Miracle-dz/UniFAR-FTUs huggingface dataset:
Chondroitin sulfate-functionalized lipid nanoreservoirs: a novel cartilage-targeting approach for intra-articular delivery of cassic acid for osteoarthritis treatment

Abstract Novel intra-articular nanoreservoirs were implemented employing different cartilage targeting approaches to improve cartilage bioavailability of a chondroprotective drug, cassic acid (CA), for effective amelioration of cartilage deterioration off-targeting CA gastrointestinal disorders. Herein, we compared active cartilage-targeting approach via chondroitin sulfate (CHS) functionalization versus passive targeting using positively charged nanoparticles to target negatively charged cartilage matrix. Firstly, CA integrated nanoreservoirs (CA-NRs) were fabricated based on ionic conjugation between CA and cationic hydrophobic surface modifier octadecylamine (ODA) and were further functionalized with CHS to develop CHS-CA-NRs. Confocal laser microscope was used to visualize the accumulation of nanoparticles into the cartilage tissue. Both targeting approaches promoted CA local cartilage availability and prolonged its residence time. Compared to passive targeted CA-NRs, active targeted CHS-CA-NRs showed higher fluorescence signals in proximity to and inside chondrocytes which lasted for up to 21 days. In MIA-osteoarthritic rats, CHS-CA-NRs showed superior antiosteoarthritic activity, exhibiting highest cartilage repair compared to CA-NRs. Additionally, CHS-CA-NRs significantly inhibited OA inflammatory cytokine, degradation enzyme and oxidative stress and improved cartilage matrix biosynthesis. Conclusively, CHS-CA-NRs improved OA repair showing a superior efficacy for articular cartilage targeting with CHS which could be a potential advance for OA therapy.
Prevalence and seasonal pattern of enteric viruses among hospitalized children with acute gastroenteritis in Samawah, Iraq

Almost all of the deaths happening under the age of 5 occur in the developed countries of Africa and Asia. This study included children admitted to the surgical care, aged 6 months to 5 years, who suffered from acute gastroenteritis and received treatment at Samawah, Iraq, from December 2018 to December 2019. Test results detected different types of rotaviruses, adenoviruses, astroviruses using ELISA. 56.6% of the infections were attributed to a viral pathogen. The main cause was attributed to rotavirus and adenovirus. The causative agents of diarrheal diseases in 28.1% of cases are rotaviruses, in 17.05% – adenoviruses, in 11.43% – astroviruses. Viral mono-infections are detected more often than mixed infections. Viral intestinal infections are characterized by seasonality and rise in the cold season, with a peak incidence of rotavirus infection in April, adenovirus infection in November, and astrovirus infection in December.
Physicochemical Changes in Bone Bioapatite During the Late Postmortem Interval Pre- and Post-Burning

Postmortem chemical transformation of bone bioapatite can take place during early diagenesis, resulting in a more thermodynamically stable mineral phase. This paper examines the impact of a one year postmortem interval on unburnt and burnt bone’s structural and chemical alterations. This question is of importance for the reconstruction of funerary practices involving cremation in the archaeological record, as well as forensic anthropological investigations. Fleshed pig (Sus scrofa) tibiae were left exposed in a field, then collected at 14, 34, 91, 180, and 365 day intervals prior to being burnt in an outdoor fire (≤750 °C bone temperature). Fresh (fleshed) tibiae acted as unburnt and burnt controls. Also included in the study were two cremated human bone fragments from Middle–Late Neolithic (ca. 3300–2500 BCE) Ireland. Samples were analyzed for major and trace elements using an electron microprobe wavelength dispersive analyzer and molecular structures using Fourier transform infrared spectroscopy. Linear regression, principal component analysis, linear discriminant analysis, and multivariate analysis of variance were performed for statistical analysis. Results indicate that the concentrations of elements associated with extracellular fluid (K, Na, and Cl) change with the postmortem interval (PMI) and survive burning. K values under 0.07 ± 0.01 wt% in the inner and mid-cortical zones of burnt bones suggest that bones were not burnt immediately after death. Using this criterion, results from the archaeological samples would indicate a PMI of at least weeks to months prior to cremation. Ca, P, Fe, Al, Si, and Sr are not significantly altered with burning, and Fe, Al, Si, and Sr are also unaffected by the PMI. In unburnt bones increased crystallinity and carbonate loss are detectable in <1 year, but both are obscured by burning. Structurally, the carbonate to phosphate ratio (C/P), the phosphate high temperature, and cyanamide to phosphate (CN/P) are the most useful ratios for discriminating between unburnt and burnt bones. Graphical Abstract
Comparative genomics analysis of bHLH genes in cucurbits identifies a novel gene regulating cucurbitacin biosynthesis

Abstract The basic helix–loop–helix (bHLH) family of transcription factors (TFs) participate in a variety of biological regulatory processes in plants, and have undergone significant expansion during land plant evolution by gene duplications. In cucurbit crops, several bHLH genes have been found to be responsible for agronomic traits such as bitterness. However, the characterization of bHLH genes across the genomes of cucurbit species has not been reported, and how they have evolved and diverged remains largely unanswered. Here we identified 1,160 bHLH genes in seven cucurbit crops and performed a comprehensive comparative genomics analysis. We determined orthologous and paralogous bHLH genes across cucurbit crops by syntenic analysis between or within species. Orthology and phylogenetic analysis of the tandem-duplicated bHLH genes in the Bt cluster, which regulate the biosynthesis of cucurbitacins, suggest that this cluster is derived from three ancestral genes after the cucurbit-common tetraploidization event. Interestingly, we identified a new conserved cluster paralogous to the Bt cluster that includes two tandem bHLH genes, and the evolutionary history and expression profiles of these two genes in the new cluster suggest the involvement of one gene (Brp) in the regulation of cucurbitacin biosynthesis in roots. Further biochemical and transgenic assays in melon hairy roots supported the function of Brp. This study provides useful information for further investigating the functions of bHLH TFs and novel insights into the regulation of cucurbitacin biosynthesis in cucurbit crops and other plants.
Chinese Pinyin: Overview, History and Use in Language Learning for Young Deaf and Hard of Hearing Students in China

Abstract:The authors discuss Pinyin, a phonetic system based on the Latin alphabet, as an auxiliary pedagogical tool in literacy instruction in China. They provide a brief history of Pinyin and its educational purposes, then describe how it is used in its spoken/auditory, written, and signed forms by teachers with students who are deaf and hard of hearing (DHH). Classroom transcripts demonstrate how Pinyin is taught via visual and tactile/kinesthetic tools such as pictures, sign language, and the Chinese Manual Alphabet for purposes of making the phonological information visible to DHH learners. The authors further discuss the different functions of Pinyin for students who are hearing versus students who are DHH and present new insights that may lead to future empirical studies on Pinyin use in early literacy interventions.
Anatomical and radiographic distribution of hepatic artery and biliary duct system applied to biochemical parameters indicative to hepatobiliary disease in Egyptian donkey (Equus asinus)

The current study was performed on ten adult Egyptian donkeys of both sexes for anatomical and radiographic studies in addition to six other donkeys for enzymatic, biochemical and statistical analysis. The aim was to illustrate the normal hepatic arterial and biliary distribution using different anatomic techniques and radiographic imaging besides, establishing an accurate laboratory profile specific for donkeys that used as standard indicators for hepatobiliary dysfunction. The right branch of the hepatic artery in donkey forms a curved arch erupting five branches, unlike the left branch that erupts six branches, being the direct continuation of the main hepatic artery. The caudate lobe artery either originated from the hepatic artery or its right division. The common hepatic duct represented a very clear enlargement called ‘gall tank’ at its terminal pouring intestinal end and compensating absence of gall bladder, cystic and common bile ducts. The intrahepatic biliary distribution is characterized by a segmental ramification into dorsal, intermediate, and ventral branches of bile ductules especially noticed in the undivided right lobe and left lateral lobe. The quadrate lobe is divided according to its biliary drainage into right and left parts where the former is drained by the left hepatic duct while the latter is drained through a branch from R. lobi medialis sinistri. The serum enzymatic activity was slightly similar to that of the horse while some biochemical parameters differentiating the donkey from the horse such as lowered total bilirubin, serum bile acids, and higher triglycerides, blood urea and prolonged prothrombin time.
Symptoms and ocular findings associated with administration of 0.01% atropine in young adults

ABSTRACT Clinical relevance This paper provides eye care practitioners with important information about the potential side effects of 0.01% atropine. Background Eye care practitioners routinely administer 0.01% atropine eye drops nightly to slow the progression of myopia, but nobody has assessed accommodative lag or facility, near phoria, intraocular pressure or comfort of drop administration. Methods All 21- to 30-year-old adults with no history of accommodative issues or therapy were eligible. During the baseline visit, participants underwent testing related to potential side effects. Participants then administered one drop of 0.01% atropine nightly to both eyes, and all tests were repeated 1 week later. Results The average ± standard deviation age of the 31 participants was 23.9 ± 1.6 years, 71% were female, and 81% were Caucasian. The only significant changes were an increase in photopic pupil size from 4.9 ± 0.8 at baseline to 5.1 ± 0.6 mm after 1 week (paired sample t-test, p = 0.002) and an increase of the average intraocular pressure of the two eyes from 15.6 ± 2.7 to 16.7 ± 3.1 mmHg (paired-sample t-test, p = 0.003), but neither of these changes was clinically meaningful. There were no other statistically significant differences before and after 1-week administration of 0.01% atropine for any of the vision, accommodation, reading speed or subjective side effects. When asked how likely they would be to take the atropine drops to delay the onset of myopia on a scale from 1 (definitely not) to 10 (definitely would), participants replied with an average of 8.2 ± 2.0 after taking atropine eye drops for 1 week (paired-sample t-test, p = 0.81). Conclusion Nightly administration of 0.01% atropine did not result in any clinically meaningful symptoms, so patients would be very likely to take the drops to delay the onset of myopia.
Analysis of effects of laryngopharyngeal reflux disease and proton pump inhibitor treatment on Eustachian tube function in patients with obstructive sleep apnea hypopnea

Objective: This study aims to explore the effects of laryngopharyngeal reflux disease (LPRD) and proton pump inhibitor (PPI) treatment on Eustachian tube function in patients with obstructive sleep apnea (OSA). Methods: The Eustachian tube score-7 (ETS-7) was observed before and after PPI treatment in the control group, OSA only group, and OSA + LPRD group. Results: Age, sex, smoking history, and drinking history showed no differences among 3 groups (P > .05). The body mass index (BMI) in the control group was lower than that in other groups (P < .017). Before PPI treatment, the abnormality rate of ETS-7 in the OSA + LPRD group statistically differed from that in the control group and the OSA only group (P < .017). After PPI treatment, the abnormality rate of ETS-7 in the OSA + LPRD group exhibited no significant differences compared with that in the control group and the OSA only group (P > .017), and it declined remarkably compared with that before PPI treatment (75% vs 35%, χ2 = 13.334, P = .001). Moreover, the multivariate analysis revealed that only LPRD had an independent correlation with the abnormality of ETS-7 (OR = 1.245, 95% CI: 1.759–6.861, P = .000). Conclusion: In view of its high incidence in OSA patients, LPRD may be a considerable factor for the high incidence of abnormality rate of ETS-7 in OSA patients, and PPI therapy is of significant value in improving Eustachian tube function in OSA patients with LPRD.
Changes in apolipoprotein abundance dominate proteome responses to prolonged fasting in elephant seals.

Unlike many animals that reduce activity during fasting, northern elephant seals (NES) undergo prolonged fasting during energy-intensive life-history stages such as reproduction and molting, fueling fasting energy needs by mobilizing fat stores accrued during foraging. NES display several unique metabolic features such as high fasting metabolic rates, elevated blood lipid and high-density lipoprotein (HDL) cholesterol levels, efficient protein sparing and resistance to oxidative stress during fasting. However, the cellular mechanisms that regulate these adaptations are still not fully understood. To examine how metabolic coordination is achieved during prolonged fasting, we profiled changes in blubber, skeletal muscle and plasma proteomes of adult female NES over a 5 week fast associated with molting. We found that while blubber and muscle proteomes were remarkably stable over fasting, over 50 proteins changed in abundance in plasma, including those associated with lipid storage, mobilization, oxidation and transport. Apolipoproteins dominated the blubber, plasma and muscle proteome responses to fasting. APOA4, APOE and APOC3, which are associated with lipogenesis and triglyceride accumulation, decreased, while APOA1, APOA2 and APOM, which are associated with lipid mobilization and HDL function, increased over fasting. Our findings suggest that changes in apolipoprotein composition may underlie the maintenance of high HDL levels and, together with adipokines and hepatokines that facilitate lipid catabolism, may mediate the metabolic transitions between feeding and fasting in NES. Many of these proteins have not been previously studied in this species and provide intriguing hypotheses about metabolic regulation during prolonged fasting in mammals.
Effects of transforming growth factor beta-activated kinase 1 (TAK1) on apoptosis of HK-2 cells in the high glucose environment

ABSTRACT To observe the role of transforming growth factor beta-activated kinase 1 (TAK1)/p38 MAPK/TGF-β1 signal pathway plays in oxidative stress and apoptosis in human renal tubular epithelial cells (HK-2) under high glucose induction. HK-2 cells were cultured in high glucose medium with and without TAK1 inhibitor 5Z-7-oxozeaenol. TUNEL and flow cytometry were used to detect cell apoptosis. The protein expression of TAK1, TGF-β1, Bax and Bcl-2 was detected by immunofluorescence. Meanwhile, flow cytometry was used to detect the production of reactive oxygen species (ROS), and MitoSOX staining was performed to detect the production of mitochondrial ROS. Moreover, real-time quantitative PCR and Western blotting was used to measure the expression of TAK1, TGF-β1, NOX1, NOX4 and HO-1, Bax, Bcl-2, p38MAPK, p-p38MAPK and TGF-β1. Results showed that high glucose up-regulated the protein expression of p-TAK1, p-p38 MAPK and TGF-β1, which induced the aggravation of oxidative stress by promoting the production of ROS, thus promote the apoptosis in HK-2 cells. However, addition of 5z −7-oxozeaenol in HK-2 cells reversed all the above functions induced by high glucose. Another experimental result also showed that SB203580, a p38MAPK inhibitor can down-regulated TGF-β1 expression and reduce ROS production, thus alleviate cell apoptosis in TAK1 overexpression group. In summary, high glucose intervention could activate TAK1 and promote apoptosis in HK-2 cells. Inhibition of TAK1 expression could block p38 MAPK/TGF-β1 signaling pathway and reduce ROS production and oxidative stress, which may be one of the signal pathways of TAK1 to reduce apoptosis of HK-2 cells induced by high glucose. Abbreviations: DN, Diabetic nephropathy; TAK1, transforming growth factor β-activated kinase-1; TGF-β, transforming growth factor-β; NG, normal glucose; HG, high glucose; p38 MAPK, p38 mitogen-activated protein kinase; ROS, reactive oxygen species. Graphical Abstract
Enhanced antibacterial properties on superhydrophobic micro-nano structured titanium surface.

Micro/nano scale surface modifications of titanium based orthopedic and cardiovascular implants has shown to augment biocompatibility. However, bacterial infection remains a serious concern for implant failure, aggravated by increasing antibiotic resistance and over usage of antibiotics. Bacteria cell adhesion on implant surface leads to colonization and biofilm formation resulting in morbidity and mortality. Hence, there is a need to develop new implant surfaces with high antibacterial properties. Recent developments have shown that superhydrophobic surfaces prevent protein and bacteria cell adhesion. In this study, a thermochemical treatment was used modify the surface properties for high efficacy antibacterial activity on titanium surface. The modification led to a micro-nano surface topography and upon modification with polyethylene glycol (PEG) and silane the surfaces were superhydrophilic and superhydrophobic, respectively. The modified surfaces were characterized for morphology, wettability, chemistry, corrosion resistance and surface charge. The antibacterial capability was characterized with Staphylococcus aureus and Escherichia coli by evaluating the bacteria cell inhibition, adhesion kinetics, and biofilm formation. The results indicated that the superhydrophobic micro-nano structured titanium surface reduced bacteria cell adhesion significantly (>90%) and prevented biofilm formation compared to the unmodified titanium surface after 24 h of incubation.
Lateral entorhinal cortex lesions impair odor‐context associative memory in male rats

Lateral entorhinal cortex (LEC) has been hypothesized to process nonspatial, item information that is combined with spatial information from medial entorhinal cortex to form episodic memories within the hippocampus. Recent studies, however, have demonstrated that LEC has a role in integrating features of episodic memory prior to the hippocampus. While the precise role of LEC is still unclear, anatomical studies show that LEC is ideally placed to be a hub integrating multisensory information. The current study tests whether the role of LEC in integrating information extends to long‐term multimodal item‐context associations. In Experiment 1, male rats were trained on a context‐dependent odor discrimination task, where two different contexts served as the cue to the correct odor. Rats were pretrained on the task and then received either bilateral excitotoxic LEC or sham lesions. Following surgery, rats were tested on the previously learned odor‐context associations. Control rats showed good memory for the previously learned association but rats with LEC lesions showed significantly impaired performance relative to both their own presurgery performance and to control rats. Experiment 2 went on to test whether impairments in Experiment 1 were the result of LEC lesions impairing either odor or context memory retention alone. Male rats were trained on simple odor and context discrimination tasks that did not require integration of features to solve. Following surgery, both LEC and control rats showed good memory for previously learned odors and contexts. These data show that LEC is critical for long‐term odor‐context associative memory.
New insights into flowering date in Prunus: fine mapping of a major QTL in sweet cherry

Abstract Flowering date is an important trait in Prunus fruit species, especially for their adaptation in a global warming context. Numerous quantitative trait loci (QTLs) have been identified and a major one was previously located on LG4. The objectives of this study were to fine-map this QTL in sweet cherry, to identify robust candidate genes by using the new sweet cherry genome sequence of the cultivar “Regina” and to define markers usable in marker-assisted selection (MAS). We performed QTL analyses on two populations derived from crosses using cultivars “Regina” and “Garnet” as parents. The first one (n = 117) was phenotyped over ten years, while the second one (n = 1386) was evaluated during three years. Kompetitive allele specific PCR (KASP) markers located within the QTL region on LG4 were developed and mapped within this region, consisting in the first fine mapping in sweet cherry. The QTL interval was narrowed from 380 kb to 68 kb and candidate genes were identified by using the genome sequence of “Regina”. Their expression was analyzed from bud dormancy period to flowering in cultivars “Regina” and “Garnet”. Several genes, such as PavBOI-E3, PavSR45a and PavSAUR71, were differentially expressed in these two cultivars and could be then considered as promising candidate genes. Two KASP markers were validated using a population derived from a cross between cultivars “Regina” and “Lapins” and two collections, including landraces and modern cultivars. Thanks to the high synteny within the Prunus genus, these results give new insights into the control of flowering date in Prunus species and pave the way for the development of molecular breeding strategies.
Vine Tea (Ampelopsis grossedentata) extract attenuates CCl4 -induced liver injury by restoring gut microbiota dysbiosis in mice.

SCOPE Vine tea (Ampelopsis grossedentata), a traditional Chinese tea, has displayed various biological activities. We aimed to investigate the effect of Vine Tea (Ampelopsis grossedentata) extract (VTE) on CCl4 -induced acute liver injury (ALI) in mice and to explore the underlying role of gut microbiota during the treatment. METHODS AND RESULTS C57BL/6J mice injected with CCl4 were treated with VTE for 6 weeks. By using H&E staining, immunofluorescence staining, RT-PCR, and western blot, it was shown that VTE treatment significantly ameliorated hepatocyte necrosis, alleviated the mRNA levels of Tlr4, Il-6, iNOS, Acc1, and increased the mRNA levels of Ppar-γ and Hmg-coar compared to the CCl4 group. Also, VTE abrogated the decreased mRNA expressions of Zo-1, Occludin, and Mucin1 in colon tissues. Using microbial 16S rDNA sequencing, VTE treatment significantly downregulated the abundances of some harmful intestinal bacteria like Helicobacter and Oscillibacter. In contrast, VTE upregulated the contents of several beneficial bacteria, such as Ruminococcaceae_UCG-014 and Eubacterium_fissicatena_group. Further, VTE failed to improve ALI in the mice with gut microbiota depletion using antibiotic treatment. CONCLUSIONS Our studies suggest that VTE exhibited a protective effect against CCl4 -induced ALI in mice by alleviating hepatic inflammation, suppressing intestinal epithelial barrier injury, and restoring gut microbiota dysbiosis. This article is protected by copyright. All rights reserved.