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Objective: To explore the diagnostic value of real-time shear wave elastography (SWE) in hepatic hemangioma (ANGI) and hepatocellular carcinoma (HCC). Methods: A total of 88 patients diagnosed with angiosarcoma (ANGI) or hepatocellular carcinoma (HCC) in our department from February 2019 to February 2020 were included in this study. These patients were assigned to two groups based on pathological diagnosis: the ANGI group (n = 42) and the HCC group (n = 46). All patients underwent SWE examination, and the clinical efficacy was analyzed by comparing the average value of Young's modulus of the two groups and plotting the receiver operator characteristic (ROC) curve. Results: There was no significant difference in lesion diameter between ANGI and HCC patients (P > 0.05). The ANGI group exhibited a significantly higher average Young's modulus for both the lesions and the adjacent liver tissues compared to the HCC group (P < 0.001); The area under the curve (AUC) of the average value of Young’s modulus of the lesion to ANGI and HCC was 0.875 (95% CI = 0.795-0.955). Conclusion: SWE demonstrates high diagnostic accuracy in distinguishing ANGI from HCC, providing valuable clinical evidence for differentiating between the two diseases.

Abstract Bone cancer pain (BCP) represents a prevalent symptom among cancer patients with bone metastases, yet its underlying mechanisms remain elusive. This study investigated the transcriptional regulation mechanism of Kv7(KCNQ)/M potassium channels in DRG neurons and its involvement in the development of BCP in rats. We show that HDAC2-mediated transcriptional repression of kcnq2/kcnq3 genes, which encode Kv7(KCNQ)/M potassium channels in dorsal root ganglion (DRG), contributes to the sensitization of DRG neurons and the pathogenesis of BCP in rats. Also, HDAC2 requires the formation of a corepressor complex with MeCP2 and Sin3A to execute transcriptional regulation of kcnq2/kcnq3 genes. Moreover, EREG is identified as an upstream signal molecule for HDAC2-mediated kcnq2/kcnq3 genes transcription repression. Activation of EREG/EGFR-ERK-Runx1 signaling, followed by the induction of HDAC2-mediated transcriptional repression of kcnq2/kcnq3 genes in DRG neurons, leads to neuronal hyperexcitability and pain hypersensitivity in tumor-bearing rats. Consequently, the activation of EREG/EGFR-ERK-Runx1 signaling, along with the subsequent transcriptional repression of kcnq2/kcnq3 genes by HDAC2 in DRG neurons, underlies the sensitization of DRG neurons and the pathogenesis of BCP in rats. These findings uncover a potentially targetable mechanism contributing to bone metastasis-associated pain in cancer patients.

Anilines and phenols are recognized as challenging organic pollutants in industrial wastewater. Herein, the coupled treatment of aniline and phenol in water was achieved through electrochemical oxidation-induced copolymerization. After the electrolysis (1,300 mA for 10 h) in the solution of aniline and phenol (200 mL, each at a concentration of 5 g/L), the organic compounds were efficiently precipitated from their mixed solution by copolymerization. These insoluble copolymers could be easily separated by filtration and collected as brown powders, and the average removal rate of aniline and phenol was calculated as 0.6 mol/h m2 in this coupled electrolysis. The chemical oxygen demand (COD) test of the filtrates showed that it reached up to 98% of the COD removal ratio. Moreover, mixed solutions containing multiple aniline and phenol derivatives were also applicable for this coupled treatment strategy, and they were efficiently removed together after electrolysis. HIGHLIGHTS Aniline and phenol with high concentrations (1–5 g/L) in water can be removed as insoluble copolymers by electrochemical-coupled treatment.; This protocol featuring electrochemical copolymerization avoids the complete oxidation of the organic pollutants to CO2, thus dramatically improving the removal efficiency and reducing energy consumption.;

Summary: Fate determination of neural stem cells (NSCs) is crucial for cortex development and is closely linked to neurodevelopmental disorders when gene expression networks are disrupted. The transcriptional corepressor chromodomain Y-like (CDYL) is widely expressed across diverse cell populations within the human embryonic cortex. However, its precise role in cortical development remains unclear. Here, we show that CDYL is critical for human cortical neurogenesis and that its deficiency leads to a substantial increase in gamma-aminobutyric acid (GABA)-ergic neurons in cortical organoids. Subsequently, neuronatin (NNAT) is identified as a significant target of CDYL, and its abnormal expression obviously influences the fate commitment of cortical NSCs. Cross-species comparisons of CDYL targets unravel a distinct developmental trajectory between human cortical organoids and the mouse cortex at an analogous stage. Collectively, our data provide insight into the evolutionary roles of CDYL in human cortex development, emphasizing its critical function in maintaining the fate of human cortical NSCs.

Abstract Reconfigurable intelligent surfaces (RISs) have attracted a great deal of interest due to the potential contributions to the next‐generation wireless networks. This letter proposes an enhancement to the physical layer security (PLS) of a multi‐hop RIS‐assisted underwater optical wireless communication (UOWC) system. Owing to the complexity of the underwater environment, a security‐based adaptive RIS (SA‐RIS) clustering strategy, which aims to reflect optical signals among clusters to improve the performance of the overall system, is evaluated. By combining the underwater channel model, the closed‐form expressions of probability density function (PDF) and cumulative distribution function (CDF) are derived. Moreover, by increasing the numbers of RIS clusters, the performance metrics such as secrecy outage probability (SOP) and average secrecy capacity (ASC) are evaluated under different scenarios. The obtained results demonstrated that, in contrast to the case without preventing the eavesdropper, the proposed strategy in evasion scenarios could improve the SOP significantly. It can be concluded that the system secrecy performances are further improved by assigning different RIS clusters with proper channel quality.

Silicosis, caused by silica exposure, is the most widespread and deadliest occupational disease. However, effective treatments are lacking. Therefore, it is crucial to elucidate the mechanisms and targets involved in the development of silicosis. We investigated the basic processes of silicosis development and onset at different exposure durations (2 or 4 weeks) using various techniques such as histopathology, immunohistochemistry, Enzyme linked immunosorbent assay(ELISA),16 S rRNA, and untargeted metabolomics.These results indicate that exposure to silica leads to progressive damage to lung tissue with significant deterioration observed over time. Time-dependent cytokines such as the IL-4, IL-13, and IL-6 are detected in lung lavage fluid, the model group consistently exhibited elevated levels of these cytokines, indicating a persistent and worsening inflammatory response in the lungs. Meanwhile, HE and Masson results show that 4-week exposure to silica causes more obvious lung injury and pulmonary fibrosis. Besides, the model group consistently exhibited a distinct lung bacterial population, known as the Lachnospiraceae_NK4A136_group, regardless of exposure duration. However, with increasing exposure duration, specific temporal changes were observed in lung bacterial populations, including Haliangium, Allobaculum, and Sandaracinus (at 4 weeks; p < 0.05). Furthermore, our study revealed a strong correlation between the mechanism of silica-induced lung injury and three factors: oxidative stress, impaired lipid metabolism, and imbalanced amino acid metabolism. We observed a close correlation between cytokine levels, changes in lung microbiota, and metabolic disturbances during various exposure periods. These findings propose that a possible mechanism of silica-induced lung injury involves the interplay of cytokines, lung microbiota, and metabolites.

To study the graded alcohol precipitation components of fucoidan from Undaria pinnatifida and its hypoglycemic activity in vitro, this study used Undaria pinnatifida as raw material, extracted Undaria pinnatifida fucoidan gum through CaCl2 solution, and precipitated it step by step to obtain four sets of polysaccharide samples (UPP-45, UPP-55, UPP-65, and UPP-75). Determined their molecular weight, total sugar content, uronic acid content, protein content, sulfate content and monosaccharide composition and analyzed by ultraviolet spectrum (UV), Fourier transform infrared spectra(FT-IR) and scanning electron microscopy(SEM). The inhibition of polysaccharides on α-amylase and α-glucosidase was determined to explore their hypoglycemic activity in vitro. The results showed that the higher the concentration of alcohol precipitation, the higher the proportion of small molecular weight polysaccharide. The highest total sugar content of UPP-65 was 84.38%, and the protein of the crude polysaccharide and sulfate contents of UPP-45 were significantly different from those of other components (P

Abstract The circadian clock regulates animal physiological activities. How temperature reorganizes circadian-dependent physiological activities remains elusive. Here, using in-vivo two-photon imaging with the temperature control device, we investigated the response of the Drosophila central circadian circuit to temperature variation and identified that DN1as serves as the most sensitive temperature-sensing neurons. The circadian clock gate DN1a’s diurnal temperature response. Trans-synaptic tracing, connectome analysis, and functional imaging data reveal that DN1as bidirectionally targets two circadian neuronal subsets: activity-related E cells and sleep-promoting DN3s. Specifically, behavioral data demonstrate that the DN1a-E cell circuit modulates the evening locomotion peak in response to cold temperature, while the DN1a-DN3 circuit controls the warm temperature-induced nocturnal sleep reduction. Our findings systematically and comprehensively illustrate how the central circadian circuit dynamically integrates temperature and light signals to effectively coordinate wakefulness and sleep at different times of the day, shedding light on the conserved neural mechanisms underlying temperature-regulated circadian physiology in animals.

Abstract Background Sufentanil-induced cough is common during the induction of anesthesia. The objective of this study was to determine whether pretreatment with a small dose of esketamine is effective in treating sufentanil-induced cough. Methods 220 patients were screened, and 200 patients who had scheduled elective surgery and were between 18 and 70 years old were randomly divided into two groups. Before sufentanil was administered, esketamine group (group K) was injected with 0.15 mg/kg esketamine at 5 s, and control group (group C) was administered with the same volume. Within 1 min after sufentanil(0.4ug/kg) injection during induction, cough incidence and severity were evaluated. After sufentanil was injected, we recorded its hemodynamic changes and side effects. Results In the esketamine group (group K) and control group (group C), there was an incidence of cough of 5 and 34%, respectively. The esketamine group (group K) had a significantly lower incidence and severity of cough compared to the control group (group C) immediately after sufentanil injection (P 0.05). Conclusion In our study, we found that sufentanil-induced cough was significantly reduced by pretreatment with 0.15 mg/kg esketamine, but with no significant changes in the hemodynamic status. Trial registration Chinese Clinical Trial Registry (ChiCTR2200063821, registered date: 17/09/2022), http://www.chictr.org.cn

Abstract Nuclear factor Y (NF-Y) gene family is an important transcription factor composed of three subfamilies of NF-YA, NF-YB and NF-YC, which is involved in plant growth, development and stress response. In this study, 63 tobacco NF-Y genes (NtNF-Ys) were identified in Nicotiana tabacum L., including 17 NtNF-YAs, 30 NtNF-YBs and 16 NtNF-YCs. Phylogenetic analysis revealed ten pairs of orthologues from tomato and tobacco and 25 pairs of paralogues from tobacco. The gene structure of NtNF-YAs exhibited similarities, whereas the gene structure of NtNF-YBs and NtNF-YCs displayed significant differences. The NtNF-Ys of the same subfamily exhibited a consistent distribution of motifs and protein 3D structure. The protein interaction network revealed that NtNF-YC12 and NtNF-YC5 exhibited the highest connectivity. Many cis-acting elements related to light, stress and hormone response were found in the promoter of NtNF-Ys. Transcriptome analysis showed that more than half of the NtNF-Y genes were expressed in all tissues, and NtNF-YB9/B14/B15/B16/B17/B29 were specifically expressed in roots. A total of 15, 12, 5, and 6 NtNF-Y genes were found to respond to cold, drought, salt, and alkali stresses, respectively. The results of this study will lay a foundation for further study of NF-Y genes in tobacco and other Solanaceae plants.

This paper considers an agent identity privacy problem in Markov decision process. There are two types of agents with different instantaneous control reward functions, e.g., two types of energy consumption activities in smart grid. An eavesdropper is assumed to intercept the observations of agent and make a statistic inference on the agent identity, which is privacy-sensitive and can be utilized by the eavesdropper to further make corresponding malicious attacks. With regard to the agent identity privacy problem, a privacy-preserving Markov decision process is formulated and a novel adversarial reinforcement learning algorithm is further proposed by exploiting the ideas of deep reinforcement learning and variational method to design the agent policies with the aim to optimally tradeoff improving cumulative control reward and preventing agent identity privacy leakage. Experiments in a modified OpenAI Gym environment show different training process patterns and justify the effectiveness of the proposed algorithm.

The IEEE 802.11bf-based wireless fidelity (WiFi) indoor positioning system has gained significant attention recently. It is important to recognize that multi-user online positioning occurs in real wireless environments. This paper proposes an indoor positioning sensing strategy that includes an optimized preprocessing process and a new machine learning (ML) method called NKCK. The NKCK method can be broken down into three components: neighborhood component analysis (NCA) for dimensionality reduction, K-means clustering, and K-nearest neighbor (KNN) classification with cross-validation (CV). The KNN algorithm is particularly suitable for our dataset since it effectively classifies data based on proximity, relying on the spatial relationships between points. Experimental results indicate that the NKCK method outperforms traditional methods, achieving reductions in error rates of 82.4% compared to naive Bayes (NB), 85.0% compared to random forest (RF), 72.1% compared to support vector machine (SVM), 64.7% compared to multilayer perceptron (MLP), 50.0% compared to density-based spatial clustering of applications with noise (DBSCAN)-based methods, 42.0% compared to linear discriminant analysis (LDA)-based channel state information (CSI) amplitude fingerprinting, and 33.0% compared to principal component analysis (PCA)-based approaches. Due to the sensitivity of CSI, our multi-user online positioning system faces challenges in detecting dynamic human activities, such as human tracking, which requires further investigation in the future.

Abstract Background A proliferation of theories, models, and frameworks (TMFs) have been developed in the implementation science field to facilitate the implementation process. The basic features of these TMFs have been identified by several reviews. However, systematic appraisals on the quality of these TMFs are inadequate. To fill this gap, this study aimed to assess the usability, applicability, and testability of the current TMFs in a structured way. Methods A scoping review method was employed. Electronic databases were searched to locate English and Chinese articles published between January 2000 and April 2022. Search terms were specific to implementation science. Additionally, hand searches were administered to identify articles from related reviews. Purpose and characteristics such as the type of TMF, analytical level, and observation unit were extracted. Structured appraisal criteria were adapted from Birken et al.’s Theory Comparison and Selection Tool (T-CaST) to conduct an in-depth analysis of the TMFs’ usability, applicability, and testability. Results A total of 143 TMFs were included in this analysis. Among them, the most common purpose was to identify barriers and facilitators. Most TMFs applied the descriptive method to summarize the included constructs or the prescriptive method to propose courses of implementation actions. TMFs were mainly mid-range theories built on existing conceptual frameworks or demonstrated grand theories. The usability of the TMFs needs to be improved in terms of the provision of conceptually matched strategies to barriers and facilitators and instructions on the TMFs usage. Regarding the applicability, little attention was paid to the constructs of macro-level context, stages of scale-up and sustainability, and implementation outcomes like feasibility, cost, and penetration. Also, fewer TMFs could propose recommended research and measurement methods to apply the TMFs. Lastly, explicit hypotheses or propositions were lacking in most of the TMFs, and empirical evidence was lacking to support the claimed mechanisms between framework elements in testability. Conclusions Common limitations were found in the usability, application, and testability of the current TMFs. The findings of this review could provide insights for developers of TMFs for future theoretical advancements.

In this paper, the flocculation effect of single flocculants and compound flocculants on emulsified wastewater under different conditions was studied. The effect of flocculant type, dose, settling time and composite ratio of flocculant on the treatment of emulsified wastewater were investigated through single-factor condition tests, and then the optimal conditions of flocculants for treating emulsified wastewater were obtained. The results showed that the single inorganic flocculant could break the stable state of the emulsion when the pH was adjusted to 7 and formed tiny flocs, but it took a long time to settle down. The single organic flocculant had no flocculation effect. The inorganic–organic composite flocculants could effectively solve the problem of emulsion breaking and flocculation, and could form large flocs and alum flower formations at the same time, with mud and water effectively separated. The best conditions for the composite flocculants were as follows: under the condition of room temperature and pH 7, the dose of PFC was 2250 mg/L and APAM was 5 mg, the homogeneous stirring time was 10 min, and the settling time was 0.5 h. The removal rate of COD and turbidity reached 84.75% and 99.86%. The study could provide a new treatment idea and method for the pretreatment of stabilized high-turbidity wastewater.

Trametes versicolor can produce aromatic flavor in growth and development, widely used in food fermentation. This study used a One-Factor-at-a-Time (OFAT) test and response surface analysis to study the optimum fermentation parameters of Rosa roxburghii tratt and coix seed yogurt by Trametes versicolor. The best fermentation process is as follows: skim milk powder 17 %, sucrose content 4 %, Rosa roxburghii tratt and coix seed liquid 36 %, fermentation temperature 39 °C, inoculum 2 %, strain ratio 2:1:1(LB12: BLH1: Q-1), fermentation time 9.5 h. Under this fermentation process, the sensory score was 82.11, the contents of vitamin C, GABA, and total live bacteria in this yogurt were 13.89, 2.58, and 1.02 times higher than in common yogurt. Correlation analyses showed a significant contribution of the leavening agent to the GABA content of yogurt. This study provides a foundation for producing Rosa roxburghii tratt and coix seed yogurt with high sensory and nutritional value.

Low acid is the main defect in the northwest wine region of China in recent years. The fermentation of unripe grape (UG) and wine grapes with low acid contents was carried out. Compared with control group (CK), the addition of UG addressed the core flaw that low acid grape bring to wine firstly, it significantly increased titratable acid, tartaric acid and malic acid while significantly decreasing alcohol and volatile acids in wine. Secondly, UG significantly improved wine color, the color parameters a*, b*, C* and L* were significantly increased to different degrees. At the same time, the addition of UG significantly improves other qualities of wine, including the phenolic substances and antioxidant capacity of wine. In addition, adding UGJ2% significantly improved the sensory quality, and pleasant volatile substances such as phenethyl alcohol, ethyl hexanoate, ethyl butyrate and isoamyl acetate were significantly increased, giving the wine more prominent floral and fruity aromas.

AbstractTo prevent water inrush hazards of mining under the Quaternary unconsolidated confined aquifer in North China coalfield, it is necessary to build a water inrush prediction model to guarantee coal safety production. The current method of evaluating mining hazards under unconsolidated confined aquifers is easy to fall into the problems of simple superposition of evaluation factors, large subjectivity of the factor selection, and low accuracy of prediction results. In this paper, an analytic hierarchy process (AHP) is improved according to contribution of information value method (IVM) to analyze the impact of water inrush factors. The factor weight values are considered in calculating the total information value of IVM to build a coupled AHP-IVM model. The information value of each factor is calculated through IVM, and area under curve (AUC) value is used to rank the factors, to exclude the subjective judgment of the importance of each factor. The geological and hydrogeological data of Qinan coal mine in Huaibei coalfield are analyzed and organized. The results suggest that the coupled AHP-IVM model has an AUC value of 0.8309, indicating its great potential and practical significance for future mining operations.

Abstract Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is currently the standard first-line therapy for EGFR-mutated advanced non-small cell lung cancer (NSCLC). The life quality and survival of this subgroup of patients were constantly improving owing to the continuous iteration and optimization of EGFR-TKI. Osimertinib, an oral, third-generation, irreversible EGFR-TKI, was initially approved for the treatment of NSCLC patients carrying EGFR T790M mutations, and has currently become the dominant first-line targeted therapy for most EGFR mutant lung cancer. Unfortunately, resistance to osimertinib inevitably develops during the treatment and therefore limits its long-term effectiveness. For both fundamental and clinical researchers, it stands for a major challenge to reveal the mechanism, and a dire need to develop novel therapeutics to overcome the resistance. In this article, we focus on the acquired resistance to osimertinib caused by EGFR mutations which account for approximately 1/3 of all reported resistance mechanisms. We also review the proposed therapeutic strategies for each type of mutation conferring resistance to osimertinib and give an outlook to the development of the next generation EGFR inhibitors. Video Abstract

With the popularization and development of the current power system, power information data asset management plays a crucial role in modern power systems. However, traditional management methods have some problems, such as low information processing efficiency, low prediction accuracy, and insufficient decision support. In order to better promote its development and achieve efficient management of power information data assets, this article aimed to use BP neural network (Back Propagation Neural Network) to design a power information data asset management system, achieving efficient processing and accurate analysis of power information data. In the article, data preprocessing was achieved through data separation, data cleaning, and data normalization processing. Compared with the traditional power asset management system, it has better management efficiency, lightens the difficulty of asset management and reduces the error rate. In this paper, the power information data is modeled and trained by BP neural network modeling, and the performance index is minimized by error back propagation, and the optimized BP neural network model is integrated into the power information data asset management system to realize data processing and decision support. In order to verify the performance of the power information data asset management system based on BP neural network, this paper tested its system performance. The research results showed that the average processing accuracy of the system under this method for basic data in 10 test cases reached 91.467 %, and the average rationality of decision support reached 89.6 %. The average processing accuracy of real-time data reached 91.625 %, and the average rationality of decision support reached 90.25 %. The average processing accuracy of application data reached 90.675 %, and the average rationality of decision support reached 90.2 %. The results showed that the system under this method has higher accuracy in data processing and can better achieve decision support. This study highlighted the important impact of BP neural networks on data processing, data prediction, decision support, and data security in power information data asset management systems, providing more possibilities for achieving efficient processing and accurate analysis of power information data.

The naturally cooled panel-type radiators are widely used for transformer heat dissipation. However, their poor heat transfer performance also restricts the overall performance of the transformer. The chimney effect can improve the airflow rate due to the thermal pressure difference between the air inside and outside the flow channel, which is widely used to improve the flow and heat transfer of natural convection. In order to improve the heat transfer performance of panel-type radiators under natural convection, a novel radiator is developed, where wind deflectors are added at both lateral sides of the radiator, and a chimney structure is added on the top of the radiator to extend the chimney channel. Then, the fluid flow and heat transfer characteristics inside and outside the radiator are studied by numerical simulation. The results show that cooling air would be effectively sucked into the radiator from the bottom due to the pressure difference generated at the inlet and top of the chimney channel. As compared with the traditional panel radiator without the chimney structure, the airflow on the outer surface of the most cost-effective radiator is increased by 19.14 %, the cooling capacity is increased by 14.76 %, and the oil temperature inside the transformer is reduced to 6.72 °C.

Adverse reactions to traditional Chinese medicine have hindered the healthy development and internationalization process of the traditional Chinese medicine industry. The critical issue that needs to be solved urgently is to evaluate the safety of traditional Chinese medicine systematically and effectively. Podophyllotoxin (PPT) is a highly active compound extracted from plants of the genus Podophyllum such as Dysosma versipellis (DV). However, its high toxicity and toxicity to multiple target organs affect the clinical application, such as the liver and kidney. Based on the concurrent effects of PPT's medicinal activity and toxicity, it would be a good example to conduct a systematic review of its safety. Therefore, this study revolves around the Toxicological Evidence Chain (TEC) concept. Based on PPT as the main toxic constituent in DV, observe the objective toxicity impairment phenotype of animals. Evaluate the serum biochemical indicators and pathological tissue sections for substantial toxic damage results. Using metabolomics, lipidomics, and network toxicology to evaluate the nephrotoxicity of PPT from multiple perspectives systematically. The results showed that PPT-induced nephrotoxicity manifested as renal tubular damage, mainly affecting metabolic pathways such as glycerophospholipid metabolism and sphingolipid metabolism. PPT inhibits the autophagy process of kidney cells through the PI3K/Akt/mTOR and Nrf2/HO1 pathways and induces the activation of oxidative stress in the body, thereby causing nephrotoxic injury. This study fully verified the feasibility of the TEC concept for the safety and toxicity evaluation of traditional Chinese medicine. Provide a research template for systematically evaluating the safety of traditional Chinese medicine.

Objective: The potential ability of probiotics to prepare angiotensin-converting enzyme （ACE） inhibitory fermentation broth from quinoa and the effects of fermentation process on it were investigated. Methods: In this study, 18 strains of lactic acid bacteria and 12 strains of yeast were screened for their ability to prepare ACE inhibitory fermentation broth using quinoa as the raw material and the ACE inhibition rate as an indicator. The inoculum amount, fermentation temperature and fermentation time were optimized by orthogonal tests. Finally, the peptides in the fermentation broth were identified, and the selected peptides were tested in vivo to evaluate the antihypertensive effect. Results: Lactobacillus paracasei L2 had the best effect among the 30 strains, and the ACE inhibition rate of the fermentation broth prepared by fermenting quinoa was as high as （86.50±0.25）%; The optimal fermentation conditions for the preparation of ACE inhibitory fermentation broth by fermenting quinoa with Lactobacillus paracasei L2 strain were 5% inoculum, 48 h fermentation time, and 34 ℃ fermentation temperature. Under these conditions, the ACE inhibition rate was the highest, which was （90.41±0.16）%; By comparing the results of liquid quality identification with the database, two peptides NIFRPFAPEL and AALEAPRILNL with better ACE inhibition effect were obtained. Both NIFRPFAPEL and AALEAPRILNL could significantly lower blood pressure in spontaneously hypertensive rats （SHR）, and both achieved the best blood pressure lowering effect at 6 h after gavage. Systolic blood pressure （SBP） decreased by （2.67±0.21） and （3.46±0.01） kPa, and diastolic blood pressure （DBP） decreased by （29.36±0.54） and （22.33±0.77） kPa, respectively. And NIFRPFAPEL and AALEAPRI-LNL had no effect on blood pressure in Wistar-Kyoto rats （WKY）. Conclusion: Therefore, quinoa is a high-quality grain raw material for preparing ACE inhibitory fermentation broth, and NIFRPFAPEL and AALEAPRILNL can be used for the development of blood pressure-lowering functional foods or medicines.

Abstract Many cardiovascular disorders, including atherosclerosis, hypertension, coronary heart disease, diabetes, etc., are characterized by endothelial cell dysfunction. Endothelial cell function is closely related to sphingolipid metabolism, and normal sphingolipid metabolism is critical for maintaining endothelial cell homeostasis. Sphingolipid metabolites or key enzymes in abnormal situation, including sphingosine, ceramide (Cer), sphingosine-1-phosphate (S1P), serine, sphingosine kinase (SPHK), ceramide kinase (Cerk), sphingosine-1-phosphate lyase (S1PL) etc., may have a protective or damaging effect on the function of endothelial cells. This review summarizes the effects of sphingolipid metabolites and key enzymes disordering in sphingolipid metabolism on endothelial cells, offering some insights into further research on the pathogenesis of cardiovascular diseases and corresponding therapeutic targets.

Objective: This study aimed to obtain a novel fermented green tea with high ACE-inhibitory activity by Eurotium cristatum and to investigate its acute hypotensive effects on spontaneously hypertensive rats （SHR）. Methods: The effects of pueraria addition, water content of substrate and spore suspension on ACE-inhibitory activity in vitro were investigated, and the fermentation process was optimized by orthogonal design experiment. The fermented tea solution was prepared by water extraction method, and SHR model was selected to study the hypotensive effect of fermented tea. Results: The optimal fermentation process for fermented tea was as follows: adding 2 g pueraria into 20 g green tea matrix, controlling the water content of the matrix to 20%, inoculatin 5% suspension of E. cristatum. Compared with the control group, different doses of fermented tea had lowering effects on blood pressure in SHR within 24 h. Conclusion: The acute hypotensive effect of the daily dose of 300~600 mg/kg was the most significant, which could lower the blood pressure of SHR in a short period of time.

Using chitosan as pretreatment agent, the dyeing properties of peanut skin extracts (PSE) to flax fabrics were improved. Flax fabrics have excellent comfort property and are loved by many people. However, flax is different to dye, especially with natural dye. In this research, chitosan was used to pretreat flax fabrics and PSE was used to dye the pretreated flax fabric. The optimal conditions of the chitosan pretreatment and dyeing conditions of PSE were investigated according to the K/S value of the dyed flax fabrics. Comparing the original flax fabric, the chitosan pretreated flax fabric significantly improved the absorption to PSE, and the dyed fabrics had an increased K/S value from 0.9 to 3.9, and had good color fastnesses. The main chemical constitution in PSE such as catechin, chitosan, and cellulose of flax fabrics may form hydrogen bond and ionic bond. Chitosan pretreated and dyed flax fabrics had a stronger ability to UV resistance and scavenging free radicals. The fluorescence intensity of the dyed flax fabrics was improved while it was decreased after chitosan pretreatment. Chitosan pretreatment combined PSE dyeing can be used to develop functional flax textiles without using metallic mordants.

Introduction: Mitochondrial disease is a spectrum of debilitating disorders caused by mutations in the mitochondrial DNA (mtDNA) or nuclear DNA that compromises the respiratory chain. Mitochondrial 3243A>G (m.3243 A>G) is the most common mutation showing great heterogeneity in phenotype. Previous studies have indicated that NADH: ubiquinone oxidoreductase (complex I) deficiency accompanied by a decreased nicotinamide adenine dinucleotide (NAD+)/reduced NAD+ (NADH) ratio may play a pivotal role in the pathogenesis of m.3243A>G mutation.Methods: To evaluate the potential effects of strategies targeting the imbalanced NAD+/NADH ratio in m.3243A>G mutation, we treated fibroblasts derived from patients with the m.3243 A>G mutation using nicotinamide riboside (NR) or mitochondria-targeted H2O-forming NADH oxidase (mitoLbNOX).Results: M.3243 A>G fibroblasts showed a significant reduction in complex I core subunit 6, complex I enzymatic activity, complex I-dependent oxygen consumption rate (OCR), and adenosine triphosphate (ATP) production compared to the controls. The NAD+/NADH ratio was also significantly reduced in m.3243 A>G fibroblasts, and, using fluorescence lifetime imaging microscopy, we also found that the NADH level was elevated in m.3243 A>G fibroblasts. After NR treatment, the NAD+/NADH ratio, complex I-dependent OCR, and ATP levels increased, whereas NADH levels remained unchanged. More excitingly, after treatment with mitoLbNOX, the NAD+/NADH ratio, complex I-independent OCR, and ATP levels increased more pronouncedly compared with the NR treatment group, accompanied by significantly reduced NADH levels.Discussion: The present study suggests that compared with repletion of NAD+ alone, the combination of this therapeutic modality with alleviation of NADH overload may amplify the treatment effect of restoring NAD+/NADH balance in m.3243A>G fibroblasts.

ObjectiveDuring the past decade, the concept of complete mesocolic excision (CME) has been developed in an attempt to minimize recurrence for right-sided colon cancer. This study aims to compare outcomes of robotic versus laparoscopic right hemicolectomy with CME for right-sided colon cancer.MethodsWe performed a retrospective multicenter propensity score matching study. From July 2016 to July 2021, 382 consecutive patients from different Chinese surgical departments were available for inclusion out of an initial cohort of 412, who underwent robotic or laparoscopic right hemicolectomy with CME. Data of all patients were retrospectively collected and reviewed. Of these, 149 cases were performed by a robotic approach, while the other 233 cases were done by laparoscopy. Propensity score matching was applied at a ratio of 1:1 to compare perioperative, pathologic, and oncologic outcomes between the robotic and the laparoscopic groups (n = 142).ResultsBefore propensity score matching, there were no statistical differences regarding the sex, history of abdominal surgery, body mass index (BMI), American Joint Committee on Cancer (AJCC) staging system, tumor location, and center between groups (p > 0.05), while a significant difference was observed regarding age (p = 0.029). After matching, two comparable groups of 142 cases were obtained with equivalent patient characteristics (p > 0.05). Blood loss, time to oral intake, return of bowel function, length of stay, and complications were not different between groups (p > 0.05). The robotic group showed a significantly lower conversion rate (0% vs. 4.2%, p = 0.03), but a longer operative time (200.9 min vs. 182.3 min, p < 0.001) and a higher total hospital cost (85,016 RMB vs. 58,266 RMB, p < 0.001) compared with the laparoscopic group. The number of harvested lymph nodes was comparable (20.4 vs. 20.5, p = 0.861). Incidence of complications, mortality, and pathologic outcomes were similar between groups (p > 0.05). The 2-year disease-free survival rates were 84.9% and 87.1% (p = 0.679), and the overall survival rates between groups were 83.8% and 80.7% (p = 0.943).ConclusionDespite the limitations of a retrospective analysis, the outcomes of robotic right hemicolectomy with CME were comparable to the laparoscopic procedures with fewer conversions to open surgery. More clinical advantages of the robotic surgery system need to be further confirmed by well-conducted randomized clinical trials with large cohorts of patients.

The species number of bryophytes is the second highest among land plants. Alpine grasslands on the Qinghai–Tibet Plateau (QTP) are the largest among global alpine biomes. However, bryophyte flora in alpine grasslands on the QTP remains poorly explored relative to its large geographic extent. A total of 347 plots were surveyed across the QTP, and 149 bryophyte taxa in 24 families and 49 genera were recorded in alpine grasslands. The largest family was Pottiaceae, followed by Bryaceae and Brachytheciaceae. The most species-rich genus was Bryum, followed by Didymodon and Brachythecium. The dominant species were Didymodon tectorus, Didymodon fallax, Bryum caespiticium, Didymodon constrictus, and Didymodon ditrichoides. The Jaccard similarity indexes of bryophyte compositions between alpine meadow and alpine steppe at the family, genus, and species levels were 0.375, 0.367, and 0.282, respectively. Turf was the most common life-form (75.2%), followed by weft (16.1%) and cushion (5.4%). Endemic species to China accounted for 8.05% of the total taxa. Bryophyte diversity in alpine grasslands on the QTP is exceptional and irreplaceable. The changes in species composition and life-forms between different grassland types reflect the adaptations of bryophytes to harsh environments.

We have developed a theory for electromigration at metal nanocontacts. In the proposed theory, a metal atom is removed by kinetic energy transfer from a “lucky electron” that ballistically traverses a metal nanocontact, when the applied voltage exceeds the surface self-diffusion potential of the metal. The histogram of the critical voltage, V _c , at which metal atoms are removed, depends on the temperature as well as the probability for an atom being removed by collision with a lucky electron. The histograms of V _c for Au, Ni, Pd are well explained by the present theory.

Virus-induced gene silencing (VIGS) is an RNA-mediated reverse genetics technique that has become an effective tool to investigate gene function in plants. Cotton is one of the most important economic crops globally. In the past decade, VIGS has been successfully applied in cotton functional genomic studies, including those examining abiotic and biotic stress responses and vegetative and reproductive development. This article summarizes the traditional vectors used in the cotton VIGS system, the visible markers used for endogenous gene silencing, the applications of VIGS in cotton functional genomics, and the limitations of VIGS and how they can be addressed in cotton.

Abstract Periodontitis is an inflammatory disease initiated by dysbiosis of the local microbial community. Periodontitis can result in destruction of tooth-supporting tissue; however, overactivation of the host immune response is the main reason for alveolar bone loss. Periodontal tissue cells, immune cells, and even further activated osteoclasts and neutrophils play pro-inflammatory or anti-inflammatory roles. Traditional therapies for periodontitis are effective in reducing the microbial quantities and improving the clinical symptoms of periodontitis. However, these methods are non-selective, and it is still challenging to achieve an ideal treatment effect in clinics using the currently available treatments and approaches. Exosomes have shown promising potential in various preclinical and clinical studies, including in the diagnosis and treatment of periodontitis. Exos can be secreted by almost all types of cells, containing specific substances of cells: RNA, free fatty acids, proteins, surface receptors and cytokines. Exos act as local and systemic intercellular communication medium, play significant roles in various biological functions, and regulate physiological and pathological processes in numerous diseases. Exos-based periodontitis diagnosis and treatment strategies have been reported to obtain the potential to overcome the drawbacks of traditional therapies. This review focuses on the accumulating evidence from the last 5 years, indicating the therapeutic potential of the Exos in preclinical and clinical studies of periodontitis. Recent advances on Exos-based periodontitis diagnosis and treatment strategies, existing challenges, and prospect are summarized as guidance to improve the effectiveness of Exos on periodontitis in clinics.

Keratin-based goat hair could be used bioadsorbent due to its large availability, biodegradability and low cost. Unfortunately, most available keratin adsorbents are either low in adsorption capacity or high in preparation cost. In this study, goat hair was steam exploded, frozen and disintegrated to prepare the exploded goat hair powder (EGHP), and was further used for the adsorption of reactive blue 19 (RB 19) in dyeing wastewater. Steam explosion significantly increased the adsorption capacity of keratin-based goat hair toward RB 19. Adsorption capacity of RB 19 in EGHP increased from 55 to 427 mg/g after a steam explosion under 1.8 MPa for 150 s. The increased adsorption capacity was mainly due to decreased crystallinity, increased specific surface area from 0.678 to 8.583 m2/g and the increased free NH2 groups for EGHP. These structure changes resulted in that more dye molecules could easily and fast entered into the amorphous region of EGHP, thereby improving the adsorption rate and amount of RB 19 dyes. Desorption and regeneration study indicated that the adsorption capacity still maintained 79% after 6 cycles. These results demonstrated that EGHP could be considered as promising bioadsorbent to treat the dyeing wastewater.

Abstract Acute high-intensity exercise can affect cardiac health by altering substance metabolism. However, few metabolomics-based studies provide data on the effect of exercise along with myocardial metabolism. Our study aimed to identify metabolic signatures in rat myocardium during acute high-intensity exercise and evaluate their diagnostic potential for sports injuries. We collected rat myocardium samples and subjects’ serum samples before and after acute high-intensity exercise for metabolite profiling to explore metabolic alterations of exercise response in the myocardium. Multivariate analysis revealed myocardium metabolism differed before and after acute high-intensity exercise. Furthermore, 6 target metabolic pathways and 12 potential metabolic markers for acute high-intensity exercise were identified. Our findings provided an insight that myocardium metabolism during acute high-intensity exercise had distinct disorders in complex lipids and fatty acids. Moreover, an increase of purine degradation products, as well as signs of impaired glucose metabolism, were observed. Besides, amino acids were enhanced with a certain protective effect on the myocardium. In this study, we discovered how acute high-intensity exercise affected myocardial metabolism and exercise-related heart injury risks, which can provide references for pre-competition screening, risk prevention, and disease prognosis in competitive sports and effective formulation of exercise prescriptions for different people.

Abstract Hepatic stem/progenitor cells are the major cell compartment for tissue repair when hepatocyte proliferation is compromised in chronic liver diseases, but the expansion of these cells increases the risk of carcinogenesis. Therefore, it is essential to explore the pathways restricting their expansion and abnormal transformation. The ligand of glucocorticoid-induced tumour necrosis factor receptor (GITRL) showed the most highly increased expression in hepatic progenitor cells treated with transforming growth factor (TGF)-β1. If overexpressed by hepatic progenitor cells, GITRL stimulated cell proliferation by activating the epithelial–mesenchymal transition pathway and enhancing ERK1/2 and Akt phosphorylation via GITRL binding to ANXA2. However, GITR, the specific GITRL receptor, suppressed the epithelial–mesenchymal transition pathway of GITRL-expressing cells and decreased their growth by dissociating ANXA2 from GITRL and reducing downstream ERK1/2 and Akt phosphorylation. This study identifies GITR/GITRL reverse signalling as a cross-interaction pathway between immune cells and hepatic stem/progenitor cells that restricts the expansion of hepatic stem/progenitor cells and reduces the possibility of carcinogenesis.

Abstract Background Acetaminophen (APAP) overdose is a major cause of the morbidity of acute liver failure. The current clinically approved treatment for APAP poisoning, N-acetylcysteine (NAC), has a limited therapeutic window, and prolonged treatment with NAC delays liver regeneration. Mesenchymal stem cells (MSCs) also have therapeutic effects on APAP-induced mouse liver failure, but whether the effects are comparable to those of NAC has not been determined, and the mechanism still needs further exploration. Methods Fasted C57BL/6 mice that received 500 mg/kg APAP were treated intravenously with 300 mg/kg NAC or different amounts of MSCs at 2 h after APAP to investigate survival, hepatocyte necrosis and neutrophil/macrophage recruitment. In vitro co-culture was performed to study the anti-necrotic effects of MSCs on the APAP-injured hepatocyte cell line L-O2. Results MSCs dose-dependently rescued the C57BL/6J mice from APAP-induced liver failure, with 87.5% of MSCs (1 × 106) surviving similar to that of NAC (90%). MSC has similar effects on reduced hepatocyte necrosis and granulocytic myeloid-derived suppressor cells (MDSC) infiltration but enhanced the proportion of regenerative monocytic MDSC when compared to NAC. Mechanistically, MSCs attenuate hepatocyte necrosis by secreting hepatocyte growth factor (HGF). When HGF was knocked down, the protective effects of MSCs were reduced on APAP-induced hepatocyte necrosis and mouse liver failure. Conclusions MSCs are comparable to NAC against APAP-induced liver failure by secreting HGF with less regenerative retardation concerns, thus facilitating the application of MSCs in clinical therapy for APAP liver failure.

Cotton fibers provide an important source of raw materials for the textile industry worldwide. Cotton fiber is a kind of single cell that differentiates from the epidermis of the ovule and provides a perfect research model for the differentiation and elongation of plant cells. Cotton fiber initiation is the first stage throughout the entire developmental process. The number of fiber cell initials on the seed ovule epidermis decides the final fiber yield. Thus, it is of great significance to clarify the mechanism underlying cotton fiber initiation. Fiber cell initiation is controlled by complex and interrelated regulatory networks. Plant phytohormones, transcription factors, sugar signals, small signal molecules, functional genes, non-coding RNAs, and histone modification play important roles during this process. Here, we not only summarize the different kinds of factors involved in fiber cell initiation but also discuss the mechanisms of these factors that act together to regulate cotton fiber initiation. Our aim is to synthesize a systematic and comprehensive review of different factors during fiber initiation that will provide the basics for further illustrating these mechanisms and offer theoretical guidance for improving fiber yield in future molecular breeding work.

The next generation of mobile communication aims to extend the capabilities of traditional communication by reshaping the environment with wireless signals. The channel state information can describe the propagation characteristics in wireless communications, which is beneficial in developing wireless communication networks towards intelligent communication and wireless sensing networks. Raspberry PI with Nexmon firmware patched can extract the channel state information from WiFi signals and realize human activity recognition. However, the phase values on some carriers are susceptible to noise, resulting in phase errors after singular value decomposition. To solve this problem, a method is proposed in this paper to find the optimal phase value by dynamic time warping algorithm utilizing the property of orthogonality between amplitude and phase. In contrast to the conventional recognition strategies, the proposed optimal phase extraction method with commercial WiFi signals can further improve the accuracy of the recognition strategy under different complicated scenarios.

As the main bioactive substance of Ganoderma lucidum, Ganoderma lucidum polysaccharide (GLP) has anti-inflammatory, antibacterial, and other biological activities. Studies have shown that GLP can regulate the expression of multiple inflammatory cytokines in different inflammatory models and diseases as part of the anti-infection immune response. We extracted crude Changbai Mountain Ganoderma lucidum polysaccharides (CGLPs), analyzed their physical and chemical properties, and then applied them to the periodontitis model to verify whether they have an inhibitory effect on mouse periodontitis. CGLP was determined to be a heteropolysaccharide with dextran as the main component. Its molecular weight was 17.40 kDa. In vivo experiments in mice showed that CGLP can inhibit the alveolar bone loss and reduced inflammation caused of periodontitis by regulating the expression of the inflammatory factors IL-1β, TNF-α, and IL-10 in a concentration-dependent manner.

Abstract Periodontitis is a chronic inflammatory disease that leads to the destruction of both soft and hard periodontal tissues. Complete periodontal regeneration in clinics using the currently available treatment approaches is still a challenge. Mesenchymal stem cells (MSCs) have shown promising potential to regenerate periodontal tissue in various preclinical and clinical studies. The poor survival rate of MSCs during in vivo transplantation and host immunogenic reaction towards MSCs are the main drawbacks of direct use of MSCs in periodontal tissue regeneration. Autologous MSCs have limited sources and possess patient morbidity during harvesting. Direct use of allogenic MSCs could induce host immune reaction. Therefore, the MSC-based indirect treatment approach could be beneficial for periodontal regeneration in clinics. MSC culture conditioned medium (CM) contains secretomes that had shown immunomodulatory and tissue regenerative potential in pre-clinical and clinical studies. MSC-CM contains a cocktail of growth factors, cytokines, chemokines, enzymes, and exosomes, extracellular vesicles, etc. MSC-CM-based indirect treatment has the potential to eliminate the drawbacks of direct use of MSCs for periodontal tissue regeneration. MSC-CM holds the tremendous potential of bench-to-bed translation in periodontal regeneration applications. This review focuses on the accumulating evidence indicating the therapeutic potential of the MSC-CM in periodontal regeneration-related pre-clinical and clinical studies. Recent advances on MSC-CM-based periodontal regeneration, existing challenges, and prospects are well summarized as guidance to improve the effectiveness of MSC-CM on periodontal regeneration in clinics.

Despite intensive effort was made to regenerate injured meniscus by cell-free strategies through recruiting endogenous stem/progenitor cells, meniscus regeneration remains a great challenge in clinic. In this study, we found decellularized meniscal extracellular matrix (MECM) preserved native meniscal collagen and glycosaminoglycans which could be a good endogenous regeneration guider for stem cells. Moreover, MECM significantly promoted meniscal fibrochondrocytes viability and proliferation, increased the expression of type II collagen and proteoglycans in vitro. Meanwhile, we designed 3D-printed polycaprolactone (PCL) scaffolds which mimic the circumferential and radial collagen orientation in native meniscus. Taken these two advantages together, a micro-structure and micro-environment dually biomimetic cell-free scaffold was manipulated. This cell-free PCL-MECM scaffold displayed superior biocompatibility and yielded favorable biomechanical capacities closely to native meniscus. Strikingly, neo-menisci were regenerated within PCL-MECM scaffolds which were transplanted into knee joints underwent medial meniscectomy in rabbits and sheep models. Histological staining confirmed neo-menisci showed meniscus-like heterogeneous staining. Mankin scores showed PCL-MECM scaffold could protect articular cartilage well, and knee X-ray examination revealed same results. Knee magnetic resonance imaging (MRI) scanning also showed some neo-menisci in PCL-MECM scaffold group. In conclusion, PCL-MECM scaffold appears to optimize meniscus regeneration. This could represent a promising approach worthy of further investigation in preclinical applications.

A virus-induced gene silencing (VIGS) system was established to induce endogenous target gene silencing by post-transcriptional gene silencing (PTGS), which is a powerful tool for gene function analysis in plants. Compared with stable transgenic plant via Agrobacterium-mediated gene transformation, phenotypes after gene knockdown can be obtained rapidly, effectively, and high-throughput through VIGS system. This approach has been successfully applied to explore unknown gene functions involved in plant growth and development, physiological metabolism, and biotic and abiotic stresses in various plants. In this system, GhCLA1 was used as a general control, however, silencing of this gene leads to leaf albino, wilting, and plant death ultimately. As such, it cannot indicate the efficiency of target gene silencing throughout the whole plant growth period. To address this question, in this study, we developed a novel marker gene, Gossypium PIGMENT GLAND FORMATION GENE (GoPGF), as the control to trace the efficiency of gene silencing in the infected tissues. GoPGF has been proved a key gene in gland forming. Suppression of GoPGF does not affect the normal growth and development of cotton. The number of gland altered related to the expression level of GoPGF gene. So it is a good marker that be used to trace the whole growth stages of plant. Moreover, we further developed a method of friction inoculation to enhance and extend the efficiency of VIGS, which facilitates the analysis of gene function in both the vegetative stage and reproductive stage. This improved VIGS technology will be a powerful tool for the rapid functional identification of unknown genes in genomes.

Summary: Bone cancer pain is a common symptom in cancer patients with bone metastases and its underlying mechanisms remain unknown. Here, we report that Runx1 directly upregulates the transcriptional activity of P2X3 receptor (P2X3R) gene promoter in PC12 cells. Knocking down Runx1 in dorsal root ganglion (DRG) neurons suppresses the functional upregulation of P2X3R, attenuates neuronal hyperexcitability and pain hypersensitivity in tumor-bearing rats, whereas overexpressing Runx1 promotes P2X3R gene transcription in DRG neurons, induces neuronal hyperexcitability and pain hypersensitivity in naïve rats. Activation of GDNF-GFRα1-Ret-ERK signaling is required for Runx1-mediated P2X3R gene transcription in DRG neurons, and contributes to neuronal hyperexcitability and pain hypersensitivity in tumor-bearing rats. These findings indicate that the Runx1-mediated P2X3R gene transcription resulted from activation of GDNF-GFRα1-Ret-ERK signaling contributes to the sensitization of DRG neurons and pathogenesis of bone cancer pain. Our findings identify a potentially targetable mechanism that may cause bone metastasis-associated pain in cancer patients.

Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of lung malignant tumor. Conventional chemotherapy has a suboptimal effectiveness. PSC has the characteristics of rapid disease progression and poor prognosis. We herein report a 56-year-old male patient with substantial smoking history was pathologically diagnosed as PSC, cT4N0M0 IIIA stage. Peripheral blood NGS showed TP53 mutation. The patient had poor tolerance to the first-line chemotherapy regimen “albumin paclitaxel + cisplatin,” but the severe anemia was significantly improved after 5 days of anti-angiogenic therapy with Anlotinib. At this time, the patient received anti-PD-1 immunotherapy with Tislelizumab. Half a month later, degree III liver injury occurred repeatedly. After excluding drug-induced liver injury, we found that HCV-RNA 3.10 × 105 IU/ml and suspended all anti-tumor therapy. After the start of anti-HCV treatment with Epclusa, the treatment of Tislelizumab combined with Anlotinib was restarted, and there was no liver injury after that. The patient received monthly maintenance therapy with Tislelizumab combined with Anlotinib to the present. The pulmonary lesions continued to decrease, and only one lung cavity is left. The patient has achieved clinical complete remission (CCR) with PSF over 20 months. Our findings suggest that Tislelizumab combined with Anlotinib may be a preferred strategy in PSC complicating TP53 mutation. Core tip: Immune-check point inhibitors (ICIs) have been reported for the treatment of PSC in a small number of case reports and retrospective analysis, but there are few reports of ICIs combined with anti-angiogenic drugs. This patient was diagnosed as locally advanced PSC complicated with TP53 mutation and hepatitis C. After 14 cycles of Tislelizumab combined with Anlotinib treatment (during the course of treatment, several courses were not treated on time for economic reasons, rather than adverse reactions), the patient has achieved CCR. III degree liver injury occurred during the treatment, and the liver function returned to normal range after anti-hepatitis C treatment, which did not affect the continued treatment of this regimen.

PurposeWe designed a J-shaped external fixator (J-EF) to provide a minimally invasive, one-step surgical method for olecranon fractures. The aim of this study is to retrospectively review the method and the outcomes in 14 patients treated with J-EF fixation.MethodsBiomechanical comparative study was performed to test the tensile properties of the J-EF using a universal testing machine. Between January 2002 and December 2005, 14 patients (age range: 25–67 years) with Mayo type II olecranon fractures were treated using the external fixation technique. Follow-up was done by standard measures (radiography, range of motion, and complications monitoring) and patient-reported outcomes (Mayo Elbow Performance Score [MEPS] and Disabilities of the Arm, Shoulder, and Hand [DASH] scores) 6 months after surgery. Eight of the patients were reviewed 15 years after the surgery.ResultsResults from biomechanical studies indicate the non-inferiority of J-EF to tension-band wiring (TBW) in tensile properties. At the time of release, the mean elbow flexion arc was 132.5° and the mean forearm rotation arc was 173.6°. The mean DASH score was 14.1 points, and the mean MEPS was 93.9 points. Operative time and intraoperative blood loss were decreased by 41.3% and 64.6%, respectively, in J-EF patients than those in a comparable group treated by TBW. All eight patients are still alive after the surgery and maintaining the original outcome.ConclusionsExternal fixation using the J-EF could be considered as an alternative treatment for Mayo type II olecranon fractures as it appears to be a reliable, minimally invasive, and time-saving.Level of EvidenceTherapeutic Level IV.

Aflatoxin B1 (AFB1), a typical fungal toxin found in feed, is highly carcinogenic. Oxidative stress is one of the main ways it exerts its toxicity; therefore, finding a suitable antioxidant is the key to reducing its toxicity. Astaxanthin (AST) is a carotenoid with strong antioxidant properties. The aim of the present research was to determine whether AST eases the AFB1-induced impairment in IPEC-J2 cells, and its specific mechanism of action. AFB1 and AST were applied to IPEC-J2 cells in different concentrations for 24 h. The AST (80 µM) significantly prevented the reduction in the IPEC-J2 cell viability that was induced by AFB1 (10 μM). The results showed that treatment with AST attenuated the AFB1-induced ROS, and cytochrome C, the Bax/Bcl2 ratio, Caspase-9, and Caspase-3, which were all activated by AFB1, were among the pro-apoptotic proteins which were diminished by AST. AST activates the Nrf2 signaling pathway and ameliorates antioxidant ability. This was further evidenced by the expression of the HO-1, NQO1, SOD2, and HSP70 genes were all upregulated. Taken together, the findings show that the impairment of oxidative stress and apoptosis, caused by the AFB1 in the IPEC-J2 cells, can be attenuated by AST triggering the Nrf2 signaling pathway.

Hepatic inflammation contributes to the development of nonalcoholic steatohepatitis (NASH). Here, the authors show that a transfer of ex vivo generated CD4 derived double negative T cells can prevent the development and progression of NASH by suppression of inflammatory Th17 cells and M1 macrophages in mouse models.

Theoretical researchers of manager psychology have excellent potential to extend its research framework to more enterprise application areas, such as innovation, performance, and safety in production. Research in these areas has also been increasing in the past 10 years. Psychological capital is composed of four aspects: self-efficacy, hope, optimism, and tenacity. It plays an essential role in stimulating organizational growth and improving organizational performance. In safety management work, managers, as the core members of the organization, have a relationship between their psychological capital and employees’ safety performance. Nevertheless, the closeness of the relationship between psychological capital and employee safety performance has not been fully demonstrated by academic circles. Based on positive psychology theory, this paper conducts a questionnaire survey of 157 managers and 314 employees related to safety work in manufacturing enterprises. From the new perspective of organizational emotional capability, this paper investigates the complex and extensive social-psychological role in organizations and combs, analyzes, and integrates relevant psychological research to construct the influence mechanism of managers’ psychological capital and employee safety performance. Finally, the three important issues found based on data analysis were: (1) Managers’ psychological capital has a significant positive impact both on employee safety performance and organizational emotional capability; (2) Organizational emotional capability has a significant positive impact on employee safety performance; (3) organizational emotional capability plays a partial mediating role in the relationship between managers’ psychological capital and employee safety performance.

Abstract Background This study aimed to investigate the regulation of CpG oligodeoxynucleotides (ODNs) on proliferation and osteogenic differentiation of MC3T3 cells. Methods The laser co-focusing and flow cytometry assay were employed to detect cell uptake of CpG ODN 2006. Twelve ODNs were sythesized, and their effects on proliferation and differentiation were detected by MTT and alkaline phosphatase (ALP) activity assay. Flow cytometry assay was used to examine the regulation of CpG ODN on cell cycle. Quantitative real-time PCR (qRT-PCR) and western blot were used to evaluate the regulation of CpG ODN on mRNA and protein expression of osteogenic differentiation genes. Results The phosphorothioate CpG ODN 2006 could efficiently enter the MC3T3 cells in 1 h and locate in the cytoplasm. The MTT assay demonstrated CpG ODNs could promote MC3T3 cell proliferation and differentiation in the early stage, and gradually attenuated along with the increase of treating time, except for BW001 and FC001. qRT-PCR assay demonstrated that all the 12 CpG ODNs could promote the relative expression level of osteogenic differentiated genes, SP7 and OCN. In addition, western blot analysis suggested the CpG ODNs of BW001 and FC001 could increase the protein expression of P27Kip1 and Runx2 and decrease the protein expression of cyclin D1. Conclusion The selected CpGODNs may be a potential gene therapy for bone regeneration of periodontitis.