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Simple Summary: Cancer-related fatigue (CRF) is the most common and distressing symptom in cancer survivors, severely affecting their quality of life. However, clinicians and patients are not well recognized for its importance and lack timely screening and assessment. With the rapid development of artificial intelligence and personalized care, early screening and assessment of CRF using machine learning to construct risk prediction models may contribute to this. Therefore, we redefined the predictors of CRF based on the predisposing, precipitating, and perpetuating (3P) model to develop a valid basis for the feature selection of future prediction models, intending to provide a more accurate and personalized plan for the clinical diagnosis and management of CRF. Cancer-related fatigue (CRF) is a widespread symptom with high prevalence in cancer patients, seriously affecting their quality of life. In the context of precision care, constructing machine learning-based prediction models for early screening and assessment of CRF is beneficial to this situation. To further understand the predictors of CRF for model construction, we conducted a comprehensive search in PubMed, Web of Science, Embase, and Scopus databases, combining CRF with predictor-related terms. A total of 27 papers met the inclusion criteria. We evaluated the above studies into three subgroups following the predisposing, precipitating, and perpetuating (3P) factor model. (1) Predisposing factors—baseline fatigue, demographic characteristics, clinical characteristics, psychosocial traits and physical symptoms. (2) Precipitating factors—type and stage of chemotherapy, inflammatory factors, laboratory indicators and metabolic changes. (3) Perpetuating factors—a low level of physical activity and poorer nutritional status. Future research should prioritize large-scale prospective studies with emerging technologies to identify accurate predictors of CRF. The assessment and management of CRF should also focus on the above factors, especially the controllable precipitating factors, to improve the quality of life of cancer survivors. [ABSTRACT FROM AUTHOR]

The Slack channel (KCNT1, Slo2.2) is a sodium-activated and chloride-activated potassium channel that regulates heart rate and maintains the normal excitability of the nervous system. Despite intense interest in the sodium gating mechanism, a comprehensive investigation to identify the sodium-sensitive and chloride-sensitive sites has been missing. In the present study, we identified two potential sodium-binding sites in the C-terminal domain of the rat Slack channel by conducting electrophysical recordings and systematic mutagenesis of cytosolic acidic residues in the rat Slack channel C terminus. In particular, by taking advantage of the M335A mutant, which results in the opening of the Slack channel in the absence of cytosolic sodium, we found that among the 92 screened negatively charged amino acids, E373 mutants could completely remove sodium sensitivity of the Slack channel. In contrast, several other mutants showed dramatic decreases in sodium sensitivity but did not abolish it altogether. Furthermore, molecular dynamics (MD) simulations performed at the hundreds of nanoseconds timescale revealed one or two sodium ions at the E373 position or an acidic pocket composed of several negatively charged residues. Moreover, the MD simulations predicted possible chloride interaction sites. By screening predicted positively charged residues, we identified R379 as a chloride interaction site. Thus, we conclude that the E373 site and the D863/E865 pocket are two potential sodium-sensitive sites, while R379 is a chloride interaction site in the Slack channel. [ABSTRACT FROM AUTHOR]

Kefir is an acidic-alcoholic fermented milk that can provide probiotic benefits, such as intestinal microecological balance regulation, antibacterial activity, and anti-inflammatory activity. In this study, Lactobacillus fermentum grx08 isolated from longevous people was used to further improve the health properties of kefir. L. fermentum grx08 and kefir grains obtained from Xinjiang, People’s Republic of China, were mixed at ratios of 1:1, 5:1, and 25:1 as starters. The six gram-positive and gram-negative foodborne pathogens were able to grow in the supernatant of kefir but not in the supernatant of kefir with L. fermentum grx08. With increasing amounts of inoculated L. fermentum grx08, the antibacterial activity of the mixed fermented kefir gradually increased. The contents of lactic acid, fumaric acid, and malic acid in the mixed fermented milk were significantly increased by adding L. fermentum grx08 (P < 0.05), while the content of acetic acid decreased with the increase of L. fermentum grx08 and the content of citric acid was unaffected. This study suggests that the addition of L. fermentum grx08 shortened the fermentation time, improved the acidity, and retained the quality of fermented milk. Moreover, the antibacterial properties of kefir is enhanced by increasing the production of certain acids. [ABSTRACT FROM AUTHOR]

A class of O²-alkyl derived diazeniumdiolates 3a-f and 4a-c were designed and synthesized as new bioorthogonal NO precursors, which can be effectively uncaged in the presence of a palladium catalyst via bioorthogonal bond cleavage reactions to generate NO in living cancer cells, eliciting potent antiproliferative activity. [ABSTRACT FROM AUTHOR]

Background: NUDT21 (Nudix Hydrolase 21) has been shown to play an essential role in multiple biological processes. Pancreatic adenocarcinoma (PAAD) is one of the most fatal cancers in the world. However, the biological function of NUDT21 in PAAD remains rarely understood. The aim of this research was to identify the prediction value of NUDT21 in diagnosis, prognosis, immune infiltration, and signal pathway in PAAD. Methods: Combined with the data in online databases, we analyzed the expression, immune infiltration, function enrichment, signal pathway, diagnosis, and prognosis of NUDT21 in PAAD. Then, the biological function of NUDT21 and its interacted protein in PAAD was identified through plasmid transduction system and protein mass spectrometry. Expression of NUDT21 was further verified in clinical specimens by immunofluorescence. Results: We found that NUDT21 was upregulated in PAAD tissues and was significantly associated with the diagnosis and prognosis of pancreatic cancer through bioinformatic data analysis. We also found that overexpression of NUDT21 enhanced PAAD cells proliferation and migration, whereas knockdown NUDT21 restored the effects through in vitro experiment. Moreover, NDUFS2 was recognized as a potential target of NUDT21.We further verified that the expression of NDUFS2 was positively correlated with NUDT21 in PAAD clinical specimens. Mechanically, we found that NUDT21 stabilizes NDUFS2 and activates the PI3K-AKT signaling pathway. Conclusion: Our investigation reveals that NUDT21 is a previously unrecognized oncogenic factor in the diagnosis, prognosis, and treatment target of PAAD, and we suggest that NUDT21 might be a novel therapeutic target in PAAD. [ABSTRACT FROM AUTHOR]

A combined method of thermal and vibratory stress relief (TVSR) to extend effects of vibratory stress relief (VSR) is presented. TVSR was implemented by imposing vibratory load on a workpiece at an assisted temperature. Residual stresses before and after treatment were measured using the modified layer removal method (MLRM) to evaluate the stress variations. A finite element (FE) model was developed to investigate and compare TVSR and VSR treatment on workpieces cut from a 7075 aluminum alloy plate. Thermal influence on TVSR equipment and vibratory treatment of the workpiece was analyzed using this model. Experiments were conducted to validate simulation results. Significant residual stress relief was observed in TVSR, however, effects of VSR were limited. [ABSTRACT FROM AUTHOR]

ABSTRACT The bioaccumulation of diniconazole in Tenebrio molitor Linne larva was investigated with tandem based on the ChiralcelOD-3R[cellulose tri-(3,5-dimethylphenyl carbamate)] column. In this study we documented the effects of dietary supplementation with wheat bran contaminated by racemic diniconazole at two dose levels of 20 mg kg-1 and 2 mg kg-1 (dry weight) in Tenebrio molitor. The results showed that both doses of diniconazole were taken up by Tenebrio molitor rapidly in the first few days, the concentrations of R-enantiomer and S-enantiomer at high doses reached the highest level of 0.55 mg kg-1 and 0.48 mg kg-1, respectively, on the 1st d, and the concentrations of them obtained a maxima of 0.129 mg kg-1 and 0.128 mg kg-1 at low dose, respectively, on the 3rd d, which means that the concentration of diniconazole was proportional to the time of achieving the highest accumulated level. It afterwards attained equilibrium after a sharp decline at both 20 mg kg-1 and 2 mg kg-1 of diniconazole. The determination results from the feces of Tenebrio molitor demonstrated that the extraction recovery (ER) values of the high dose group were higher than that of the low dose group and the values were all above 1; therefore, it could be inferred that enantiomerization existed in Tenebrio molitor. Additionally, the biota accumulation factor was used to evaluate the bioaccumulation of diniconazole enantiomers, showing that the bioaccumulation of diniconazole in Tenebrio molitor was with preferential accumulation of S-enantiomer. Chirality 25:917-922, 2013. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

This study mainly evaluates the thermal aging properties of a new room temperature cured structural adhesive. Multiple adhesive specimens were thermal aged at 80℃, 100℃, 120℃ and 140℃, respectively, and subjected to the dynamic mechanical analysis (DMA) at different temperatures and frequencies. According to the results of DMA and thermodynamic analysis, the performance of the adhesive changes little after aging at 80℃, 100℃ and 120℃ for 30 days. However, the adhesive performance became unstable at 140℃, and deteriorated rapidly with the extension of aging time. Hence, this structural adhesive is suitable for the environment below 120℃. In addition, the generalized curve of the structural adhesive aging for 20 days at 100℃ was obtained, following the principles of time-temperature equivalence superposition and time-aging time equivalence superposition. The test time was shortened significantly. This research provides an accelerated characterization strategy for the long-term mechanical properties of other polymers, making it possible to obtain the generalized curve of polymers aging for a specific time at a specific temperature. [ABSTRACT FROM AUTHOR]

This paper firstly explores the hydrothermal aging performance of a new room temperature cured structural adhesive at four different levels of relative humidity through dynamic mechanical analysis (DMA). The results show that the strengthening effect of post-curing was stronger than weakening effect of humidity. Then, the Arrhenius equation was introduced to calculate the ratio of the apparent activation energy of this adhesive at the glass transition temperature before and after hydrothermal aging. The little change of the ratio suggests that the adhesive boasts a strong resistance to hydrothermal aging. In addition, the adhesive was tested on concrete structures at room temperature to observe its repairing effect of concrete cracks. The observations reveal that the compressive strength of the cracked concrete block repaired by the adhesive was as high as 90.5% of that of the intact concrete block. Furthermore, the adhesive was used to bond rebars to concrete under three different constant tensile speeds. The results demonstrate that the bonding effect was better under slow constant loading. [ABSTRACT FROM AUTHOR]

Anlotinib-mediated angiogenic remodeling was delineated in various tumors. Meanwhile, we previously showed that anlotinib inhibited tumor angiogenesis in anaplastic thyroid cancer (ATC). However, the potential role of anlotinib on cell lethality in ATC remains an enigma. Herein, we found that anlotinib inhibited the viability, proliferation, and migration of KHM-5M, C643, and 8505C cells in a dose-dependently manner. Under anlotinib treatment, PANoptosis (pyroptosis, apoptosis, and necroptosis) markers were not changed; however, ferroptosis targets (transferrin, HO-1, FTH1, FTL, and GPX4) were significantly downregulated. ROS levels also increased in a concentration-dependent manner after anlotinib treatment in KHM-5M, C643, and 8505C cells. In addition, protective autophagy was activated in response to anlotinib, and autophagic blockade potentiated anlotinib-mediated ferroptosis and antitumor effects in vitro and in vivo. Our new discovery identified autophagy-ferroptosis signaling pathway which provides mechanistic insight into anlotinib-mediated cell death, and synergistic combination therapy may help develop new ATC treatment strategies. [ABSTRACT FROM AUTHOR]

Purpose: International students are highly vulnerable to the risk of mental health worsening before and during the pandemic (COVID-19). This study investigated international students' mental health pre- and post-pandemic (COVID-19). Methods: It is a longitudinal study, and data were collected online, pre-pandemic (N = 470) and during the pandemic (N = 420). Using a random sampling technique, a self-administered questionnaire was used to measure mental health, including depression and anxiety. Results: Findings show that international students' mental health was good in pre-pandemic. Meanwhile, international students were found to be more depressed and anxious during the pandemic. Findings also investigated that in the pre-pandemic phase, young students' and mainly females' mental health was worsened. Conclusion: This study concluded that students' mental problems are alarming, so the university should provide psychological services for the student's mental health. Post-pandemic is leaving long-lasting psychological effects and will require further investigation. [ABSTRACT FROM AUTHOR]

CdS–reduced graphene oxide (RGO) composites are successfully synthesized viathe microwave-assisted reduction of graphite oxide in a CdS precursor solution using a microwave synthesis system. The photocatalytic performances of CdS–RGO composites in the reduction of Cr(vi) are investigated. The results show that CdS–RGO composites exhibit enhanced photocatalytic performance for the reduction of Cr(vi) with a maximum removal rate of 92% under visible light irradiation as compared with pure CdS (79%) due to the increased light absorption intensity and the reduction of electron–hole pair recombination in CdS with the introduction of RGO. [ABSTRACT FROM AUTHOR]

The cardiac mechanosensitive BK (Slo1) channels are gated by Ca2+, voltage, and membrane stretch. The neuropeptide GsMTx4 is a selective inhibitor of mechanosensitive (MS) channels. It has been reported to suppress stretch-induced cardiac fibrillation in the heart, but the mechanism underlying the specificity and even the targeting channel(s) in the heart remain elusive. Here, we report that GsMTx4 inhibits a stretch-activated BK channel (SAKcaC) in the heart through a modulation specific to mechano-gating. We show that membrane stretching increases while GsMTx4 decreases the open probability (Po) of SAKcaC. These effects were mostly abolished by the deletion of the STREX axis-regulated (STREX) exon located between RCK1 and RCK2 domains in BK channels. Single-channel kinetics analysis revealed that membrane stretch activates SAKcaC by prolonging the open-time duration (τO) and shortening the closed-time constant (τC). In contrast, GsMTx4 reversed the effects of membrane stretch, suggesting that GsMTx4 inhibits SAKcaC activity by interfering with mechano-gating of the channel. Moreover, GsMTx4 exerted stronger efficacy on SAKcaC under membrane-hyperpolarized/resting conditions. Molecular dynamics simulation study revealed that GsMTx4 appeared to have the ability to penetrate deeply within the bilayer, thus generating strong membrane deformation under the hyperpolarizing/resting conditions. Immunostaining results indicate that BK variants containing STREX are also expressed in mouse ventricular cardiomyocytes. Our results provide common mechanisms of peptide actions on MS channels and may give clues to therapeutic suppression of cardiac arrhythmias caused by excitatory currents through MS channels under hyper-mechanical stress in the heart. [ABSTRACT FROM AUTHOR]

Hepatic transcatheter arterial chemoembolization (TACE), a minimally invasive procedure to block the blood supply of tumors and release of cytotoxic agents, is preferentially applied to patients with hepatocellular carcinoma (HCC) who are not able to receive radical treatments. However, the long-term effects of TACE are unsatisfactory, as the microenvironment following procedure stimulates tumor angiogenesis, which promotes recurrence and metastasis of residual tumors. Tumor associated macrophages (TAMs) have been revealed to stimulate tumor growth and angiogenesis associated with poor prognosis in HCC. The present study focused on the changes in TAMs following TACE, and explored the effects of TACE in combination with the TAM inhibitor zoledronic acid (ZA) in rat HCC models. Orthotropic HCC rats were divided into three groups: Sham TACE, TACE alone and TACE combined with ZA treatment. At 7 or 14 days following TACE, tumor growth was evaluated by magnetic resonance imaging (MRI). Infiltration of TAMs was assessed by histological analysis and flow cytometry. Tumor angiogenesis was measured as the mean vessel density, and initial slope was calculated from dynamic contrast enhancement MRI. Local and systemic levels of vascular endothelial growth factor (VEGF) were determined by western blotting or an ELISA, respectively. The results revealed that TACE inhibited tumor growth at 7 days following the procedure, but this inhibition was attenuated at 14 days following the procedure compared with the sham TACE control. If combined with ZA treatment, TACE exhibited a stable inhibition effect on tumor growth until the end of observation. Investigation of the underlying mechanisms demonstrated that TACE combined with ZA treatment inhibited infiltration of F4/80 positive TAMs and tumor angiogenesis compared with the TACE alone group at 14 days following the procedure. Additionally, the combination treatment significantly inhibited secretion of VEGF in the present models. In conclusion, ZA treatment enhanced the effects of TACE through inhibiting TAM infiltration and tumor angiogenesis in rat HCC models. [ABSTRACT FROM AUTHOR]

Abstract: As an important active constituent of Ginkgo biloba extract, ginkoglide B is a highly selective and competitive PAF receptor antagonist which has been widely used in clinical applications. A novel high-performance liquid chromatography–electrospray ionization mass spectromentry (LC–ESI-MS) method was developed for the determination of ginkgolide B in dog plasma. After liquid/liquid extraction with ether and high-performance liquid chromatography (HPLC) gradient separation with 0.01% of ammonia water (v/v)—methanol as the mobile phase, the deprotonized anions [M–H]−1 at m/z 423 of ginkoglide B, and [M–H]−1 at m/z 492 of internal standard (IS) glibenclamide were analyzed by LC–ESI-MS in selected ion monitoring (SIM) mode. Chromatographic separation was achieved in less than 9min and calibration curve was linear over a concentration range of 0.1–20ng/ml. The described assay method was successfully applied to the pre-clinical pharmacokinetic study of ginkoglide B. After intragastric administration of ginkgolide B to beagle dogs, C max and T max of ginkgolide B were 43.8±6.24ng/ml and 0.5h, respectively, and the elimination half-life (t 1/2) was 2.85±0.54h. [Copyright &y& Elsevier]