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Purpose: This study aims to investigate the joint effects of cancer and sleep disorders on the health-related quality of life (HRQoL), healthcare resource utilization, and expenditures among US adults. Methods: Utilizing the 2018-2019 Medical Expenditure Panel Survey (MEPS) database, a sample of 25,274 participants was categorized into four groups based on cancer and sleep disorder status. HRQoL was assessed using the VR-12 questionnaire. Generalized linear model (GLM) with a log-linear regression model combined gamma distribution was applied for the analysis of healthcare expenditure data. Results: Individuals with both cancer and sleep disorders (C+/S+) exhibited notably lower physical health (PCS) and mental health (MCS) scores—1.45 and 1.87 points lower, respectively. They also showed significantly increased clinic visits (2.12 times), outpatient visits (3.59 times), emergency visits (1.69 times), and total medical expenditures (2.08 times) compared to those without cancer or sleep disorders (C-/S-). In contrast, individuals with sleep disorders alone (C-/S+) had the highest number of prescription drug usage (2.26 times) and home health care days (1.76 times) compared to the reference group (C-/S-). Conclusions: Regardless of cancer presence, individuals with sleep disorders consistently reported compromised HRQoL. Furthermore, those with cancer and sleep disorders experienced heightened healthcare resource utilization, underscoring the considerable impact of sleep disorders on overall quality of life. Implications for cancer survivors: The findings of this study address the importance of sleep disorders among cancer patients and their potential implications for cancer care. Healthcare professionals should prioritize screening, education, and tailored interventions to support sleep health in this population. [ABSTRACT FROM AUTHOR]

We present here a novel strategy for the chemical recycling of bio-based poly(ethylene furanoate)s (PEF) to value-added high-performance bio-based poly(ethylene-co-isosorbide furanoate) (PEIF) copolyesters by the combination of cyclodepolymerization method with rapid cascade polycondensation-coupling ring-opening polymerization (PROP). The solution cyclodepolymerization of commercially available PEF affords cyclic oligo(ethylene 2,5-furandicarboxylate)s (COEFs), and the effects of reaction conditions on the yield of COEFs were studied. PEIF copolyesters with different isosorbide (IS) contents were synthesized via the cascade PROP of COEFs with IS, which show significant enhanced glass transition temperature. By melt spinning, PEIF fibers with different orientation factors were prepared, with excellent thermal stability and mechanical performance. The obtained PEIF fibers can lift a weight ∼25000 times higher than its weight. The PEIF fibers are stable under ambient conditions but are biodegradable following the "surface erosion" mechanism. These sustainable value-added biodegradable PEIF fibers offer a solution to the environmentally friendly fibers. [ABSTRACT FROM AUTHOR]

Presence of higher breast density (BD) and persistence over time are risk factors for breast cancer. A quantitatively accurate and highly reproducible BD measure that relies on precise and reproducible whole-breast segmentation is desirable. In this study, we aimed to develop a highly reproducible and accurate whole-breast segmentation algorithm for the generation of reproducible BD measures. Three datasets of volunteers from two clinical trials were included. Breast MR images were acquired on 3 T Siemens Biograph mMR, Prisma, and Skyra using 3D Cartesian six-echo GRE sequences with a fat-water separation technique. Two whole-breast segmentation strategies, utilizing image registration and 3D U-Net, were developed. Manual segmentation was performed. A task-based analysis was performed: a previously developed MR-based BD measure, MagDensity, was calculated and assessed using automated and manual segmentation. The mean squared error (MSE) and intraclass correlation coefficient (ICC) between MagDensity were evaluated using the manual segmentation as a reference. The test-retest reproducibility of MagDensity derived from different breast segmentation methods was assessed using the difference between the test and retest measures (Δ2-1), MSE, and ICC. The results showed that MagDensity derived by the registration and deep learning segmentation methods exhibited high concordance with manual segmentation, with ICCs of 0.986 (95%CI: 0.974-0.993) and 0.983 (95%CI: 0.961-0.992), respectively. For test-retest analysis, MagDensity derived using the registration algorithm achieved the smallest MSE of 0.370 and highest ICC of 0.993 (95%CI: 0.982-0.997) when compared to other segmentation methods. In conclusion, the proposed registration and deep learning whole-breast segmentation methods are accurate and reliable for estimating BD. Both methods outperformed a previously developed algorithm and manual segmentation in the test-retest assessment, with the registration exhibiting superior performance for highly reproducible BD measurements. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to present information on the past sea-level fluctuations of sedimentary rock succession of the Perlis area that covers the Mempelam Limestone, Timah Tasoh Formation, Sanai Limestone, Telaga Jatoh Formation, Kubang Pasu Formation, and Chuping Formation at Bukit Tungku Lembu and Guar Sanai, Perlis, Malaysia. Based on sedimentology logging, cycle stacking patterns, and accommodation variations revealed by Fischer plots, 51 cyclic sequences of third-order depositional sequences are recognized. These sequences generally consist of transgressive and regressive events. As the thickness of the cycle column increases, it forms an increase in accommodation space and subsidence rate and results in rising sea level. As the thickness of the cycle column decreases, it will form a decrease in accommodation space and subsidence rate, resulting in sea-level fall. Generally, the facies of the cycle are vertically arranged, forming coarsening and fining upward patterns observed from sedimentology logging. The Silurian Mempelam Limestone-Carboniferous Chepor Member sequence is characterized by a progressive increase and decrease in accommodation space, indicating a rise and fall in sea level. In contrast, the Carboniferous Uppermost Kubang Pasu-Permian Chuping Limestone sequence is characterized by a progressive decrease in accommodation space, indicating a longer-term fall in sea level. The regressive-transgressive cycles recognize deviations in the accommodation space and sediment supply from the cyclic successions. In turn, these cycles express the long-term of Perlis's sea-level fluctuations. The results notably reflect the cycles consistent with the long-term rising and falling trend in different regions globally in Paleozoic times. [ABSTRACT FROM AUTHOR]

The Grain for Green Project (GGP) is an important measure for the prevention of sloping farmland and the restoration of natural vegetation. This project has been critical to the restoration of ecological environments in western China. However, the effect of the GGP on freshwater ecosystem services under extreme climates remains unclear. Thus, taking the middle and upper reaches of the Wujiang River Basin in western China as an example, this study assessed the variation of three freshwater ecosystem services (e.g., water yield, soil retention and nutrient retention) impacted by the GGP under drought stress by employing the Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) model. In addition, the trade-off/synergistic relationship between three freshwater ecosystem services was analyzed based on the Pearson correlation coefficient. As revealed from the results, the effect of the GGP on the water yield and nutrient retention under drought stress was significantly higher than that on the soil retention. With the increase in the drought degree, the variation rate of the water yield and nutrient retention impacted by the GGP increased, whereas that of the soil retention decreased. The GGP in droughts of different seasons resulted in a significant heterogeneity in the changes of three freshwater ecosystem services. The correlation coefficients between the water yield and soil retention as well as that between the water yield and the nutrient retention increased, and the correlation coefficients declined between soil and nutrient retention under different drought degrees following the GGP. Unlike for the summer drought case, there were no significant changes in the correlation coefficients between three freshwater ecosystem services in spring, autumn and winter droughts. The results suggest that the amount of farmland converted to shrubland should be regulated to reduce the trade-off intensity between freshwater ecosystem services. In addition, food security and ecological environment protection should be balanced during the implementation of the GGP, and the most concentrated distribution region of farmland-to-forest conversion will be the key area of ecological management in the future. [ABSTRACT FROM AUTHOR]

Lymph node involvement increases the risk of breast cancer recurrence. An accurate non-invasive assessment of nodal involvement is valuable in cancer staging, surgical risk, and cost savings. Radiomics has been proposed to pre-operatively predict sentinel lymph node (SLN) status; however, radiomic models are known to be sensitive to acquisition parameters. The purpose of this study was to develop a prediction model for preoperative prediction of SLN metastasis using deep learning-based (DLB) features and compare its predictive performance to state-of-the-art radiomics. Specifically, this study aimed to compare the generalizability of radiomics vs DLB features in an independent test set with dissimilar resolution. Dynamic contrast-enhancement images from 198 patients (67 positive SLNs) were used in this study. Of these subjects, 163 had an in-plane resolution of 0.7 × 0.7 mm2, which were randomly divided into a training set (approximately 67%) and a validation set (approximately 33%). The remaining 35 subjects with a different in-plane resolution (0.78 × 0.78 mm2) were treated as independent testing set for generalizability. Two methods were employed: (1) conventional radiomics (CR), and (2) DLB features which replaced hand-curated features with pre-trained VGG-16 features. The threshold determined using the training set was applied to the independent validation and testing dataset. Same feature reduction, feature selection, model creation procedures were used for both approaches. In the validation set (same resolution as training), the DLB model outperformed the CR model (accuracy 83% vs 80%). Furthermore, in the independent testing set of the dissimilar resolution, the DLB model performed markedly better than the CR model (accuracy 77% vs 71%). The predictive performance of the DLB model outperformed the CR model for this task. More interestingly, these improvements were seen particularly in the independent testing set of dissimilar resolution. This could indicate that DLB features can ultimately result in a more generalizable model. [ABSTRACT FROM AUTHOR]

Phosphorus (P) acts as one of the essential macronutrients and plays critical roles in regulating growth, development, and yield formation capacity of the crop plants. Elucidating the physiological and molecular processes underlying plant P deprivation responses benefit the crop cultivation with high P use efficiency (PUE). In this study, we investigated the P-associated and agronomic traits as well as the transcriptome profile under contrasting inorganic phosphorus (Pi) levels combined with deficit irrigation, using two wheat cultivars contrasted by PUE (i.e., high PUE Shixin 828 and P deprivation sensitive Jimai 518). The deficient-P (DP) treatment decreased P accumulative amounts, photosynthetic function, and biomass in plants at various growth stages and reduced yields with respect to sufficient-P (SP) condition. Although the two cultivars were comparable on growth and P-associated traits as well as yields under SP, Shixin 828 displayed better growth traits, more P accumulation, and higher yields than Jimai 518 under DP, suggesting that the high PUE cultivars with enhanced P uptake positively affects photosynthetic function, biomass production, and productivity of plants under P deprivation conditions. A large quantity of genes with differential expression patterns, including 2948 upregulated and 1844 downregulated, were identified based on RNA-seq analysis in the Shixin 828 plants treated with P deprivation. These DE genes were shown to be associated with biological process (i.e., metabolic process and cellular process etc.), cellular components (cell body and organelle etc.), and molecular function (binding and catalytic activity), and phytohormone signaling pathways. Transgene analysis on TaZFP1, a gene in ZFP transcription factor family that exhibited upregulated expression in P-deprived plants, validated its role in enhancing P accumulation and P starvation adaptation of plants. Our results suggested that plant P deprivation response is underlying modulation of various physiological processes via modifying gene transcription at global level. Key message: RNA-seq sequencing combined with physiological and transgene analyses dissected the molecular processes related to P-associated and agronomic traits in wheat cultivated under Pi deprivation condition. [ABSTRACT FROM AUTHOR]

Background: Intra-articular bleeds in patients with inherited bleeding disorders lead to active synovitis which may progress to a chronic state over time. We explored the diagnostic value of color Doppler ultrasound in detecting synovitis in boys with bleeding disorders. Results: Sixty boys with hemophilia and 3 boys with type 3 von Willebrand disease aged 5 to 18 years (median 12.3 years) were imaged by gray-scale and color Doppler ultrasound (US) in three centers (Beijing, China [n = 22], Guangzhou, China [n = 12] and Toronto, Canada [n = 29])) in this observational study. Images were independently reviewed by two radiologists blinded to clinical data using a subjective semi-quantitative scoring system and objective measurements of synovial thickness and vascularity. Inter-reader reliability for using subjective versus objective color Doppler US methods for assessing synovial vascularity was excellent for the subjective method and moderate/lower range of substantial for the objective method. Agreement between degree of vascularity on color Doppler and extent of synovial hypertrophy on gray-scale US was overall poor for Canada data and moderate for China data. Correlations between degree of vascularity on color Doppler and synovial hypertrophy on gray-scale US, and clinical constructs (total and itemized HJHS scores and total Pettersson X-ray scores) for assessment of blood-induced arthropathy were all poor. Conclusion: Color Doppler US is a valuable scoring method for evaluating reactive synovitis in joints of subjects with inherited bleeding disorders and holds potential for assessing post-bleed reactive synovitis once further information on its association with timing of the joint bleed becomes available in the literature. [ABSTRACT FROM AUTHOR]

The surface of graphene oxide (GO) with different oxidation levels is widely used in gas sensing applications. 1,1-Dimethylhydrazine (unsymmetrical dimethylhydrazine, UDMH) as a highly toxic and volatile pollution gas has long been investigated and discussed. The research reported here examined the stable structure of GO surface by first principles calculation. Furthermore, the adsorption mechanism of UDMH on the stable GO surface was explored and the optimal adsorption distance and upper limit of adsorption quantity were determined with their adsorption energy calculated. The results reveal that the hydroxyl group on GO did a great service to the UDMH adsorption and the UDMH tends to approach GO from the direction of -NH2, with distance being 2.9 Å. [ABSTRACT FROM AUTHOR]

The principal objective of this study was to investigate the strengthened remediation effect and relevant mechanism of P. aeruginosa on ryegrass (Lolium multiflorum Lam.) for soil contaminated by Cu-Pb-Cd compound heavy metals. The results showed that the complex heavy metals' contamination had remarkable inhibiting effect on the growth of plants (P < 0.01), and the biomass of ryegrass's stem and leaves declined by 28.2%, while that of roots decreased by 34.7% after 45 days. The inoculation of P. aeruginosa promoted the growth of ryegrass in polluted soil, in which the biomass recovered to the same level of that in normal plant; the activity of both catalase and urease in the soil also increased strikingly (by 29.3% and 75.7%, respectively); the ratio of residual heavy metals in the soil decreased, while the acid extractable heavy metals increased notably. Therefore, the absorption and accumulation of ryegrass to the heavy metals in soil were improved to some extent; the bioconcentration factor of Cu, Pb, and Cd in ryegrass increased by 35.9%, 55.6%, and 283.5%, respectively. The exterior microorganism allowed the accumulation of Cu, Pb, and Cd in shoots of ryegrass increasing remarkably, while in roots, only the accumulation of Pb increased by 16.3%, and that of both Cu and Cd decreased. Besides, in the P. aeruginosa-inoculated system, the transfer factor of Cu and Cd in plants increased strikingly, while that of Pb decreased. [ABSTRACT FROM AUTHOR]

Under the influence of various natural and human factors, the relationship between the ecosystem services provided for human beings by a karst ecosystem is becoming increasingly complex, profoundly limiting the effective and sustainable development of the social economy and ecosystem protection in karst areas. Taking Guizhou, China as an example, which includes both karst (including five different landforms) and non-karst area, the study explored and compared the tradeoff and synergy between ecosystem services in both terrain types. The results showed higher change rates of water yield and soil retention in karst areas than those in non-karst areas, with only small differences in the carbon storage and crop production change. The ecosystem service relationships in the karst area from 1995 to 2005 were consistent with the relationships in the non-karst area. However, differences were observed in most of these relationships from 2005 to 2015. The relationships between ecosystem services in different karst landforms from 1995 to 2005 remained the same, but there are differences found in the relationships of ecosystem services from 2005 to 2015. The trade-off and synergistic relationships between ecosystem services in the different landforms were closely related to the changes of climate and land use, particularly related to rainfall, rainfall erosivity, farmland, and forestland. [ABSTRACT FROM AUTHOR]

There are significant differences in clinical presentation and treatment of atrial fibrillation (AF) between women and men. The primary goal of AF management is to restore sinus rhythm and to prevent various complications, including stroke and heart failure. In many areas of AF, such as prevalence, clinical manifestations, morbidity, risk factors, pathophysiology, treatment strategies, and complications, gender-specific variability is observed and needs to be further addressed by large-scale population researches or randomized clinical trials, which help to promote the customization of AF treatment programs, hence to maximize the success rate of AF therapy in both sexes. This review highlights our current understanding of these gender differences in AF and how these differences affect treatment decisions on AF. [ABSTRACT FROM AUTHOR]

Dilated cardiomyopathy (DCM) is the most prevalent cause of non-ischemic cardiac failure and the commonest indication for cardiac transplantation. Compelling evidence highlights the pivotal roles of genetic defects in the occurrence of DCM. Nevertheless, the genetic determinants underpinning DCM remain largely obscure. In this study, the coding regions of ISL1, which encodes a transcription factor critical for embryonic cardiogenesis and postnatal cardiac remodeling, were sequenced in 216 unrelated patients with DCM, and a novel heterozygous ISL1 mutation, NM_002202.2: c.631A>T; p.(Lys211*), was identified in a proband. The mutation, which co-segregated with DCM in the family, was absent in 238 unrelated controls, as well as in the Genome Aggregation and the Exome Aggregation Consortium population databases. Functional analyses unveiled that the mutant ISL1 protein lost transcriptional activity alone or in synergy with TBX20 or GATA4, two other transcription factors associated with DCM. These findings indicate ISL1 as a new gene of DCM. [ABSTRACT FROM AUTHOR]

Congenital heart defect (CHD) is the most common form of birth deformity and is responsible for substantial morbidity and mortality in humans. Increasing evidence has convincingly demonstrated that genetic defects play a pivotal role in the pathogenesis of CHD. However, CHD is a genetically heterogeneous disorder and the genetic basis underpinning CHD in the vast majority of cases remains elusive. This study was sought to identify the pathogenic mutation in the ISL1 gene contributing to CHD. A cohort of 210 unrelated patients with CHD and a total of 256 unrelated healthy individuals used as controls were registered. The coding exons and splicing boundaries of ISL1 were sequenced in all study subjects. The functional effect of an identified ISL1 mutation was evaluated using a dual-luciferase reporter assay system. A novel heterozygous ISL1 mutation, c.409G > T or p.E137X, was identified in an index patient with congenital patent ductus arteriosus and ventricular septal defect. Analysis of the proband's pedigree revealed that the mutation co-segregated with CHD, which was transmitted in the family in an autosomal dominant pattern with complete penetrance. The nonsense mutation was absent in 512 control chromosomes. Functional analysis unveiled that the mutant ISL1 protein failed to transactivate the promoter of MEF2C, alone or in synergy with TBX20. This study firstly implicates ISL1 loss-of-function mutation with CHD in humans, which provides novel insight into the molecular mechanism of CHD, implying potential implications for genetic counseling and individually tailored treatment of CHD patients. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Elucidating the molecular mechanisms of fat accumulation and its metabolic consequences is crucial to understanding and treating obesity, an epidemic disease. We have previously observed that Usp19 deubiquitinating enzyme-null mice (Usp19−/−) have significantly lower fat mass than wild-type (WT) mice. Thus, this study aimed to provide further understanding of the role of ubiquitin-specific peptidase 19 (USP19) in fat development, obesity and diabetes.Methods: In this study, the metabolic phenotypes of WT and Usp19−/− mice were compared. The stromal vascular fractions (SVFs) of inguinal fat pads from WT and Usp19−/− mice were isolated and cells were differentiated into adipocytes in culture to assess their adipogenic capacity. Mice were fed a high-fat diet (HFD) for 18 weeks. Body composition, glucose metabolism and metabolic variables were assessed. In addition, following insulin injection, signalling activity was analysed in the muscle, liver and adipose tissue. Finally, the correlation between the expression of Usp19 mRNA and adipocyte function genes in human adipose tissue was analysed.Result: Upon adipogenic differentiation, SVF cells from Usp19−/− failed to accumulate lipid and upregulate adipogenic genes, unlike cells from WT mice. Usp19−/− mice were also found to have smaller fat pads throughout the lifespan and a higher percentage of lean mass, compared with WT mice. When fed an HFD, Usp19−/− mice were more glucose tolerant, pyruvate tolerant and insulin sensitive than WT mice. Moreover, HFD-fed Usp19−/− mice had enhanced insulin signalling in the muscle and the liver, but not in adipose tissue. Finally, USP19 mRNA expression in human adipose tissue was positively correlated with the expression of important adipocyte genes in abdominal fat depots, but not subcutaneous fat depots.Conclusions/interpretation: USP19 is an important regulator of fat development. Its inactivation in mice exerts effects on multiple tissues, which may protect against the negative metabolic effects of high-fat feeding. These findings suggest that inhibition of USP19 could have therapeutic potential to protect from the deleterious consequences of obesity and diabetes. [ABSTRACT FROM AUTHOR]

Dilated cardiomyopathy (DCM) is a common primary myocardial disease leading to congestive heart failure, arrhythmia and sudden cardiac death. Increasing studies demonstrate substantial genetic determinants for DCM. Nevertheless, DCM is of substantial genetic heterogeneity, and the genetic basis for DCM in most patients remains unclear. The present study was sought to investigate the association of a genetic variant in the ZBTB17 gene with DCM. A cohort of 158 unrelated patients with idiopathic DCM and a total of 230 unrelated, ethnically matched healthy individuals used as controls were recruited. The coding exons and splicing boundaries of ZBTB17 were sequenced in all study participants. The functional effect of the mutant ZBTB17 was characterized by a dual-luciferase reporter assay system. A novel heterozygous ZBTB17 mutation, p.E243X, was discovered in an index patient. Genetic scan of the mutation carrier’s available relatives showed that the mutation was present in all affected family members but absent in unaffected family members. Analysis of the proband’s pedigree revealed that the mutation co-segregated with DCM, which was transmitted in an autosomal dominant pattern with complete penetrance. The nonsense mutation was absent in the 460 control chromosomes. Functional assays demonstrated that the truncated ZBTB17 protein had no transcriptional activity as compared with its wild-type counterpart. This study firstly associates ZBTB17 loss-of-function mutation with enhanced susceptibility to DCM in humans, which provides novel insight into the molecular mechanism underpinning DCM, implying potential implications for genetic counseling and personalized management of DCM. [ABSTRACT FROM AUTHOR]

Aim: Nowadays, cathepsins have been reported to be related to aging. The aim of this study is to evaluate the association between serum levels of cathepsin D (CTSD) and human aging. Methods: In the present study, we analyzed the serum levels of CTSD and its relation with levels of sirtuin1 (SIRT1) and endothelial nitric oxide synthase (eNOS) activity, which were known having an important role in aging. This study recruited 90 healthy subjects (62 men and 28 women), which were subdivided into three groups with respect to age: young (about 19 years old, n = 30), middle-age (about 40 years old, n = 30), and aged (above 65 years old, n = 30). Altered serum levels of CTSD and SIRT1 were measured by enzyme-linked immunosorbent assay, and eNOS activity was assessed by the conversion of 14- l-arginine to 14-L-citrulline. Results: Elderly subjects had significantly lower CTSD, SIRT1, and eNOS than younger ones. Serum levels of CTSD were negatively correlated with age. There was a statistically significant positive correlation between serum levels of CTSD, eNOS, and SIRT1. Conclusions: This study shows lower serum CTSD values in elderly subjects than in younger subjects. This is the first to demonstrate age-related changes in cathepsin D levels in humans and the association between SIRT1 and eNOS. [ABSTRACT FROM AUTHOR]

Aims: Previous studies have suggested that high mobility group box-1 protein (HMGB1) binds to the toll-like receptor 4 (TLR4) signaling mediates the progression of various inflammatory diseases. But the roles of HMGB1 and TLR4 in aging remain poorly unknown. In this study, we aimed to investigate the serum levels of HMGB1 and myeloid differentiation factor 88 (MyD88), which is one of TLR4's intracellular adaptor proteins during human aging process and their relevance with cathepsin B (CTSB). Methods: This research was conducted using the blood samples provided by healthy people ( n = 90, 63 men and 27 women). Subjects were subdivided into groups with respect to age: young (about 25 years old, n = 30), middle age (about 40 years old, n = 30), and aged (above 65 years old, n = 30). Altered serum levels of HMGB1, MyD88 and CTSB were measured using an enzyme-linked immunosorbent assay. Results: The serum levels of HMGB1 and MyD88 were significantly decreased in the aged group compared with those in the young group. Linear regression analysis showed that HMGB1 and MyD88 positively correlated with CTSB among the whole healthy people. A negative correlation was determined between MyD88 and age. Conclusions: The serum levels of HMGB1 and MyD88 significantly decreased with age. MyD88, but not HMGB1, was negatively correlated with age. [ABSTRACT FROM AUTHOR]

Many microorganisms could naturally produce ( R, R)-2,3-butanediol (( R, R)-2,3-BD), which has unique applications due to its special chiral group and spatial configuration. But the low enantio-purity of the product hindered the development of large-scale production. In this work, a synthetic constitutive metabolic pathway for enantiomerically pure ( R, R)-2,3-BD biosynthesis was constructed in Escherichia coli with vector pUC6S, which does not contain any lac sequences. The expression of this artificial constructed gene cluster was optimized by using two different strength of promoters (AlperPLTet01 (P) and AlperBB (P)). The strength of P is twice stronger than P. The fermentation results suggested that the yield of ( R, R)-2,3-BD was higher when using the stronger promoter. Compared with the wild type, the recombinant strain E. coli YJ2 produced a small amount of acetic acid and showed higher glucose consumption rate and higher cell density, which indicated a protection against acetic acid inhibition. In order to further increase the ( R, R)-2,3-BD production by reducing the accumulation of its precursor acetoin, the synthetic operon was reconstructed by adding the strong promoter P in front of the gene ydjL coding for the enzyme of ( R, R)-2,3-BD dehydrogenase which catalyzes the conversion of acetoin to ( R, R)-2,3-BD. The engineered strain E. coli YJ3 showed a 20 % decrease in acetoin production compared with that of E. coli YJ2. After optimization the fermentation conditions, 30.5 g/L of ( R, R)-2,3-BD and 3.2 g/L of acetoin were produced from 80 g/L of glucose within 18 h, with an enantio-purity over 99 %. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the correlation between clinical complete response (cCR) and pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (CRT) for esophageal squamous cell cancer (ESCC). Methods: Between May 2001 and April 2013, a total of 158 patients with thoracic ESCC treated with neoadjuvant CRT followed by surgery were analyzed. Of these patients, 31 had stage IIb disease and 127 had stage III disease. All patients received concurrent platinum-based chemotherapy with conformal radiotherapy (40 Gy in 20 fractions, five fractions per week for 4 weeks). Results: A total of 65 patients (41.1 %) achieved pCR. Of 44 patients (27.8 %) who achieved cCR after neoadjuvant CRT, 32 (72.7 %) also achieved pCR. On the other hand, only 33 (28.9 %) of 114 patients with non-cCR had pCR. The sensitivity, specificity, positive predictive value, and negative predictive value of cCR for predicting pCR was 87.1, 49.2, 71.1, and 72.7 %, respectively. The median follow-up period was 28.9 months, and overall survival (OS) for the entire group was 38.1 months. Patients who achieved cCR had significantly better 3-year OS than those with non-cCR (71.6 % vs. 46.9 %; p = 0.012). Conclusions: Our results indicate that cCR after neoadjuvant CRT is significantly correlated with pCR and survival of patients with ESCC. Further studies are required to confirm the prognostic value of cCR after neoadjuvant CRT. [ABSTRACT FROM AUTHOR]

Congenital heart disease (CHD) is the most common birth defect and is the most prevalent non-infectious cause of infant death. Aggregating evidence demonstrates that genetic defects are involved in the pathogenesis of CHD. However, CHD is genetically heterogeneous and the genetic determinants for CHD in an overwhelming majority of patients remain unknown. In this study, the coding regions and splice junctions of the NKX2.6 gene, which encodes a homeodomain transcription factor crucial for cardiovascular development, were sequenced in 210 unrelated CHD patients. As a result, a novel heterozygous NKX2.6 mutation, p.K152Q, was identified in an index patient with ventricular septal defect (VSD). Genetic analysis of the proband's available family members showed that the mutation cosegregated with VSD transmitted as an autosomal dominant trait with complete penetrance. The missense mutation was absent in 400 control chromosomes and the altered amino acid was completely conserved evolutionarily across species. Due to unknown transcriptional targets of NKX2.6, the functional characteristics of the identified mutation at transcriptional activity were analyzed by using NKX2.5 as a surrogate. Alignment between human NKX2.6 and NKX2.5 proteins displayed that K152Q-mutant NKX2.6 was equivalent to K158Q-mutant NKX2.5, and introduction of K158Q into NKX2.5 significantly reduced its transcriptional activating function when compared with its wild-type counterpart. This study firstly links NKX2.6 loss-of-function mutation with increased susceptibility to isolated VSD, providing novel insight into the molecular mechanism underpinning VSD and contributing to the development of new preventive and therapeutic strategies for this common form of CHD. [ABSTRACT FROM AUTHOR]

The development of lung cancer is significantly associated with genetic susceptibility. Findings from previous individual studies regarding the effect of X-ray repair cross-complementing group 3 Thr241Met (XRCC3 Thr241Met) polymorphism on lung cancer risk remained conflicting and inconclusive. Thus, a meta-analysis of previous relevant studies was performed to estimate this effect more precisely and to shed some light on the contradictory findings. The pooled odds ratios (ORs) with the corresponding 95 % confidence intervals (95 % CIs) were calculated to assess the correlation of XRCC3 Thr241Met polymorphism with lung cancer susceptibility. Stratified analysis according to ethnicity and sensitivity analysis was both conducted for further confirmation. Seventeen independent case-control studies involving 12,610 subjects totally were included into this meta-analysis. Overall, meta-analysis of total included studies showed that the XRCC3 Thr241Met polymorphism was not associated with risk of lung cancer in all genetic contrast models (OR = 1.01, 95 % CI 0.91-1.13, P = 0.810; OR = 1.16, 95 % CI 0.88-1.54, P = 0.281; OR = 0.95, 95 % CI 0.86-1.04, P = 0.240; OR = 0.97, 95 % CI 0.89-1.06, P = 0.538; OR = 1.18, 95 % CI 0.91-1.52, P = 0.204). Stratified analyses in Asians and Caucasians showed similar results. Sensitivity analysis confirmed the stability and reliability of the findings. This meta-analysis of all available data did not support any appreciable association between the XRCC3 Thr241Met polymorphism and lung cancer risk in any populations. [ABSTRACT FROM AUTHOR]

Aim:Low plasma ghrelin level was found to be associated with diabetes, and ghrelin was shown to inhibit pro-atherogenic changes in experimental models of atherosclerosis. The aim of this study was to investigate the relationship between plasma ghrelin levels and coronary atherosclerotic lesions in Chinese patients with diabetes.Methods:Plasma ghrelin levels were measured using an ELISA kit. The severity of coronary artery disease (CAD) was determined via angiography. Composition of atherosclerotic plaques was detected via coronary CT angiography.Results:A total of 178 patients with diabetes were recruited. Among the patients, 70 were diagnosed with acute coronary syndrome (ACS), 82 with stable angina pectoris (SAP) and 26 without coronary angiographic finding (controls). A negative correlation was found between ghrelin levels and the severity of the CAD, as determined via the Gensini score (r=-0.2434; P=0.0217). In diabetic patients with CAD and a complex lesion, the plasma ghrelin levels were significantly lower than in those with a simple lesion (ACS group: 3.81±0.49 ng/mL vs 4.72±0.50 ng/mL, P<0.0001; SAP group: 4.21±0.52 ng/mL vs 4.76±0.59 ng/mL, P=0.0397). Angiographically-detected complex lesion was an independent factor associated with ghrelin levels (adjusted beta coefficient=-0.67, 95% CI -0.97 to -0.37, P<0.0001).Conclusion:Low plasma ghrelin level is closely related to angiographically-detected severity and the complex lesion morphology in Chinese diabetic patients with CAD. [ABSTRACT FROM AUTHOR]

Aim:To investigate the anticancer effect of crocetin, a major ingredient in saffron, and its underlying mechanisms.Methods:Cervical cancer cell line HeLa, non-small cell lung cancer cell line A549 and ovarian cancer cell line SKOV3 were treated with crocetin alone or in combination with vincristine. Cell proliferation was examined using MTT assay. Cell cycle distribution and sub-G1 fraction were analyzed using flow cytometric analysis after propidium iodide staining. Apoptosis was detected using the Annexin V-FITC Apoptosis Detection Kit with flow cytometry. Cell death was measured based on the release of lactate dehydrogenase (LDH). The expression levels of p53 and p21WAF1/Cip1 as well as caspase activation were examined using Western blot analysis.Results:Treatment of the 3 types of cancer cells with crocetin (60-240 μmol/L) for 48 h significantly inhibited their proliferation in a concentration-dependent manner. Crocetin (240 μmol/L) significantly induced cell cycle arrest through p53-dependent and -independent mechanisms accompanied with p21WAF1/Cip1 induction. Crocetin (120-240 μmol/L) caused cytotoxicity in the 3 types of cancer cells by enhancing apoptosis in a time-dependent manner. In the 3 types of cancer cells, crocetin (60 μmol/L) significantly enhanced the cytotoxicity induced by vincristine (1 μmol/L). Furthermore, this synergistic effect was also detected in the vincristine-resistant breast cancer cell line MCF-7/VCR.Conclusion:Ccrocetin is a potential anticancer agent, which may be used as a chemotherapeutic drug or as a chemosensitizer for vincristine. [ABSTRACT FROM AUTHOR]

Abstract  Wolfram syndrome (WFS), also known as DIDMOAD, is an infrequent cause of diabetes mellitus. WFS is an autosomal recessive neurodegenerative disease characterized by various clinical manifestations such as diabetes mellitus, optic atrophy, diabetes insipidus, deafness, neurological symptoms, renal tract abnormalities, psychiatric disorders, and gonadal disorders. The majority of patients with WFS carry the loss of function mutations in the WFS1 gene. The exons 2–8 of the WFS1 gene from one Chinese WFS patient were amplified by the polymerase chain reaction (PCR), subcloning techniques and direct sequence determination was applied to the amplified fragments. The compound heterozygous mutation of a 3-bp (GAC) deletion (V434del) and another compound heterozygous mutation (G→N)(W666X) in exon 8 of WFS1 gene was identified in the patient. Other seventeen members of her family were investigated. Four cases with heterozygotes had been found through screening for the mutation V434del and five cases for the mutation W666X in the whole family. This is the first report of WFS with the mutation V434del and W666X in the WFS1 gene. [ABSTRACT FROM AUTHOR]

This study uses classroom videotapes to examine the phenomenon of students who are left behind during whole-class teaching. Zooming in via these videos enabled us to analyze these classroom situations by means of a compact, multi-perspective set of theories – van Hiele theory, conceptualization, and visual perception. The analysis provided a picture of the classroom interaction in which the sound of silence of those students who might not share understanding during the class discourse is ignored. Based on a sample of Taiwanese junior high school geometry classes, the study demonstrated how investigating situations of silence uncovered the possibility of teachers’ unawareness of student difficulties or their unsuccessful efforts to cope with them. Teachers’ post-lesson interviews and questionnaires shed additional light on the perspective of left-behind students. Implications of this method for pre- and in-service teachers’ programs are briefly discussed, and some recommendations for change are proposed. [ABSTRACT FROM AUTHOR]

We have investigated the chronic effects of low concentrations of lead (Pb) on oxidative damage and DNA damage in testes of the frog Rana nigromaculata. Sixty adult male frogs were randomly divided into six groups of ten. Based on the levels of the Integrated Wastewater Discharge Standard (GB 8978-1996) of China, five groups (II-VI) were treated by epidermal absorption with a PbNO3 solution at concentrations of 0.1, 0.2, 0.4, 0.8, 1.6 mg/l, respectively. The first group (I), which served as a control, was treated with distilled water only. Thirty days after treatment, all frogs were sacrificed and the testis tissues removed for the measurement of malondialdehyde (MDA) and glutathione (GSH) levels. DNA damage, including indicators of damage rate, DNA tail length (TL), and DNA tail moment (TM), was also analyzed by comet assays. Our data suggest that MDA levels in all treatment groups and GSH levels in the 0.2-1.6 mg/l Pb groups increased significantly relative to the controls (P < 0.01). Treatment with Pb at concentrations >0.4 mg/l also increased DNA damage rate and TM, while TL increased when the Pb level was >0.2 mg/l (P < 0.01 for DNA damage rate and TM, P < 0.05 for TL). Positive correlations were also found between DNA damage levels in the testes and MDA levels (r = 0.796 for DNA damage rate, r = 0.811 for TL, r = 0.796 for TM; P < 0.01 for all) as well between MDA and GSH levels (r = 0.455, P < 0.05) in the testes. Results from MDA measurements indicated that Pb-induced DNA damage in the testes of R. nigromaculata was possibly due to oxidative damage. Taken together, we conclude that Pb can induce male reproductive toxicity in R. nigromaculata. [ABSTRACT FROM AUTHOR]

Abstract??Leafy spurge (Euphorbia esulaL.) is a deep-rooted perennial weed that propagates both by seeds and underground adventitious buds located on the crown and roots. To enhance our understanding of growth and development during seed germination and vegetative propagation, a leafy spurge gene (Accession No. AF230740) encoding a CDK-activating kinase (Ee;CDKF;1) involved in cell-cycle progression was identified, and its function was confirmed based on its ability to rescue a yeast temperature-sensitiveCAKmutant (GF2351) and through in vitro kinase assays. Site-directed mutagenesis ofEe;CDKF;1indicated that two threonine residues (Thr291 and Thr296) were mutually responsible for intra-molecular autophosphorylation and for phosphorylating its substrate protein, cyclin-dependent kinase (CDK). Polyclonal antibodies generated against the Ee;CDKF;1 protein or against a phosphorylated Ee;CDKF;1 peptide [NERYGSL(pT)SC] were used to examine abundance and phosphorylation of CDKF;1 during seed germination and bud growth. The levels of CDKF;1 were lower in dry or imbibed seeds than in germinating seeds or seedlings. Differences in CDKF;1 were also observed during adventitious bud development; small buds appeared to have greater levels of CDKF;1 than large buds. Similar patterns of CDKF;1 expression were detected with either the polyclonal antibody developed using the CDKF;1 protein or the phosphorylated peptide. These results indicated that Thr291 is constitutively phosphorylated in vivo and associated with Ee;CDKF;1 activity. Our results further suggest that a certain level of CDKF;1 activity is maintained in most tissues and may be an important phenomenon for enzymes that regulate early steps in cell-cycle signaling pathways. [ABSTRACT FROM AUTHOR]

Belle has observed surprisingly copious production of ψ(3770) in the B meson decay B → ψ(3770) K, whose rate is comparable to that of B → ψ(3686) K. We study this puzzling process in the QCD factorization approach with the effect of the S- D mixing considered. We find that the soft scattering effects in the spectator interactions play an essential role. With a proper parametrization for the higher-twist soft end-point singularities associated with kaon, and with the S- D mixing angle θ = - 12°, the calculated decay rates can be close to the data. Implications of these soft spectator effects to other charmonium production in B exclusive decays are also emphasized. [ABSTRACT FROM AUTHOR]

An accurate, simple and sensitive method based on reversed-phase high-performance liquid chromatography with UV detection has been developed for determination of tiopronin (TP) in human plasma. TP in plasma was reacted with p-bromophenacyl bromide ( p-BPB) to give the TP- p-BPB adduct and this derivative was then extracted from the plasma on a silica gel cartridge. Potential interfering compounds were removed by washing with water, and the TP- p-BPB adduct was then eluted with acetonitrile. The organic phase obtained was evaporated to complete dryness under a stream of nitrogen. The residue was dissolved in acetonitrile and this solution was injected on to a reversed-phase ODS HPLC column. The mobile phase was usually the ternary mixture acetonitrile–water–trifluoroacetic acid, 40:59.88:0.12 ( v/v). The retention times of TP- p-BPB and the internal standard adduct were 14.4 and 17.9 min, respectively. No interfering peaks were encountered in several blank plasma samples examined. The limit of detection for TP was 12 ng mL−1. Extraction recovery exceeded 70%. The calibration plot for the TP derivative was linear in the range 40−4000 ng mL−1, regression coefficient 0.9989, and the coefficient of the variation of the points of the calibration plot was below 10%. The method was validated appropriately and successfully applied to the determination of TP in human plasma. [ABSTRACT FROM AUTHOR]

Two subtractive cDNA libraries were developed to study genes associated with bud dormancy (reverse library) and initiation of shoot growth (forward library) in leafy spurge. To identify unique sequences represented in each library, 15744 clones were screened to reduce the level of redundancy within both libraries. A total of 516 unique sequences were obtained from 2304 minimally redundant clones. Radioactive probes developed from RNAs extracted from crown buds of either intact (para-dormant control) or a series of growth-induced (2 h, 2, and 4 d after decapitation) plants were used to identify differentially expressed genes by macroarray analysis. Semi-quantitative RT-PCR was used to confirm results obtained by macroarray analysis and to determine the expression profiles for other transcripts identified within the subtractive libraries. Selected clones were also used to examine gene expression in crown buds after growth induction and/or during normal seasonal growth. In this study, four distinct patterns of gene expression were observed during the transition from para-dormancy to growth-induction. Many of the differentially regulated genes identified have unknown or hypothetical functions while others are known to play important roles in molecular functions. Gene ontology analysis identified a greater proportion of genes involved with catalytic activity in the forward library while the reverse library had a greater proportion of genes involved in DNA/RNA binding. [ABSTRACT FROM AUTHOR]

A concept of mean last passage time at the saddle point is proposed in order to compute both the lifetime and the escape rate of a particle in a metastable potential, where the backstreaming across the saddle point is taken into account. It is shown that the mean oscillating time around the saddle point is the longest one among all the time scales at high temperatures and the inverse of the mean last passage time at the saddle point is more close to the steady escape rate. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) physiologically stimulates the sarco/endoplasmic reticulum calcium (Ca2+) ATPase (SERCA) to decrease intracellular Ca2+ concentration and relax cardiac, skeletal and vascular smooth muscle. Here, we show that NO-derived peroxynitrite (ONOO-) directly increases SERCA activity by S-glutathiolation and that this modification of SERCA is blocked by irreversible oxidation of the relevant cysteine thiols during atherosclerosis. Purified SERCA was S-glutathiolated by ONOO- and the increase in Ca2+-uptake activity of SERCA reconstituted in phospholipid vesicles required the presence of glutathione. Mutation of the SERCA-reactive Cys674 to serine abolished these effects. Because superoxide scavengers decreased S-glutathiolation of SERCA and arterial relaxation by NO, ONOO- is implicated as the intracellular mediator. NO-dependent relaxation as well as S-glutathiolation and activation of SERCA were decreased by atherosclerosis and Cys674 was found to be oxidized to sulfonic acid. Thus, irreversible oxidation of key thiol(s) in disease impairs NO-induced relaxation by preventing reversible S-glutathiolation and activation of SERCA by NO/ONOO-. [ABSTRACT FROM AUTHOR]

An expansion of a CTG repeat at the DM1 locus causes myotonic dystrophy (DM) by altering the expression of the two adjacent genes, DMPK and SIX5, and through a toxic effect of the repeat-containing RNA. Here we identify two CTCF-binding sites that flank the CTG repeat and form an insulator element between DMPK and SIX5. Methylation of these sites prevents binding of CTCF, indicating that the DM1 locus methylation in congenital DM would disrupt insulator function. Furthermore, CTCF-binding sites are associated with CTG/CAG repeats at several other loci. We suggest a general role for CTG/CAG repeats as components of insulator elements at multiple sites in the human genome. [ABSTRACT FROM AUTHOR]

Is the radiomic approach, utilizing diffusion-weighted imaging (DWI), capable of predicting the various pathological grades of intrahepatic mass-forming cholangiocarcinoma (IMCC)? Furthermore, which model demonstrates superior performance among the diverse algorithms currently available? The objective of our study is to develop DWI radiomic models based on different machine learning algorithms and identify the optimal prediction model. We undertook a retrospective analysis of the DWI data of 77 patients with IMCC confirmed by pathological testing. Fifty-seven patients initially included in the study were randomly assigned to either the training set or the validation set in a ratio of 7:3. We established four different classifier models, namely random forest (RF), support vector machines (SVM), logistic regression (LR), and gradient boosting decision tree (GBDT), by manually contouring the region of interest and extracting prominent radiomic features. An external validation of the model was performed with the DWI data of 20 patients with IMCC who were subsequently included in the study. The area under the receiver operating curve (AUC), accuracy (ACC), precision (PRE), sensitivity (REC), and F1 score were used to evaluate the diagnostic performance of the model. Following the process of feature selection, a total of nine features were retained, with skewness being the most crucial radiomic feature demonstrating the highest diagnostic performance, followed by Gray Level Co-occurrence Matrix lmc1 (glcm-lmc1) and kurtosis, whose diagnostic performances were slightly inferior to skewness. Skewness and kurtosis showed a negative correlation with the pathological grading of IMCC, while glcm-lmc1 exhibited a positive correlation with the IMCC pathological grade. Compared with the other three models, the SVM radiomic model had the best diagnostic performance with an AUC of 0.957, an accuracy of 88.2%, a sensitivity of 85.7%, a precision of 85.7%, and an F1 score of 85.7% in the training set, as well as an AUC of 0.829, an accuracy of 76.5%, a sensitivity of 71.4%, a precision of 71.4%, and an F1 score of 71.4% in the external validation set. The DWI-based radiomic model proved to be efficacious in predicting the pathological grade of IMCC. The model with the SVM classifier algorithm had the best prediction efficiency and robustness. Consequently, this SVM-based model can be further explored as an option for a non-invasive preoperative prediction method in clinical practice., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)