Miracle-dz/UniFAR-FTUs huggingface dataset:
Mitochondrial NIX Promotes Tumor Survival in the Hypoxic Niche of Glioblastoma.

Cancer cells rely on mitochondrial functions to regulate key survival and death signals. How cancer cells regulate mitochondrial autophagy (mitophagy) in the tumor microenvironment as well as utilize mitophagy as a survival signal is still not well understood. Here we elucidate a key survival mechanism of mitochondrial NIX-mediated mitophagy within the hypoxic region of glioblastoma, the most malignant brain tumor. NIX was overexpressed in the pseudopalisading cells that envelop the hypoxic-necrotic regions, and mitochondrial NIX expression was robust in patient-derived glioblastoma tumor tissues and glioblastoma stem cells (GSC). NIX was required for hypoxia and oxidative stress-induced mitophagy through NFE2L2/NRF2 transactivation. Silencing NIX impaired mitochondrial reactive oxygen species (ROS) clearance, cancer stem cell maintenance, and HIF/mTOR/RHEB signaling pathways under hypoxia, resulting in suppression of glioblastoma survival in vitro and in vivo. Clinical significance of these findings was validated by the compelling association between NIX expression and poor outcome for glioblastoma patients. Taken together, our findings indicate that the NIX-mediated mitophagic pathway may represent a key therapeutic target for solid tumors including glioblastoma.
A Hash-Based RFID Authentication Mechanism for Context-Aware Management in IoT-Based Multimedia Systems

With the technological advances in the areas of Machine-To-Machine (M2M) and Device-To-Device (D2D) communication, various smart computing devices now integrate a set of multimedia sensors such as accelerometers, barometers, cameras, fingerprint sensors, gestures, iris scanners, etc., to infer the environmental status. These devices are generally identified using radio-frequency identification (RFID) to transfer the collected data to other local or remote objects over a geographical location. To enable automatic data collection and transition, a valid RFID embedded object is highly recommended. It is used to authorize the devices at various communication phases. In smart application devices, RFID-based authentication is enabled to provide short-range operation. On the other hand, it does not require the communication device to be in line-of-sight to gain server access like bar-code systems. However, in existing authentication schemes, an adversary may capture private user data to create a forgery problem. Also, another issue is the high computation cost. Thus, several studies have addressed the usage of context-aware authentication schemes for multimedia device management systems. The security objective is to determine the user authenticity in order to withhold the eavesdropping and tracing. Lately, RFID has played a significant for the context-aware sensor management systems (CASMS) as it can reduce the complexity of the sensor systems, it can be available in access control, sensor monitoring, real time inventory and security-aware management systems. Lately, this technology has opened up its wings for CASMS, where the challenging issues are tag-anonymity, mutual authentication and untraceability. Thus, this paper proposes a secure hash-based RFID mechanism for CASMS. This proposed protocol is based on the hash operation with the synchronized secret session-key to withstand any attacks, such as desynchronization, replay and man-in-the-middle. Importantly, the security and performance analysis proves that the proposed hash-based protocol achieves better security and performance efficiencies than other related schemes. From the simulation results, it is observed that the proposed scheme is secure, robust and less expensive while achieving better communication metrics such as packet delivery ratio, end-to-end delay and throughput rate.
Preparation of Magnetic g-C3N4/Fe3O4 Composite and Its Application in the Separation of Catechol from Water

Catechol has strong toxicity and deformity as well as carcinogenicity, and it is difficult to degrade naturally. Therefore, it is of great practical significance to develop efficient adsorbents to separate catechol from water quickly and effectively. In this work, g-C3N4/Fe3O4 magnetic nanocomposites were prepared using g-C3N4 as the matrix by chemical co-precipitation, mixing with Fe2+ and Fe3+ solutions. Then, g-C3N4/Fe3O4 was used, for the first time, as an adsorbent to investigate the removal rate of catechol under different conditions by the magnetic field separation method. The adsorption parameters of the g-C3N4/Fe3O4 nanocomposite were evaluated by the Langmuir and Freundlich adsorption models. The results showed that the g-C3N4/Fe3O4 nanocomposite presented a two-step adsorption behavior and a considerably high adsorption capacity. The removal rate of catechol reached 70% at the dosage of 50 mg, adsorption time of 30 min, and pH value of 6. Five adsorption–desorption cycles demonstrated that the g-C3N4/Fe3O4 material had good stability and reusability.
Assessing Cachexia Acutely after Autologous Stem Cell Transplant

Autologous hematopoietic stem cell transplantation (AHCT) is an accepted strategy for various hematologic malignancies that can lead to functional impairment, fatigue, muscle wasting, and reduced quality of life (QOL). In cancer cachexia, these symptoms are associated with inflammation, hypermetabolism, and decreased anabolic hormones. The relative significance of these factors soon after AHCT setting is unclear. The purpose of this study was to characterize the acute effects of AHCT on physical function, body composition, QOL, energy expenditure, cytokines, and testosterone. Outcomes were assessed before (PRE) and 30 ± 10 days after (FU) AHCT in patients with multiple myeloma (n = 15) and non-Hodgkin lymphoma (n = 6). Six-minute walk test (6MWT; p = 0.014), lean mass (p = 0.002), and fat mass (p = 0.02) decreased; nausea and fatigue increased at FU (both p = 0.039). Recent weight change and steroid exposure were predictors of reduced aerobic capacity (p < 0.001). There were no significant changes in interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF), energy expenditure, or bioavailable testosterone. Alterations in cytokines, energy expenditure, and testosterone were not associated with functional impairment acutely following AHCT. Recent history of weight loss and steroid exposure were predictors of worse physical function after AHCT, suggesting that targeting nutritional status and myopathy may be viable strategies to mitigate these effects.
Influence of Carrier Filling Ratio on the Advanced Nitrogen Removal from Wastewater Treatment Plant Effluent by Denitrifying MBBR

The filling ratio (FR) of a carrier has an influence on the pollutant removal of the aerobic moving bed biofilm reactor (MBBR). However, the effect of the polyethylene (PE) carrier FR on the performance and microbial characteristics of the denitrifying MBBR for the treatment of wastewater treatment plant (WWTP) effluent has not been extensively studied. A bench-scale denitrifying MBBR was set up and operated with PE carrier FRs of 20%, 30%, 40%, and 50% for the degradation of chemical oxygen demand (COD) and nitrogen from WWTP effluent at 12 h hydraulic retention time (HRT). The nitrate removal rates with FRs of 20%, 30%, 40%, and 50% were 94.3 ± 3.9%, 87.7 ± 7.3%, 89.7 ± 11.6%, and 94.6 ± 4.0%, and the corresponding denitrification rates (rNO3--N) were 8.0 ± 5.6, 11.3 ± 4.6, 11.6 ± 4.6, and 10.0 ± 4.9 mg NO3−-N/L/d, respectively. Nitrous oxide reductase (nosZ) gene-based terminal restriction fragment length polymorphism (T-RFLP) analysis illustrated that the highest functional diversity (Shannon’s diversity index, H′) of biofilm microbial community was obtained at 30% FR. The quantitative polymerase chain reaction (qPCR) results indicated that the abundance of nitrate reductase (narG) and nosZ genes at 30% FR was significantly higher than that at 20% FR, and no significant changes were observed at 40% and 50% FRs. Thus, 30% FR was recommended as the optimal carrier FR for the denitrifying MBBR.
Comparative Analysis of KGF-2 and bFGF in Prevention of Excessive Wound Healing and Scar Formation in a Corneal Alkali Burn Model.

PURPOSE Basic fibroblast growth factor (bFGF) is an effective drug for corneal injury. However, the explicit role of bFGF in corneal scar formation still remains unclear. Keratinocyte growth factor-2 (KGF-2) is associated with the treatment of wound healing. We aimed to compare the efficacy of bFGF and KGF-2 in prevention of excessive wound healing and consequent scar formation in a rat alkali burn model, which provides important clues on the significance of KGF-2 to be developed as a new drug for such injuries. METHODS The epithelial defect area was evaluated using fluorescein sodium at a concentration of 0.5%. The therapeutic effect of KGF-2 and bFGF on proliferation of rabbit corneal fibroblasts (RCFs) was evaluated by methylthiazoletetrazolium. RCF migration assays were performed with a modified scratch method. Activation of mitogen-activated protein kinase (MAPK) was evaluated by Western blot with specific antibodies. RESULTS All corneal wounds treated with KGF-2 were found closed within 7 days; however, the wounds treated with bFGF or phosphate buffer saline (PBS) required 14 days to close. RCFs treated with KGF-2 or bFGF showed similar dose-dependent proliferation. The KGF-2 group significantly promoted cell migration compared with the bFGF group. The KGF-2 group showed less expression of α-smooth muscle actin (SMA) and numbers of myofibroblasts compared with the bFGF group. Our findings suggested identification of cascade reaction of extracellular regulated protein kinases (ERK)1/2 and p38 signals in KGF-2- and bFGF-induced proliferation and migration of RCFs. In addition, KGF-2 showed stronger effects during ERK1/2 and p38 phosphorylation in methylthiazoletetrazolium proliferation assay and scratch migration assay. CONCLUSIONS KGF-2 exhibited better effects than bFGF in reepithelialization, acceleration of migration, and reduction of scar formation, which has potential to become a new drug to cure corneal injury.
Analysis of anticholinergic and sedative medicine effects on physical function, cognitive function, appetite and frailty: a cross-sectional study in Australia

Objective To test the association between use of medicines with anticholinergic or sedative properties and physical function, cognitive function, appetite and frailty. Design, setting and participants This cross-sectional study analysed baseline data collected as part of the Australian Longitudinal Study of Ageing, a population-based cohort of 2087 participants aged 65 years or over living in South Australia. Main outcome measures Physical function was measured at baseline using measures including hand grip strength, walking speed, chair stands, activities of daily living and instrumental activities of daily living (IADL). Cognitive function was measured using Mini-Mental State Examination. Appetite was measured using Center for Epidemiologic Studies Depression question 2. Frailty was measured using frailty index. The association between use of anticholinergics or sedatives and physical or cognitive function, appetite, or frailty was assessed using analysis of covariance and ordinal or binary logistic regression. Results Almost half of the population were using anticholinergics or sedatives (n=954, 45.7%). Use of anticholinergics was significantly associated with poorer grip strength, slower walking speed, poorer IADL and poorer appetite. Use of sedatives was significantly associated with poorer grip strength, slower walking speed and poorer IADL. We found no significant association between medicine use and cognitive function. Users of anticholinergics or sedatives were significantly more likely to be frail compared with non-users. Conclusion Use of medicines with anticholinergic or sedative properties is significantly associated with poorer physical function, poorer appetite and increased frailty. Early identification of signs and symptoms of deterioration associated with medicine use is particularly important in older people so that worsening frailty and subsequent adverse events are prevented.
Cerebral Blood Flow Regulation in Pregnancy, Hypertension, and Hypertensive Disorders of Pregnancy

The regulation of cerebral blood flow (CBF) allows for the metabolic demands of the brain to be met and for normal brain function including cognition (learning and memory). Regulation of CBF ensures relatively constant blood flow to the brain despite changes in systemic blood pressure, protecting the fragile micro-vessels from damage. CBF regulation is altered in pregnancy and is further altered by hypertension and hypertensive disorders of pregnancy including preeclampsia. The mechanisms contributing to changes in CBF in normal pregnancy, hypertension, and preeclampsia have not been fully elucidated. This review summarizes what is known about changes in CBF regulation during pregnancy, hypertension, and preeclampsia.
Schwann cells expressing nociceptive channel TRPA1 orchestrate ethanol-evoked neuropathic pain in mice.

Excessive alcohol consumption is associated with spontaneous burning pain, hyperalgesia and allodynia. Although acetaldehyde has been implicated in the painful alcoholic neuropathy, the mechanism by which the ethanol metabolite causes pain symptoms is unknown. Acute ethanol ingestion caused delayed mechanical allodynia in mice. Inhibition of alcohol dehydrogenase (ADH) or deletion of transient receptor potential ankyrin 1 (TRPA1), a sensor for oxidative and carbonyl stress, prevented allodynia. Acetaldehyde generated by ADH in both liver and Schwann cells surrounding nociceptors was required for TRPA1-induced mechanical allodynia. Plp1-Cre;Trpa1fl/fl mice with a tamoxifen-inducible specific deletion of TRPA1 in Schwann cells revealed that channel activation by acetaldehyde in these cells initiates a NADPH oxidase-1 (NOX-1)-dependent production of hydrogen peroxide (H2O2) and 4-hydroxynonenal (4-HNE), which sustains allodynia by paracrine targeting of nociceptor TRPA1. Chronic ethanol ingestion caused prolonged mechanical allodynia and loss of intraepidermal small nerve fibers in WT mice. While Trpa1-/- or Plp1-Cre;Trpa1fl/fl mice did not develop mechanical allodynia, they did not show any protection from the small fiber neuropathy. Human Schwann cells express ADH/TRPA1/NOX1 and recapitulate the proalgesic functions of mouse Schwann cells. TRPA1 antagonists might attenuate some symptoms of alcohol-related pain.
Transient receptor potential ankyrin1 channel is endogenously expressed in T cells and is involved in immune functions

Transient receptor potential channel subfamily A member 1 (TRPA1) is a non-selective cationic channel, identified initially as a cold sensory receptor. TRPA1 responds to diverse exogenous and endogenous stimuli associated with pain and inflammation. However, the information on the role of TRPA1 toward T-cell responses remains scanty. In silico data suggest that TRPA1 can play an important role in the T-cell activation process. In this work, we explored the endogenous expression of TRPA1 and its function in T cells. By reverse transcription polymerase chain reaction (RT-PCR), confocal microscopy and flow cytometry, we demonstrated that TRPA1 is endogenously expressed in primary murine splenic T cells as well as in primary human T cells. TRPA1 is primarily located at the cell surface. TRPA1-specific activator namely allyl isothiocyanate (AITC) increases intracellular calcium ion (Ca2+) levels while two different inhibitors namely A-967079 as well as HC-030031 reduce intracellular Ca2+ levels in T cells; TRPA1 inhibition also reduces TCR-mediated calcium influx. TRPA1 expression was found to be increased during αCD3/αCD28 (TCR) or Concanavalin A (ConA)-driven stimulation in T cells. TRPA1-specific inhibitor treatment prevented induction of cluster of differentiation 25 (CD25), cluster of differentiation 69 (CD69) in ConA/TCR stimulated T cells and secretion of cytokines like tumor necrosis factor (TNF), interferon γ (IFN-γ), and interleukin 2 (IL-2) suggesting that endogenous activity of TRPA1 may be involved in T-cell activation. Collectively these results may have implication in T cell-mediated responses and indicate possible role of TRPA1 in immunological disorders.
Exosomes from miR‐20b‐3p‐overexpressing stromal cells ameliorate calcium oxalate deposition in rat kidney

Hyperoxaluria‐induced calcium oxalate (CaOx) deposition is the key factor in kidney stone formation, for which adipose‐derived stromal cells (ADSCs) have been used as a therapeutic treatment. Studies revealed that miR‐20b‐3p is down‐regulated in hypercalciuric stone‐forming rat kidney. To investigate whether ADSC‐derived miR‐20b‐3p‐enriched exosomes protect against kidney stones, an ethylene glycol (EG)‐induced hyperoxaluria rat model and an in vitro model of oxalate‐induced NRK‐52E cells were established to explore the protective mechanism of miR‐20b‐3p. The results showed that miR‐20b‐3p levels were decreased following hyperoxaluria in the urine of patients and in kidney tissues from animal models. Furthermore, treatment with miR‐20b‐3p‐enriched exosomes from ADSCs protected EG‐induced hyperoxaluria rats, and cell experiments confirmed that co‐culture with miR‐20b‐3p‐enriched exosomes alleviated oxalate‐induced cell autophagy and the inflammatory response by inhibiting ATG7 and TLR4. In conclusion, ADSC‐derived miR‐20b‐3p‐enriched exosomes protected against kidney stones by suppressing autophagy and inflammatory responses.
Mice With a Combined Deficiency of Superoxide Dismutase 1 (Sod1), DJ-1 (Park7), and Parkin (Prkn) Develop Spontaneous Retinal Degeneration With Aging

Purpose Chronic oxidative stress is an important mechanism of disease in aging disorders. We do not have a good model to recapitulate AMD and other retinal disorders in which chronic oxidative stress plays an important role. We hypothesized that mice with a combined deficiency in superoxide dismutase 1 (Sod1), DJ-1 (Park-7), and Parkin (Prkn) (triple knock out, TKO) would have an increased level of chronic oxidative stress in the retina, with anatomic and functional consequences just with aging. Methods Eyes of TKO and B6J control mice were (1) monitored with optical coherence tomography (OCT) and electroretinography (ERG) over time, and (2) collected for oxidative marker protein analysis by ELISA or immunohistochemistry and for transmission electron microscopy studies. Results TKO mice developed qualitative disruptions in outer retinal layers in OCT by 3 months, increased accumulation of fundus spots and subretinal microglia by 6 months of age, significant retinal thinning by 9 months, and decreased ERG signal by 12 months. Furthermore, we found increased accumulation of the oxidative marker malondialdehyde (MDA) in the retina and increased basal laminal deposits (BLD) and mitochondria number and size in the retinal pigment epithelium of aging TKO mice. Conclusions TKO mice can serve as a platform to study retinal diseases that involve chronic oxidative stress, including macular degeneration, retinal detachment, and ischemic retinopathies. In order to model each of these diseases, additional disease-specific catalysts or triggers could be superimposed onto the TKO mice. Such studies could provide better insight into disease mechanisms and perhaps lead to new therapeutic approaches.
Effect of Short-Term Increase in Meal Frequency on Glucose Metabolism in Individuals with Normal Glucose Tolerance or Impaired Fasting Glucose: A Randomized Crossover Clinical Trial

Effects of meal frequency on blood glucose levels and glucose metabolism were evaluated over 3 days in adult males with normal glucose tolerance (NGT, n = 9) or impaired fasting glucose (IFG, n = 9) in a randomized, crossover comparison study. Subjects were provided with an isocaloric diet 3 times daily (3M) or 9 times daily (9M). Blood glucose was monitored on Day 3 using a continuous glucose monitoring system, and subjects underwent a 75-g oral glucose tolerance test (OGTT) on Day 4. Daytime maximum blood glucose, glucose range, duration of glucose ≥180 mg/dL, and nighttime maximum glucose were significantly lower in the NGT/9M condition than in the NGT/3M condition. Similar findings were observed in the IFG subjects, with a lower daytime and nighttime maximum glucose and glucose range, and a significantly higher daytime minimum glucose in the 9M condition than in the 3M condition. The OGTT results did not differ significantly between NGT/3M and NGT/9M conditions. In contrast, the incremental area under the curve tended to be lower and the maximum plasma glucose concentration was significantly lower in the IFG/9M condition than in the IFG/3M condition. In IFG subjects, the 9M condition significantly improved glucose metabolism compared with the 3M condition. Higher meal frequency may increase glucagon-like peptide 1 secretion and improve insulin secretion.
Studying excipient modulated physical stability and viscosity of monoclonal antibody formulations using small angle scattering.

Excipients are substances that are added to therapeutic products to improve stability, bioavailability and manufacturability. Undesirable protein-protein interactions (PPI) can lead to self-association and/or high solution viscosity in concentrated protein formulations that are typically greater than 50 mg/mL. Therefore, understanding the effects of excipients on non-specific PPI is important for more efficient formulation development. In this study, we used National Institute of Standards and Technology monoclonal antibody (NISTmAb) reference material as a model antibody protein to examine the physical stability and viscosity of concentrated formulations using a series of excipients, by varying pH, salt composition and the presence of co-solutes including amino acids, sugars and non-ionic surfactants. Small angle X ray scattering (SAXS) together with differential scanning calorimetry (DSC), dynamic light scattering (DLS) and viscosity measurements were used to obtain various experimental parameters to characterize excipient modulated PPI and bulk solution viscosities. In particular, good correlation was found between SAXS and DLS results, suggesting that the use of DLS is valid for predicting colloidal stability of NISTmAb in concentrated solutions. Moreover, further analysis of effective structure factor S(q)eff measured from SAXS enabled the dissection of net PPI into hydrodynamic forces due to excluded volume, as well as any additional attractive or repulsive interactions with the presence of excipients. It was found that although no denaturation or aggregation of NISTmAb was observed, and that the net PPI were repulsive, the use of ionic excipients such as pH and salts lead to increased short-range attraction, while the non-ionic excipients including sugars, amino acids, and polysorbate surfactants lead to increased repulsive PPI with increasing protein concentration. Results obtained from viscosity measurements showed that the use of excipients can lead to increased solution viscosities, especially at higher protein concentrations. The use of S(q)eff, interaction parameter kD and second virial coefficient B22 as predictors for solution viscosity was also evaluated by comparing the predicted results with the measured viscosities. Although B22 and S(q)eff appeared to be better predictors than kD, disagreement between the predicted and measured results suggests other factors apart from PPI contribute to the bulk rheological properties of concentrated protein solutions.