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AbstractMelanoma poses a challenge in oncology because of its aggressive nature and limited treatment modalities. The tumour microenvironment (TME) in melanoma contains unique properties such as an immunosuppressive and high-density environment, unusual vasculature, and a high number of stromal and immunosuppressive cells. In recent years, numerous experiments have focused on boosting the immune system to effectively remove malignant cells. Adjuvants, consisting of phytochemicals, toll-like receptor (TLR) agonists, and cytokines, have shown encouraging results in triggering antitumor immunity and augmenting the therapeutic effectiveness of anticancer therapy. These adjuvants can stimulate the maturation of dendritic cells (DCs) and infiltration of cytotoxic CD8+ T lymphocytes (CTLs). Furthermore, nanocarriers can help to deliver immunomodulators and antigens directly to the tumour stroma, thereby improving their efficacy against malignant cells. The remodelling of melanoma TME utilising phytochemicals, agonists, and other adjuvants can be combined with current modalities for improving therapy outcomes. This review article explores the potential of adjuvants, drugs, and their nanoformulations in enhancing the anticancer potency of macrophages, CTLs, and natural killer (NK) cells. Additionally, the capacity of these agents to repress the function of immunosuppressive components of melanoma TME, such as immunosuppressive subsets of macrophages, stromal and myeloid cells will be discussed. [ABSTRACT FROM AUTHOR]

The severity of crashes on national/provincial roads, urban roads, and rural roads was analyzed. Random parameters logit models with heterogeneity in means and variances under different time periods of the day and roadway classifications were employed. Analysis of factors influencing injury severity of single-vehicle crashes in the driver, vehicle, road, and environment to explore correlation and difference between influencing factors and crash severity. The results showed that the effect of factors that determine injury severity varied significantly across different roadway classifications. Specifically, driver age (<30) and summer were only significantly associated with single-vehicle crashes on urban roads. Dawn/dusk was only significant in single-vehicle crashes on rural roads. Meanwhile, overall spatiotemporal instability was observed in the study. While several indicators were also reported to show relative spatial or temporal stability such as male, driver age (>55), motorcycle, traffic control, and visibility (<100 m). [ABSTRACT FROM AUTHOR]

Orthogonal Latin hypercube designs (LHDs) and maximum projection (MaxPro) LHDs are widely used in computer experiments. They are efficient for estimating the trend part and the Gaussian process part of the universal Kriging (i.e., the Gaussian process) model, respectively, especially when only some of the factors are active. Yet, the orthogonality and the MaxPro criteria often do not agree with each other. In this work, we propose a new class of optimal designs, called orthogonal-MaxPro LHDs, optimizing a well-defined multi-objective criterion combining the correlation and the MaxPro metrics. An efficient parallel algorithm via level permutations and expansions is developed, whose efficiency is guaranteed by theories. Numerical results are presented to show that the construction is fast and the obtained designs are attractive, especially for large computer experiments. [ABSTRACT FROM AUTHOR]

To study the time-of-day variations and temporal stabilities of factors influencing single-vehicle crashes on rural highways, random parameters logit models with heterogeneity in means and variances under different time periods of the day and from year to year were estimated to identify significant factors. The potential crash-influencing factors in drivers, vehicles, roads, and the environment were analyzed to dissect the correlation and variability between the influencing factors and crash injury severity. Likelihood ratio tests were conducted to assess the transferability of model estimation results from different times of the day and from year to year. The results showed that the effect of factors that determine injury severity varied significantly across time-of-day/time-period combinations. Overall temporal instability was observed in the study. However, several explanatory variables showed temporally stable effects in terms of their impact on resulting injury severities. Such as male, driver age (<30), truck, non-dry road surface, and visibility (100–200 m). [ABSTRACT FROM AUTHOR]

A new type of experiment that aims to determine the optimal quantities of a sequence of factors is eliciting considerable attention in medical science, bioengineering, and many other disciplines. Such studies require the simultaneous optimization of both quantities and sequence orders of several components which are called quantitative-sequence (QS) factors. Given the large and semi-discrete solution spaces in such experiments, efficiently identifying optimal or near-optimal solutions by using a small number of experimental trials is a nontrivial task. To address this challenge, we propose a novel active learning approach, called QS-learning, to enable effective modeling and efficient optimization for experiments with QS factors. QS-learning consists of three parts: a novel mapping-based additive Gaussian process (MaGP) model, an efficient global optimization scheme (QS-EGO), and a new class of optimal designs (QS-design). The theoretical properties of the proposed method are investigated, and optimization techniques using analytical gradients are developed. The performance of the proposed method is demonstrated via a real drug experiment on lymphoma treatment and several simulation studies. for this article are available online. [ABSTRACT FROM AUTHOR]

Although numerous studies have linked asthma to air temperature and pollution, few studies have examined their interactive effects on asthma outpatient visits. This study investigated how air pollutants and their interactions with temperature affect asthma outpatient visits in a city in northern Chinaduring the time period 2018 - 2020.. As the results, 24,163 asthma outpatients were recorded, a 10-μg/m3 increase in PM10, PM2.5, SO2, and NO2 concentrations was associated with significant increases in visits of 3.47% (95% CI: 2.35%–4.60%), 0.83% (95% CI: 0.36%–1.30%), 3.17% (95% CI: 1.47%–4.90%), and 8.90% (95% CI: 6.09%–11.79%), respectively. The effect was stronger in females than males, and stronger in the elderly (≥65 years) than among the young. The interaction between low temperatures and high air pollution levels significantly increased the number of asthma outpatient visits. This study emphasizesthe importance of reducing air pollution in order to lessen the effects of cold. [ABSTRACT FROM AUTHOR]

An inverted AluYb8 insertion in the MUTYH intron 15 (AluYb8MUTYH variant) has been reported to be associated with reduced MUTYH1 expression and mitochondrial dysfunction with age. However, the underlying mechanism remains unknown. In this study, we identified a novel transcript associated with the AluYb8MUTYH variant, which revealed that this transcript is about 780 nucleotides in length with a poly-A tail, lacks protein-coding potential, referred to as lncMUTYH. The results from the reporter gene system confirmed that the lncMUTYH down-regulates MUTYH1 expression at the translational level. Site-directed mutagenesis on the 5′-terminal exon sequences of α-MUTYH and lncMUTYH constructs revealed that lncMUTYH can act as a trans-regulator that depends on the partial base pairing between its exonized AluYb8 sequence and the 5′UTR of α-MUTYH to impede MUTYH 1 expression. Furthermore, we have demonstrated a correlation between decreased mitochondrion-localized MUTYH1 caused by lncMUTYH and lowered levels of mitochondrial biological function indicators, such as mtDNA content, mitochondrial regulatory gene expression, oxygen consumption rate, ATP product, and mitochondrial respiratory capacity. Notably, we found that lncMUTYH inhibited the M2-like polarization of macrophages, and CD68/CD206-positive cell fractions were significantly lower in lncMUTYH ectopically expressing cells. The results confirmed that the AluYb8MUTYH-associated lncMUTYH, derived from an AluYb8 insertion mutation, acts as a trans-regulatory factor that inhibits the MUTYH1 protein expression, leading to a progressive mitochondrial dysfunction that may disrupt macrophage differentiation. In summary, lncMUTYH can contribute to AluYb8MUTYH-associated mitochondrial dysfunction with age and hamper the macrophage polarization process, potentially increasing the risk of developing age-related diseases. A novel non-coding RNA was identified derived from the AluYb8 insertion in the MUTYH gene, namely lncMUTYH. LncMUTYH selectively decreased the MUTYH1 protein localized in mitochondrial, which is dependent on the sequence and orientation derived from AluYb8 insertion. Overexpression of lncMUTYH dampens the mitochondrial function and M2-like polarization of macrophages, partly due to the suppression of the MUTYH1 protein. [ABSTRACT FROM AUTHOR]

Corona Virus Disease 2019 (COVID-19) has a significant impact on sleep quality. However, the effects on sleep quality in the post-COVID-19 pandemic era remain unclear, and there is a lack of a screening tool for Chinese older adults. This study aimed to understand the prevalence of poor sleep quality and determine sensitive variables to develop an effective prediction model for screening sleep problems during infectious diseases outbreaks. The Peking University Health Cohort included 10,156 participants enrolled from April to May 2023. The Pittsburgh Sleep Quality Index (PSQI) scale was used to assess sleep quality. The data were randomly divided into a training-testing cohort (n = 7109, 70%) and an independent validation cohort (n = 3027, 30%). Five prediction models with 10-fold cross validation including the Least Absolute Shrinkage and Selection Operator (LASSO), Stochastic Volatility Model (SVM), Random Forest (RF), Artificial Neural Network (ANN), and XGBoost model based on the area under curve (AUC) were used to develop and validate predictors. The prevalence of poor sleep quality (PSQI >7) was 30.69% (3117/10,156). Among the generated models, the LASSO model outperformed SVM (AUC 0.579), RF (AUC 0.626), ANN (AUC 0.615) and XGBoost (AUC 0.606), with an AUC of 0.7. Finally, a total of 12 variables related to sleep quality were used as parameters in the prediction models. These variables included age, gender, ethnicity, educational level, residence, marital status, history of chronic diseases, SARS-CoV-2 infection, COVID-19 vaccination, social support, depressive symptoms, and cognitive impairment among older adults during the post-COVID-19 pandemic. The nomogram illustrated that depressive symptoms contributed the most to the prediction of poor sleep quality, followed by age and residence. This nomogram, based on twelve-variable, could potentially serve as a practical and reliable tool for early identification of poor sleep quality among older adults during the post-pandemic period. The poor sleep quality (PSQI >7) was still prevalent among older adults during the post-COVID-19 pandemic. The LASSO model was the best model to predict poor sleep quality among older adults, compared with SVM, RF, ANN and XGBoost. This prediction model, based on twelve variables, may potentially serve as a practical and reliable tool for the early identification of poor sleep quality among older adults during the post-pandemic period. [ABSTRACT FROM AUTHOR]

Gadolinium-based MR cisternography has been mainly applied in clinical evaluation of cerebrospinal fluid leaking, that is conducted by intrathecal administration of contrast media. Recently, we have reported one novel technique of intrathecal targeted drug delivery with prepontine cisternal routine to treat orofacial cancer pain. The aim of this study was to examine the distribution pattern of this intrathecal drug delivery strategy. Here, we introduce one case who suffered severe orofacial pain caused by sublingual gland tumor, and successfully attenuated by prepontine cisternal administration of analgesic agents. To assess the distribution of intrathecal drugs, postoperative MR images of brain, cervical, thoracic, and lumbar segments in axial, coronal, and sagittal planes were obtained after application of gadolinium. The perfusion rate of contrast medium was set at 0.01 mmol per hour for 24 hours prior to MR scanning. In the T1-weighted images, we can identify contrast spread not only locating around the site of the intrathecal catheter tip, but also concentrated to the lateral sides. None obvious side effect was found after intrathecal injection of contrast media. Thus, our finding demonstrated the local distribution phenomenon of intrathecal drugs through prepontine cisternal access, and the bilateral perfusion pattern may provide insights underlying the analgesic mechanism of trigeminal pain provided by this novel intrathecal therapy. Gadolinium-based MR cisternography may serve as a potential tool to confirm the therapeutic effect of intrathecal targeted drug delivery via prepontine cisternal routine in orofacial pain management. [ABSTRACT FROM AUTHOR]

Objectives: High reactive oxygen species (ROS) levels lead to cell death, and the testes are among the most vulnerable organs to oxidative damage. Rg1, an active ingredient extracted from the natural medicine ginseng, has potential anti-inflammatory, antioxidant and antiapoptotic properties. Our previous studies showed that Rg1 can effectively improve spermatogenic function in mice, but the specific mechanism remains unclear. The purpose of this study was to investigate the effect of Rg1 on oxidative stress and spermatogonium apoptosis in D-gal-induced testicular toxicity and elucidate the associated mechanism. Methods: Male C57BL/6 mice at 6–8 weeks of age were intraperitoneally injected with D-gal (200 mg/kg) for 42 days to establish a testicular injury model, and on day 16, 40 mg/kg Rg1-rich saline was injected intraperitoneally. Concurrently, we established an in vitro model of D-gal-damaged spermatogonia, which was treated with Rg1. Results: We found that treatment with the ginsenoside Rg1 reduced D-gal-induced oxidative stress and spermatogonium apoptosis in vivo and in vitro. Mechanistically, we found that Rg1 activated Akt/bad signaling and reduced D-gal-induced spermatogonium apoptosis. Discussion: We provide evidence showing that the antioxidant effect of Rg1 is mediated by the Akt/GSK-3β/NRF2 axis. Based on these findings, we consider Rg1 a potential treatment for testicular oxidative damage. [ABSTRACT FROM AUTHOR]

5-Fluorouracil (5-FU)-injured stromal cells may cause chronic bone marrow suppression; however, the underlying mechanism remains unclear. Angelica sinensis polysaccharide (ASP), the main biologically active ingredient of the Chinese herb, Angelica sinensis (Oliv.) Diels (Apiaceae), may enrich the blood and promote antioxidation. This study investigated the protective antioxidative effects of ASP on perivascular mesenchymal progenitors (PMPs) and their interactions with hematopoietic cells. PMPs were dissociated from C57BL/6 mouse femur and tibia and were subsequently divided into the control, ASP (0.1 g/L), 5-FU (0.025 g/L), and 5-FU + ASP (pre-treatment with 0.1 g/L ASP for 6 h, together with 0.025 g/L 5-FU) then cultured for 48 h. Hematopoietic cells were co-cultured on these feeder layers for 24 h. Cell proliferation, senescence, apoptosis, and oxidative indices were detected, along with stromal osteogenic and adipogenic differentiation potentials. Intercellular and intracellular signaling was analyzed by real-time quantitative reverse transcription polymerase chain reaction and Western blotting. ASP ameliorated the reactive oxygen species production/scavenge balance in PMPs; improved osteogenic differentiation; increased SCF, CXCL12, VLA-4/VCAM-1, ICAM-1/LFA1, and TPO/MPL, Ang-1/Tie-2 gene expression. Further, the ASP-treated feeder layer alleviated hematopoietic cells senescence (from 21.9 ± 1.47 to 12.1 ± 1.13); decreased P53, P21, p-GSK-3β, β-catenin and cyclin-D1 protein expression, and increased glycogen synthase kinase (GSK)-3β protein expression in co-cultured hematopoietic cells. ASP delayed oxidative stress-induced premature senescence of 5-FU-treated feeder co-cultured hematopoietic cells via down-regulation of overactivated Wnt/β-catenin signaling. These findings provide a new strategy for alleviating myelosuppressive stress. [ABSTRACT FROM AUTHOR]

The tilting of the cab seat when the tractor is in deep ploughing operation changes the sitting position of the driver, which may accelerate lumbar spine injury. This paper adopts the musculoskeletal model and the finite element model of the lumbar L4–L5 segment to predict the maximum Von-Mises stress and maximum strain of the driver's lumbar L4–L5 segment intervertebral disc. In this study, we used 3D motion capture to obtain the driver's spine position spatial data when the tractor tilted at different angles. A tractor-driver musculoskeletal model and a finite element model of the lumbar spine L4–L5 segments were created in AnyBody™ and Abaqus, respectively. The tractor-driver musculoskeletal model was used to calculate the load of the driver's lumbar spine L4–L5 segment at different angles of tractor tilt, which was used as the load condition of the finite element model of the lumbar spine L4–L5 segment, and then the influence of tractor tilt angle and vibration on the driver's lumbar spine L4–L5 disc was studied. The results show that the maximum Von-Mises stress and maximum strain of the driver's lumbar L4–L5 intervertebral disc will increase due to the tilt. The maximum Von-Mises stress occurs in the annulus II, and the maximum strain occurs in the upper end plate of the intervertebral disc. With the occurrence of tilt, the position of the maximum Von-Mises stress changes, which can lead to disc injury to the driver, and vibration may exacerbate this injury. [ABSTRACT FROM AUTHOR]

The study investigates the impact of microstructure modifications on the corrosion, passivation, and plasma-nitriding behaviour of 316L steel. Microstructure modifications are achieved through the laser powder bed fusion (L-PBF) process and surface mechanical attrition treatment (SMAT). Three scanning strategies (concerning the orientation of the sample surface with scanning directions) are used in the L-PBF process, and the corresponding samples are labelled as HNS (0°), INS (45°), and VNS (90°). The scanning strategies have altered the average grain size (maximum for HNS and minimum for VNS) and porosity (HNS has the highest). Porosity disappears after SMAT. The surface of the SMATed specimen (VS) has equiaxed austenite nanograins (∼32 nm) with a fine distribution of α'-martensite, nanotwins, and high dislocation density. Microstructure affects the passivation, corrosion, and nitriding behaviour of the steel. The VNS has the lowest corrosion rate, decreasing further after SMAT. The SMATed sample exhibits the lowest nitrided layer thickness (∼65 μm). SMAT followed by nitriding causes a gradient-structured layer (with improved hardness) consisting of a nitrided layer, SMATed layer, and core. The nitrided HNS sample (∼78 μm thick nitrided layer) is dominated by γ'-Fe4N, while the nitrided VNS and VS samples have a relatively higher proportion of expanded austenite. [ABSTRACT FROM AUTHOR]

Active and passive continental rifts are generally attributed to plume and subduction mechanisms, respectively. However, controversy surrounding the role of the two mechanisms continues, especially for the mid-Neoproterozoic rifts in the South China Craton. Here, we use geochemical and zircon Hf isotope data from the craton's rift successions to examine the mechanism of rifting. The compiled geochemical data support the existence of subduction-related magmatic belts along the Jiangnan Orogen and western Yangtze margin of the craton during the mid-Neoproterozoic, consistent with a conventional subduction-related passive rift mechanism. But evidence of asthenospheric upwelling and subsequent lithospheric uplift, metamorphism, volcanism and magma-rich rift infill indicate rifting was active. Compiled zircon εHf(t) values and crustal incubation times suggest a ca. 830–780 Ma transition from advancing to retreating subduction that coincides with rifting across the craton. We therefore propose a subduction-related active rifting model in which the onset of transitionalsubduction triggered mantle convection and plume activity that led to the mid-Neoproterozoic initiation of active rifting in the South China Craton. This suggests a mixed mechanism for rifting rather than two distinct end-members. [ABSTRACT FROM AUTHOR]

The tilting of the tractors' seat during deep tillage operations affects the drivers' sitting position, which can lead to lumbar spine injuries. To investigate the effect of seat tilting on the driver's L4 biomechanics, we built a tractor-driver musculoskeletal model in AnyBody™. The maximum activity of the driver's erector spinae at different tilted angles were measured by sEMG and compared with the simulation results to validate the model. The spatial position of the driver's spine at different tilted angles were obtained by 3 D motion capture. The model simulated the driver's spine posture during the actual tilt and investigated the effects of different tilted angles and vibration on the biomechanics of the driver's L4. The results showed that as the tilt angle of the tractor increased, the load on the driver's L4 also increased, especially the shear force increased at a faster rate than the axial and normal forces, with the shear force on the driver's L4 increasing from 0 N to 138.7 N when the tractor was tilted from 0° to 15°. When vibration was applied to the musculoskeletal model, the maximum value of the shear force on the driver became progressively greater as the angle of tilt of the tractor increased. Overall, tilting the tractor can have a large impact on the biomechanics of the driver's L4, and tilting the tractor may be an important cause of lumbar spine injuries for tractor drivers. [ABSTRACT FROM AUTHOR]

People living with human immunodeficiency virus (HIV) are more likely to develop tuberculosis (TB), and their co-infection (HIV-TB) increases the risk of death. We aimed to describe the global trends, regional differences and age distribution of HIV-TB. Annual new cases, age-standardized incidence rates (ASRs) and age-specific incidence rates with 95% uncertainty intervals (UIs) of HIV-infected drug-susceptible tuberculosis (HIV-DS-TB), HIV-infected multidrug-resistant tuberculosis without extensive drug resistance (HIV-MDR-TB) and HIV-infected extensively drug-resistant tuberculosis (HIV-XDR-TB) during 1990–2019 were collected from the Global Burden of Disease Study 2019. To reveal the trends of HIV-TB by region and age, the percentage change of new cases and estimated annual percentage change (EAPC) of ASRs were calculated. The ASR of HIV-XDR-TB increased significantly by an average of 14.77% (95% CI: 11.05%–18.62%) per year during 1990–2019 worldwide, while the ASRs of HIV-DS-TB and HIV-MDR-TB decreased after 2005. HIV-XDR-TB was a great threat to Eastern Europe for the largest number of new cases (792, 95% UI: 487–1167) and the highest ASR (0.34 per 100,000 population, 95% UI: 0.21–0.50). In addition, Oceania had the largest rise in ASRs of HIV-MDR-TB (EAPC = 22.56, 95% CI: 18.62–26.64) and HIV-XDR-TB (EAPC = 32.95, 95% CI: 27.90–38.20) during 1990–2019. Recently, age-specific incidence rates of HIV-XDR-TB increased in all age groups, especially in the 50–69 age groups among high, low-middle and low Socio-Demographic Index regions. Additionally, the proportion of patients aged <15 years was nearly 10% of new cases in sub-Saharan Africa in 2019, which was higher than in other regions. HIV-infected drug-resistant TB is common in Oceania and Eastern Europe. Moreover, HIV-XDR-TB among elderly people became increasingly prevalent. In the future, the collaboration of management for HIV and TB should be intensified in Oceania and Eastern Europe, and more concerns need to be paid in elderly people. [ABSTRACT FROM AUTHOR]

The nano-drug delivery system activated by the tumour microenvironment (TME) can effectively treat tumours with low toxicity. Based on a high level of reductive GSH in TME and the different coordination properties of Fe ions, this project intended to prepare a GSH-activated cascade catalytic nanoreactor for breast cancer treatment using Fe3+/Fe2+ as the molecular switch. In this study, the glucose oxidase (GOx) loaded iron alginate nano hydrogel (FeAlg/GOx) was prepared by the simple one-step titration method. Results showed that FeAlg/GOx could remain stable during in vivo circulation to avoid hypoglycaemia. When it reached the targeted tumour site, reductive GSH can reduce Fe3+ to Fe2+. Thereafter, FeAlg/GOx nanogel was broken and GOx was released to consume the essential nutrient glucose (Glu) to achieve tumour starvation therapy. Next, the substrate H2O2 generated by the reaction between GOx and Glu can be catalysed by Fe2+ to produce highly cytotoxic •OH in situ, which could further kill tumour cells. The in vivo pharmacodynamics results demonstrated that compared with the control group (V/V0 = 8.36 ± 1.73), FeAlg/GOx group showed the most significant anti-tumour effect with V/V0 of 3.08 ± 1.06. In conclusion, this "inactivated" FeAlg/GOx nanogel can be converted into "activated" therapeutic substances in situ to achieve starvation-chemodynamic combined treatment for breast cancer. [ABSTRACT FROM AUTHOR]

Space-filling designs are widely used in both computer and physical experiments. Column-orthogonality, maximin distance, and projection uniformity are three basic and popular space-filling criteria proposed from different perspectives, but their relationships have been rarely investigated. We show that the average squared correlation metric is a function of the pairwise L2-distances between the rows only. We further explore the connection between uniform projection designs and maximin L1-distance designs. Based on these connections, we develop new lower and upper bounds for column-orthogonality and projection uniformity from the perspective of distance between design points. These results not only provide new theoretical justifications for each criterion but also help in finding better space-filling designs under multiple criteria. for this article are available online. [ABSTRACT FROM AUTHOR]

MutY homolog (MUTYH), an important protein in base excision repair (BER) system, excises adenine in the nascent strand opposite 8-oxoguanine in template DNA and restores G:C base-pair to maintain the fidelity of DNA replication. The loss of MUTYH causes oxidative stress and influences cardiac function, but the mechanism remains to be addressed. Here we demonstrate that Mutyh deficiency alters mitochondrial structure and impairs mitochondrial function through downregulation of mitochondrial fusion protein Mfn2 and alteration of the ratio of L-Opa1/S-Opa1 accompanied by reduction of α-ketoglutaric acid (α-KG) under oxidative stress condition. Further analysis reveals that the Mutyh deficiency may cause downregulation of histone demethylases and DNA demethylases and inhibition of the Mfn2 transcription. Oxidative stress associated with tert-butyl hydroperoxide (t-BHP) exposure results in the degradation of L-Opa1 and impairs the balance of L-Opa1/S-Opa1. Interestingly, α-KG supplementation alleviates the damage associated with Mutyh deficiency, restores the expression of Mfn2 and prevents degradation of L-Opa1. The current study demonstrates the relationship among Mutyh deficiency-coupled oxidative stress, the altered expressions of Mfn2 and Opa1, and the mitochondrial dysfunction, in which an intermediate in the tricarboxylic acid (TCA) cycle, α-KG has a key regulatory role. [ABSTRACT FROM AUTHOR]

The phenolic extracts of walnut cultivars with a red pellicle (HWE), a purple pellicle (ZWE) and a yellow pellicle (WWE) were compared. The total contents of phenolics, flavonoids and condensed tannins, as well as in vitro antioxidant activities (ABTS and DPPH) of the phenolic extracts were evaluated. The results showed that 25 phenolic compounds were identified in three colored walnuts. The HWE contained the highest contents of total phenolics and condensed tannins, while the ZWE contained the highest content of flavonoids. The DPPH and ABTS assays indicated that the phenolic extracts of colored-walnut pellicles showed a higher free radical scavenging ability than butylated hydroxytoluene (BHT) at the same concentration. Phenolic extracts of colored walnuts were also evaluated as natural antioxidants in walnut oil, substituting for BHT. The efficacy of phenolic extracts in walnut oil preservation was evaluated using accelerated storage (60 °C) for 12 days. After accelerated storage, walnut oil enriched with the phenolic extracts kept better qualities, with significantly lower peroxides, p-anisidine, and TOTOX values. The volatiles were measured and identified using the headspace solid phase micro-extraction gas chromatography to further assess oil quality. Aldehydes such as hexanal and 2-heptenal were identified as representative oxidative volatiles. Hexanal and 2-heptenal content indicated that adding phenolic extracts could prevent flavor deterioration of the oil. This study suggested that phenolic extracts of walnut pellicles could offer an effective alternative to synthetic antioxidants for walnut oil preservation. [ABSTRACT FROM AUTHOR]

Severe malnutrition evaluated by patient-generated subjective global assessment results in poor outcome among adult patients with acute leukemia: a retrospective cohort study. Moreover, although no statistically significant difference was observed, patients with malnutrition tended to have lower EFS than those without malnutrition at diagnosis (86.7 ± 7.4% vs. 94.7 ± 2.1%, I p i = 0.301) (Figure 2(c)). Over the past several decades, the 5-year relative survival for childhood acute lymphoblastic leukemia (ALL) has exceeded 90% due to improvements in treatment and support care [[1]]. The prevalence of patients with malnutrition (undernutrition and overnutrition) increased from 20.3% to 36.6% during induction therapy. [Extracted from the article]

Objectives: A total of 156 adult acute myeloid leukemia (AML) patients were enrolled in this study to explore the clinical characteristics and prognostic impact of ASXL1 mutations. Methods: Clinical characteristics, prognostic impact and the association between ASXL1 mutations and some other mutations were analyzed. Results: We found ASXL1 mutations were most frequently found in M5 subtype and intermediate risk karyotype and were correlated with TET2, DNMT3A and PHF6 mutations. A total of 145 patients were included in prognostic analysis; results showed ASXL1 mutations had no impact on OS and DFS. In normal karyotype-AML (CN-AML) and older (≥60 years) AML, ASXL1 mutations showed adverse impact on OS (P = 0.022; p = 0.019, respectively) and showed adverse prognostic tendency on DFS (p = 0.173; p = 0.108, respectively). ASXL1 mutations were also independent unfavourable prognostic factors for OS on CN-AML and older (≥60 years) AML patients and unfavourable factors for DFS on older (≥60 years) AML in multivariate analysis. Results also indicated that though ASXL1 mutations were associated with TET2, DNMT3A and PHF6 mutations, when coinciding with ASXL1 mutations, the prognosis of AML was not significantly impacted. Discussion: The reliability of our results need to be further confirmed by prospective randomized controlled studies covering a large numbers of AML patients. Conclusion: The results showed ASXL1 mutations may act as a poor prognostic index especially in elder AML and CN-AML patients. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a degenerative neurologic disease. The study aimed to identify the key differentially expressed genes (DEGs) and pathways in AD pathogenesis and obtain potential biomarkers in AD diagnosis. Methods: An integrated analysis of publicly available Gene Expression Omnibus datasets of AD was performed. DEGs in hippocampus tissue (HIP), temporal gyrus tissue (TG), frontal gyrus tissue (FG) and whole blood (WB) were identified. Bioinformatics analyses were used to insight into the functions of DEGs. The expression levels of candidate DEGs were preliminarily validated in GSE1297. The discriminatory ability of candidate DEGs in WB samples of AD patients and healthy individuals was evaluated in GSE63060 and GSE63061 datasets through receiver operating characteristic (ROC) analysis. Results: The DEGs in HIP, TG and FG tissues of AD were identified. Functions involved in regulation of apoptotic process, apoptotic process and cell death were significantly enriched from DEGs in AD. MAPK signaling pathway and Wnt signaling pathway were significantly enriched. YAP1, MAPK9 and GJA1 were the hub proteins in protein–protein interaction network in HIP, TG and FG. The expression levels of 14 DEGs in GSE1297 dataset were consistent with our integrated analysis. Moreover, 7 out of 14 DEGs had the diagnostic value in distinguishing AD patients from healthy controls in both GSE630060 and GSE630061 datasets. Conclusion: The DEGs including YAP1, MAPK1, GJA1 and pathways including MAPK signaling pathway and Wnt signaling pathway may be related to AD progression. RAD51C, SAFB2, SSH3 and TXNDC9 might be potential biomarkers in AD diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: Case-based learning (CBL) is now used as a teaching strategy to promote clinical problem-solving ability. The purpose of this study was to determine whether CBL is superior to the traditional teaching method in teaching lung cancer curriculum to oncology students. Methods: This study was a randomized controlled trial, enrolled 80 first-year oncology postgraduates from Bengbu medical college in the past 3 years. They were randomized to divide into 2 groups, had courses with the same lung cancer contents and timing. The experimental group (n = 40) utilized the CBL method while the control group (n = 40) used the traditional lecture-based teaching method. A questionnaire was used to attain the students' learning satisfaction and self-efficacy of the course, and a post-study examination was used to assess end-of-course performance. Results: Complete data were obtained from participating students (n = 40 in CBL; n = 40 in traditional teaching). The CBL group performed significantly better in questionnaire and examination compared to traditional teaching groups. Students showed high levels of satisfaction and problem-solving ability in the CBL group. Conclusion: Compared with the traditional teaching method. The case teaching method is a more effective teaching method to improve the ability of problem-solving for graduate students in medical oncology. [ABSTRACT FROM AUTHOR]

In a migration network system, any change of regional characteristics may affect outflows and inflows from and to the region itself and potentially its neighbouring regions. To explore the impact of spatial spillovers on interprovincial migration flows in China, we proposed four spatial autoregressive interaction models by introducing different network structures to gravity models. The results indicate that the model taking account of dependence structure among origins, destinations and flows is more accurate than the other models. Population size is the most critical determinant in interprovincial migration from 2005 to 2010 in China and is greatly strengthened by spatial spillovers. [ABSTRACT FROM AUTHOR]

A multi-elemental certified reference material (CRM) based on Arctic marine sediment was prepared and labeled GBW 07481. Approximately 4.5 kg of the sediment was collected during the third Chinese Arctic Expedition. The sediment was processed in procedures that included air drying, debris removal, drying, and milling. The final product contained particles that were generally smaller than 74 ;m representing 99% of the total mass. The powder was poured into clean 10-mL brown glass vials and a total of 300 vials were obtained. The homogeneity and stability were preliminarily investigated to assess the suitability of the marine sediment as a candidate CRM. The candidate material was demonstrated to be suitable for this purpose; and hence the certification project was accomplished with nine reputable laboratories. More than 10 reliable analytical methods, including inductively coupled plasma-mass spectrometry (ICP-MS), inductively coupled plasma-atomic emission spectrometry (ICP-AES), and x-ray fluorescence (XRF), were used for analyzing the sediment for 68 elements. The results should be useful for assessing the analytical accuracy of major, minor, and trace elements in marine sediments. Therefore, the CRM is expected to play an important role in Arctic geochemical surveys and environmental assessment. [ABSTRACT FROM AUTHOR]

Benefit-risk (BR) assessment is important to ensure safety and effectiveness of medical projects in clinical development and post marketing surveillance. The evaluation of the balance between benefits and risks of a drug is fundamental to all stakeholders involved in the development, registration, and use of drugs. Many quantitative approaches have been developed that may draw together data from different sources to present them in ways that can aid decision-making. Among these quantitative approaches, multicriteria decision analysis (MCDA) is one of the most useful approaches, since it provides a framework for systematic and replicable analyses of complex decision problems involving value tradeoffs. In most real-life situations, decision makers are not able to get exact preference information (weights). To overcome this limitation of MCDA, a method called stochastic multicriteria acceptability analysis (SMAA) was proposed as a quantitative approach to BR assessment in drug development. The chief advantage of SMAA over most other MCDA methodologies is that it can be used with limited or no preference information and a data-driven approach can be used to obtain the inherent weighting among multicriteria. In this article, we propose the stochastic multicriteria discriminatory method (SMDM) that is based on the SMAA method with a focus on providing straightforward and informative assistance to decision making. We use SMDM to derive probability of better treatment, probability of significantly better treatment and the expectedp-values of the evaluation results, on the basis of limited partial weight information or no weight information at all. [ABSTRACT FROM AUTHOR]

ContextGinseng is a widely used herbal medicine in China but its mechanism of action remains unclear. ObjectiveThe objectives of this work were to study the protective effect of ginsenoside Rg1 on subacute murine renal damage induced byd-galactose and its mechanism. Materials and methodsC57BL/6J mice were injected with 120 mg/kg/d (sc)d-galactose for 1 week, followed by a combined treatment of Rg1 20 mg/kg/d (ip) and 120 mg/kg/dd-galactose (sc) for 5 weeks. Mice were injected with the 0.9% saline 0.2 mL/d (sc) and 120 mg/kg/dd-galactose (sc) for 6 weeks in the control group and thed-galactose group, respectively. After 6 weeks, urea, creatinine, uric acid, cystatin (Cys-C), senescence-associated β-galactosidase (SA-β-gal) staining positive kidney cells, superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), malondialdehyde (MDA), glycation end products (AGEs) and 8-hydroxy-2 deoxyguanosine (8-OH-dG) were measured. ResultsTreatment with Rg1 ameliorated kidney function and aging state (urea from 17.19 ± 1.09 to 15.77 ± 1.22 mmol·L − 1, creatinine from 29.40 ± 5.72 to 22.60 ± 3.97 μmol·L − 1, uric acid from 86.80 ± 5.97 to 72.80 ± 10.61 μmol·L − 1, Cys-C from 0.23 ± 0.03 to 0.18 ± 0.05 mg·L − 1, ROD of SA-β-gal from 56.32 ± 10.48 to 26.78 ± 7.34, SOD from 150.22 ± 19.07 to 190.56 ± 15.83 U·(mg·prot) −1, MDA from 9.28 ± 1.59 to 3.17 ± 0.82 nmol·(mg·prot) −1, GSH-PX from 15.68 ± 2.11 to 20.32 ± 2.96 U·(mg·prot) −1as well as regulated glomerulus morphology (glomerulus diameter from 775.77 ± 18.41 to 695.04 ± 14.61 μm, renal capsule width from 39.56 ± 3.51 to 31.42 ± 2.70 μm, glomerulus basement membrane from 206.03 ± 16.22 to 157.27 ± 15.70 nm, podocyte slit from 55.21 ± 8.55 to 37.63 ± 6.65 nm). ConclusionsGinsenoside Rg1 can antagonised-galactose subacute renal damage in mice and this may occur due to alleviating oxidative stress injury. [ABSTRACT FROM PUBLISHER]

We examine the effect of corporate ownership structure on the market value of excess cash in Chinese listed firms. We find that state ownership has a positive effect, as the market value of excess cash is greater in state-owned firms (SOEs) than in privately controlled firms. Furthermore, we show that expropriation by controlling shareholders is significantly higher in privately controlled firms than in SOEs and increases with excess cash. The evidence is consistent with the view that the market believes private controlling shareholders are more likely to extract the private benefits associated with cash reserves. [ABSTRACT FROM AUTHOR]

We use the occasion of a change in tax policy that raised the tax rate for many of the listed companies in China to examine tax-induced earnings management (TEM) from the perspective of political connections. We find that when the tax rate increased, only those affected firms with politically connected management engaged in TEM. This suggests that, in addition to motivation for managing earnings, capability of influencing tax authorities is also an important determinant of TEM. We also find that TEM helped the firms with politically connected management to reduce their tax burden. [ABSTRACT FROM AUTHOR]

Acute lymphoblastic leukemia (ALL) is a clonal hematologic disease, and is the most common cause of childhood malignancy. Recently, a new locus was identified at 10p12.31-12.2 through a genome-wide association study (GWAS) that included racially and ethnically diverse populations. We conducted a replication study with 570 cases of ALL and 673 cancer-free controls to validated the association of this locus with ALL susceptibility in a Chinese population. The results of our study confirmed that the 10p12.31-12.2 locus was linked to childhood ALL susceptibility in the Chinese population. Interestingly, we alsofound that the single nucleotide polymorphisms (SNPs) in this locus had a larger effect on susceptibility to high-risk ALL than on susceptibility to low-risk ALL. [ABSTRACT FROM AUTHOR]

Political cost theory and political power theory are two views on the effect of firm size on effective tax rate (ETR) in extant literature. The size effect of ETR can be investigated further by focusing on the relationship between firms and the government. This paper uses state ownership and tax status to capture this relationship and examines how firm size, state ownership and tax status jointly affect effective tax rates. It is found that, when firms do not enjoy a preferential tax status, firm size is positively associated with effective tax rates for privately controlled firms and negatively associated for state-controlled firms. The results show that political cost theory explains the relationship between size and effective tax rate for privately controlled firms, whereas political power theory explains this relationship for state-controlled firms. For those firms that already enjoy a preferential tax status, there is no significant relationship between their size and their tax burdens. [ABSTRACT FROM AUTHOR]

Neo-liberalism has dominated policy formulation and implementation for three decades and been influential in reshaping urban housing provision in different countries. However, the nature and impact of neo-liberal housing policy developments are also affected by previous arrangements, the exact nature, timing and pace of policy change and by how governments and markets have responded to emerging global and local challenges. This paper examines neo-liberal urban housing reform and market development in China and focuses on market performance and government responses following initial reform. The era of neo-liberal housing policy has been associated with turbulence, market changes and unequal housing and asset distribution. Housing reform and regulation policies have changed frequently in response; and this maturation of the neo-liberal system has important implications for policy and the structure and operation of the market. [ABSTRACT FROM AUTHOR]

The dramatic changes in urban housing provision in China after 1980 have been widely described and assessed. This paper updates earlier accounts of policy change in China and reflects upon the significance of these changes for theoretical and conceptual frameworks used in comparative housing studies. Housing privatisation and commercialisation transformed the Chinese socialist housing system into a dynamic housing market but new housing problems characteristic of market economies have emerged. Government at the national level has responded by developing new policies to support affordable and social housing; and at local level various new housing provision schemes have been tested, but their scale and impact have been limited because of the priority given by the local state to economic growth and securing local land related revenues. This paper suggests that the new phase of policy involves a distinctive hybrid approach rather than convergence on familiar market based, residual or corporatist approaches. [ABSTRACT FROM PUBLISHER]

Earnings management is an indicator of the corporate governance quality and investor protection standard. We study the frequencies and magnitudes of earnings management under two different thresholds, zero earnings and prior earnings, in the Chinese market from 1997 to 2004. We model earnings as a mixed-normal distribution and obtain parameter estimators that measure the frequency and magnitude of earnings management. We show that the practice of earnings management has gone up both in frequency and magnitude during the post-2000 period. We also find that the frequency and magnitude of earnings management are higher when firms try to avoid negative earnings than when firms try to report earnings increase. Our findings reflect the current economic environment in China and caution investors on the low-disclosure quality in the Chinese stock market. [ABSTRACT FROM AUTHOR]

An improved and mild glycosylation reaction was developed and used for the synthesis of ononin and rothindin, two naturally occurring isoflavone glycosides by a modified phase transfer catalyzed process. [ABSTRACT FROM AUTHOR]

Abstract Momordica charantia L. is a well-known medicine and food homology plant with high pharmaceutical and nutritional values. Polysaccharides are carbohydrate polymers connected by glycosidic bonds, one of the key functional ingredients of M. charantia. Recently, M. charantia polysaccharides (MCPs) have attracted much attention from industries and researchers due to their anti-oxidant, anti-tumor, anti-diabetes, anti-bacteria, immunomodulatory, neuroprotection, and organ protection activities. However, the development and utilization of MCPs-based functional foods and medicines were hindered by the lack of a deeper understanding of the structure-activity relationship (SAR), structural modification, applications, and safety of MCPs. Herein, we provide an overview of the extraction, purification, structural characterization, bioactivities, and mechanisms of MCPs. Besides, SAR, toxicities, application, and influences of the modification associated with bioactivities are spotlighted, and the potential development and future study direction are scrutinized. This review provides knowledge and research underpinnings for the further research and application of MCPs as therapeutic agents and functional food additives. [ABSTRACT FROM AUTHOR]