Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of iNOS in osteoarthritis: Pathological and therapeutic aspects

Accumulating evidence suggests that inflammation has a key role in the pathogenesis of osteoarthritis (OA). Nitric oxide (NO) has been established as one of the major inflammatory mediators in OA and drives many pathological changes during the development and progression of OA. Excessive production of NO in chondrocytes promotes cartilage destruction and cellular injury. The synthesis of NO in chondrocytes is catalyzed by inducible NO synthase (iNOS), which is thereby an attractive therapeutic target for the treatment of OA. A number of direct and indirect iNOS inhibitors, bioactive compounds, and plant‐derived small molecules have been shown to exhibit chondroprotective effects by suppressing the expression of iNOS. Many of these iNOS inhibitors hold promise for the development of new, disease‐modifying therapies for OA; however, attempts to demonstrate their success in clinical trials are not yet successful. Many plant extracts and plant‐derived small molecules have also shown promise in animal models of OA, though further studies are needed in human clinical trials to confirm their therapeutic potential. In this review, we discuss the role of iNOS in OA pathology and the effects of various iNOS inhibitors in OA.
Inactivation of mesotrypsin by chymotrypsin C prevents trypsin inhibitor degradation

Mesotrypsin is an unusual human trypsin isoform with inhibitor resistance and the ability to degrade trypsin inhibitors. Degradation of the protective serine protease inhibitor Kazal type 1 (SPINK1) by mesotrypsin in the pancreas may contribute to the pathogenesis of pancreatitis. Here we tested the hypothesis that the regulatory digestive protease chymotrypsin C (CTRC) mitigates the harmful effects of mesotrypsin by cleaving the autolysis loop. As human trypsins are post-translationally sulfated in the autolysis loop, we also assessed the effect of this modification. We found that mesotrypsin cleaved in the autolysis loop by CTRC exhibited catalytic impairment on short peptides due to a 10-fold increase in Km, it digested β-casein poorly and bound soybean trypsin inhibitor with 10-fold decreased affinity. Importantly, CTRC-cleaved mesotrypsin degraded SPINK1 with markedly reduced efficiency. Sulfation increased mesotrypsin activity but accelerated CTRC-mediated cleavage of the autolysis loop and did not protect against the detrimental effect of CTRC cleavage. The observations indicate that CTRC-mediated cleavage of the autolysis loop in mesotrypsin decreases protease activity and thereby protects the pancreas against unwanted SPINK1 degradation. The findings expand the role of CTRC as a key defense mechanism against pancreatitis through regulation of intrapancreatic trypsin activity.
Facilitative and synergistic interactions between fungal and plant viruses

Significance Unlike other eukaryotic viruses, fungal viruses generally lack an extracellular phase in their life cycle. It thus remains unclear whether fungal viruses can spread beyond their native hosts. Herein, we investigated the infectivity of a fungal virus, Cryphonectria hypovirus 1 (CHV1) in Nicotiana tabacum plants. CHV1 is able to systemically infect plants after mechanical coinoculations with plant viruses such as tobacco mosaic virus (TMV) or when inoculated to transgenic plants expressing the TMV movement protein. In the fungal inoculation experiment, we demonstrated that plant virus infections in plants enable horizontal transfer of CHV1 from fungi to plants and to other heterologous fungal species. Hence, our results reveal a facilitative effect of plant viruses in spreading fungal viruses. Plants and fungi are closely associated through parasitic or symbiotic relationships in which bidirectional exchanges of cellular contents occur. Recently, a plant virus was shown to be transmitted from a plant to a fungus, but it is unknown whether fungal viruses can also cross host barriers and spread to plants. In this study, we investigated the infectivity of Cryphonectria hypovirus 1 (CHV1, family Hypoviridae), a capsidless, positive-sense (+), single-stranded RNA (ssRNA) fungal virus in a model plant, Nicotiana tabacum. CHV1 replicated in mechanically inoculated leaves but did not spread systemically, but coinoculation with an unrelated plant (+)ssRNA virus, tobacco mosaic virus (TMV, family Virgaviridae), or other plant RNA viruses, enabled CHV1 to systemically infect the plant. Likewise, CHV1 systemically infected transgenic plants expressing the TMV movement protein, and coinfection with TMV further enhanced CHV1 accumulation in these plants. Conversely, CHV1 infection increased TMV accumulation when TMV was introduced into a plant pathogenic fungus, Fusarium graminearum. In the in planta F. graminearum inoculation experiment, we demonstrated that TMV infection of either the plant or the fungus enabled the horizontal transfer of CHV1 from the fungus to the plant, whereas CHV1 infection enhanced fungal acquisition of TMV. Our results demonstrate two-way facilitative interactions between the plant and fungal viruses that promote cross-kingdom virus infections and suggest the presence of plant–fungal-mediated routes for dissemination of fungal and plant viruses in nature.
Quantitative Study of Dual Circadian Oscillator Models under Different Skeleton Photoperiods

The daily proportion of light and dark hours (photoperiod) changes annually and plays an important role in the synchronization of seasonal biological phenomena, such as reproduction, hibernation, and migration. In mammals, the first step of photoperiod transduction occurs in the suprachiasmatic nuclei (SCN), the circadian pacemaker that also coordinates 24-h activity rhythms. Thus, in parallel with its role in annual synchronization, photoperiod variation acutely shapes day/night activity patterns, which vary throughout the year. Systematic studies of this behavioral modulation help understand the mechanisms behind its transduction at the SCN level. To explain how entrainment mechanisms could account for daily activity patterns under different photoperiods, Colin Pittendrigh and Serge Daan proposed a conceptual model in which the pacemaker would be composed of 2 coupled, evening (E) and morning (M), oscillators. Although the E-M model has existed for more than 40 years now, its physiological bases are still not fully resolved, and it has not been tested quantitatively under different photoperiods. To better explore the implications of the E-M model, we performed computer simulations of 2 coupled limit-cycle oscillators. Four model configurations were exposed to systematic variation of skeleton photoperiods, and the resulting daily activity patterns were assessed. The criterion for evaluating different model configurations was the successful reproduction of 2 key behavioral phenomena observed experimentally: activity psi-jumps and photoperiod-induced changes in activity phase duration. We compared configurations with either separate light inputs to E and M or the same light inputs to both oscillators. The former replicated experimental results closely, indicating that the configuration with separate E and M light inputs is the mechanism that best reproduces the effects of different skeleton photoperiods on day/night activity patterns. We hope this model can contribute to the search for E and M and their light input organization in the SCN.
Shale gas development has limited effects on stream biology and geochemistry in a gradient-based, multiparameter study in Pennsylvania

Significance This investigation provides a comprehensive evaluation of the geochemical and biological effects of shale gas development on 25 small watersheds over the course of 2 y. Sampling headwater streams seasonally over two consecutive years yielded no statistically significant relationships between the intensity, presence, or absence of shale gas development and any signal in a comprehensive set of chemical constituents (including those recognized as oil and gas geochemical tracers) or any changes in microbial or benthic macroinvertebrate community composition. This work provides a framework for investigations of anthropogenic effects stemming from natural resource development, and highlights the importance of conducting studies which control for regional and temporal variability. The number of horizontally drilled shale oil and gas wells in the United States has increased from nearly 28,000 in 2007 to nearly 127,000 in 2017, and research has suggested the potential for the development of shale resources to affect nearby stream ecosystems. However, the ability to generalize current studies is limited by the small geographic scope as well as limited breadth and integration of measured chemical and biological indicators parameters. This study tested the hypothesis that a quantifiable, significant relationship exists between the density of oil and gas (OG) development, increasing stream water concentrations of known geochemical tracers of OG extraction, and the composition of benthic macroinvertebrate and microbial communities. Twenty-five headwater streams that drain lands across a gradient of shale gas development intensity were sampled. Our strategy included comprehensive measurements across multiple seasons of sampling to account for temporal variability of geochemical parameters, including known shale OG geochemical tracers, and microbial and benthic macroinvertebrate communities. No significant relationships were found between the intensity of OG development, shale OG geochemical tracers, or benthic macroinvertebrate or microbial community composition, whereas significant seasonal differences in stream chemistry were observed. These results highlight the importance of considering spatial and temporal variability in stream chemistry and biota and not only the presence of anthropogenic activities in a watershed. This comprehensive, integrated study of geochemical and biological variability of headwater streams in watersheds undergoing OG development provides a robust framework for examining the effects of energy development at a regional scale.
Functional COL1A1 variants are associated with the risk of acute musculoskeletal soft tissue injuries

Studies have reported the association of the COL1A1 Sp1 binding site variant (rs1800012) with the risk of acute musculoskeletal soft tissue injuries. Interaction with the COL1A1 promoter variant (rs1107946) has also been proposed to modulate acute injury risk. Conversely, neither of these loci have been associated with chronic musculoskeletal soft tissue phenotypes. Therefore, the primary aim of this study involved characterizing these variants in a cohort of participants with chronic Achilles tendinopathy. Second, this study aimed to support the contribution of the rs1107946 and rs1800012 variants to the profile predisposing for acute musculoskeletal soft tissue injuries including Achilles tendon and anterior cruciate ligament (ACL) ruptures. A hypothesis‐driven association study was conducted. In total, 295 control participants, 210 participants with clinically diagnosed Achilles tendinopathy, and 72 participants with Achilles tendon ruptures recruited independently from South Africa and the United Kingdom were genotyped for the prioritized variants. In addition, a cohort including 232 control participants and 234 participants with surgically diagnosed ACL ruptures was also analyzed. Although no associations were observed in the recruited cohorts, the rare rs1800012 TT genotype was associated with decreased ACL injury risk when the results from the current study were combined with that from previously published studies (P = .040, OR: 2.8, 95% CI: 1.0‐11.0). In addition, the G‐T (rs1107946‐rs1800012) inferred haplotype was associated with decreased risk for Achilles tendon ruptures. These results support previous observations and reiterate the heterogeneity of musculoskeletal phenlotypes whereby certain markers may be common to the predisposing profiles while others may be unique.
Kidney transplantation on extracorporeal life support for primary cardiac allograft dysfunction

Patients undergoing heart‐kidney transplants who have primary graft dysfunction (PGD) of the heart are at risk of losing both organs, which may cause reluctance on the part of the transplant team to proceed with transplanting the kidney while the transplanted heart is being supported by mechanical device. We describe a case series in which 2 patients received kidney transplants while on veno‐arterial ECMO support for PGD after heart transplant. Both patients are alive more than 1 year following transplant, with good cardiac and renal function and no signs of cardiac rejection. Kidney transplant surgery is safe for patients on veno‐arterial ECMO support for cardiac PGD. It allows the heart recipient to receive a kidney from the same donor with both immunologic and survival advantages.
Simple and Efficient AlN-Based Piezoelectric Energy Harvesters

In this work, we demonstrate the simple fabrication process of AlN-based piezoelectric energy harvesters (PEH), which are made of cantilevers consisting of a multilayer ion beam-assisted deposition. The preferentially (001) orientated AlN thin films possess exceptionally high piezoelectric coefficients d33 of (7.33 ± 0.08) pC∙N−1. The fabrication of PEH was completed using just three lithography steps, conventional silicon substrate with full control of the cantilever thickness, in addition to the thickness of the proof mass. As the AlN deposition was conducted at a temperature of ≈330 °C, the process can be implemented into standard complementary metal oxide semiconductor (CMOS) technology, as well as the CMOS wafer post-processing. The PEH cantilever deflection and efficiency were characterized using both laser interferometry, and a vibration shaker, respectively. This technology could become a core feature for future CMOS-based energy harvesters.
LncRNA CASC2 regulates high glucose-induced proliferation, extracellular matrix accumulation and oxidative stress of human mesangial cells via miR-133b/FOXP1 axis.

OBJECTIVE Diabetic nephropathy (DN) is one of the primary complications of diabetes. Long non-coding RNA cancer susceptibility candidate 2 (CASC2) has been established to function in DN, while its role in high glucose (HG)-induced human mesangial cells (HMCs) remains limited. MATERIALS AND METHODS The expression level of CASC2 and miR-133b was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was assessed using cell counting kit-8 (CCK-8) assay. Extracellular matrix (ECM) accumulation was monitored through the expression levels of collagen IV (Col IV) and fibronectin (FN) using qRT-PCR and western blot analyses. Oxidative stress was observed through the expression of NADPH oxidase2 (NOX2) and the activity of malondialdehyde (MDA) and superoxide dismutase (SOD) using western blot or corresponding detection kit. The expression of forkhead box P1 (FOXP1) at mRNA and protein levels was determined by qRT-PCR and Western blot, respectively. The relationship between miR-133b and CASC2 or FOXP1 was predicted by online bioinformatics tools and verified by dual-luciferase reporter assay or RNA pull-down. RESULTS The expression of CASC2 was reduced in serum from DN patients and HG-induced HMCs. CASC2 upregulation inhibited HG-induced HMCs proliferation, ECM accumulation and oxidative stress. MiR-133b was a target of CASC2 with a high level in serum from DN patients and HG-induced HMCs, and its enrichment reversed the effects of CASC2 upregulation. Besides, FOXP1 was a target of miR-133b with a low level in HG-induced HMCs, and its knockdown abolished the impacts of CASC2 upregulation. CONCLUSIONS CASC2 upregulation suppressed HG-induced proliferation, ECM accumulation and oxidative stress of HMCs through miR-133b /FOXP1 regulatory axis, suggesting that CASC2 was a novel biomarker for DN treatment.
Association of Vitamin D Receptor Gene Polymorphisms With Melanoma Risk: A Meta-analysis and Systematic Review

Background/Aim: Increasing evidence indicates a relevance of the vitamin D endocrine system for pathogenesis of malignant melanoma. We performed a systematic review and meta-analysis to update previous reports that investigated the association between vitamin D receptor (VDR) gene polymorphisms and melanoma risk. Materials and Methods: A comprehensive literature search (PubMed, ISI Web of Science) identified a total of 14 studies that were eligible for inclusion in our meta-analysis. In the statistical analysis, the ORs and the 95% CIs were calculated for the dominant and recessive models for seven VDR gene polymorphisms, namely rs2228570 (FokI), rs731236 (TaqI), rs1544410 (BsmI), rs4516035 (A-1012G), rs11568820 (Cdx2), rs7975232 (ApaI) and rs739837 (BglI). Results were illustrated in Forest Plots. Publication bias was tested using Funnel Plots and the Egger's test. Results: Our meta-analysis showed in the dominant model (Bb + BB vs. bb) a significant association of a 15% risk reduction in malignant melanoma incidence for carriers of the rarer allele B of rs1544410 (Bsml). Notably, the dominant model (Ff + ff vs. FF) of rs2228570 (FokI) demonstrates that carriers of the rarer allele f are 22% more likely to develop malignant melanoma. For rs7975232 (ApaI), there is a 20% higher risk of melanoma for carriers of the rarer a allele (Aa + aa vs. AA). The results of the meta-analysis revealed no significant association between melanoma risk and the other investigated VDR polymorphisms. Conclusion: The VDR variants FokI, ApaI and BsmI may influence the susceptibility to developing melanoma. These findings support the concept, that the vitamin D endocrine system is of importance for pathogenesis of malignant melanoma.
Differences among Saudi and Expatriate Students: Body Composition Indices, Sitting Time Associated with Media Use and Physical Activity Pattern

Background: Being overweight at a young age is a predictor of developing obesity and related complications later in adulthood, posing a high risk to public health. Various ethnic subgroups have been identified as having a higher prevalence of overweight or obese. Saudi Arabia is one of the fastest-growing economies in the world, where the expatriate population comprises 33% of its total population. The objective of this study was to investigate differences in body composition indices, sitting time associated with media use, and physical activity pattern among a sample of local and expatriate school students in Saudi Arabia. Methods: 500 students (aged 8–18 years) from various schools were invited to participate in this study. Body weight, waist circumference (WC) and height were measured using a portable digital metric scale, standard measuring tape and wall mounted tape respectively. Participants and their parents were jointly asked to report the average time that the participant spent sitting using media (watching TV, playing video games, and using the internet and other screen-based devices etc.) per day. The pattern of physical activity among participants was measured using a short form of the International Physical Activity Questionnaire (IPAQ). Basal metabolic rate (BMR) and total daily energy expenditure (TEE) were estimated from body weight, height, age, sex and physical activity, according to the Harris–Benedict equation. Results: Data from 450 (90%) of the participants were used for analysis. The mean age of the participants was 14.55 ± 1.74 years. Body mass index (BMI), WC, waist to height ratio (WHtR), BMR and TEE differed significantly among the participants. Physical fitness score negatively correlated with BMI and WC, while sitting time associated with media use positively correlated with BMI, WC, WHtR and physical fitness score, among both Saudi and expatriate participants. Conclusions: Body composition indices and sitting time associated with media use were higher among Saudi boys and expatriate girls. Expatriate boys and girls were reported to be physically more active than their Saudi counterparts. BMR and TEE were higher among expatriate boys and Saudi girls. Although this study provides useful information about the association of body composition indices, sitting time associated with media use, and physical activity pattern among local and expatriate school students in SA, similar studies involving a larger study sample, with equal gender representation, are further required to determine various factors associated with this link.
Improved Saliency Detection in RGB-D Images Using Two-Phase Depth Estimation and Selective Deep Fusion

To solve the saliency detection problem in RGB-D images, the depth information plays a critical role in distinguishing salient objects or foregrounds from cluttered backgrounds. As the complementary component to color information, the depth quality directly dictates the subsequent saliency detection performance. However, due to artifacts and the limitation of depth acquisition devices, the quality of the obtained depth varies tremendously across different scenarios. Consequently, conventional selective fusion-based RGB-D saliency detection methods may result in a degraded detection performance in cases containing salient objects with low color contrast coupled with a low depth quality. To solve this problem, we make our initial attempt to estimate additional high-quality depth information, which is denoted by Depth+. Serving as a complement to the original depth, Depth+ will be fed into our newly designed selective fusion network to boost the detection performance. To achieve this aim, we first retrieve a small group of images that are similar to the given input, and then the inter-image, nonlocal correspondences are built accordingly. Thus, by using these inter-image correspondences, the overall depth can be coarsely estimated by utilizing our newly designed depth-transferring strategy. Next, we build fine-grained, object-level correspondences coupled with a saliency prior to further improve the depth quality of the previous estimation. Compared to the original depth, our newly estimated Depth+ is potentially more informative for detection improvement. Finally, we feed both the original depth and the newly estimated Depth+ into our selective deep fusion network, whose key novelty is to achieve an optimal complementary balance to make better decisions toward improving saliency boundaries.
Chitosan-Stabilized Noble Metal Nanoparticles: Study of their Shape Evolution and Post-Functionalization Properties

Noble metal anisotropic nanostructures have achieved a growing interest in both academic and industrial domains mostly because of their shape-dependent plasmonic properties in the near-infrared region. In this paper, gold and gold-silver anisotropic nanostructures were synthesized in very high shape-yields through a wet, seed-mediated approach based on the use of nearly spherical silver nanoparticles as seeds and chitosan as stabilizing agent. Two chitosans of different origin and molecular properties were selected for the synthetic pathway, leading to the formation of variously sized and shaped end products. In detail, quite homogeneous nanoplatelets of about 25-nm size and 7-nm thickness or nearly spherical, highly porous nanocages of about 50-nm size were obtained, depending on the type of polysaccharide employed. The shape transition towards anisotropic morphologies occurred through a slow, spontaneous process, in which the chitosan nature seemed to play a key role. As expected, both nanoplatelets and nanocages exhibit shape-dependent plasmonic features and surface properties tunable for a variety of application fields. To prove this point, the nanostructures were successfully post-functionalized with poly(10,12-pentacosadiynoic acid) (PCDA), a carboxylic-endowed diacetylene able to anchor on noble metal substrates, to obtain versatile, chromic platforms suitable for sensing and spectroscopic purposes.