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Osteoarthritis (OA) is the most common joint disease characterized by degeneration of articular cartilage and causes severe joint pain, physical disability, and impaired quality of life. Recently, it was found that mitochondria not only act as a powerhouse of cells that provide energy for cellular metabolism, but are also involved in crucial pathways responsible for maintaining chondrocyte physiology. Therefore, a growing amount of evidence emphasizes that impairment of mitochondrial function is associated with OA pathogenesis; however, the exact mechanism is not well known. Moreover, the AMP-activated protein kinase (AMPK)–Sirtuin (SIRT) signaling pathway, long non-coding RNA (lncRNA), and microRNA (miRNA) are important for regulating the physiological and pathological processes of chondrocytes, indicating that these may be targets for OA treatment. In this review, we first focus on the importance of mitochondria metabolic dysregulation related to OA. Then, we show recent evidence on the AMPK-SIRT mediated pathway associated with OA pathogenesis and potential treatment options. Finally, we discuss current research into the effects of lncRNA and miRNA on OA progression or inhibition.

The quality of the natural sound environment is important for the well-being of humans and for urban sustainability. Therefore, it is important to study how the soundscape of the natural environment affects humans with respect to the different densities of vegetation, and how this affects the frequency of singing events and the sound pressure levels of common birds that generate natural sounds in a commonly visited urban park in Abuja, Nigeria. This study involves the recording of birdsongs, the measurement of sound pressure levels, and a questionnaire evaluation of sound perception and the degree of acoustic comfort in the park. Acoustic comfort, which affects humans, describes the fundamental feelings of users towards the acoustic environment. The results show that first, there is a significant difference between the frequency of singing events of birds for each category of vegetation density (low, medium, and high density) under cloudy and sunny weather conditions, but there is no significant difference during rainy weather. Secondly, the measured sound pressure levels of the birdsongs are affected by vegetation density. This study shows a significant difference between the sound pressure levels of birdsongs and the vegetation density under cloudy, sunny, and rainy weather conditions. In addition, the frequency of singing events of birds is affected by the sound pressure levels of birdsongs with respect to different vegetation densities under different weather conditions. Thirdly, the results from the respondents (N = 160) in this study indicated that the acoustic perception of the park was described as being pleasant, vibrant, eventful, calming, and not considered to be chaotic or annoying in any sense. It also shows that the human perception of birdsong in the park was moderately to strongly correlated with different densities of vegetation, and that demographics play an important role in how natural sounds are perceived in the environment under different weather conditions.

This article discusses the current progress of the on-going design efforts in creating an AI-enabled gamified web-based online learning application in the university introductory physics courses. The application aims to cater to the learning needs of students with diversity of the background, particularly students with little or weak background. The overall design architecture and principles are discussed, focusing on the rationale and design of the gamified elements that have been incorporated within the application, namely: (i) incremental difficulties, (ii) points and streaks, (iii) leaderboard, and (iv) gamified and animated user interface. Particularly, the gamified elements are considered through the lens of the ‘Head, Hands, and Heart’ of the students, with the objective to first encourage and motivate participation, stimulate practice, and strengthen the students’ domain knowledge of physics. In this article, an architecture to incorporate AI program into the web-based gamification platform by including various AI models (learner model, pedagogy model and domain model) is proposed. With the architecture, we aim to create a personalized tutor that provide effective and unique learning experience to help a learner achieve learning objectives. The AI enabled gamification platform also serves as an efficient feedback tool to teacher for optimization and redesigning of curriculum to best suit the need of individual learner.

The PD-1/PD-L1 pathway blockade can generate a good clinical response by reducing immunosuppression and provoking durable antitumor immunity. In addition to antibodies, aptamers can also block the interaction between PD-1 and PD-L1. For the in vivo application, however, free aptamers are usually too small in size and quickly removed from blood via glomerular filtration. To avoid renal clearance of aptamer, we conjugated the PD-L1 aptamer to albumin to form a larger complex (BSA-Apt) and evaluated whether BSA-Apt would enhance the in vivo antitumor efficacy. The PD-L1 aptamer was thiol-modified and conjugated to the amino group of BSA via a SMCC linker. The average size of BSA-Apt was 11.65 nm, which was above the threshold for renal clearance. Functionally, BSA-Apt retained the capability of the PD-L1 aptamer to bind with PDL1-expressing tumor cells. Moreover, both the free aptamer and BSA-Apt augmented the PBMC-induced antitumor cytotoxicity in vitro. Furthermore, BSA-Apt generated a significantly stronger antitumor efficacy than the free PD-L1 aptamer in vivo without raising systemic toxicity. The results indicate that conjugating the PD-L1 aptamer to albumin may serve as a promising strategy to improve the in vivo functionality of the aptamer and that BSA-Apt may have application potential in cancer immunotherapy.

Abstract Background Genome-wide association analysis is a powerful tool for annotating phenotypic effects on the genome and knowledge of genes and chromosomal regions associated with dairy phenotypes is useful for genome and gene-based selection. Here, we report results of a genome-wide analysis of predicted transmitting ability (PTA) of 31 production, health, reproduction and body conformation traits in contemporary Holstein cows. Results Genome-wide association analysis identified a number of candidate genes and chromosome regions associated with 31 dairy traits in contemporary U.S. Holstein cows. Highly significant genes and chromosome regions include: BTA13's GNAS region for milk, fat and protein yields; BTA7's INSR region and BTAX's LOC520057 and GRIA3 for daughter pregnancy rate, somatic cell score and productive life; BTA2's LRP1B for somatic cell score; BTA14's DGAT1-NIBP region for fat percentage; BTA1's FKBP2 for protein yields and percentage, BTA26's MGMT and BTA6's PDGFRA for protein percentage; BTA18's 53.9-58.7 Mb region for service-sire and daughter calving ease and service-sire stillbirth; BTA18's PGLYRP1-IGFL1 region for a large number of traits; BTA18's LOC787057 for service-sire stillbirth and daughter calving ease; BTA15's CD82, BTA23's DST and the MOCS1-LRFN2 region for daughter stillbirth; and BTAX's LOC520057 and GRIA3 for daughter pregnancy rate. For body conformation traits, BTA11, BTAX, BTA10, BTA5, and BTA26 had the largest concentrations of SNP effects, and PHKA2 of BTAX and REN of BTA16 had the most significant effects for body size traits. For body shape traits, BTAX, BTA19 and BTA3 were most significant. Udder traits were affected by BTA16, BTA22, BTAX, BTA2, BTA10, BTA11, BTA20, BTA22 and BTA25, teat traits were affected by BTA6, BTA7, BTA9, BTA16, BTA11, BTA26 and BTA17, and feet/legs traits were affected by BTA11, BTA13, BTA18, BTA20, and BTA26. Conclusions Genome-wide association analysis identified a number of genes and chromosome regions associated with 31 production, health, reproduction and body conformation traits in contemporary Holstein cows. The results provide useful information for annotating phenotypic effects on the dairy genome and for building consensus of dairy QTL effects.

Data presented in this article are supplementary materials to the research article entitled “IGFBP2 regulates PD-L1 expression by activating the EGFR-STAT3 signaling pathway in malignant melanoma”. Data for melanoma patients who did not receive anti-PD-1 treatment were obtained from Tianjin Medical University Cancer Institute & Hospital from February 1981 to May 2013. Kaplan–Meier was used for survival analysis. RNA sequencing data from 28 melanoma patients receiving anti-PD-1 therapy were download from GEO database (GSE78220). Cluster analysis of RNA expression was performed using R (package pheatmap). The difference of PD-L1 expression was analysed by the Boxplot (R ggplot2 package). Differences between each group were analyzed by Fisher exact test. Information of 13 melanoma patients who had failed prior chemotherapy and treated in the Tianjin Medical University Cancer Institute & Hospital between July 2015 and December 2018 was collected. The response was captured by Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1).

Understanding the temporal and spatial patterns of soil water extraction and their impacts on growth response of winter wheat to deficit subsurface drip irrigation (SDI) conditions is critical for managing water scarcity and stabilizing yield. A field experiment was conducted from 2016 to 2018 involving five SDI amounts: 0.25, 0.4, 0.6, 0.8, and 1.0 ETc, representing 25, 40, 60, 80, and 100% of crop evapotranspiration (ETc), respectively. The results showed that the 0.6 ETc treatment significantly increased soil water extraction from 40–80 and 80–140-cm from jointing to maturity as compared to the 1.0 ETc treatment. Whereas the 0.8 ETc treatment significantly increased soil water extraction from 80–140-cm deep soil from flowering to maturity in the first growing season. The crop was most water-stressed under the 0.25 and 0.4 ETc treatments, thus extracted more soil water from 0–140-cm soil profile. However, both treatments exhibited minimum plant tillers, lowest leaf water content, leaf area index (LAI), photosynthetic rate (Pn), and transpiration rate (Tr) as well as grain yield. All these parameters, except for leaf water content, Pn after the flowering stage, and grain productivity, were also reduced in the 0.6 ETc treatment than the 1.0 ETc treatment. The differences between the 0.8 and 1.0 ETc treatments were minor in terms of plant height, LAI, spike number, Pn and Tr, but infertile tillers were fewer in the 0.8 ETc treatment. We obtained high yield from the 0.8 ETc treatment, and the 0.6ETc treatment resulted in the highest harvest index with improved WUE than other treatments. Integrating deficit irrigation into SDI can save water in winter wheat production in water-limited regions, which can not only enhance soil water extraction from deep soil layers, but also sustained yield by stimulating crop growth. Therefore, a deficit SDI system would be used to conserve water in water-limited regions.

Abstract Background Genetic polymorphisms at 23 short tandem repeat (STR) loci were investigated in 1,215 Jining Han individuals from Jining city, Shandong province, eastern China. Methods We used population genetic data of 23 autosomal STR loci included in the Huaxia Platinum system to evaluate 1,215 unrelated Chinese Han individuals in the Jining Han population. Allele frequencies and forensic parameters of the STR loci were determined and genetic relationships among the Jining Han and other Chinese populations were evaluated. Results In total, we observed 321 alleles, with frequencies ranging from 0.00041 to 0.52222. The combined discrimination power and probability of excluding paternity were 0.99999999999999999999999999919 and 0.99999999962, respectively. No deviations from HWE were observed at any loci. Population comparisons showed that the Xinjiang groups (Uyghur and Kazakh) and the Mongolian and Tibetan groups were isolated, while the Jining Han population clustered together with other populations, except the Guizhou Han population. Conclusion This study demonstrated that 23 autosomal STR loci included in the Huaxia Platinum system are highly polymorphic and suitable for personal forensic identification and paternity testing in this population.

Work zones widely exist on urban roads in many countries and have a significant negative impact on traffic. Few studies have focused on modeling the traffic flow of the work zone on the urban arterials, especially on the work zone at the intersections. In this paper, a microscopic model based on the social force theory for the traffic flow of the intersection with a specific work zone, called straddling work zone, is proposed. The model can capture the no lane division and irregular boundary characteristics of the traffic of the intersection with a straddling work zone and also can reflect the interaction of the intersection traffic flows from the two opposite directions. The proposed model is calibrated and validated using the real work zone data, and the results display that the MARE values are all less than 10%. The factors affecting the traffic flow in the straddling work zone are analyzed through simulation. Our study reveals that the distance from the lower edge of the work zone to the median divider of the road and the proportion of large vehicles in the work zone have the greatest impact on the signalized intersection, which provides a reference for the future traffic control at the intersection with the straddling work zone.

In this study the authors build lncRNA-drug response models for 265 anti-cancer agents across 27 cancer types. They report their cancer cell line based lncRNA EN-models are able to effectively predict therapeutic outcome for breast cancer, ovarian cancer, endometrial cancer and stomach cancer patients.

Abstract In this study, we synthesized a periodic polystyrene nanosphere (PS NS) array using the dip-drop method with post-deposition etching to improve the light extraction efficiency (LEE) of InGaN/GaN light-emitting diodes (LEDs). The dip-drop method has advantages such as simple procedure, inexpensive equipment, room temperature deposition, and easy implementation in LEDs. The arrangement of PS NSs on an indium-tin-oxide (ITO)-coated glass substrate depends on the average dip-drop speed and the concentration of the PS NS suspension. The periodic PS NS array can modulate the in-plane wave vector of emission light from a semiconductor to free space and thus increase the escape probability. The calculated and experimental results indicated that the light output intensity of the InGaN/GaN LEDs can be improved by using the periodic PS NS array as a window layer; this array comprises PS NSs with a diameter of 100 nm separated with periods of 100 and 100 nm in the x and y directions. Because of the improved LEE, the InGaN/GaN LEDs with the optimal PS NS array window layers exhibited a 38% increase in light output intensity compared with the conventional InGaN/GaN LEDs under 20-mA driving current.

Abstract Background The relationship between platelet reactivity and long-term clinical outcomes remains controversial. The present prospective study was designed to explore the association between high platelet reactivity (HPR) on clopidogrel and long-term clinical outcomes following implantation of drug eluting stents (DES). Methods A total of 1769 consecutive patients assessed by Aggrestar (PL-11) were enrolled at our center from February 2011 to December 2017. The primary end point was major adverse cardiovascular and cerebrovascular events (MACCE), defined as definite or probable stent thrombosis, spontaneous myocardial infarction, all cause death, clinically driven target vessel revascularization (TVR), or ischemic stroke. Bleeding served as the safety endpoint. Propensity score matching (PSM) analysis was performed to adjust for baseline differences in the overall cohort. Results Finally, 409 patients (23.1%) were identified with HPR on clopidogrel. At a median follow-up of 4.1 years (interquartile range, 1.8 years), the occurrence of MACCE was significantly higher in HPR on clopidogrel group than normal platelet reactivity (NPR) on clopidogrel group (15.6% vs. 5.4%, p

Identifying biomarkers for hearing impairments (HIs) in patients with neonatal hypoxic–ischemic encephalopathy (HIE), to initialize early hearing habilitation, is crucial. Seventy-eight neonates with HIE were divided into the following two groups: those with HIs and those without HIs. We compared those patients with 11,837 newborns without HIE, and analyzed the risk factors of HIs among neonatal HIE. Of the 78 patients, 11 were confirmed to have an HI, which is a substantially higher percentage than in the 11,837 newborns without HIE (14.1% vs. 0.87%; p < 0.001). More patients with moderate-to-severe HIE had confirmed HIs (p = 0.020; odds ratio, 8.61) than those with mild HIE. Clinical staging, and blood lactate and glucose levels could be predictive factors for HIs among patients with HIE. The patients who exhibited HIs had significantly higher lactate (104.8 ± 51.0 vs. 71.4 ± 48.4; U = 181, p = 0.032) and serum glucose (159.5 ± 86.1 vs. 112.1 ± 62.3; U = 166, p = 0.036) levels than those without HIs. A higher prevalence of HIs was noted in the patients with stage III HIE than those with stage II HIE (43.8% vs. 10%; p = 0.008). The degree of HI correlated with brain anomalies and neurodevelopmental outcomes at 1 year of age. Clinical staging, and blood lactate and glucose levels could be predictive factors for HIs among patients with HIE.

An InGaN laser diode with InGaN–GaN–InGaN delta barriers was designed and investigated numerically. The laser power–current–voltage performance curves, carrier concentrations, current distributions, energy band structures, and non-radiative and stimulated recombination rates in the quantum wells were characterized. The simulations indicate that an InGaN laser diode with InGaN–GaN–InGaN delta barriers has a lower turn-on current, a higher laser power, and a higher slope efficiency than those with InGaN or conventional GaN barriers. These improvements originate from modified energy bands of the laser diodes with InGaN–GaN–InGaN delta barriers, which can suppress electron leakage out of, and enhance hole injection into, the active region.

Simulated Moving Bed (SMB) chromatography separation is an innovative technology that combines conventional fixed bed adsorption and true moving bed (TMB) chromatography separation techniques. Through analysis of the SMB chromatography isolation method, we have identified auxiliary variables for the soft-sensing model and key economic and technical indicators for the forecasting model. Our objective is to predict the component purity and yield of the elicit and residual solution in the SMB chromatographic separation process. To achieve this, we have utilized three different soft-sensing modeling methods: incremental extreme learning machine (I-ELM), inverse-free extreme learning machine (IF-ELM), and incremental regularized extreme learning machine (IR-ELM). Our simulation results demonstrate the effectiveness and accuracy of these ELM methods in predicting essential economic and technical gauges in the SMB chromatographic separation process. These methods enable instantaneous, optimized, and resilient operation of SMB chromatography separation. Overall, SMB chromatography separation represents an advanced technology that enhances traditional techniques, and our study highlights the efficacy of various ELM methods in predicting essential process indicators, thereby ensuring optimal operation. [ABSTRACT FROM AUTHOR]

Heavy oil is characterized by high viscosity. High viscosity makes it challenging to recover and transport. HZSM-5, MoO3/HZSM-5, ZrO2/HZSM-5 and MoO3eZrO2/HZSM-5 catalysts were developed to promote in situ desulfurization and viscosity reduction of heavy oil. The physical and chemical properties of catalysts were characterized by XPS, XRD, TEM, NH3-TPD, etc. The effects of temperature, catalyst type and addition amount on viscosity and composition of heavy oil were evaluated. The results showed that the presence of MoO3eZrO2/HZSM-5 nanoparticles during aquathermolysis could improve the oil quality by reducing the heavy fractions. It reduced viscosity by 82.56% after the reaction at 280 °C and catalyst addition of 1 wt%. The contents of resins and asphaltic in the oil samples were 5.69% lower than that in the crude oil. Sulfur content decreased from 1.45% to 1.03%. The concentration of H2S produced by the reaction was 2225 ppm. The contents of sulfur-containing functional groups sulfoxide and sulfone sulfur in the oil samples decreased by 19.92% after the catalytic reaction. The content of stable thiophene sulfur increased by 5.71%. This study provided a basis for understanding the mechanism of heavy oil desulfurization and viscosity reduction. [ABSTRACT FROM AUTHOR]

Abstract Interleukin-6 acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. IL-6/IL-6R signaling pathway, in particular, has been proposed to be a pivotal cytokine promoting ovarian cancer progression. This study aimed to elucidate potential clinical and biological function of IL-6R mRNA expression in ovarian cancer. We used the keywords “ovarian cancer” and searched through GEO database and finally a total of 7 studies together with TCGA database were incorporated in this analysis. We used Cutoff Finder to determine a cutoff point and stratified patients into two groups and found that high-expression of IL-6R mRNA in tumor tissues was a positive prognostic factor for overall survival. Simultaneously, high expression level of IL-6R mRNA correlates with better survival of patients who had additional chemotherapy treatment. These analyses suggested a possible role of tumoral expression of IL-6R in ovarian cancer. In conclusion, our results showed that mRNA levels of IL-6R in ovarian cancer was positively associated with better prognosis and sensitivity to chemotherapy and can potentially be used as a prognostic marker for this cancer.