Search

Summary: Obesity and fatty liver diseases—metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH)—affect over one-third of the global population and are exacerbated in individuals with reduced functional aldehyde dehydrogenase 2 (ALDH2), observed in approximately 560 million people. Current treatment to prevent disease progression to cancer remains inadequate, requiring innovative approaches. We observe that Aldh2−/− and Aldh2−/−Sptbn1+/− mice develop phenotypes of human metabolic syndrome (MetS) and MASH with accumulation of endogenous aldehydes such as 4-hydroxynonenal (4-HNE). Mechanistic studies demonstrate aberrant transforming growth factor β (TGF-β) signaling through 4-HNE modification of the SMAD3 adaptor SPTBN1 (β2-spectrin) to pro-fibrotic and pro-oncogenic phenotypes, which is restored to normal SMAD3 signaling by targeting SPTBN1 with small interfering RNA (siRNA). Significantly, therapeutic inhibition of SPTBN1 blocks MASH and fibrosis in a human model and, additionally, improves glucose handling in Aldh2−/− and Aldh2−/−Sptbn1+/− mice. This study identifies SPTBN1 as a critical regulator of the functional phenotype of toxic aldehyde-induced MASH and a potential therapeutic target.

Objective Current studies lack a comprehensive understanding of the environmental factors influencing type 2 diabetes, hindering an in-depth grasp of the overall etiology. To address this gap, we utilized network science tools to highlight research trends, knowledge structures, and intricate relationships among factors, offering a new perspective for a profound understanding of the etiology. Methods The Web of Science database was employed to retrieve documents relevant to environmental risk factors in type 2 diabetes from 2012 to 2024. Bibliometric analysis using Microsoft Excel and OriginPro provided a detailed scientific production profile, including articles, journals, countries, and authors. Co-occurrence analysis was employed to determine the collaboration state and knowledge structures, utilizing social network tools such as Gephi, Tableau, and R Studio. Additionally, theme evolutionary analysis was conducted using SciMAT to offer insights into research trends. Results The publications and themes related to environmental factors in type 2 diabetes have consistently risen, shaping a well-established research domain. Lifestyle environmental factors, particularly diet and nutrition, stand out as the most represented and rapidly growing topics. Key focal hotspots include sedentary and digital behavior, PM 2.5 , ethnicity and socioeconomic status, traffic and greenspace, and depression. The theme evolutionary analysis revealed three distinct paths: (1) oxidative stress–air pollutants–PM 2.5 –air pollutants; (2) calcium–metabolic syndrome–cardiovascular disease; and (3) polychlorinated biphenyls (PCBs)–persistent organic pollutants (POPs)–obesity. Conclusions Digital behavior signifies a novel approach for preventing and managing type 2 diabetes. The influence of PM 2.5 and calcium on oxidative stress and abnormal vascular contraction is intricately linked to microvascular diabetes complications. The transition from PCBs and POPs to obesity underscores the disruption of endocrine function by chemicals, elevating the risk of diabetes. Future studies should explore the connections between environmental factors, microvascular complications, and long-term outcomes in diabetes.

Abstract The α-bromination reaction of carbonyl compounds is a significant topic in the field of organic chemistry. However, due to the lack of suitable brominating reagents, the application of this reaction in undergraduate organic chemistry experiments is limited. In this study, three junior undergraduates successfully conducted an innovative experiment under the guidance of teachers. The bromination of various acetophenone derivatives was investigated by employing pyridine hydrobromide perbromide as the brominating agent, with a focus on exploring the effects of reaction time, reaction temperature, and dosage of the brominating agent. The results demonstrated that 4-chloro-α-bromo-acetophenone could be synthesized at 90 ℃ using 4-chloroacetophenone as a substrate and acetic acid as a solvent with a molar ratio of substrate to brominator being 1.0:1.1. Through the experimental teaching of 18 junior undergraduates, it was observed that all the students successfully completed the experiment within a time frame of 4–5 h, with a notable achievement yield exceeding 80% observed in 14 students. This innovative experiment exhibits significant advantages in terms of safety, high yield, cost-effectiveness, and repeatability. Furthermore, while reinforcing fundamental skills in chemistry experimentation among students, it enhances their scientific literacy levels and fosters innovation consciousness as well as practical aptitude. Consequently, this approach is highly suitable for widespread implementation and integration into undergraduate experimental pedagogy.

Macrocyclic polyamines constitute a significant class of macrocyclic compounds that play a pivotal role in the realm of supramolecular chemistry. They find extensive applications across diverse domains including industrial and agricultural production, clinical diagnostics, environmental protection and other multidisciplinary fields. Macrocyclic polyamines possess a distinctive cavity structure with varying sizes, depths, electron-richness degrees and flexibilities. This unique feature enables them to form specific supramolecular structures through complexation with diverse objects, thereby attracting considerable attention from chemists, biologists and materials scientists alike. However, there is currently a lack of comprehensive summaries on the synthesis methods for macrocyclic polyamines. In this review article, we provide an in-depth introduction to the synthesis of macrocyclic polyamines while analysing their respective advantages and disadvantages. Furthermore, we also present an overview of the recent 5-year advancements in using macrocyclic polyamines as non-viral gene vectors, fluorescent probes, diagnostic and therapeutic reagents as well as catalysts. Looking ahead to future research directions on the synthesis and application of macrocyclic polyamines across various fields will hopefully inspire new ideas for their synthesis and use.

Hainan is the first province in China to announce a comprehensive ban on the sale of fuel vehicles by 2030, aimed at promoting low-carbon transportation development. This paper uses the top-down method of the IPCC to estimate the transportation carbon emissions in Hainan Province from 2006 to 2020. At the same time, considering the impact of structural adjustments, technological advancements, and urbanization developments, the traditional LMDI model was improved and combined with the Tapio model to analyze the decoupling status of transportation carbon emissions and economic development in Hainan Province, as well as the contribution values and rates of various influencing factors. The study reveals: 1) The total transportation carbon emissions increased by 208.68 ten thousand tons, showing a trend of rapid initial rise followed by gradual slowdown, with oil energy accounting for 99% of emissions, of which kerosene contributed the highest proportion and exhibited the greatest increase; 2) The decoupling index displayed an “M” curve fluctuation, indicating an initial deterioration followed by improvement, reflecting an unstable decoupling status; 3) The introduction of urbanization effects showed that positive drivers include income urbanization, spatial urbanization, transportation intensity, and industrial structure effects, while negative drivers encompass energy intensity, population urbanization, and energy structure effects. Among these, the paramount factor driving the increase in carbon emissions is income urbanization effect, whereas the paramount factor curbing carbon emissions is energy intensity effect. Finally, policy recommendations are proposed for carbon emission reduction in the transportation sector of Hainan Province.

This paper aims to address the time-dependent multi-depot vehicle routing problem with time windows (MDVRPTW) in urban cold chain logistics under a dynamic road network. The study considers the impact of carbon emissions and traffic congestion on urban cold chain logistics distribution activities. It proposes a cross-period road segment travel time calculation method, constructs a multi-objective optimization model that minimizes total costs encompassing comprehensive transportation costs, carbon emission costs, time penalty costs, cargo damage costs, and refrigeration costs. An adaptive large neighborhood search ant colony optimization algorithm (ALNS_ACO) is designed, which combines the exploration capability of ant colony optimization algorithm (ACO) with the local search capability of adaptive large neighborhood search algorithm (ALNS) to optimize and solve the model. Finally, the model is optimized and solved through simulation using six sets of C-type, R-type, and RC-type instances from the Solomon test database. The results indicate that: 1) The planned routes can reasonably avoid peak congestion periods in the morning and evening. Compared to the single-center scenario, the multi-center approach achieves superior solutions in terms of the total cost, carbon emissions, and total travel time in urban cold chain logistics distribution; 2) The exacerbation of traffic congestion leads to increased costs, and different optimization objectives have a significant impact on the model solutions; 3) Finally, through multidimensional comparisons of simulation performance with ACO and GA algorithms, the effectiveness of the proposed optimization algorithm is validated.

Inflammatory bowel disease (IBD) is characterized by recurrent attacks and long courses, and the number of patients has expanded rapidly year by year. Additionally, current conventional strategies exist serious adverse effects. In this case, it is an urgent issue to find out an effective and safe treatment. Functional oligosaccharides possess safe and excellent physiological activities, and have attracted enormous attention due to their great therapeutic potential for IBD. This review emphasizes the attenuating effects of distinct functional oligosaccharides on IBD and their structure, and summarizes the main mechanisms from the aspects of regulating intestinal flora structure, repairing intestinal barrier, modulating immune function and mediating related signaling pathways in order to reveal the relationship between functional oligosaccharides, immune regulation, intestinal epithelial cells, gut flora and IBD treatment. Oligosaccharides possess excellent protective effects on IBD, and can be considered as safe and functional ingredients in the health food and pharmaceutical industry.

Abstract Background Previous studies have reported that transcranial focused ultrasound stimulation can significantly decrease the time to emergence from intraperitoneal ketamine-xylazine anaesthesia in rats. However, how transcranial focused ultrasound stimulation modulates neural activity in anaesthetized rats is unclear. Methods In this study, to answer this question, we used low-intensity transcranial ultrasound stimulation (TUS) to stimulate the brain tissue of propofol-anaesthetized mice, recorded local field potentials (LFPs) in the mouse motor cortex and electromyography (EMG) signals from the mouse neck, and analysed the emergence and recovery time, mean absolute power, relative power and entropy of local field potentials. Results We found that the time to emergence from anaesthesia in the TUS group (20.3 ± 1.7 min) was significantly less than that in the Sham group (32 ± 2.6 min). We also found that compared with the Sham group, 20 min after low-intensity TUS during recovery from anaesthesia, (1) the absolute power of local field potentials in mice was significantly reduced in the [1–4 Hz] and [13–30 Hz] frequency bands and significantly increased in the [55–100 Hz], [100–140 Hz] and [140–200 Hz] frequency bands; (2) the relative power of local field potentials in mice was enhanced at [30–45 Hz], [100–140 Hz] and [140–200 Hz] frequency bands; (3) the entropy of local field potentials ([1-200 Hz]) was increased. Conclusion These results demonstrate that low-intensity TUS can effectively modulate neural activities in both awake and anaesthetized mice and has a positive effect on recovery from propofol anaesthesia in mice.

In order to study the enzymatic hydrolysis process conditions of instant asparagus powder and its improvement of sleep function in mice, the market Enyang asparagus was as raw materials, the powder yield and saponin content of instant asparagus powder were as two indicators, and pectinase and cellulas were compounded to enzymatic hydrolysis asparagus after scalded and pulped. The addition of enzyme compound (the mass ratio of pectinase to cellulase was 1:1), enzymolysis temperature, time, and pH were as experimental factors, and the optimum enzymatic hydrolysis process conditions was determined through single factor test and response surface test. Meanwhile, sleep-producing test with subthreshold dose of sodium pentobarbital, sleep latency test and prolonged sleep time test were conducted to investigate its function of improving sleep in mice by comparing the number of sleeping animals and the incidence of sleep, sleep latency and time in each group. The results showed that the optimal enzymolysis conditions for the instant asparagus powder were 0.12% dose of complex enzyme, enzymolysis temperature was 68 ℃, time was 2.2 h, and pH was 5.2. Under these conditions, the powder yield of instant asparagus powder was 42.7% and the saponin content was 21.4%. The incidence of sleep (26.7%, 36.7% and 43.3% respectively), sleep latency (29.0, 26.3 and 25.1 min respectively) and sleep time (36.4, 39.5 and 46.6 min respectively) in the low, medium and high dose groups of the instant asparagus powder were significantly better than those in the blank control group, and the dose-dependent increase or decrease was observed. The results indicated that the instant asparagus powder prepared by this method could improve the sleep function of mice to some extent.

Historic buildings hold significant cultural value and their repair and protection require diverse approaches. With the advent of 3D digitalization, drones have gained significance in heritage studies. This research focuses on applying digital methods for restoring architectural heritage. It utilizes non-contact measurement technology, specifically unmanned aerial vehicles (UAVs), for data collection, creating 3D point cloud models using heritage building information modeling (HBIM), and employing virtual reality (VR) for architectural heritage restoration. Employing the “close + surround” oblique photography technique combined with image matching, computer vision, and other technologies, a detailed and comprehensive 3D model of the real scene can be constructed. It provides crucial data support for subsequent protection research and transformation efforts. Using the case of the Santo Stefano Church in Volterra, Italy, an idealized reconstructed 3D model database was established after data collection to preserve essential resources such as the original spatial data and relationships of architectural sites. Through the analysis of relevant historical data and the implementation of VR, the idealized and original appearance of the case was authentically restored. As a result, in the virtual simulation space, the building’s style was realistically displayed with an immersive experience. This approach not only safeguards cultural heritage but also enhances the city’s image and promotes tourism resources, catering to the diverse needs of tourists.

Abstract The differentiation of pluripotent stem cells (PSCs) into diverse functional cell types provides a promising solution to support drug discovery, disease modeling, and regenerative medicine. However, functional cell differentiation is currently limited by the substantial line-to-line and batch-to-batch variabilities, which severely impede the progress of scientific research and the manufacturing of cell products. For instance, PSC-to-cardiomyocyte (CM) differentiation is vulnerable to inappropriate doses of CHIR99021 (CHIR) that are applied in the initial stage of mesoderm differentiation. Here, by harnessing live-cell bright-field imaging and machine learning (ML), we realize real-time cell recognition in the entire differentiation process, e.g., CMs, cardiac progenitor cells (CPCs), PSC clones, and even misdifferentiated cells. This enables non-invasive prediction of differentiation efficiency, purification of ML-recognized CMs and CPCs for reducing cell contamination, early assessment of the CHIR dose for correcting the misdifferentiation trajectory, and evaluation of initial PSC colonies for controlling the start point of differentiation, all of which provide a more invulnerable differentiation method with resistance to variability. Moreover, with the established ML models as a readout for the chemical screen, we identify a CDK8 inhibitor that can further improve the cell resistance to the overdose of CHIR. Together, this study indicates that artificial intelligence is able to guide and iteratively optimize PSC differentiation to achieve consistently high efficiency across cell lines and batches, providing a better understanding and rational modulation of the differentiation process for functional cell manufacturing in biomedical applications.

Abstract The hepatotoxicity of regorafenib is one of the most noteworthy concerns for patients, however the mechanism is poorly understood. Hence, there is a lack of effective intervention strategies. Here, by comparing the target with sorafenib, we show that regorafenib-induced liver injury is mainly due to its nontherapeutic target Eph receptor A2 (EphA2). EphA2 deficiency attenuated liver damage and cell apoptosis under regorafenib treatment in male mice. Mechanistically, regorafenib inhibits EphA2 Ser897 phosphorylation and reduces ubiquitination of p53 by altering the intracellular localization of mouse double minute 2 (MDM2) by affecting the extracellular signal-regulated kinase (ERK)/MDM2 axis. Meanwhile, we found that schisandrin C, which can upregulate the phosphorylation of EphA2 at Ser897 also has protective effect against the toxicity in vivo. Collectively, our findings identify the inhibition of EphA2 Ser897 phosphorylation as a key cause of regorafenib-induced hepatotoxicity, and chemical activation of EphA2 Ser897 represents a potential therapeutic strategy to prevent regorafenib-induced hepatotoxicity.

Abstract Nephrotoxicity has become prominent due to the increase in the clinical use of nilotinib, a second‐generation BCR‐ABL1 inhibitor in the first‐line treatment of Philadelphia chromosome‐positive chronic myeloid leukemia. To date, the mechanism of nilotinib nephrotoxicity is still unknown, leading to a lack of clinical intervention strategies. Here, it is found that nilotinib could induce glomerular atrophy, renal tubular degeneration, and kidney fibrosis in an animal model. Mechanistically, nilotinib induces intrinsic apoptosis by specifically reducing the level of BCL2 like 1 (Bcl‐XL) in both vascular endothelial cells and renal tubular epithelial cells, as well as in vivo. It is confirmed that chloroquine (CQ) intervenes with nilotinib‐induced apoptosis and improves mitochondrial integrity, reactive oxygen species accumulation, and DNA damage by reversing the decreased Bcl‐XL. The intervention effect is dependent on the alleviation of the nilotinib‐induced reduction in ubiquitin specific peptidase 13 (USP13) and does not rely on autophagy inhibition. Additionally, it is found that USP13 abrogates cell apoptosis by preventing excessive ubiquitin‒proteasome degradation of Bcl‐XL. In conclusion, the research reveals the molecular mechanism of nilotinib's nephrotoxicity, highlighting USP13 as an important regulator of Bcl‐XL stability in determining cell fate, and provides CQ analogs as a clinical intervention strategy for nilotinib's nephrotoxicity.

Architectural heritage preservation and dissemination are an important and interesting field in Cultural Heritage. However, for the surveying, mapping and monitoring of architectural heritage, traditional survey methods cost a lot, take much time, and easily cause secondary damage to ancient architectural heritage. Due to the high efficient of the Unmanned Aerial Vehicle (UAV) which may be a smart solution for safe and fast data collection, Taking the Sisheng ancestral hall as a case study, this paper obtains a high-precision point cloud data model and creates an HBIM model through UAV data, which provides a workable solution for the digital protection and the monitoring of architectural heritage. The collected data is processed not only to provide reference data support for cultural relics protection, but also as a reference for long-term heritage monitoring.DOI: https://doi.org/10.20365/disegnarecon.29.2022.13

Abstract Background The variation of right main stem bronchus leads to the orifice of the right upper lobe bronchus may be obstructed or increase the incidence of malposition intraoperatively when the right sided double-lumen tube is used. Therefore, the aim of this study was to compare the accuracy of three methods measured the length of the right main stem bronchus via chest computed tomography as a guide to the use of right sided double-lumen tube. Methods In this study, 168 adult patients undergoing left sided thoracic surgery were included. All these patients were allocated to carina-proximal (C-P) group, carina-distal (C-D) group and carina-carina (C-C) group. The position of endobronchial cuff observed via Fiberoptic bronchoscopy after successful initial placement and after turning the patients to the lateral decubitus position, as well as the incidence of malposition of right sided double-lumen tube intraoperative were recorded to assess the accuracy of three methods in predicting the position of right sided double-lumen tube. Results The distance between the carina to the proximal margin of the right upper lobe orifice, carina to the distal margin of the right upper lobe orifice and carina to the first right interlobar carina of the right upper lobe orifice were 17.2 ± 2.3 mm, 25.4 ± 3.7 mm and 28.5 ± 3.1 mm (P

Carbapenem-resistant (CR) Klebsiella oxytoca complex can be associated with high mortality, emerging as a new threat to the public health. K. oxytoca complex is phylogenetically close to K. pneumoniae, one of most common species associated with multidrug resistance in Enterobacterale. The latest research showed that K. oxytoca is a complex of six species. Currently, the epidemiological and genomic characteristics of CR K. oxytoca complex in China are still unclear. Here, we conducted a multi-center study on 25 CR K. oxytoca complex collected from five representative regions in China. These isolates were, respectively, recovered from respiratory tract (12 cases, 48.0%), abdominal cavity (5 cases, 20.0%), blood (4 cases, 16.0%), urine tract (3 cases, 12.0%) and skin or soft tissue (1 cases, 4.0%). Among them, 32.0% (8/25) of patients infected with K. oxytoca complex had a poor prognosis. In this study, three K. oxytoca complex species were detected, namely K. michiganensis, K. oxytoca and K. pasteurii, among which K. michiganensis was the most common. Three carbapenemase genes were identified, including blaNDM-1 (10, 38.5%), blaKPC-2 (9, 34.6%) and blaIMP (6 blaIMP-4 and 1 blaIMP-8; 7, 26.9%). Subsequent multilocus sequence typing identified various sequence types (STs), among which ST43, ST92 and ST145 were relatively common. Different from the clonal dissemination of high-risk carbapenem-resistant K. pneumoniae strains, our research revealed a polyclonal dissemination characteristic of CR K. oxytoca complex in China. S1-nuclease PFGE and Southern blot experiment showed that carbapenemase genes were encoded in plasmids of different sizes. Two blaNDM-harboring plasmids were subsequently sequenced, and were characterized to be IncX3 and IncC incompatibility groups, respectively. This is the first multi-center study of CR K. oxytoca complex in China, which improved our understanding of the prevalence and antimicrobial resistance characteristics of CR K. oxytoca complex in China.

Abstract Background Osteoarthritis (OA) is a common chronic degenerative joint disease. At present, there is no effective treatment to check the progression of osteoarthritis. Osteochondral units are considered to be one of the most important structures affecting the occurrence and development of osteoarthritis. Osteoclasts mediate an increase in abnormal bone remodeling in subchondral bone in the early stage of osteoarthritis. Here, alendronate (ALN) that inhibit osteoclasts was used to study the regulatory effect of osteoclast-derived leukemia inhibitory factor (LIF) on early abnormal bone remodeling. Methods This study involved 10-week-old wild-type female C57BL/6 mice and female SOST knockout (KO) mice that were divided into the sham, vehicle, ALN, and SOST KO groups. Results The expression of LIF was found to decrease by inhibiting osteoclasts, and the histological OA score suggested that the degeneration of articular cartilage was attenuated. Additionally, micro-CT showed that osteoclasts inhibited in the early stage of OA could maintain the microstructure of the subchondral bone. The parameters of bone volume fraction (BV/TV), subchondral bone plate thickness (SBP.Th), and trabecular separation (Tb.Sp) of the treated group were better than those of the vehicle group. Conclusions These results suggested that downregulating the expression of sclerostin in osteocytes by secreting LIF from osteoclasts, activate the Wnt/β-catenin signaling pathway, and promote abnormal bone remodeling in OA. Therefore, clastokine LIF might be a potential molecular target to promote abnormal bone remodeling in early OA.

Background: There have been many studies on long non-coding RNAs (lncRNAs) as tumor markers. LINC00958 is a lncRNA that has been studied in a variety of tumor types. This meta-analysis aims to explore the relationship between LINC00958 and clinical prognosis and pathological characteristics in various cancers.Methods: We searched for related studies from PubMed, Web of Science, The Cochrane Library and Embase (up to October 2021). The association of LINC00958 expression with clinicopathological characteristics and prognosis was evaluated using the pooled odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs).Results: 16 studies (1,121 patients) were included in this meta-analysis, we found that overexpression of LINC00958 was associated with poor overall survival (OS) (HR = 1.84; 95% CI: 1.36–2.49; p < 0.001). We also found that LINC00958 overexpression was correlated with positive lymph node metastasis (LNM) (OR = 1.91; 95% CI: 1.39–2.63; p < 0.001), advanced degree of infiltration (OR = 1.64; 95% CI: 1.11–2.41; p = 0.013), advanced tumor-node-metastasis (TNM) stage (OR = 2.80; 95% CI: 1.48–5.33; p = 0.002). Other clinicopathological characteristics have no obvious correlation, such as age, sex, tumor size, distant metastasis, and differentiation grade (p > 0.05).Conclusion: In summary, the overexpression of LINC00958 is significantly correlated with poor OS, positive LNM, advanced degree of infiltration, and advanced TNM stage. LINC00958 might serve as a potential prognostic biomarker and therapeutic target for a variety of cancers. However, rigorous studies with large sample sizes are still needed for further research and demonstration.

Abstract Background and aims A simplified magnetic resonance index of activity (MaRIAs) was recently proposed. Our aim was to verify whether MaRIAs can accurately assess the activity degree of CD. Methods We retrospectively analyzed the MRI, ileocolonoscopy, fecal calprotectin (FC), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) data of 93 CD patients. With the SES-CD as the gold standard, MaRIAs’ accuracy, the correlation of MaRIAs and SES-CD, FC, ESR, CRP, and interevaluator reliability were assessed. Results MaRIAs ≥ 1 detected segments with active CD with 90.80% specificity and 81.37% sensitivity (area under the curve was 0.91, 95% confidence interval 0.87–0.94). MaRIAs score of 2 or more detected severe lesions with 88.89% specificity and 95.12% sensitivity (AUC was 0.96, 95% confidence interval was 0.94–0.98). The MaRIAs score showed a high correlation with the SES-CD in the terminal ileum, transverse colon, right colon, and left colon (r = 0.85, 0.91, 0.88, 0.86, P

Metabolic syndrome (MetS) has become a worldwide public health problem with increasing global morbidity. Existing surgical and pharmaceutical treatments have certain side effects. Consequently, the search for anti-MetS active ingredients with long-lasting stable therapeutic effects and less toxic side effects has become a focal point of contemporary research. Functional polysaccharides with safe and excellent physiological activities have attracted more and more attention in the regulation of MetS, but a comprehensive understanding is still lacking. In this review, the effects and mechanisms of plant polysaccharides in the prevention and improvement of MetS by regulating intestinal flora, improving glucose and lipid metabolism disorders, maintaining the balance of islet internal environment and reducing systemic inflammation are summarized. Plant polysaccharides can be used to reduce the risk of metabolic diseases in a safe and dependable manner.

Abstract Background There are many factors affecting the success rate of awake orotracheal intubation via fiberoptic bronchoscope. We performed this study was to investigate the effects of head positions on awake Fiberoptic bronchoscope oral intubation. Methods Seventy-five adult patients, received general anaesthesia were included in this study. After written informed consent, these patients were undergoing awake orotracheal intubation via fiberoptic-bronchoscope and according to the head position, the patients were randomized allocated to neutral position group (NP group), sniffing position group (SP group) or extension position group (EP group). After sedation the patients were intubated by an experienced anesthesiologist. The time to view the vocal cords, the percentage of glottic opening scores (POGO), the time to insert the tracheal tube into trachea and the visual analog scale (VAS) scores for ease experienced of passing the tracheal tube through glottis, the hemodynamic changes and the adverse events after surgery were recorded. Results The time to view the vocal cords was significantly shorter and the POGO scores was significantly higher in the EP group compared with the other two groups (P 0.05). There were also no significant differences regard to the incidence of postoperative complications, mean arterial pressure and heart rate among the groups (P > 0.05). Conclusions The head at extension position had a best view of glottic opening than neutral position or sniffing position during awake Fiberoptic bronchoscope oral intubation, so extension position was recommended as the starting head position for awake Fiberoptic bronchoscope oral intubation. Trial registration Clinical Trials.gov. no. NCT02792855. Registered at https://register.clinicaltrials.gov on 23 september 2017.

Long-term live-cell imaging technology has emerged in the study of cell culture and development, and it is expected to elucidate the differentiation or reprogramming morphology of cells and the dynamic process of interaction between cells. There are some advantages to this technique: it is noninvasive, high-throughput, low-cost, and it can help researchers explore phenomena that are otherwise difficult to observe. Many challenges arise in the real-time process, for example, low-quality micrographs are often obtained due to unavoidable human factors or technical factors in the long-term experimental period. Moreover, some core dynamics in the developmental process are rare and fleeting in imaging observation and difficult to recapture again. Therefore, this study proposes a deep learning method for microscope cell image enhancement to reconstruct sharp images. We combine generative adversarial nets and various loss functions to make blurry images sharp again, which is much more convenient for researchers to carry out further analysis. This technology can not only make up the blurry images of critical moments of the development process through image enhancement but also allows long-term live-cell imaging to find a balance between imaging speed and image quality. Furthermore, the scalability of this technology makes the methods perform well in fluorescence image enhancement. Finally, the method is tested in long-term live-cell imaging of human-induced pluripotent stem cell-derived cardiomyocyte differentiation experiments, and it can greatly improve the image space resolution ratio.

Background Peritoneal dialysis (PD) patients experience accelerated arterial aging, which is characterized by elastin degradation. Elastin-derived peptides (EDPs) are direct products of elastin fragmentation. This study tried to explore the association between serum EDPs and abdominal aortic calcification (AAC) in PD patients. Methods Serum levels of EDPs were analyzed in 126 eligible PD patients and 30 controls. PD patients were grouped according to the annularity of AAC evaluated by an abdominal computed tomography (CT) scan. Serum EDPs were analyzed in relation to the presence of AAC or severe AAC in PD patients by logistic regression analysis. Results Serum EDPs in PD patients were significantly higher than age-matched controls. In 126 PD patients, higher EDPs was associated with greater risk of present AAC (OR = 1.056, 95%CI 1.010–1.103) and severe AAC (OR = 1.062, 95%CI 1.004–1.123). A combination of EDPs substantially improved the accuracy of diagnostic performance for AAC and severe AAC. Conclusions EDPs can predict the presence and extent of AAC in PD patients, indicating its possible role to recognize PD patients at risk for AAC and severe AAC.

Central nervous system leukemia (CNS-L) is caused by leukemic cells infiltrating into the meninges or brain parenchyma and remains the main reason for disease relapse. Currently, it is hard to detect CNS-L accurately by clinically available imaging models due to the relatively low amount of tumor cells, confined blood supply, and the inferior glucose metabolism intensity. Recently, integrin α6-laminin interactions have been identified to mediate CNS-L, which suggests that integrin α6 may be a promising molecular imaging target for the detection of CNS-L. The acute lymphoblastic leukemia (ALL) cell line NALM6 stabled and transfected with luciferase was used to establish the CNS-L mouse model. CNS-L-bearing mice were monitored and confirmed by bioluminescence imaging. Three of our previously developed integrin α6-targeted peptide-based molecular imaging agents, Cy5-S5 for near-infrared fluorescence (NIRF), Gd-S5 for magnetic resonance (MR), and 18F-S5 for positron emission tomography (PET) imaging, were employed for the molecular imaging of these CNS-L-bearing mice. Bioluminescence imaging showed a local intensive signal in the heads among CNS-L-bearing mice; meanwhile, Cy5-S5/NIRF imaging produced intensive fluorescence intensity in the same head regions. Moreover, Gd-S5/MR imaging generated superior MR signal enhancement at the site of meninges, which were located between the skull bone and brain parenchyma. Comparatively, MR imaging with the clinically available MR enhancer Gd-DTPA did not produce the distinguishable MR signal in the same head regions. Additionally, 18F-S5/PET imaging also generated focal radio-concentration at the same head regions, which generated nearly 5-times tumor-to-background ratio compared to the clinically available PET radiotracer 18F-FDG. Finally, pathological examination identified layer-displayed leukemic cells in the superficial part of the brain parenchyma tissue, and immunohistochemical staining confirmed the overexpression of the integrin α6 within the lesion. These findings suggest the potential application of these integrin α6-targeted molecular imaging agents for the accurate detection of CNS-L.

In recent years, the problem of k-core has attracted wide-spread research attention due to the popularity of the graph-related applications, such as social network analysis, community detection, and collaboration networks. To efficiently support group-based activity planning, the organizers need to guarantee the size and closeness of the group. Current applications of the k-core only support searching for the maximum k-core group or adding the minimum number of edges to obtain the k-core. However, no research has focused on the problem of enlarging the k-core. In reality, when new tasks arrive, a work team needs to not only recruit new team members based on the requirements but also guarantee sufficient closeness among the members for good cooperation. In this paper, we first formalize a new query, a social group enlarging query with size constraints (SGEQ), which aims to find n users to enlarge a subgraph from a k-core of size m to a (k+Δ)-core of size (m+n) by inserting the minimum number of edges. We prove that the SGEQ problem is NP-hard. To solve this problem, we first propose a novel algorithm, namely, the maximum connection edges algorithm (MCEA), which searches for the inserted vertex that has the most edges with an induced subgraph every time. Then, we develop an optimizing algorithm, namely, the maximum contribution degree algorithm (MCDA), which on average adds a number of edges in the expanded query less than that obtained by the MCEA. Finally, we conduct extensive experiments on two real-world datasets, and the results demonstrate the efficiency of the proposed algorithms.

Currently, chemotherapy is the main treatment for tumors, but there are still problems such as unsatisfactory chemotherapy results, susceptibility to drug resistance, and serious adverse effects. Natural compounds have numerous pharmacological activities which are important sources of drug discovery for tumor treatment. The combination of chemotherapeutic drugs and natural compounds is gradually becoming an important strategy and development direction for tumor treatment. In this paper, we described the role of natural compounds in combination with chemotherapeutic drugs in synergizing, reducing drug resistance, mitigating adverse effects and related mechanisms, and providing new insights for future oncology research.

Gene therapy, as an emerging therapeutic approach, has shown remarkable advantages in the treatment of some major diseases. With the deepening of genomics research, people have gradually realized that the emergence and development of many diseases are related to genetic abnormalities. Therefore, nucleic acid drugs are gradually becoming a new boon in the treatment of diseases (especially tumors and genetic diseases). It is conservatively estimated that the global market of nucleic acid drugs will exceed $20 billion by 2025. They are simple in design, mature in synthesis, and have good biocompatibility. However, the shortcomings of nucleic acid, such as poor stability, low bioavailability, and poor targeting, greatly limit the clinical application of nucleic acid. Liposome nanoparticles can wrap nucleic acid drugs in internal cavities, increase the stability of nucleic acid and prolong blood circulation time, thus improving the transfection efficiency. This review focuses on the recent advances and potential applications of liposome nanoparticles modified with nucleic acid drugs (DNA, RNA, and ASO) and different chemical molecules (peptides, polymers, dendrimers, fluorescent molecules, magnetic nanoparticles, and receptor targeting molecules). The ability of liposome nanoparticles to deliver nucleic acid drugs is also discussed in detail. We hope that this review will help researchers design safer and more efficient liposome nanoparticles, and accelerate the application of nucleic acid drugs in gene therapy.

Hepatocellular carcinoma (HCC), the most prevalent subtype of liver cancer, is the second main reason for cancer-related deaths worldwide. In recent decades, sufficient evidence supported that immunotherapy was a safe and effective treatment option for HCC. However, tolerance and frequent recurrence and metastasis occurred in patients after immunotherapy due to the complicated crosstalk in the tumor immunosuppressive microenvironment (TIME) in HCC. Therefore, elucidating the TIME in HCC and finding novel modulators to target TIME for attenuating immune suppression is critical to optimize immunotherapy. Recently, studies have shown the potentially immunoregulatory activities of natural compounds, characterized by multiple targets and pathways and low toxicity. In this review, we concluded the unique role of TIME in HCC. Moreover, we summarized evidence that supports the hypothesis of natural compounds to target TIME to improve immunotherapy. Furthermore, we discussed the comprehensive mechanisms of these natural compounds in the immunotherapy of HCC. Accordingly, we present a well-grounded review of the naturally occurring compounds in cancer immunotherapy, expecting to shed new light on discovering novel anti-HCC immunomodulatory drugs from natural sources.

Objective This meta-analysis explored the diagnostic value of anti-cyclic citrullinated peptide antibody (anti-CCP) and rheumatoid factor (RF) for rheumatoid arthritis (RA) in the Asian population. Methods Embase, Medline, Cochrane Library, Chinese Science and Technology Periodicals, China National Knowledge Infrastructure, and China Wanfang Databases were searched from 1 January 2000 to 1 February 2021 to collect studies on the combined detection of anti-CCP and RF for diagnosing RA. The sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (+LR), and negative likelihood ratio (−LR) were combined and analyzed. Summary receiver operating characteristic (SROC) curves were drawn. Results Twenty-four published papers were analyzed, including 21 combined in series and 8 combined in parallel. In the tandem analysis, the sensitivity = 0.64 [95% confidence interval (CI): 0.58–0.70], specificity = 0.97 (95%CI: 0.95–0.98), +LR = 19.70 (95%CI: 12.74–30.46), −LR = 0.37 (95%CI: 0.31–0.43), DOR = 53.43 (95%CI: 34.46–82.40), and area under the SROC curve = 0.89. In the parallel combination, the sensitivity = 0.87 (95%CI: 0.80–0.92), specificity = 0.76 (95%CI: 0.67–0.84), +LR = 3.68 (95%CI: 2.62–5.17), −LR = 0.17 (95%CI: 0.11–0.26), DOR = 21.56 (95%CI: 11.63–39.99), and area under the SROC curve = 0.89. Conclusion Anti-CCP and RF combined detection improves the diagnostic efficiency of RA, providing a potential strategy for early clinical screening in the Asian population. This trial was retrospectively registered in the INPLASY/Research Registry ( https: //inplasy.com/ ) with the registration number INPLASY202180106.

Abstract Background The anesthesia of patients with large mediastinal mass is at high-risk. Avoidance of general anesthesia in these patients is the safest option, if this is unavoidable, maintenance of spontaneous ventilation is the next safest technique. In these types of patients, it is not applicable to use double-lumen tube (DLT) to achieve one-lung ventilation (OLV) because the DLT has a larger diameter and is more rigid than single-lumen tube (SLT), so the mass may rupture and bleed during intubation. Even using a bronchial blocker, a small size of SLT is required for once the trachea collapses the SLT can pass through the narrowest part of trachea. However, it is difficult to control the fiberoptic bronchoscopy (FOB) and the bronchial blocker simultaneously within the lumen of a small size SLT with traditional intubation methods. Case presentation The current study presented a 66 years old female patient with a large mediastinal mass that presented with difficulty breathing when lying flat. In this case, we combined use of dexmedetomidine and remifentanil to preserve the patient’s spontaneous ventilation during intubation and achieved one-lung ventilation with extraluminal use of Uniblocker. Conclusions Extraluminal use of Uniblocker and maintenance of spontaneous ventilation during intubation may be an alternative to traditional methods of lung isolation in such patients with a large mediastinal mass.

Background: Precursor of nerve growth factor (proNGF) was previously considered biologically inactive; however, it has recently been identified as having important roles in the pathology of cancer development. Aim: This study aimed to explore the therapeutic effects of proNGF siRNA on the proliferation, invasion, and anoikis of pancreatic cancer cells and determine the functions of proNGF. Methods: Pancreatic ductal adenocarcinoma (PDAC) and paired paracancerous tissue samples were collected from 60 patients for evaluation of proNGF expression by immunohistochemistry staining, qPCR, and western blotting. PDAC cell proliferation, migration, apoptosis, and anoikis following proNGF siRNA knockdown were investigated in two pancreatic cancer cell lines, Panc-1 and Bxpc-3, using BrdU incorporation assays, EdU staining, Ki-67 immunofluorescence (IF) staining, wound-healing assays, transwell invasion assays, and EthD-1 IF staining. Autophagy-related proteins were also measured by western blotting. Results: Levels of proNGF protein were higher in pancreatic cancer tissues and cells lines than those in paracancerous tissues and normal pancreatic duct epithelial cells, respectively. In vitro, ProNGF knockdown by siRNA led to significantly reduced cell proliferation, remarkably inhibited wound-healing, and reduced the number of invaded PDAC cells in migration and transwell assays. Treatment with proNGF siRNA also downregulated ATG5 and Beclin 1 protein levels, increased those of P62, and increased EthD-1 staining in PDAC cells. Conclusion: ProNGF expression is elevated in PDAC tissues and cell lines, and proNGF siRNA can inhibit cell proliferation, migration, and invasion, and promote anoikis of pancreatic cancer cells, in which decreased proNGF may participate.

Although the direction aspect is as important as the distance aspect when retrieving spatial objects, the studies of direction-aware queries are limited. The direction-based surrounder query cannot guarantee good directional diversity. In this paper, we propose the direction-aware nearest neighbor query (DNN query), which can recommend the nearest objects and ensure that the results have good directional diversity. Given a query point q and an angular threshold θ, the DNN query searches for the nearest neighbors on various directions around q. The DNN query can apply to the scenario where the user searches for the nearest objects around him. It can also apply to the scenario where the user searches for the photos of a geographic object according to the locations where the photos are taken. It can find photos that capture different views of the query object. In this paper, we propose the point-DNN query, where the query object is a point, and extend it to the range-DNN query, where the query object is a rectangle. We design algorithms to answer the DNN queries and also conduct comprehensive experiments to evaluate the performances of the algorithms.

With the rapid development of mobile Internet and sharing economy, carpooling over real-time taxi-calling service has attracted more and more attention. Many popular taxi-calling service platforms, e.g., didi and Uber, have developed carpooling service to the passengers. Their goal is maximizing overall profit while meeting passengers' convenience and economic benefits. Many researchers have deeply studied this problem. They usually focus on minimizing the total travel distance of drivers or making passengers' cost as fair as possible. However, these efforts ignore the fact that a “high quality” planning path crowed with potential passengers is more valuable than a “low quality” path for both workers and passengers. An effective high quality path planning algorithm is more desired. In this paper, we propose an efficient framework, named PPVF(short for path prediction and verification-based framework) for path planning over the road network. We first select a group of high quality paths from the historical transaction record set and manage them by proposing a novel index named PCR-Tree. Then we use them for supporting the path planning. Furthermore, we propose a searching and verification-based algorithm for further improving the path planning quality. Theoretical analysis and extensive experimental results demonstrate the effectiveness of the proposed algorithms.

Phosphating sesbania gum (DESG) was obtained by modifying sesbania gum (SG) with 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) and endic anhydride (EA). The structure of DESG was determined using Fourier transform infrared (FTIR) spectroscopy and nuclear magnetic resonance spectroscopy (1H-NMR). Flame-retardant polylactic acid (PLA) composites were prepared by melt-blending PLA with DESG, which acted as a carbon source, and ammonium polyphosphate (APP), which acted as an acid source and a gas source. The flame retardancy of the PLA composite was investigated using vertical combustion (UL-94), the limiting oxygen index (LOI) and the cone calorimeter (CONE) test. Thermal properties and morphology were characterized via thermogravimetric analysis (TGA) and field emission scanning electron microscopy (FESEM), respectively. Experimental results indicated that when the mass ratio of DESG/APP was equal to 12/8 the LOI value was 32.2%; a vertical burning test (UL-94) V-0 rating was achieved. Meanwhile, the sample showed a lowest total heat release (THR) value of 52.7 MJ/m2, which is a 32.5% reduction compared to that of neat PLA. Using FESEM, the uniform distribution of DESG and APP in the PLA matrix was observed. The synergistic effect of DESG and APP effectively enhanced the flame retardancy of PLA. Additionally, the synergistic mechanism of DESG and APP in PLA was proposed.

Chemoresistance is one of the leading causes for the failure of tumor treatment. Hence, it is necessary to study further and understand the potential mechanisms of tumor resistance to design and develop novel anti-tumor drugs. Post-translational modifications are critical for proteins’ function under physiological and pathological conditions, among which ubiquitination is the most common one. The protein degradation process mediated by the ubiquitin-proteasome system is the most well-known function of ubiquitination modification. However, ubiquitination also participates in the regulation of many other biological processes, such as protein trafficking and protein-protein interaction. A group of proteins named deubiquitinases can hydrolyze the isopeptide bond and disassemble the ubiquitin-protein conjugates, thus preventing substrate proteins form degradation or other outcomes. Ubiquitin-specific protease 7 (USP7) is one of the most extensively studied deubiquitinases. USP7 exhibits a high expression signature in various malignant tumors, and increased USP7 expression often indicates the poor tumor prognosis, suggesting that USP7 is a marker of tumor prognosis and a potential drug target for anti-tumor therapy. In this review, we first discussed the structure and function of USP7. Further, we summarized the underlying mechanisms by which tumor cells develop resistance to anti-tumor therapies, provided theoretical support for targeting USP7 to overcome drug resistance, and some inspiration for the design and development of USP7 inhibitors.

Objective Endometriosis is a common disease in women of childbearing age, leading to sexual dysfunction or loss of libido. We aimed to evaluated the effect of endometriosis on women’s sexual function. Methods We performed a prospective case–control study to determine the effect of endometriosis on women’s sexual function using a self-administered questionnaire from September 2017 to August 2018. The simplified Chinese version of the Female Sexual Function Index (FSFI) was used to assess sexual function. Results We found that sexual function of women in the endometriosis group (n=77) in all dimensions was significantly lower compared with that in the control group (n=63). The total FSFI score in patients was 25.5, which tended to be lower than that in the control group (26.7). Sexual arousal, sexual pain, and satisfaction were significantly different between the two groups. Sexual arousal and sexual pain scores were significantly lower in the endometriosis group than in the control group at the ages of 31 to 40 years. Conclusion Women with endometriosis suffer from sexual dysfunction, especially those aged 31 to 40 years. Our findings suggest that the quality of sexual life in this subpopulation needs to be improved.

Direct conversion of fibroblasts into induced cardiomyocytes (iCMs) holds promising potential to generate functional cardiomyocytes for drug development and clinical applications, especially for direct in situ heart regeneration by delivery of reprogramming genes into adult cardiac fibroblasts in injured hearts. For a decade, many cocktails of transcription factors have been developed to generate iCMs from fibroblasts of different tissues in vitro and some were applied in vivo. Here, we aimed to develop genetic cocktails that induce cardiac reprogramming directly in cultured cardiac fibroblasts isolated from adult mice with myocardial infarction (MICFs), which could be more relevant to heart diseases. We found that the widely used genetic cocktail, Gata4, Mef2c, and Tbx5 (GMT) were inefficient in reprogramming cardiomyocytes from MICFs. In a whole well of a 12-well plate, less than 10 mCherry+ cells (

Numerous protein kinases encoded in the genome have become attractive targets for the treatment of different types of cancer. As of January 2020, a total of 52 small-molecule kinase inhibitors (SMKIs) have been approved by the FDA. With the numerous clinical trials and a heavy focus on drug safety, SMKI-induced cardiotoxicity, which is a life-threatening risk, has greatly attracted the attention of researchers. In this review, the SMKIs with cardiotoxicity incidence were described exhaustively. The data were collected from 42 clinical trials, 25 FDA-published documents, seven meta-analysis/systematic reviews, three case reports and more than 50 other types of articles. To date, 73% (38 of 52) of SMKIs have reported treatment-related cardiotoxicity. Among the 38 SMKIs with known cardiotoxicity, the rates of incidence of cardiac adverse events were QT prolongation: 47% (18 of 38), hypertension: 40% (15 of 38), left ventricular dysfunction: 34% (13 of 38), arrhythmia: 34% (13 of 38), heart failure: 26% (10 of 38) and ischemia or myocardial infarction: 29% (11 of 38). In the development process of novel SMKIs, more attention should be paid to balancing the treatment efficacy and the risk of cardiotoxicity. In preclinical drug studies, producing an accurate and reliable cardiotoxicity evaluation model is of key importance. To avoid the clinical potential cardiotoxicity risk and discontinuation of a highly effective drug, patients treated with SMKIs should be proactively monitored on the basis of a global standard. Moreover, the underlying mechanisms of SMKI-induced cardiotoxicity need to be further studied to develop new therapies for SMKI-induced cardiotoxicity.

In spatial databases, the objects have semantic attributes as well as geographic coordinates. Considering the two aspects, we propose the diameter-aware extreme group query (DiaEG query), which searches for good $k$ -item groups of objects. We mark the $k$ -groups according to both semantic closenesses and geographic diameters. On the one hand, the semantic closeness ensures that in the good group the members should be close to the semantic query point $q$ . On the other hand, the geographic diameter ensures that the members should be close to (or far from) each other geographically. The importances of the two aspects are evaluated by the weights $\alpha $ and $1-\alpha $ . Since for non-expert users it is difficult to assign an appropriate $\alpha $ , we propose two types of DiaEG queries, namely, the threshold-satisfaction query and the best-satisfaction query. The first type searches for good groups such that their total satisfaction is not smaller than a given threshold. The second type searches for the best group that has the highest satisfaction. The satisfaction of a group is the length of the $\alpha $ range, where the group keeps having the highest score. If we map the groups into the (semantic, geographic)-space, the query results are in fact the extreme points on the convex hull in the space. Using the properties of the convex hull, we propose efficient algorithms to answer two types of queries. Instead of enumerating all $k$ -groups, our algorithms can construct the groups incrementally and terminate once the results have been found. We conduct experiments on both real and synthetic data sets, and the experimental results show that the proposed algorithms can answer the DiaEG queries efficiently.

Historical villages bear historical, cultural, architectural, aesthetic, and landscape values, but they are facing a series of dangers and problems during the process of urbanization. Digital survey for traditional villages plays a crucial role in the preservation, planning, and development of this kind of heritage. The introduction of the terrestrial laser scanning technique is essential for heritage surveying, mapping, and modeling due to its advantages of noncontact measurement, accurate sensing of complex objects, and efficient operation. In recent years, TLS and related processing software (“SCENE”) have been widely presented as effective techniques for dealing with the management and protection of historical buildings in Fenghuang village. Thus, this paper highlights the process of using laser scanning to obtain architectural data, process point clouds, and compare the characteristics of historical buildings in Fenghuang village. The cloud-to-cloud registration technique is applied to build point clouds. As a result of model construction, some architectural patterns are summarized in this village, such as the spatial sequence of ancestral halls, the dominant position of memorial halls, and the character of building decorations and roof slopes. Furthermore, a BIM model is also explained to fulfill the statistical function for architectural components. In the future, more research can be fulfilled based on the built point cloud model, which will be beneficial for the development of the whole village.

Visual impairment is a global public health problem that needs new candidate drugs. Chrysanthemum is a traditional Chinese drug, famous for its eye-protective function, with an unclear mechanism of action. To determine how chrysanthemum contributes to vision, we identified, for the first time, the component of chrysanthemum, diosmetin (DIO), which acts in protecting the injured retina in an adriamycin (ADR) improving model. We observed that DIO could attenuate the apoptosis of retinal cells in Sprague–Dawley rats and verified this effect in cultured human retinal pigment epithelium (RPE) cells, ARPE-19. Our further study on the mechanism revealed the counteractive effect of DIO on the attenuation of DNA damage and oxidative stress, which occurs in a wide range of retinal disorders. These results collectively promise the potential value of DIO as a retinal-protective agent for disorders that lead to blindness. In addition, we identified, for the first time, the component of chrysanthemum, DIO, which acts in protecting the injured retina. Keywords: Apoptosis, Chrysanthemum, Diosmetin, DNA damage, Oxidative stress, Retinal injury, Retinal pigment epithelium

Real-time and accurate interaction technology is required to realize new wearable Mixed Reality (MR) solutions. At present, the mainstream interaction method relies on gesture detection technology, which has two shortcomings: 1. the hand feature points may easily be obstructed by obstacles and cannot be detected and 2. the kinds of gesture that can be recognized are limited. Hence, it cannot support complex interactions well. Moreover, the traditional collision detection algorithm has difficulty detecting the collision between real and virtual objects under motion. Because location information of real objects needs updating in real time, it is easy to lose collision detection under high speeds. In the implementation of our system, Mixed Reality Table Tennis System, we propose novel methods which overcome these shortcomings. Instead of using gesture detection technology, we use a locator as the main input device and build a data exchange channel for the devices, so that the system can update the motion state of the racket in real time. Besides, we adjust the thickness of the collider dynamically to solve the collision detection problem and calculate rebound results responding to the motion state of the racket and the ball. Experimental results show that our method avoids losing collision detection and improves the authenticity of simulation. It keeps good interaction in real time.

Collaboration efficiency is of primary importance in software development. It is widely recognized that choosing suitable developers is an efficient and effective practice for improving the efficiency of software development and collaboration. Recommending suitable developers is complex and time-consuming due to the difficulty of learning developers’ expertise and willingness. Existing works focus on learning developers’ expertise and interactions from their explicit historical information and matching them to specific task. However, such procedures may suffer low accuracy because they ignore implicit information, such as (1) developer–developer collaboration relationships, (2) developer–task implicit interaction relationships, and (3) task–task association relationships, etc. To that end, this paper proposes a multi-relationship fused approach for software developer recommendation (termed SoftRec). First, in addition to explicit developer–task interactions, it considers multivariate implicit relationships, including the three types mentioned above. Second, it integrates these relationships based on joint matrix factorization and generates forecast results upon the architecture of deep neural network. Furthermore, we propose a fast update method to address the cold start issue by making online recommendations for new developers and new tasks. Extensive experiments are conducted on two real-world datasets, and a user study is conducted in a well-known software company. The results demonstrate that SoftRec outperforms four state-of-the-art works.

Purpose. To determine the efficacy and safety of preoperative intravitreal conbercept (IVC) injection before vitrectomy for proliferative diabetic retinopathy (PDR). Methods. 107 eyes of 88 patients that underwent pars plana vitrectomy (PPV) for active PDR were enrolled. All patients were assigned randomly to either preoperative IVC group or control group. Follow-up examinations were performed for three months after surgery. The primary bioactivity measures were severity of intraoperative bleeding, incidence of early and late recurrent VH, vitreous clear-up time, and best-corrected visual acuity (BCVA) levels. The secondary safety measures included intraocular pressure, endophthalmitis, rubeosis, tractional retinal detachment, and systemic adverse events. Results. The incidence and severity of intraoperative bleeding were significantly lower in IVC group than in the control group. The average vitreous clear-up time of early recurrent VH was significantly shorter in IVC group compared with that in control group. There was no significant difference in vitreous clear-up time of late recurrent VH between the two groups. Patients that received pretreatment of conbercept had much better BCVA at 3 days, 1 week, and 1 month after surgery than control group. Moreover, both patients with improved BCVA were greater in IVC group than in control group at each follow-up. Conclusions. Conbercept pretreatment could be an effective adjunct to vitrectomy in accelerating postoperative vitreous clear-up and acquiring stable visual acuity restoration for PDR.