemistry, pharmacology, toxicity and quality control of Pinellia ternata to help increase its efficiency. In addition, this review will discuss the future research trends and development prospects of this plant. Materials and methods: Data was obtained through a systematic search of published literature and online databases such as Google Scholar, Web of Science, PubMed, Science Direct, and Sci-Finder. The botanical names were confirmed using the World Flora Online and chemical structures were drawn using the ChemBio Draw Ultra Version 19.0 Software. Results: Pinellia ternata is distributed in regions of China and other areas. Pinellia ternata and its compound preparations can be used for cough, vomiting, gastric ulcer and other diseases. Approximately 212 chemical constituents have been isolated from Pinellia ternata, including alkaloids, volatile oils, amino acids, organic acids, flavonoids, cerebrosides, phenylpropanoids and other compounds. Considerable pharmacological experiments in vitro and in vivo have demonstrated that Pinellia ternata possessed antitumor effect, antitussive effects, antiasthmatic effects, increasing resistance to gastric ulcer, and antidiarrheal effect. However, these extracts can also lead to various toxicities such as irritant toxicity, cardiotoxicity, hepatotoxicity and embryonic toxicity. Considerable experiments have demonstrated that different processing methods and suitable compatibility with other herbs can effectively reduce the toxicities and increase the efficiency of Pinellia ternata. Conclusions: Pinellia ternata is an ancient herbal medicine with a broad spectrum of pharmacological activities that has been used for thousands of years in China. Future studies should perform an in-depth analyses of the pharmacokinetics and mechanisms of toxicity of Pinellia ternata. Quality standards should be developed to correspond to the various application methods to ensure the efficacy of drugs in actual treatment.

Resumo Fundamento: O manejo da insuficiência cardíaca (IC) tem melhorado acentuadamente, mas uma melhora clinicamente significativa na capacidade funcional e na qualidade de vida talvez seja mais importante para os pacientes do que viver mais. Objetivo: Este estudo teve como objetivo revisar a melhora na qualidade de vida com sacubitril/valsartan em pacientes com IC e fração de ejeção (FE) reduzida/preservada a partir de ensaios clínicos prospectivos. Métodos: PubMed, Embase e Cochrane Library foram pesquisados em busca de ensaios clínicos randomizados (ECRs) e estudos de coorte prospectivos publicados desde o início até julho de 2021. Um total de 6 ensaios clínicos e 16.854 pacientes com IC foram incluídos. O desfecho primário foi a alteração da linha de base na pontuação do resumo clínico do KCCQ. Os desfechos secundários foram pontuações em outros domínios do KCCQ, ocorrência de eventos adversos graves (EAs) e mortalidade geral. Valores de p < 0,05 foram considerados estatisticamente significativos. Resultados: O tratamento de sacubitril/valsartan mostrou KCCQ-CSS significativamente maior em comparação com o controle (DMP=0,975, IC 95%:0,885, 1,064, p

Frequent outbreak of cyanobacteria is a serious problem for drinking water treatment. The microcystins released from Microcystis aeruginosa (M. aeruginosa) could cause irreversible damage to human health. Catalyst-free solar/periodate (PI) system has recently presented great potential for bacterial inactivation, whereas the application potential and underlying mechanisms of the effective M. aeruginosa control remain unclear. Our work delineated the key role of ROS that inactivating/harmless disposing M. aeruginosa in the simulated sunlight (SSL)/PI system. Singlet oxygen may specifically cause DNA damage but maintain membrane integrity, preventing the risk of microcystins leakage. The SSL/PI 300 μM system could also effectively inhibit M. aeruginosa recovery for >7 days and completely degrade microcystin-LR (50.0 μg/L) within 30 min. Non-targeted metabolomic analysis suggested that the SSL/PI system inactivated M. aeruginosa mainly by interrupting the Calvin-Benson cycle, which damaged the metabolic flux of glycolysis and its downstream pathways such as the oxidative PPP pathway and glutathione metabolism. Furthermore, the activated PI system exhibited an even better algal inhibition under natural sunlight irradiation, evidenced by the seriously damaged cell membrane of M. aeruginosa. Overall, this study reported the comprehensive mechanisms of algal control and application potentials of solar/PI systems. The findings facilitated the development of emerging algicidal technology and its application in controlling environmental harmful algae.

Polygonum perfoliatum L. is an herbal medicine that has been extensively used in traditional Chinese medicine to treat various health conditions ranging from ancient internal to surgical and gynecological diseases. Numerous studies suggest that P. perfoliatum extract elicits significant anti-tumor, anti-inflammatory, anti-bacterial, and anti-viral effects. Nevertheless, the underlying mechanisms of its anti-liver cancer effects remain poorly understood. Our study suggests that P. perfoliatum stem extract (PPLA) has a favorable safety profile and exhibits a significant anti-liver cancer effect both in vitro and in vivo. We identified that PPLA activates the cGMP-PKG signaling pathway, and key regulatory genes including ADRA1B, PLCB2, PRKG2, CALML4, and GLO1 involved in this activation. Moreover, PPLA modulates the expression of genes responsible for the cell cycle. Additionally, we identified four constituents of PPLA, namely taxifolin, myricetin, eriodictyol, and pinocembrin, that plausibly act via the cGMP-PKG signaling pathway. Both in vitro and in vivo experiments confirmed that PPLA, along with its constituting compounds taxifolin, myricetin, and eriodictyol, exhibit potent anti-cancer activities and hold the promise of being developed into therapeutic agents.

This article presents fully integrated 39-GHz bidirectional up- and down-conversion mixers for 5G millimeter-wave (mmWave) applications. Fabricated in a 65-nm CMOS process with a 1.2-V supply voltage, the up- and down-conversion mixers consume 39 and 43 mW, respectively. For 5G time-division duplexing (TDD) operation, intermediate-frequency (IF)/local-oscillator (LO)/radio-frequency (RF) T/R switches are introduced. For better isolation and low insertion loss between the up- and down-conversion mixer, a series-shunt single-pole double-throw (SPDT) structure and an equivalent lumped λ/4 transmission line are proposed for IF and RF T/R switches, respectively. To realize compact area and wide bandwidth, a transformer-based matching network is adopted in this design. Targeting multi-channel phased array applications, the measurement result shows that the up-conversion mixer achieves a 2.5-dB peak conversion gain with 6.5 GHz 3-dB bandwidth. Including the insertion loss of the switch and IF signal routing, at the maximum gain of 36.5 GHz, the up-conversion mixer achieves an output 1-dB gain compression point (OP1dB) of 2.5 dBm. Furthermore, the down-conversion mixer achieves a 5-dB peak conversion gain with a 9.7-GHz 3-dB bandwidth.

Abstract Controversy exists as toward the association of excessive fruits intake and certain disease risks. Longan is an edible fruit rich in high levels of fructose, glucose and sucrose. Herein, the effect of longan fruit on the development of nonalcoholic fatty liver disease (NAFLD) was investigated. Longan extracts at the doses of 4.0 g/kg, 8.0, and 16.0 g/kg were orally administered for 4 weeks to healthy C57BL/6J mice or to C57BL/6J mice fed with a HFD diet. In mice fed with a normal diet, repeated longan intake for 4 weeks at excess doses (8 or 16 g/kg), but not the normal dose (4 g/kg), promoted inflammation and gut dysbiosis‐like status and reduced short‐chain fatty acids (SCFAs) production. In high‐fat diet (HFD)‐fed mice, longan intake at 4 g/kg hardly influenced the NAFLD development. In contrast, excess longan intake (8 or 16 g/kg) promoted NAFLD pathogenesis, including increased abnormality in hepatic indices, elevated inflammation, and gut permeability associated with more severe liver steatosis and fibrosis. Moreover, the exacerbated pathogenic markers were positively correlated with increased blood sugar, aggravated HFD‐associated microbial dysbiosis. Effects mediated by excess longan intake resembled that of equivalent free sugars supplementation, suggesting that high level of free sugars in fruits contributed to the promotion of NAFLD development as demonstrated in case of excessive longan intake.

Abstract B7 family members act as co-stimulatory or co-inhibitory molecules in the adaptive immune system. Thisstudy aimed to investigate the dysregulation, prognostic value and regulatory network of B7 family members in non-small cell lung cancer (NSCLC). Data for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients were extracted from public databases. Patient prognosis was determined by Kaplan–Meier analysis. The downstream signaling pathways of B7 family were identified via GO and KEGG analysis. The key B7 related genes were selected by network, correlation and functional annotation analysis. Most B7 family members were dysregulated in LUAD and LUSC. The expression of B7-1/2/H3 and B7-H5 were significantly associated with overall survival in LUAD and LUSC, respectively. The major pathway affected by B7 family was the EGFR tyrosine kinase inhibitor resistance and ErbB signaling pathway. MAPK1, MAPK3 and MAP2K1 were pivotal B7 related genes in both LUAD and LUSC. This study reveals an overall dysregulation of B7 family members in NSCLC and highlights the potential of combination use of tyrosine kinase inhibitors or MEK/ERK inhibitors with B7 member blockade for NSCLC treatment.

Abstract A bulk of evidence identified that macrophages, including resident alveolar macrophages and recruited macrophages from the blood, played an important role in the pathogenesis of acute respiratory distress syndrome (ARDS). However, the molecular mechanisms of macrophages-induced acute lung injury (ALI) by facilitating oxidative stress and inflammatory responses remain unclear. Herein, we noticed that the levels of mitochondrial reactive oxygen species (mtROS), SPHK2 and activated NLRP3 inflammasome were higher in peripheral blood mononuclear cells (PBMCs) of ARDS patients than that in healthy volunteers. Similar observations were recapitulated in LPS-treated RAW264.7 and THP-1 cells. After exposure to LPS, the SPHK2 enzymatic activity, NLRP3 inflammasome activation and mtROS were significantly upregulated in macrophages. Moreover, knockdown SPHK2 via shRNA or inhibition SPHK2 could prominently decrease LPS-induced M1 macrophage polarization, oxidative stress and NLRP3 inflammasome activation. Further study indicated that upregulated SPHK2 could increase nuclear sphingosine-1-phosphate (S1P) levels and then restrict the enzyme activity of HDACs to facilitate p53 acetylation. Acetylation of p53 reinforced its binding to the specific region of the NLRP3 promoter and drove expression of NLRP3. In the in vivo experiments, it was also observed that treating with Opaganib (ABC294640), a specific SPHK2 inhibitor, could observably alleviate LPS-induced ALI, evidencing by lowered infiltration of inflammatory cells, increased M2 macrophages polarization and reduced oxidative damage in lung tissues. Besides, SPHK2 inhibition can also decrease the accumulation of acetylated p53 protein and the activation of NLRP3 inflammasome. Taken together, our results demonstrated for the first time that nuclear S1P can regulate the acetylation levels of non-histone protein through affecting HDACs enzyme activities, linking them to oxidative stress and inflammation in response to environmental signals. These data provide a theoretical basis that SPHK2 may be an effective therapeutic target of ARDS.