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Abstract Cognitive decline is a critical hallmark of brain aging. Although aging is a natural process, there is significant heterogeneity in cognition levels among individuals; however, the underlying mechanisms remain uncertain. In our study, we classified aged male Sprague‒Dawley rats into aged cognition-unimpaired (AU) group and aged cognition-impaired (AI) group by using an attentional set-shifting task. The transcriptome sequencing results of medial prefrontal cortex (mPFC) demonstrated significant differences in microglial activation and inflammatory response pathways between the two groups. Specifically, compared to AU rats, AI rats exhibited a greater presence of CD86-positive microglia and major histocompatibility complex class II (MHC-II)-positive microglia, along with elevated inflammatory molecules, in mPFC. Conversely, AI rats exhibited a reduction in the percentage of microglia expressing CD200R and the anti-inflammatory molecules Arg-1 and TGF-β. Additionally, peripheral blood analysis of AI rats demonstrated elevated levels of Th17 and Th1 cells, along with proinflammatory molecules; however, decreased levels of Treg cells, along with anti-inflammatory molecules, were observed in AI rats. Our research suggested that peripheral Th17/Treg cells and central microglial activation were associated with cognitive heterogeneity in aged rats. These findings may provide a new target for healthy aging.

Abstract Background Carbon monoxide (CO), hypothetically linked to prebiotic biosynthesis and possibly the origin of the life, emerges as a substantive growth substrate for numerous microorganisms. In anoxic environments, the coupling of CO oxidation with hydrogen (H2) production is an essential source of electrons, which can subsequently be utilized by hydrogenotrophic bacteria (e.g., organohalide-respring bacteria). While Dehalococcoides strains assume pivotal roles in the natural turnover of halogenated organics and the bioremediation of chlorinated ethenes, relying on external H2 as their electron donor and acetate as their carbon source, the synergistic dynamics within the anaerobic microbiome have received comparatively less scrutiny. This study delves into the intriguing prospect of CO serving as both the exclusive carbon source and electron donor, thereby supporting the reductive dechlorination of trichloroethene (TCE). Results The metabolic pathway involved anaerobic CO oxidation, specifically the Wood-Ljungdahl pathway, which produced H2 and acetate as primary metabolic products. In an intricate microbial interplay, these H2 and acetate were subsequently utilized by Dehalococcoides, facilitating the dechlorination of TCE. Notably, Acetobacterium emerged as one of the pivotal collaborators for Dehalococcoides, furnishing not only a crucial carbon source essential for its growth and proliferation but also providing a defense against CO inhibition. Conclusions This research expands our understanding of CO’s versatility as a microbial energy and carbon source and unveils the intricate syntrophic dynamics underlying reductive dechlorination. Graphical Abstract Video Abstract

Introduction: Cervical spine disease is a leading cause of pain and disability. Degenerative conditions of the spine can result in neurologic compression of the cervical spinal cord or nerve roots and may be surgically treated with an anterior cervical discectomy and fusion (ACDF) in up to 137,000 people per year in the United States. A common sequelae of ACDF is reduced cervical range of motion (CROM) with patient-based complaints of stiffness and neck pain. Currently, tools for assessment of CROM are manual, subjective, and only intermittently utilized during doctor or physical therapy visits. We propose a skin-mountable acousto-mechanic sensor (ADvanced Acousto-Mechanic sensor; ADAM) as a tool for continuous neck motion monitoring in postoperative ACDF patients. We have developed and validated a machine learning neck motion classification algorithm to differentiate between eight neck motions (right/left rotation, right/left lateral bending, flexion, extension, retraction, protraction) in healthy normal subjects and patients. Methods: Sensor data from 12 healthy normal subjects and 5 patients were used to develop and validate a Convolutional Neural Network (CNN). Results: An average algorithm accuracy of 80.0 ± 3.8% was obtained for healthy normal subjects (94% for right rotation, 98% for left rotation, 65% for right lateral bending, 87% for left lateral bending, 89% for flexion, 77% for extension, 50% for retraction, 84% for protraction). An average accuracy of 67.5 ± 5.8% was obtained for patients. Discussion: ADAM, with our algorithm, may serve as a rehabilitation tool for neck motion monitoring in postoperative ACDF patients. Sensor-captured vital signs and other events (extubation, vocalization, physical therapy, walking) are potential metrics to be incorporated into our algorithm to offer more holistic monitoring of patients after cervical spine surgery.

Abstract There have been over 769 million cases of COVID-19, and up to 50% of infected individuals are asymptomatic. The purpose of this study aimed to assess the use of a clinical-grade physiological wearable monitoring system, ANNE One, to develop an artificial intelligence algorithm for (1) cough detection and (2) early detection of COVID-19, through the retrospective analysis of prospectively collected physiological data from longitudinal wear of ANNE sensors in a multicenter single arm study of subjects at high risk for COVID-19 due to occupational or home exposures. The study employed a two-fold approach: cough detection algorithm development and COVID-19 detection algorithm development. For cough detection, healthy individuals wore an ANNE One chest sensor during scripted activity. The final performance of the algorithm achieved an F-1 score of 83.3% in twenty-seven healthy subjects during biomarker validation. In the COVID-19 detection algorithm, individuals at high-risk for developing COVID-19 because of recent exposures received ANNE One sensors and completed daily symptom surveys. An algorithm analyzing vital parameters (heart rate, respiratory rate, cough count, etc.) for early COVID-19 detection was developed. The COVID-19 detection algorithm exhibited a sensitivity of 0.47 and specificity of 0.72 for detecting COVID-19 in 325 individuals with recent exposures. Participants demonstrated high adherence (≥ 4 days of wear per week). ANNE One shows promise for detection of COVID-19. Inclusion of respiratory biomarkers (e.g., cough count) enhanced the algorithm's predictive ability. These findings highlight the potential value of wearable devices in early disease detection and monitoring.

Background: Hepatocellular carcinoma (HCC) is a fatal primary malignancy characterized by high invasion and migration. We aimed to explore the underlying metastasis-related mechanism supporting the development of HCC. Methods: The dataset of single cell RNA-seq (GSE149614) were collected for cell clustering by using the Seurat R package, the FindAllMarkers function was used to find the highly expression and defined the cell cluster. The WebGestaltR package was used for the GO and KEGG function analysis of shared genes, the Gene Set Enrichment Analysis (GSVA) was performed by clusterProfiler R package, the hTFtarget database was used to identify the crucial transcription factors (TFs), the Genomics of Drug Sensitivity in Cancer (GDSC) database was used for the drug sensitivity analysis. Finally, the overexpression and trans-well assay was used for gene function analysis. Results: We obtained 9 cell clusters from the scRNA-seq data, including the nature killer (NK)/T cells, Myeloid cells, Hepatocytes, Epithelial cells, Endothelial cells, Plasma B cells, Smooth muscle cells, B cells, Liver bud hepatic cells. Further cell ecological analysis indicated that the Hepatocytes and Endothelial cell cluster were closely related to the cancer metastasis. Subsequently, the NDUFA4L2-Hepatocyte, GTSE1-Hepatocyte, ENTPD1-Endothelial and NDUFA4L2-Endothelial were defined as metastasis-supporting cell clusters, in which the NDUFA4L2-Hepatocyte cells was closely related to angiogenesis, while the NDUFA4L2-Endothelial was related with the inflammatory response and complement response. The overexpression and trans-well assay displayed that NDUFA4L2 exhibited clearly metastasis-promoting role in HCC progression. Conclusion: We identified and defined 4 metastasis-supporting cell clusters by using the single cell technology, the specify shared gene was observed and played crucial role in promoting cancer progression, our findings were expected to provide new insight in control cancer metastasis.

Silver nanoparticles (AgNPs) have wide clinical applications because of their excellent antibacterial properties; however, they can cause liver inflammation in animals. Macrophages are among the main cells mediating inflammation and are also responsible for the phagocytosis of nanomaterials. The NLRP3 inflammasome is a major mechanism of inflammation, and its activation both induces cytokine release and triggers inflammatory cell death (i.e., pyroptosis). In previous studies, we demonstrated that mitophagy activation plays a protective role against AgNP-induced hepatotoxicity. However, the exact molecular mechanisms underlying these processes are not fully understood. In this study, we demonstrate that AgNP exposure induces NLRP3 inflammasome activation, mitochondrial damage and pyroptosis in vivo and in vitro. NLRP3 silencing or inhibiting mitochondrial reactive oxygen species (ROS) overproduction reduces PINK1-Parkin-mediated mitophagy. Meanwhile, the inhibition of mitophagy ROS production, mitochondrial, NLRP3-mediated inflammation, and pyroptosis in RAW264.7 cells were more pronounced than in the control group. These results suggest that PINK1-Parkin-mediated mitophagy plays a protective role by reducing AgNP-induced mitochondrial ROS and subsequent NLRP3 inflammasome activation.

Abstract Background The FLT3/ITD mutation exists in many acute myeloid leukemia (AML) patients and is related to the poor prognosis of patients. In this study, we attempted to evaluate the antitumor activity of simvastatin, a member of the statin class of drugs, in vitro and in vivo models of FLT3/ITD AML and to identify the potential mechanisms. Methods Cell Counting Kit-8 (CCK-8) and Annexin V/propidium iodide (PI) staining kits were used to detect cell viability and apoptosis, respectively. Subsequently, Western blot and rescue experiment were applied to explore the potential molecular mechanism. In vivo anti-leukemia activity of simvastatin was evaluated in xenograft mouse models. Results In vitro experiments revealed that simvastatin inhibited AML progression in a dose- and time-dependent manner, while in vivo experiments showed that simvastatin significantly reduced tumor burden in FLT3/ITD xenograft mouse models. After simvastatin treatment of FLT3/ITD AML cells, intracellular Rap1 was downregulated and the phosphorylation levels of its downstream targets MEK, ERK and p38 were significantly inhibited. The rescue experiment showed that mevalonate, an intermediate product of the metabolic pathway of mevalonate, and its downstream geranylgeranyl pyrophosphate (GGPP) played a key role in this process. Finally, we demonstrate that simvastatin can induce apoptosis of primary AML cells, while having no effect on peripheral blood mononuclear cells from normal donors. Conclusions Simvastatin can selectively and effectively eradicate FLT3/ITD AML cells in vitro and in vivo, and its mechanism may be related to the disruption of the HMG-CoA reductase pathway and the downregulation of the MEK/ERK and p38-MAPK signaling pathways.

In order to evaluate the influence of the assimilation of different observational data such as conventional ground observations, radiosonde and radar radial wind on the meso-scale model of heavy rain forecast in Sichuan Province, a heavy rainstorm process in Sichuan from 14 to 18 June, 2020 is used as an example. Using Weather Research And Forecasting (WRF) model and Grid Point Statistical Interpolation (GSI) assimilation system, we assimilated the conventional and radar data respectively and simultaneously, and compared the results of three assimilation experiments qualitatively and quantitatively. The results show that the WRF model combined with the GSI assimilation system can simulate the rainstorm well. For the 21-h cumulative precipitation forecast, assimilating conventional observation data can better improve the trend of rain belt and the fall area of the rainstorm. The assimilated radar data showed better performance in precipitation intensity, rainstorm range and the light to moderate rain forecast, The average ETS score of the light to moderate rain was increased by 0.05. Assimilation of both the conventional observation and radar data improved ETS, POD, FAR and BIAS scores for heavy rain. For the12-h cumulative precipitation forecast, the simulation performance of the precipitation trend is the best with the assimilation of radar data, and the experiment involving the assimilation of radar data has better improvement on the precipitation area. For the 3-h cumulative precipitation forecast, the assimilation experiment improved the precipitation evolution, and the assimilation of radar data showed the best performance. The simulation of precipitation at night was generally better than that in the daytime, and the improvement period of assimilation experiment was mainly concentrated in the nighttime, and the assimilation of conventional observation data showed significant performance improvement. Based on the scores of 21-h, 12-h and 3-h cumulative precipitation forecast, the precipitation forecast effect of assimilating multiple data is not absolutely better than those of assimilating only one data, but the assimilation of multiple data can achieve better scores than those of assimilating only one data.

ABSTRACTBackground Acute myeloid leukemia (AML) is a malignant blood cancer with a poor prognosis and complex pathogenesis. Recently, the critical role of circular RNAs (circRNAs) has been demonstrated in the malignant progression of AML. This study aimed to investigate the functional role and underlying mechanism of circ_0001602 in AML development.Methods Quantitative real-time polymerase chain reaction (qRT-PCR) assay was conducted for detecting the expression of circ_0001602, CCND3, microRNA-192-5p (miR-192-5p), and Zinc Finger and BTB Domain-Containing Protein 20 (ZBTB20) mRNA. RNase R assay and Actinomycin D assay were implemented to determine the characteristics of circ_0001602. Cell counting Kit-8 (CCK-8) assay was performed to evaluate cell proliferation. Flow cytometry was employed for assessing cell cycle distribution and apoptosis. Dual-luciferase reporter assay and RIP assay were utilized for confirming the interactions between miR-192-5p and circ_0001602 or ZBTB20.Results Circ_0001602 and ZBTB20 were upregulated and miR-192-5p level was reduced in AML tissues and cells. Depletion of circ_0001602 repressed cell proliferation and induced cell cycle arrest and apoptosis in AML cells. Functionally, circ_0001602 was identified to be the sponge of miR-192-5p, and miR-192-5p silence restored the suppressive effects of circ_0001602 knockdown on AML cell progression. Furthermore, ZBTB20 was a target of miR-192-5p, and ZBTB20 overexpression neutralized the miR-192-5p-mediated inhibiting actions on the malignant phenotypes of AML cells. Besides, circ_0001602 could sponge miR-192-5p to positively regulate ZBTB20 expression.Conclusion Circ_0001602 contributed to AML cell development at least partially through modulating the miR-192-5p/ZBTB20 axis, which provided new insights for AML treatment.

Abstract Objectives Treatments for advanced small‐cell lung cancer (SCLC) patients who are resistant to first‐line chemotherapy are limited. Given that antiangiogenic agents and immune‐checkpoint inhibitors (ICIs) can confer synergistic therapeutic benefits, combination therapy should be considered. We explored the efficacy and safety of combination therapy with anlotinib and programmed cell death protein 1 (PD‐1)/programmed cell death‐ligand 1 (PD‐L1) inhibitors as second‐line and subsequent therapy for advanced SCLC. Materials and Methods We reviewed advanced SCLC patients at Shanghai Chest Hospital who had received anlotinib in combination with ICIs from November 2016 to November 2020 as second‐ and subsequent‐line treatment. Patients with advanced SCLC who had received paclitaxel monotherapy as second‐line treatment were included as the control group. Results A total of 141 patients were included in the final analysis (40 in the combination therapy group and 101 in the paclitaxel monotherapy group). The median progression‐free survival (PFS) times for the combination therapy and paclitaxel monotherapy groups were 3.40 and 2.83 months (p = 0.022), respectively, while the median overall survival (OS) times for the combination therapy and paclitaxel monotherapy groups were 8.20 and 5.87 months (p = 0.048), respectively. Hypertension and hepatic dysfunction were the most pronounced adverse events of combination therapy and two patients changed regimens due to severe fatigue and anorexia. Conclusion The combination of anlotinib and PD‐1/PD‐L1 blockade has promising efficacy and safety as a second‐line or subsequent therapy for SCLC.

We synthesized a series of Ru-Ti-Ni/CNT electrodes to degrade levofloxacin in wastewater. The unique structure of Ni single-atom-kernelled Ru nanoparticles regulates the reaction process, producing a notable synergistic effect. The reaction kinetics constant of Ru-Ti-Ni/CNT with a Ru: Ti ratio of 10:0 outperforms Ni/CNT by 3.7 times and CNT alone by 16.4 times. Comprehensive characterizations revealed its morphology and structure nature. Ru nanoparticles can shield Ni, while Ni single-atom facilitates electron transfer in Ru nanoparticles, generating abundant reactive oxygen radicals (ROS) that degrade pollutants.

As chloride (Cl−) is a commonly found anion in natural water, it has a significant impact on electrocatalytic oxidation processes; yet, the mechanism of radical transformation on different types of anodes remains unexplored. Therefore, this study aims to investigate the influence of chlorine-containing environments on the electrocatalytic degradation performance of levofloxacin using BDD, Ti4O7, and Ru-Ti electrodes. The comparative analysis of the electrode performance demonstrated that the presence of Cl− improved the removal and mineralization efficiency of levofloxacin on all the electrodes. The enhancement was the most pronounced on the Ti4O7 electrode and the least significant on the Ru-Ti electrode. The evaluation experiments and EPR characterization revealed that the increased generation of hydroxyl radicals and active chlorine played a major role in the degradation process, particularly on the Ti4O7 anode. The electrochemical performance tests indicated that the concentration of Cl− affected the oxygen evolution potentials of the electrode and consequently influenced the formation of hydroxyl radicals. This study elucidates the mechanism of Cl− participation in the electrocatalytic degradation of chlorine-containing organic wastewater. Therefore, the highly chlorine-resistant electrocatalytic anode materials hold great potential for the promotion of the practical application of the electrocatalytic treatment of antibiotic wastewater.

Background and objectiveCOVID-19 has imposed burdens on public health systems globally. Owing to the urgency of vaccination, this study aimed at comparing the differences in preference and willingness to pay of COVID-19 vaccine among Chinese and American middle-aged and elderly adults.MethodsA cross-sectional survey containing demographic questions, rating their acceptance of COVID-19 vaccination with and without recommendations from friends, family members or employers (the social cues referred to in our study), and a discrete choice experiment understanding COVID-19 vaccine preference and willingness to pay was conducted to collect data. Propensity score matching was utilized to adjust confounding factors of baseline characteristics and the relative importance of respondents' preference for each attribute and its level was estimated using a conditional logit model. Then, willingness to pay was calculated.ResultsIn total, 3,494 (2,311 and 1,183 from China and the United States, respectively) completed the questionnaire, among which 3,444 questionnaires were effective. After propensity score matching, 1,604 respondents with 802 from the US and 802 from China were included. Under the influence of the social cues, Chinese respondents' vaccine acceptance decreased from 71.70 to 70.70%, while American respondents' vaccine acceptance increased from 74.69 to 75.81%. The discrete choice experiment showed that American respondents regarded the efficacy of COVID-19 vaccine as the most important attribute, whereas Chinese respondents attached the highest importance to the cost of vaccination. But overall, the COVID-19 vaccine with the higher efficacy, the milder adverse effect, the lower cost, and the longer duration will promote the preference of the public in both countries. Additionally, the public were willing to spend the most money for a reduction in COVID-19 vaccine adverse effect from moderate to very mild (37.476USD for the United States, 140.503USD for China), followed by paying for the 1% improvement in its efficacy and paying for the one-month extension of its duration.ConclusionGiven the impact of social cues on vaccine acceptance, Chinese government should promote reasonable vaccine-related information to improve national vaccination acceptance. Meanwhile, considering the influence of COVID-19 attributes on public preference and willingness to pay, regulating the vaccine pricing, improving the efficacy of the vaccine, reducing its adverse effect, and prolonging the duration of the vaccine works will contribute to vaccine uptake.

BackgroundThe obesity rate in the Chinese population is increasing and there is a lack of short and reliable scales for measuring obesity-related eating behavior in China. The EBS-SF (Sakata Eating Behavior Scale short form) has only 7 entries and has shown good reliability in studies such as those in Japan.ObjectiveTo translate the EBS-SF into Chinese, check its reliability, validity and explore the related factors.MethodThe EBS-SF was translated into Chinese. 3,440 residents were investigated and 34 respondents were retested. Item analysis and reliability and validity tests were carried out. Personality characteristics, family health status and depression were investigated using the BFI-10, FHS-SF and PHQ-9 to investigate the factors associated with EBS-SF. The t-test, ANOVA and Pearson correlation was used to explore the related factors of its scores.ResultAmong 3,440 residents, 1,748 (50.81%) were male and 1,692 (49.19%) were female; 1,373 (39.91%) were aged 36–50 years. All 7 items were qualified in the item analysis. As for reliability, the Cronbach's α was 0.870, the split-half reliability was 0.830, the test-retest correlation coefficient was 0.868. As for the structural validity, the standardized factor loadings were above 0.50, χ2 / df = 2.081,GFI = 0.999; NFI = 0.999; RFI = 0.996; RMSEA = 0.018, all qualified. The characteristics, personality, family health and depression were correlated with the score of the Chinese version of EBS short form.ConclusionThe structural validity and reliability of the Chinese version of the EBS-SF are good and it can be used as a measurement tool to evaluate the eating behavior of Chinese. The scores of the EBS-SF may be related to the sociological characteristics, personality, family health, and depression status.

Background: Over-the-counter (OTC) drugs facilitates residents self-medication. However, inappropriate self-medications have become a serious problem in China and even all over the world.Objectives: To make an investigation on the current status of Chinese residents’ self-medication behaviors and important considerations, and to explore the factors related to the considerations of drug efficacy and safety.Design: A quantitative, cross-sectional study.Methods: Multi-stage sampling was used to conduct a cross-sectional investigation in China 22 provinces, 5 autonomous regions and 4 municipalities directly under the Central Government. State that an interviewer-administrated questionnaire, was used for data collection. The questionnaire that was used in the investigation included demographic sociological characteristics, health literacy scale-short form (HLS-SF), the 10-item Big Five Inventory (BFI-10), the EuroQol-5D visual analogue scale (EQ-5D VAS), self-medication status and important considerations when self-medicating. Descriptive statistics were performed, and the Chi-square test was used for univariate analysis. Log-binomial regression was used for multivariate analysis on whether residents regard drug efficacy or safety as an important consideration.Results: 9256 respondents were included in the data analysis. The self-medication rate of Chinese adults was as high as 99.1%. Paracetamol and other analgesics were the most common types of OTC medication that respondents purchased, followed by vitamins/minerals. Medical staff recommendations, drug safety and efficacy were the top three important considerations. The residents in the east, central and western regions who consider safety is 63.5%, 61.5%, and 66.8% respectively. The proportion of curative effect was 60.2%, 55.7%, and 61.4% respectively. Log-binomial regression showed that western respondents, retired people, those who mainly used ways including basic medical insurance for employees, commercial medical insurance, free medical treatment to cover their medical cost, respondents with high neuroticism, high health literacy were more likely to consider drug safety as an important factor (p < 0.05). Eastern respondents, employed, main way of medical expenses borne was Out-of-pocket Payment, those with chronic disease were more likely to consider drug efficacy as an important factor (p < 0.05). Female, respondents with high levels of agreeableness, conscientiousness, openness, and self-rated health status were more likely to regard both drug safety and efficacy as important considerations (p < 0.05).Conclusion: Self-medication is practiced by most Chinese adults. Whether Chinese adults take drug efficacy or safety as an important consideration is related to their demographic and sociological characteristics, Big Five personality characteristics, health literacy and self-assessed health status. There is a need to strengthen the management of OTC drugs and public education about self-medication.

BackgroundPrevious studies have emphasized the media as an essential channel for understanding information about depression. However, they have not divided groups according to the degree of media use to study their differences in depression. Therefore, this study aims to explore the influence of media use on depression and the influencing factors of depression in people with different media use degrees.MethodsBased on seven items related to media use, a total of 11, 031 respondents were categorized by the frequency of media use using latent profile analysis (LPA). Secondly, multiple linear regression analyzes were conducted to analyze the effects of depression in people with different degrees of media use. Finally, factors influencing depression among people with different degrees of media use were explored separately.ResultsAll respondents were classified into three groups: media use low-frequency (9.7%), media use general (67.1%), and media use high-frequency (23.2%). Compared with media use general group, media use low-frequency (β = 0.019, p = 0.044) and media use high-frequency (β = 0.238, p

ObjectiveTo investigate the status of Chinese residents' self-medication behavior and the important factors to consider when purchasing OTC drugs, and to explore the related factors of the possibility that Chinese residents take medical staff's suggestions as important factors to consider when purchasing OTC drugs.Study designA cross-sectional survey.MethodsA questionnaire was developed for exploring the sociodemographic characteristics of the respondents, their self-medication status, and important considerations. The questionnaire includes several scales including Health Literacy Scale-Short Form (HLS-SF), EQ-5D Visual Analog Scale (EQ-5D-VAS), Big Five Inventary-10 Items (BFI-10), and New General Self Efficacy Scale (NGSES). After carrying out a multi-stage sampling method, the questionnaire was conducted nationwide from July 10 to September 15, 2021. Next, descriptive statistics were conducted to analyze the general features. Logistic regression was then used to analyze the related factors of the possibility that the respondents took the suggestions of medical staff as an important consideration when purchasing OTC drugs.ResultsNine thousand two hundred fifty-six qualified questionnaires were received. 99.06% of Chinese adults had self-medication behaviors. The types of OTC drugs purchased most by the respondents were NSAIDs (5,421/9,256 people, 58.57%) and vitamins/minerals (4,851/9,256 people, 52.41%). 86.2% of the respondents took the suggestions of medical staff as an important consideration when purchasing OTC drugs. The results of multi-factor logistic regression showed that women, those living in the central and western regions of China, those suffering from chronic diseases, those with high agreeableness, high conscientiousness, high neuroticism and openness, high health literacy, high EQ-5D-VAS, and those with high self-efficacy are more likely to take medical staff's suggestions as important factors to consider.ConclusionThe vast majority of Chinese adults have self-medication behavior. Important considerations when purchasing OTC drugs include medical staff's suggestions, drug safety and drug efficacy. Whether residents take the suggestions of medical staff as an important consideration is related to their sociological characteristics, agreeableness, conscientiousness, neuroticism, openness, health literacy, self-assessment health status, and self-efficacy. When purchasing and using OTC drugs, residents should carefully listen to the suggestions from medical staff. They should also carefully consider their own conditions before buying OTC drugs.

Selenium-containing polysaccharide from Spirulina platensis (Se-SPP) has been demonstrated to help in inhibiting cadmium-induced injury in mice, but the underlying mechanism has not been determined. This study aimed to investigate the beneficial effects of Se-SPP on alleviating Cd-induced toxicity in mice by targeting liver inflammatory and gut microbiota. Se-SPP supplementation for 28 days in Cd-induced toxic mice significantly mitigated liver pathological damage and inflammation, which was correlated to the upregulation of antioxidant enzyme activity. Furthermore, Se-SPP effectively restored Cd-induced disruption of the intestinal barrier compared to model group, as indicated by the depletion of Muribaculaceae and the enrichment of Ruminococcaceae. Spearman's correlation analysis revealed that the Se-SPP-altered microbes were highly correlated with inflammation-related indexes in Cd-induced toxic mice. Noteworthily, the modulation of Se-SPP on the Ruminococcaceae population contributed to the improvement of Cd-induced inflammation-related diseases by downregulating the tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in the liver. These findings suggested that Se-SPP may act as prebiotics for ameliorating Cd-induced toxicity in mice by inhibiting liver inflammation mediated by gut microbiota, and target-specific microbiota of Cd-induced inflammation-related diseases deserve further attention.

Acoustic emission (AE) testing is a widely used nondestructive testing method for the early detection of failures in materials and structures. In this paper, an AE detection sensor combining optical fiber sensing with laser self-mixing interference (SMI) technology is proposed. A multi-coil optical fiber ring wound round a cylindrical acrylic skeleton was designed in order to sense the deformation caused by AE elastic waves, which was then demodulated using self-mixing interference technology. Finite element analyses were conducted in order to investigate the deformation of fiber under acoustic sources. AE signals induced via ball-dropping impact experiments were successfully detected by the proposed experimental system. The proposed SMI optical fiber AE sensing system has the advantages of being free from electromagnetic interference and having a simple structure, low implementation cost and high measurement resolution and sensitivity.

Molybdenum disulfide (MoS2) is a layered transition metal-sulfur compound semiconductor that shows promising prospects for applications in optoelectronics and integrated circuits because of its low preparation cost, good stability and excellent physicochemical, biological and mechanical properties. MoS2 with high quality, large size and outstanding performance can be prepared via chemical vapor deposition (CVD). However, its preparation process is complex, and the area of MoS2 obtained is difficult to control. Machine learning (ML), as a powerful tool, has been widely applied in materials science. Based on this, in this paper, a ML Gaussian regression model was constructed to explore the growth mechanism of MoS2 material prepared with the CVD method. The parameters of the regression model were evaluated by combining the four indicators of goodness of fit (r2), mean squared error (MSE), Pearson correlation coefficient (p) and p-value (p_val) of Pearson’s correlation coefficient. After comprehensive comparison, it was found that the performance of the model was optimal when the number of iterations was 15. Additionally, feature importance analysis was conducted on the growth parameters using the established model. The results showed that the carrier gas flow rate (Fr), molybdenum sulfur ratio (R) and reaction temperature (T) had a crucial impact on the CVD growth of MoS2 materials. The optimal model was used to predict the size of molybdenum disulfide synthesis under 185,900 experimental conditions in the simulation dataset so as to select the optimal range for the synthesis of large-size molybdenum disulfide. Furthermore, the model prediction results were verified through literature and experimental results. It was found that the relative error between the prediction results and the literature and experimental results was small. These findings provide an effective solution to the preparation of MoS2 materials with a reduction in the time and cost of trial and error.

Tight oil reservoirs are featured by tight formations, large oil area, locally enriched "sweet spots", complex oil-water distribution, and complicated reservoir conditions brought by later engineering transformation, which determines the development performance of single well. The distribution of recoverable reserves has great variability and uncertainty, so it is difficult to obtain a reasonable and definite understanding using conventional reserve evaluation methods. By introducing the evaluation methods of unconventional shale oil and gas reserves in North America, the developed wells were used to determine the reserves of single wells, and the probability distribution characteristics of reserves of developed wells were used to characterize the reserves of blocks or reservoirs. The Chang 8 (the eight member of Yanchang Formation) tight and ultra-low permeability reservoir in the Honghe oil field was studied. The initial production performance and production decline characteristics of a single well were tracked, and the correlations between recoverable reserves and geological characteristics, oil-bearing properties and initial production performance were analyzed to determine the key factors affecting the estimation of recoverable reserves. The P10/P90 values were used to judge the uncertainty of the estimates. The minimum sample size required for 90% confidence can be obtained when the value is 3-8; if the value is greater than 10, it indicates that the reservoir has the complexity of geological and engineering transformation and the difference of different blocks. The key influencing parameters and the probability distribution of recoverable reserves of single well were established by using the uncertainty method, and the rapid evaluation of recoverable reserves of a single well were realized.

Vaccine hesitancy is a considerable obstacle to achieving vaccine protection worldwide. There needs to be more evidence-based research for interventions for vaccine hesitancy. Existing effectiveness evaluations are limited to one particular hypothesis, and no studies have compared the effectiveness of different interventions. A megastudy takes a large-scale, multi-intervention, uniform participant and the same evaluation criteria approach to evaluate many interventions simultaneously and find the most effective ones. Therefore, megastudies can help us find the most effective interventions for vaccine hesitancy. Additionally, considering the complex causes of vaccine hesitancy, we design interventions that involve social factors in megastudies. Lastly, quality control and justice are critical issues for megastudies in the future.

The benefits of surgical resection for patients with stage N2 limited-disease small-cell lung cancer (LD-SCLC) remain controversial. This retrospective study analyzed the survival and recurrence patterns of the patients diagnosed with pathological N2 (p-N2) LD-SCLC after radical resection. A total of 171 p-N2 LD-SCLC patients who underwent radical pulmonary resection and systematic lymphadenectomies at Shanghai Chest Hospital from July 2005 to June 2015 were enrolled. The influence of the mediastinal lymph node status (single or multiple nodes, single- or multiple-station) on the survival and recurrence patterns was retrospectively analyzed. The main recurrence sites were outside the chest cavity (54.8%) and hematogenous metastasis (67.4%). The bone and liver as initial recurrence sites had a poor prognosis, with a median overall survival (OS) of 13.100 months and 11.900 months, respectively. The median disease-free survival (DFS) of patients diagnosed with single and multiple p-N2 after surgery were 19.233 and 9.367 months (P = 0.001), and the median OS were 43.033 and 17.100 months (P < 0.001), respectively. In conclusion, recurrence occurred in the form of hematogenous metastasis mostly in the extra-thoracic part. Interestingly, patients diagnosed with single p-N2 benefited from radical resection. Surgery may be a treatment option regardless of the T stage if N2 SCLC with a single metastatic lymph node can be identified preoperatively.

Camera traps are widely used in wildlife surveys and biodiversity monitoring. Depending on its triggering mechanism, a large number of images or videos are sometimes accumulated. Some literature has proposed the application of deep learning techniques to automatically identify wildlife in camera trap imagery, which can significantly reduce manual work and speed up analysis processes. However, there are few studies validating and comparing the applicability of different models for object detection in real field monitoring scenarios. In this study, we firstly constructed a wildlife image dataset of the Northeast Tiger and Leopard National Park (NTLNP dataset). Furthermore, we evaluated the recognition performance of three currently mainstream object detection architectures and compared the performance of training models on day and night data separately versus together. In this experiment, we selected YOLOv5 series models (anchor-based one-stage), Cascade R-CNN under feature extractor HRNet32 (anchor-based two-stage), and FCOS under feature extractors ResNet50 and ResNet101 (anchor-free one-stage). The experimental results showed that performance of the object detection models of the day-night joint training is satisfying. Specifically, the average result of our models was 0.98 mAP (mean average precision) in the animal image detection and 88% accuracy in the animal video classification. One-stage YOLOv5m achieved the best recognition accuracy. With the help of AI technology, ecologists can extract information from masses of imagery potentially quickly and efficiently, saving much time.

High-grade B-cell lymphoma with concurrent MYC and BCL2 rearrangements (HGBL-DHL) is a rare, aggressive mature B-cell malignancy with a high likelihood of treatment failure following front-line immunochemotherapies. Patients with HGBL-DHL who develop a relapsed or refractory disease have little effective therapeutic strategies and show very poor clinical outcomes, thus calling for development of novel therapies for this specific patient population. In this study, we investigated the preclinical anti-lymphoma efficacies and potential mechanism of action of a novel treatment approach, combining the BCL2 inhibitor venetoclax with CS2164, a new orally active multitarget inhibitor, in HGBL-DHL models. This combination therapy exhibited a robust synergistic cytotoxicity against HGBL-DHL cells, evidenced by cooperatively inducing loss of cell viability and promoting cell apoptosis. Moreover, coadministration of CS2164 and venetoclax resulted in significant superior suppression of HGBL-DHL cell growth and remarkably abrogated tumor burden in a HGBL-DHL-xenografted mouse model. The synergistic lethality of CS2164 and venetoclax in HGBL-DHL cells was associated with induction of DNA damage and impairment of DNA repair ability. Of importance, the combined treatment almost abolished the expression of both BCL2 and MYC, two hallmark proteins of HGBL-DHL, and substantially blunted the activity of PI3K/AKT/mTOR signaling cascade. In addition, MCL1 and BCL-XL, two well-characterized contributors for venetoclax resistance, were significantly lessened in the presence of CS2164 and venetoclax, thus leading to the accumulation of proapoptotic proteins BAX and PUMA and then initiating the intrinsic apoptosis pathway. Taken together, these findings suggest that the regimen of CS2164 and venetoclax is highly effective to eliminate HGBL-DHL cells in the preclinical setting, warranting further clinical investigations of this regimen for the treatment of unfavorable HGBL-DHL patients.

Therapeutic outcome for the treatment of glioma was often limited due to the two barriers involved: the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB). Therefore, the development of nanocarriers that possess both BBB and BBTB permeability and glioma-targeting ability is of great importance for the chemotherapy of glioma. New frontiers in nanomedicine are advancing the research of new biomaterials. Here we constructed a natural high-density lipoprotein particle (HDL)-based drug delivery system with the dual-modification of T7 and dA7R peptide ligand (T7/dA7R-HDL) to achieve the above goals. HDL, the smallest lipoprotein, plays a biological role and is highly suitable as a platform for delivering imaging and therapeutic agents. T7 is a seven-peptide ligand of transferrin receptors (TfR) capable of circumventing the BBB and then targeting glioma. dA7R is a d-peptide ligand of vascular endothelial growth factor receptor 2 (VEGFR 2) overexpressed on angiogenesis, presenting excellent glioma-homing property. 10-Hydroxycamptothecin (HCPT), a hydrophobic anti-cancer drug, was used as the model drug in this study. By combining the dual-targeting delivery effect, the dual-modified HDL displayed higher glioma localization than that of single ligand-modified HDL or free HCPT. After loading with HCPT, T7/dA7R-HDL showed the most favorable anti-glioma effect in vivo. These results demonstrated that the dual-targeting natural nanocarriers strategy provides a potential method for improving brain drug delivery and anti-glioma treatment efficacy.

Therapeutic outcome for the treatment of glioma was often limited due to the non-targeted nature of drugs and the physiological barriers, including the blood-brain barrier (BBB) and the blood-brain tumor barrier (BBTB). An ideal glioma-targeted delivery system must be sufficiently potent to cross the BBB and BBTB and then target glioma cells with adequate optimized physiochemical properties and biocompatibility. However, it is an enormous challenge to the researchers to engineer the above-mentioned features into a single nanocarrier particle. New frontiers in nanomedicine are advancing the research of new biomaterials. In this study, we demonstrate a strategy for glioma targeting by encapsulating vincristine sulfate (VCR) into a naturally available apoferritin nanocage-based drug delivery system with the modification of GKRK peptide ligand (GKRK-APO). Apoferritin (APO), an endogenous nanosize spherical protein, can specifically bind to brain endothelial cells and glioma cells via interacting with the transferrin receptor 1 (TfR1). GKRK is a peptide ligand of heparan sulfate proteoglycan (HSPG) over-expressed on angiogenesis and glioma, presenting excellent glioma-homing property. By combining the dual-targeting delivery effect of GKRK peptide and parent APO, GKRK-APO displayed higher glioma localization than that of parent APO. After loading with VCR, GKRK-APO showed the most favorable antiglioma effect in vitro and in vivo. These results demonstrated that GKRK-APO is an important potential drug delivery system for glioma-targeted therapy.

Amorphous formulations provide a general approach to improving the solubility and bioavailability of drugs. Amorphous medicines for global health should resist crystallization under the stressful tropical conditions (high temperature and humidity) and often require high drug loading. We discuss the recent progress in employing drug–polymer salts to meet these goals. Through local salt formation, an ultra-thin polyelectrolyte coating can form on the surface of amorphous drugs, immobilizing interfacial molecules and inhibiting fast crystal growth at the surface. The coated particles show improved wetting and dissolution. By forming an amorphous drug–polymer salt throughout the bulk, stability can be vastly enhanced against crystallization under tropical conditions without sacrificing the dissolution rate. Examples of these approaches are given, along with suggestions for future work.

Using high-brilliance high-energy synchrotron X-ray radiation, for the first time the total scattering of a thin organic glass film deposited on a strongly scattering inorganic substrate has been measured in transmission mode. The organic thin film was composed of the weakly scattering pharmaceutical substance indomethacin in the amorphous state. The film was 130 µm thick atop a borosilicate glass substrate of equal thickness. The atomic pair distribution function derived from the thin-film measurement is in excellent agreement with that from bulk measurements. This ability to measure the total scattering of amorphous organic thin films in transmission will enable accurate in situ structural studies for a wide range of materials.

Therapeutic outcome for the treatment of glioma was often limited due to drug resistance and low permeability of drug across the multiple physiological barriers, including the blood-brain barrier (BBB), and the blood-tumor barrier (BTB). In order to overcome these hurdles, we designed T7 and DA7R dual peptides-modified liposomes (abbreviated as T7/DA7R-LS) to efficiently co-delivery doxorubicin (DOX) and vincristine (VCR) to glioma in this study. T7 is a seven-peptide ligand of transferrin receptors (TfR) capable of circumventing the BBB and then targeting glioma. DA7R is a d-peptide ligand of vascular endothelial growth factor receptor 2 (VEGFR 2) overexpressed on angiogenesis, presenting excellent glioma-homing property. By combining the dual-targeting delivery effect, the dual-modified liposomes displayed higher glioma localization than that of single ligand-modified liposomes or free drug. After loading with DOX and VCR, T7/DA7R-LS showed the most favorable antiglioma effect in vivo. In conclusion, this dual-targeting, co-delivery strategy provides a potential method for improving brain drug delivery and antiglioma treatment efficacy.

In an attempt to improve therapeutic efficacy of dexamethasone (DXM)-loaded solid lipid nanoparticles (NPs) for renal ischemia-reperfusion injury (IRI)-induced acute renal injury (AKI), sialic acid (SA) is used as a ligand to target the inflamed vascular endothelium. DXM-loaded SA-conjugated polyethylene glycol (PEG)ylated NPs (SA-NPs) are prepared via solvent diffusion method and show the good colloidal stability. SA-NPs reduce apoptotic human umbilical vein endothelial cells (HUVECs) via downregulating oxidative stress-induced Bax, upregulating Bcl-xL, and inhibiting Caspase-3 and Caspase-9 activation. Cellular uptake results suggest SA-NPs can be specifically internalized by the inflamed vascular endothelial cells (H2O2-pretreated HUVECs), and the mechanism is associated with the specific binding between SA and E-selectin receptor expressed on the inflamed vascular endothelial cells. Bio-distribution results further demonstrated the enhanced renal accumulation of DXM is achieved in AKI mice treated with SA-NPs, and its content is 2.70- and 5.88-fold higher than those treated with DXM and NPs at 6 h after intravenous administration, respectively. Pharmacodynamic studies demonstrate SA-NPs effectively ameliorate renal functions in AKI mice, as reflected by improved blood biochemical indexes, histopathological changes, oxidative stress levels and pro-inflammatory cytokines. Moreover, SA-NPs cause little negative effects on lymphocyte count and bone mineral density while DXM leads to severe osteoporosis. It is concluded that SA-NPs provide an efficient and targeted delivery of DXM for ischemia-reperfusion-induced injury-induced AKI, with improved therapeutic outcomes and reduced adverse effects.

Hand, foot, and mouth disease (HFMD) is a global health concern, especially in the Asia-Pacific region. HFMD caused by Enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16) infection is usually self-limited but occasionally leads to severe pulmonary edema, neurological complications, and even death. Unfortunately, no effective drugs are currently available in clinical practice for the prevention and treatment of HFMD. Thus, anti-HFMD drugs must be urgently developed. A previous study had reported that lycorine could inhibit EV71 replication. In the present study, we found that LY-55, a lycorine derivative, inhibited the replication of EV71 and CVA16 in vitro and provided partial protection to mice from EV71 infection, as indicated by the decreased viral load and protein expression levels in muscles, clinical scores, and increased survival rates of infected mice. Mechanistically, LY-55 was not directly viricidal. Instead, the LY-55-mediated inhibition of EV71 and CVA16 was found to be mechanistically possible, at least in part, through downregulating autophagy, which plays an important role for EV71 and CVA16 replication. These findings suggest that LY-55 could be a potential lead or supplement for the development of anti-HFMD agents in the future.

DNA ploidy analysis of cells is an automation technique applied in pathological diagnosis. It is important for this technique to classify various nuclei images accurately. However, the lack of overlapping nuclei images in training data (imbalanced training data) results in low recognition rates of overlapping nuclei images. To solve this problem, a new method which synthesizes overlapping nuclei images with single-nuclei images is proposed. Firstly, sample selection is employed to make the synthesized samples representative. Secondly, random functions are used to control the rotation angles of the nucleus and the distance between the centroids of the nucleus, increasing the sample diversity. Then, the Lambert-Beer law is applied to reassign the pixels of overlapping parts, thus making the synthesized samples quite close to the real ones. Finally, all synthesized samples are added to the training sets for classifier training. The experimental results show that images synthesized by this method can solve the data set imbalance problem and improve the recognition rate of DNA ploidy analysis systems.

Cyprinus carpio triploid is induced by temperature shock technology. It has been extensively cultivated and got great economic value in China. The complete mitochondrial genome of C. carpio triploid is the 16,580 bp length and contains 37 genes (13 protein-coding genes (PGCs), two ribosomal RNA, 22 transfer RNA genes, and one control region). The overall base composition of the heavy strand is that the 31.92% for A, the 27.53% for C, the 15.73% for G, and the 24.83% for T. The percentage of G + C content is 43.26% and A + T content is 56.74%. The result of phylogenetic analysis indicated that C. carpio triploid was clustered in genus Cyprinus as expected. The complete mitogenome may provide important date set for genetic status and the evolutionary study of genetic mechanism of C. carpio.

Further chemical investigation of the fruits of the mangrove, Avicennia marina, afforded three new phenylethyl glycosides, marinoids J–L (1–3), and a new cinnamoyl glycoside, marinoid M (4). The structures of isolates were elucidated on the basis of extensive spectroscopic analysis and by comparison of the data with those of related secondary metabolites. The antioxidant activity of the isolates was evaluated using the cellular antioxidant assay (CAA), and compounds 1–4 showed antioxidant activities, with EC50 values ranging from 23.0 ± 0.71 μM to 247.8 ± 2.47 μM.

Ag nanoparticles loaded onto TiO2 nanosheets with exposed {001} facets were synthesized by solvothermal hydrolysis and photoreduction deposition methods. The results suggested that Ag NPs were uniformly dispersed on the surface of anatase TiO2 NSs with a metallic state. The Raman scattering and visible light absorption performances of Ag/TiO2 NSs were enhanced by Ag NPs due to their surface plasmon resonance effect. Photocatalytic oxidation experiments for HCHO were carried out under visible light, and the enhanced photocatalytic activity of Ag/TiO2 NSs can be attributed to the synergistic effects of the following factors: (1) the {001} facets, which possessed higher surface energy, showed higher photocatalytic activity; (2) the Ag NPs, the increased oxygen vacancies, and O2 adsorption on {001} facets can trap photoelectrons, thus inhibiting the recombination of photoelectrons and holes; (3) the Ag NPs can extend the light response range of TiO2 into visible light. The in situ FTIR results showed that higher mineralization efficiency of HCHO was achieved on Ag/TiO2 NSs than on Ag/TiO2 NPs. Additionally, the mechanism for HCHO photocatalytic oxidation was also discussed.

C9H12BrN3O3, monoclinic, P21/c, a = 12.0359(15) Å, b = 5.4815(6) Å, c = 20.1931(18) Å, β = 120.780(5)°, V = 1144.6(2) Å3, Z = 4, Rgt(F) = 0.0234, wRref(F2) = 0.0984, T = 298(2) K.

Taking the Kenjiyak Oilfield in Kazakhstan as an example, the fracture characteristics and genetic mechanism of carbonate reservoirs with overpressure were discussed. The study showed that carbonate reservoirs are formed under overpressure developed hydraulic fractures besides tectonic fractures and karstic fractures. The Carboniferous sub-salt hydraulic fractures in Kenkiyak are mainly formed in the Mesozoic and Cenozoic, on a macroscopic level they cut rocks into brecciated texture or are packed by calcite veins, on a microscopic level they are in a radiant distribution around pores. The formation and evolution of the fracture system in the region experienced three main stages, including structure transforming and uplifting, structure stretching and subsiding, and hydraulic cracking. In the stage of hydraulic cracking, salt movement and tectonic movement lead to the formation of overpressure zone, with the pressure coefficient of 1.84. Overpressure leads to the formation of hydraulic fractures in the Carboniferous low permeable carbonate reservoirs under the Permian non-permeable mudstones, and also leads to reopening, widening and prolonging of former tectonic fractures. Hydraulic fractures are mainly the extensional fracture, which has late opening time and low filling degree, thus is the main effective fractures in the study area. 摘要: ：以哈萨克斯坦肯基亚克油田为例讨论了异常高压碳酸盐岩油藏储集层裂缝特征及形成机制。异常高压条件下形成的碳酸盐岩储集层除发育构造裂缝和岩溶裂缝外，还发育水力破裂缝。盐下石炭系水力破裂缝形成于中、新生代，宏观上表现为将岩体切割成角砾状及充填方解石脉，微观上表现为沿孔隙周围呈放射状分布。该区裂缝系统的形成与演化经历了3个主要阶段，即构造变形与抬升阶段、构造拉张与沉降阶段、水力破裂阶段。在水力破裂阶段，在盐丘活动、构造运动等多种因素作用下，盐下地层中形成异常高压带，压力系数高达1.84，在异常高压条件下，二叠系泥岩不渗透层下的石炭系碳酸盐岩低渗透层发生破裂，形成水力破裂缝，同时使早期闭合的裂缝开启、扩张和延伸。水力破裂缝以张性裂缝为主，其张开时间晚，充填程度低，是研究区主要的有效裂缝。图8参13 Key words: carbonates, overpressure, tectonic fracture, hydraulic fracture, genetic mechanism

The big data oriented blockchain for trade clearing was introduced,including consensus,secure transmission of trading data storage,data search,encryption and decryption of trading data and trade clearing business.The analysis of the framework design on dismantlement and combination of the composite trading was emphasized,and the potential value and significant meaning of blockchain data on risk decision and assessment through the big data analysis were identified.