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With the advancement of computer-based testing, log file data has drawn considerable attention from researchers. Although emerging studies have begun to explore log file data, there is a gap in the exploitation of log file data for capturing and understanding participants' cognitive processes. The debate on how to maximize insights from log file data has not yet reached a consensus. Therefore, we present this protocol for a scoping review that aims to characterize the application of log file data in current publications, including the data pre-processing techniques, analytical methodologies, and theoretical frameworks used by researchers. This review will also aim to illuminate how log file data can enhance psychological and educational assessments. Our findings will highlight the opportunities and challenges presented by log file data as an emerging and essential source of evidence for future advancements in psychological and educational assessment. [ABSTRACT FROM AUTHOR]

Purpose: The resurgence of pertussis has occurred around the world. However, the epidemiological profiles of pertussis cannot be well understood by current diseases surveillance. This study was designed to understand the seroepidemiological characteristics of pertussis infection in the general population of Huzhou City, evaluate the prevalence infection of pertussis in the population, and offer insights to inform adjustments in pertussis prevention and control strategies. Methods: From September to October 2023, a cross-sectional serosurvey was conducted in Huzhou City, involving 1015 permanent residents. Serum samples were collected from the study subjects, and pertussis toxin IgG antibodies (Anti-PT-IgG) were quantitatively measured using enzyme-linked immunosorbent assay (ELISA). The analysis included the geometric mean concentration (GMC) of Anti-PT-IgG, rates of GMC≥40IU/mL, ≥100IU/mL, and <5IU/mL. Stratified comparisons were made based on age, vaccination history, and human categories. Results: Among the 1015 surveyed individuals, the geometric mean concentration (GMC) of Anti-PT-IgG was 10.52 (95% CI: 9.96–11.11) IU/mL, with a recent infection rate of 1.58%, a serum positivity rate of 11.43%, and a proportion with <5IU/mL of 40.49%. Among 357 children with clear vaccination history, susceptibility decreased with an increasing number of vaccine doses (Z = -6.793, P < 0.001). The concentration of Anti-PT-IgG exhibited a significant post-vaccination decline over time (Z = -5.143, P < 0.001). In women of childbearing age, the GMC of Anti-PT-IgG was 7.71 (95% CI: 6.90–8.62) IU/mL, with no significant difference in susceptibility among different age groups (χ2 = 0.545, P = 0.909). The annual pertussis infection rate in individuals aged ≥3 years was 9321 (95%CI: 3336–16039) per 100,000, with peak infection rates in the 20–29, 40–49, and 5–9 age groups at 34363 (95%CI: 6327–66918) per 100,000, 22307.72 (95%CI: 1380–47442) per 100,000, and 18020(95%CI: 1093–37266) per 100,000, respectively. Conclusions: In 2023, the actual pertussis infection rate in the population of Huzhou City was relatively high. Vaccine-induced antibodies exhibit a rapid decay, and the estimated serum infection rate increases rapidly from post-school age, peaking in the 20–29 age group. It is recommended to enhance pertussis monitoring in adolescents and adults and refine vaccine immunization strategies. [ABSTRACT FROM AUTHOR]

Based on a sample of Chinese public manufacturing firms, this study empirically investigates whether and how analyst coverage drives corporate social responsibility (CSR) under different governance or information conditions. The results show that firms with greater analyst coverage take more social responsibility, representing magnified concerns and better CSR visibility for legitimacy and reputation. This relationship could be strengthened under high governance condition (high institutional ownership ratio, none CEO duality, low executive ownership) or low information situation (high earnings management and low accounting conservatism). These findings provide new evidence of information-based mechanism underlying the promotions of CSR in imperfect information environments. [ABSTRACT FROM AUTHOR]

Purpose: To assess the epidemiology of seasonal influenza in Huzhou City, Zhejiang Province, China, during 2018–2022 and provide insights for influenza prevention. Methods: Following the National Influenza Surveillance Program, we conducted pathogen surveillance by randomly sampling throat swabs from cases with influenza-like illness (ILI) at two sentinel hospitals. Results: From 2018 to 2022, a total of 3,813,471 cases were treated at two hospitals in Huzhou, China. Among them, there were 112,385 cases of Influenza-Like Illness (ILI), accounting for 2.95% of the total number of cases. A total of 11,686 ILI throat swab samples were tested for influenza viruses, with 1,602 cases testing positive for influenza virus nucleic acid, resulting in a positivity rate of 13.71%. Among the positive strains, there were 677 strains of A(H3N2) virus, 301 strains of A(H1N1) virus, 570 strains of B/Victoria virus, and 54 strains of B/Yamagata virus. The ILI percentage (ILI%) and influenza nucleic acid positivity rate showed winter-spring peaks in the years 2018, 2019, 2021, and 2022, with the peaks concentrated in January and February. Additionally, a small peak was observed in August 2022 during the summer season. No peak was observed during the winter-spring season of 2020. The highest proportion of ILI cases was observed in children aged 0–4 years, followed by school-age children aged 5–14 years. There was a positive correlation between ILI% and influenza virus nucleic acid positivity rate (r = 0.60, p < 0.05). Conclusions: The influenza outbreak in Huzhou from 2020 to 2022 was to some extent influenced by the COVID-19 pandemic and public health measures. After the conclusion of the COVID-19 pandemic, the influenza outbreak in Huzhou may become more severe. Therefore, it is crucial to promptly assess the influenza outbreak trends based on the ILI% and the positivity rate of influenza virus nucleic acid tests. [ABSTRACT FROM AUTHOR]

The continuous development of science and technology has led to the gradual digitization and intelligence of campus construction. To apply facial recognition technology to construct smart libraries in higher education, this study optimizes traditional facial recognition algorithm models. Firstly, a smart management system for university libraries is designed with facial recognition as the core, and secondly, the traditional FaceNet network is optimized. Combined with MobileNet, Attention mechanism, Receptive field module and Mish activation function, the improved multitask face recognition convolutional neural network is built and used in the construction of university smart library. The performance verification of the constructed model shows that the feature matching error value of the model in a stable state is only 0.04. The recognition accuracy in the dataset is as high as 99.05%, with a recognition error as low as 0.51%. The facial recognition model used in university smart libraries can achieve 97.6% teacher satisfaction and 96.8% student satisfaction. In summary, the facial recognition model constructed by this paper has good recognition performance and can provide effective technical support for the construction of smart libraries. [ABSTRACT FROM AUTHOR]

Collaborative problem-solving (CPS) competency is critical for 21st century students. However, reports from the Programme for International Student Assessment (PISA) 2015 have revealed significant deficiencies in this competency among young students globally, indicating a critical need for the cultivation of CPS skills. Therefore, it is essential for educators and researchers to examine the factors that influence CPS competency and understand the potential role of CPS in secondary education. The present study aims to investigate the relationship between collaboration dispositions and students' CPS competency as well as the relationships of CPS competency and inquiry-based science instruction (IBSI) with science achievement using the PISA 2015 data. A total of 408,148 students from 52 countries and economies (i.e., regions) were included in our analysis. Unlike most previous studies that only investigated one country at a time and neglected the multilevel data structure of PISA, this study provided a global view through adopting multilevel modeling to account for the cluster effect at the school and country levels. Our findings revealed that valuing relationship was positively associated with CPS, whereas valuing teamwork was negatively associated with CPS. Furthermore, CPS competency was found to be a dominant and positive predictor of science achievement among all study variables, underscoring the importance of integrating CPS into teaching practices to promote student success in science. Additionally, different IBSI activities show varying relationships with science achievement, indicating that caution should be taken when recommending any specific practices associated with IBSI to teachers. [ABSTRACT FROM AUTHOR]

Researchers and engineers have developed exoskeletons capable of reducing the energetic cost of walking by decreasing the force their users' muscles are required to produce while contracting. The metabolic effect of assisting concentric and isometric muscle contractions depends, in part, on assistance magnitude. We conducted human treadmill experiments to explore the effects of assistance magnitude on the biomechanics and energetics of walking with an energy-removing exoskeleton designed to assist eccentric muscle contractions. Our results demonstrate that the assistance magnitude of an energy-removing device significantly affects the energetics, muscle activity, and biomechanics of walking. Under the moderate assistance magnitude condition, our device reduced the metabolic cost of walking below that of normal walking by 3.4% while simultaneously producing 0.29 W of electricity. This reduction in the energetic cost of walking was also associated with an 8.9% decrease in hamstring activity. Furthermore, we determined that there is an assistance magnitude threshold that, when crossed, results in the device transitioning from assisting to hindering its user. This transition is marked by significant increases in muscle activity and the metabolic cost of walking. These results could aid in the future design of exoskeletons and biomechanical energy harvesters, as well as adaptive control systems, that identify user-specific control parameters associated with minimum energy expenditure. [ABSTRACT FROM AUTHOR]

Background: Despite China's Expanded Program on Immunization (EPI) provides 2 doses of group A and group C meningococcal polysaccharide vaccine (MPV-AC) for children at 3 years and 6 years old, more self-paying group ACYW135 meningococcal polysaccharide vaccines (MPV-ACYW135) have been used as an alternative to MPV-AC to prevent Neisseria meningitidis serogroup C,Y,W135. We provide recommendations for Chinese booster immunization of meningococcal meningitis vaccine by analyzing the service status of MPV-AC and MPV-ACYW135. Methods: Reported data of routine immunization coverage from all districts of Hangzhou registered in the China Information Management System For Immunization Programming (CIMSFIP) between 2014 to 2019 were described and evaluated. Descriptive epidemiological methods were used to characterize the data. Adverse event following immunization (AEFI) were collected from Chinese national adverse event following immunization information system (CNAEFIIS) to compare the safety of MPV-AC and MPV-ACYW135. Results: 1376919 doses of booster immunization of meningococcal meningitis vaccine (MenV) in CIMSFIP were conducted in China Hangzhou from 2014 to 2019, with reported immunization coverage rates above 95%. The proportion of children using MPV-ACYW135 increased from 12.63% in 2014 to 29.45% in 2019. The incidence of AEFI of MPV-AC and MPV-ACYW135 were 49.75 per 100,000 and 45.44 per 100,000, respectively, without statistical difference. Conclusion: Children in Hangzhou had high booster immunization of MenV coverage. The use amount and use rate of MPV-ACYW135 increased year by year, indicating more and more parents had chosen MPV-ACYW135 as an alternative to MPV-AC at their own expense for children. The use proportions of MPV-ACYW135 were different in urban, suburban and rural areas. Both MPV-AC and MPV-ACYW135 were safe for children. [ABSTRACT FROM AUTHOR]

Background: Aim of this meta-analysis was to evaluate the overall diagnostic value of circulating mini miRNAs for papillary thyroid carcinoma (PTC) and to find the possible molecular marker with higher diagnostic value for PTC. Methods: We searched the Pubmed, Cochrane and Embase database until June 2020. We selected relevant literatures associated with the diagnosis of PTC with circulating miRNAs. The number of cases in experimental group and the control group, sensitivity and specificity could be extracted from the literatures. Results: We got 9 literatures including 2114 cases of PTC. Comprehensive sensitivity was 0.79, comprehensive specificity was 0.82, positive likelihood ratio was 4.3, negative likelihood ratio was 0.26, diagnostic advantage ratio was 16. The summary receiver operating characteristic curve was drawn and the Area Under the Curve was 0.87. Conclusions: Circulating microRNAs may be promising molecular markers for the diagnosis of papillary thyroid carcinoma. Combined detection of certain serum microRNAs can improve the diagnostic accuracy of papillary thyroid carcinoma. Especially MiR-222 and miR-146b may be prime candidates for the diagnosis of PTC in Asian population. [ABSTRACT FROM AUTHOR]

The use of non-motorized vehicles in urban city has improved the convenience of short-distance travel and reduced traffic pollution. However, the overtaking behaviour of non-motorized vehicles impacts traffic safety and efficiency significantly. The objective of this study is to model the durations of overtaking behaviour in the non-motorized vehicle exclusive lane. A total of 3010 overtaking events of non-motorized vehicles were extracted from two locations in Chengdu, China. The nonparametric survival analysis was conducted to model the overtaking duration of non-motorized vehicles. The categorical variables that significantly influence the overtaking duration were examined by the Log-rank test. The results show that the overtaking durations of female riders is longer than that of male riders. It takes longer for electrical bikes to complete overtaking than conventional bikes. When the non-motorized vehicle is under the load state (i.e. passengers or goods on the non-motorized vehicle), the overtaking behaviour takes more time than the un-load state. Moreover, it takes less time to overtake the non-motorized vehicle with load than to overtake the one without load. When there is a wrong-way driving phenomenon or under higher traffic volume, the duration is longer compared to the normal traffic and lower traffic volume conditions. The findings of this study attempt to provide a more profound understanding of non-motorized vehicles overtaking behaviour under different traffic conditions and give insights to the safety research of non-motorized vehicles. [ABSTRACT FROM AUTHOR]

Six putative α-galactosidase genes (α-Gals), three acid forms (CsGAL1, CsGAL2, CsGAL3) and three alkaline forms (CsAGA1, CsAGA2, CsAGAL3), were found in the cucumber genome. It is interesting to know the expression pattern and possible function of these α-Gals in the cucumber plant since it is a stachyose-translocating species. In this study, full-length cDNAs of six α-Gals were cloned and heterologously expressed. The result showed that all recombinant proteins revealed acid or alkaline α-Gal activities with different substrate specificities and pH or temperature responding curves, indicating their distinct roles in cucumber plants. Phylogenetic analysis of collected α-Gal amino acid sequences from different plants indicated that the ancestor of both acid and alkaline α-Gals existed before monocots and dicots separated. Generally, six α-Gal genes are universally expressed in different cucumber organs. CsGAL2 highly expressed in fasting-growing leaves, fruits and germinating seeds; CsGAL3 mainly distributes in vacuoles and significantly expressed in cucumber fruits, senescent leaves and seeds during late stage germination; The expression of CsAGA1 increased from leaf 1 to leaf 3 (sink leaves) and then declined from leaf 4 to leaf 7 (source leaves), and this isoform also highly expressed in male flowers and germinating seeds at early stage; CsAGA2 significantly expressed in cucumber leaves and female flowers; CsAGA3 is localized in plastids and also actively expressed in senescent leaves and germinating seeds; The role of CsGAL1 in cucumber plants is now unclear since its expression was relatively low in all organs. According to their expression patterns, subcellular localizations and previously reported functions of these isoforms in other plants, combining the data of soluble sugars contents in different tissues, the possible functions of these α-Gals were discussed. [ABSTRACT FROM AUTHOR]

Background: The results of current studies on metabolic-dysfunction associated steatotic liver disease (MASLD)-related diseases, cognition and dementia are inconsistent. This study aimed to elucidate the effects of MASLD-related diseases on cognition and dementia. Methods: By using single-nucleotide polymorphisms (SNPs) associated with different traits of NAFLD (chronically elevated serum alanine aminotransferase levels [cALT], imaging-accessed and biopsy-proven NAFLD), metabolic dysfunction-associated steatohepatitis, and liver fibrosis and cirrhosis, we employed three methods of mendelian randomization (MR) analysis (inverse-variance weighted [IVW], weighted median, and MR-Egger) to determine the causal relationships between MASLD-related diseases and cognition and dementia. We used Cochran's Q test to examine the heterogeneity, and MR-PRESSO was used to identify outliers (NbDistribution = 10000). The horizontal pleiotropy was evaluated using the MR-Egger intercept test. A leave-one-out analysis was used to assess the impact of individual SNP on the overall MR results. We also repeated the MR analysis after excluding SNPs associated with confounding factors. Results: The results of MR analysis suggested positive causal associations between MASLD confirmed by liver biopsy (p of IVW = 0.020, OR = 1.660, 95%CI = 1.082–2.546) and liver fibrosis and cirrhosis (p of IVW = 0.009, OR = 1.849, 95%CI = 1.169–2.922) with vascular dementia (VD). However, there was no evidence of a causal link between MASLD-related diseases and cognitive performance and other types of dementia (any dementia, Alzheimer's disease, dementia with lewy bodies, and frontotemporal dementia). Sensitivity tests supported the robustness of the results. Conclusions: This two-sample MR analysis suggests that genetically predicted MASLD and liver fibrosis and cirrhosis may increase the VD risk. Nonetheless, the causal effects of NAFLD-related diseases on VD need more in-depth research. [ABSTRACT FROM AUTHOR]

Efficient strategies to contain the coronavirus disease 2019 (COVID-19) pandemic are peremptory to relieve the negatively impacted public health and global economy, with the full scope yet to unfold. In the absence of highly effective drugs, vaccines, and abundant medical resources, many measures are used to manage the infection rate and avoid exhausting limited hospital resources. Wearing masks is among the non-pharmaceutical intervention (NPI) measures that could be effectively implemented at a minimum cost and without dramatically disrupting social practices. The mask-wearing guidelines vary significantly across countries. Regardless of the debates in the medical community and the global mask production shortage, more countries and regions are moving forward with recommendations or mandates to wear masks in public. Our study combines mathematical modeling and existing scientific evidence to evaluate the potential impact of the utilization of normal medical masks in public to combat the COVID-19 pandemic. We consider three key factors that contribute to the effectiveness of wearing a quality mask in reducing the transmission risk, including the mask aerosol reduction rate, mask population coverage, and mask availability. We first simulate the impact of these three factors on the virus reproduction number and infection attack rate in a general population. Using the intervened viral transmission route by wearing a mask, we further model the impact of mask-wearing on the epidemic curve with increasing mask awareness and availability. Our study indicates that wearing a face mask can be effectively combined with social distancing to flatten the epidemic curve. Wearing a mask presents a rational way to implement as an NPI to combat COVID-19. We recognize our study provides a projection based only on currently available data and estimates potential probabilities. As such, our model warrants further validation studies. [ABSTRACT FROM AUTHOR]

Background: Epidemiological data suggests that obstructive sleep apnea (OSA) is associated with increased cancer incidence and mortality. We investigate the effects of cyclical intermittent hypoxia (CIH), akin to the underlying pathophysiology of OSA, on lung cancer progression and metastatic profile in a mouse model. Methods: Intrathoracic injection of Ad5CMVCre virus into a genetically engineered mouse (GEM) KrasG12D+/-; p53fl/fl; myristolated-p110αfl/fl-ROSA-gfp was utilized to induce a solitary lung cancer. Male mice were then exposed to either CIH or Sham for 40–41 days until harvest. To monitor malignant progression, serial micro CT scans with respiratory gating (no contrast) was performed. To detect spontaneous metastases in distant organs, H&E and immunohistochemistry were performed. Results: Eighty-eight percent of injected Ad5CMVCre virus was recovered from left lung tissue, indicating reliable and accurate injections. Serial micro CT demonstrated that CIH increases primary lung tumor volume progression compared to Sham on days 33 (p = 0.004) and 40 (p<0.001) post-injection. In addition, CIH increases variability in tumor volume on day 19 (p<0.0001), day 26 (p<0.0001), day 33 (p = 0.025) and day 40 (p = 0.004). Finally, metastases are frequently detected in heart, mediastinal lymph nodes, and right lung using H&E and immunohistochemistry. Conclusions: Using a GEM mouse model of metastatic lung cancer, we report that male mice with solitary lung cancer have accelerated malignant progression and increased variability in tumor growth when exposed to cyclical intermittent hypoxia. Our results indicate that cyclical intermittent hypoxia is a pathogenic factor in non-small cell lung cancer that promotes the more rapid growth of developing tumors. [ABSTRACT FROM AUTHOR]

Recent advance in the direct-acting antivirals (DAAs) offers the potentials to eradicate hepatitis C virus (HCV) worldwide and makes universal screening more urgent. A point-of-care (POC) oral anti-HCV assay, the Fortune assay, was developed and its performance was evaluated. Individuals with or without HCV infection were recruited in three Centers. Paired oral and serum samples were tested using the Fortune and InTec anti-HCV assays. The Kehua serum anti-HCV assay served as a supplemental test to verify the discordant results. Some oral samples were also tested using the OraQuick anti-HCV assay. Furthermore, the Fortune assay results were compared with the documented RNA results. Sensitivity, specificity, and accuracy of the Fortune assay was 93.11%, 98.48%, and 96.58%, respectively (n = 1,022). Consistency between the Fortune and OraQuick assays was 96.35% (264/274); the Fortune assay detected additional 8 positive oral samples missed by the OraQuick assay. The Fortune assay demonstrated a 97.46% (115/118) positivity among the viremic patients. Furthermore, its sensitivity was HCV genotype independent. In conclusion, the Fortune assay was highly specific and accurate. It had comparable sensitivity as the serum assays for the diagnosis of active HCV infection. It provides a completely non-invasive and reliable tool for HCV screening in the DAA era. [ABSTRACT FROM AUTHOR]

Phylogeny of hard ticks (Ixodidae) remains unresolved. Mitochondrial genomes (mitogenomes) are increasingly used to resolve phylogenetic controversies, but remain unavailable for the entire large Hyalomma genus. Hyalomma asiaticum is a parasitic tick distributed throughout the Asia. As a result of great morphological variability, two subspecies have been recognised historically; until a morphological data-based synonymization was proposed. However, this hypothesis was never tested using molecular data. Therefore, objectives of this study were to: 1. sequence the first Hyalomma mitogenome; 2. scrutinise the proposed synonymization using molecular data, i.e. complete mitogenomes of both subspecies: H. a. asiaticum and kozlovi; 3. conduct phylogenomic and comparative analyses of all available Ixodidae mitogenomes. Results corroborate the proposed synonymization: the two mitogenomes are almost identical (99.6%). Genomic features of both mitogenomes are standard for Metastriata; which includes the presence of two control regions and all three "Tick-Box" motifs. Gene order and strand distribution are perfectly conserved for the entire Metastriata group. Suspecting compositional biases, we conducted phylogenetic analyses (29 almost complete mitogenomes) using homogeneous and heterogeneous (CAT) models of substitution. The results were congruent, apart from the deep-level topology of prostriate ticks (Ixodes): the homogeneous model produced a monophyletic Ixodes, but the CAT model produced a paraphyletic Ixodes (and thereby Prostriata), divided into Australasian and non-Australasian clades. This topology implies that all metastriate ticks have evolved from the ancestor of the non-Australian branch of prostriate ticks. Metastriata was divided into three clades: 1. Amblyomminae and Rhipicephalinae (Rhipicephalus, Hyalomma, Dermacentor); 2. Haemaphysalinae and Bothriocrotoninae, plus Amblyomma sphenodonti; 3. Amblyomma elaphense, basal to all Metastriata. We conclude that mitogenomes have the potential to resolve the long-standing debate about the evolutionary history of ticks, but heterogeneous evolutionary models should be used to alleviate the effects of compositional heterogeneity on deep-level relationships. [ABSTRACT FROM AUTHOR]

Background: Acupuncture has been demonstrated to be effective and safe for chronic severe functional constipation (CSFC). However, which patients with CSFC will have a better response to acupuncture remains unclear. Objective: To explore factors related to acupuncture response in patients with CSFC. Methods: We performed a secondary analysis of a previous multicenter randomized controlled trial consisting of a 2-week run-in period, 8-week treatment, and 12-week follow-up without treatment in which patients with CSFC were randomly allocated to an electroacupuncture group or a sham electroacupuncture group. Responders were defined as participants with an increase of at least one complete spontaneous bowel movement (CSBM) in week 20 compared with the baseline period. The CSBM responder rate in both groups was described, and the baseline characteristics of participants potentially related to acupuncture response were mainly analyzed using logistic regression analysis with bootstrapping techniques. Results: A total of 1021 participants were analyzed in this study, of whom 516 (50.5%) were classified as responders. The CSBM responder rate in week 20 was significantly greater in the electroacupuncture group than in the sham electroacupuncture group (62.9% vs. 37.9%, respectively; P<0.001). Both age and comorbidity were negatively associated with clinical response: with every one-year increase in age, the likelihood of clinical response was reduced by 1.2% (OR 0.988, 95%CI 0.980 to 0.996; P = 0.005), and patients with comorbidities were approximately 42% less likely to respond to treatment (OR 0.581, 95%CI 0.248 to 0.914; P = 0.001). Conclusion: CSFC patients with increasing age and comorbidity may be less likely to respond to acupuncture. These findings contribute to guiding clinical practice in terms of pretreatment patient selection. Further research is needed to confirm the association. [ABSTRACT FROM AUTHOR]

Hereditary mutations in Tamm-Horsfall protein (THP/uromodulin) gene cause autosomal dominant kidney diseases characterized by juvenile-onset hyperuricemia, gout and progressive kidney failure, although the disease pathogenesis remains unclear. Here we show that targeted expression in transgenic mice of a mutation within the domain of 8 cysteines of THP in kidneys’ thick ascending limb (TAL) caused unfolded protein response in younger (1-month old) mice and apoptosis in older (12-month old) mice. While the young mice had urine concentration defects and polyuria, such defects progressively reversed in the older mice to marked oliguria, highly concentrated urine, fibrotic kidneys and reduced creatinine clearance. Both the young and the old transgenic mice had significantly higher serum uric acid and its catabolic product, allantoin, than age-matched wild-type mice. This THP mutation apparently caused primary defects in TAL by compromising the luminal translocation and reabsorptive functions of NKCC2 and ROMK and secondary responses in proximal tubules by upregulating NHE3 and URAT1. Our results strongly suggest that the progressive worsening of kidney functions reflects the accumulation of the deleterious effects of the misfolded mutant THP and the compensatory responses. Transgenic mice recapitulating human THP/uromodulin-associated kidney diseases could be used to elucidate their pathogenesis and test novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Accurate and automatic brain metastases target delineation is a key step for efficient and effective stereotactic radiosurgery (SRS) treatment planning. In this work, we developed a deep learning convolutional neural network (CNN) algorithm for segmenting brain metastases on contrast-enhanced T1-weighted magnetic resonance imaging (MRI) datasets. We integrated the CNN-based algorithm into an automatic brain metastases segmentation workflow and validated on both Multimodal Brain Tumor Image Segmentation challenge (BRATS) data and clinical patients' data. Validation on BRATS data yielded average DICE coefficients (DCs) of 0.75±0.07 in the tumor core and 0.81±0.04 in the enhancing tumor, which outperformed most techniques in the 2015 BRATS challenge. Segmentation results of patient cases showed an average of DCs 0.67±0.03 and achieved an area under the receiver operating characteristic curve of 0.98±0.01. The developed automatic segmentation strategy surpasses current benchmark levels and offers a promising tool for SRS treatment planning for multiple brain metastases. [ABSTRACT FROM AUTHOR]

This paper forecasts the 2016 canine Anaplasma spp. seroprevalence in the United States from eight climate, geographic and societal factors. The forecast’s construction and an assessment of its performance are described. The forecast is based on a spatial-temporal conditional autoregressive model fitted to over 11 million Anaplasma spp. seroprevalence test results for dogs conducted in the 48 contiguous United States during 2011–2015. The forecast uses county-level data on eight predictive factors, including annual temperature, precipitation, relative humidity, county elevation, forestation coverage, surface water coverage, population density and median household income. Non-static factors are extrapolated into the forthcoming year with various statistical methods. The fitted model and factor extrapolations are used to estimate next year’s regional prevalence. The correlation between the observed and model-estimated county-by-county Anaplasma spp. seroprevalence for the five-year period 2011–2015 is 0.902, demonstrating reasonable model accuracy. The weighted correlation (accounting for different sample sizes) between 2015 observed and forecasted county-by-county Anaplasma spp. seroprevalence is 0.987, exhibiting that the proposed approach can be used to accurately forecast Anaplasma spp. seroprevalence. The forecast presented herein can a priori alert veterinarians to areas expected to see Anaplasma spp. seroprevalence beyond the accepted endemic range. The proposed methods may prove useful for forecasting other diseases. [ABSTRACT FROM AUTHOR]

The rising tide of sepsis, a leading cause of death in the US and globally, is not adequately controlled by current antimicrobial therapies and supportive measures, thereby requiring new adjunctive treatments. Severe microvascular injury and multiple organ failure in sepsis are attributed to a “genomic storm” resulting from changes in microbial and host genomes encoding virulence factors and endogenous inflammatory mediators, respectively. This storm is mediated by stress-responsive transcription factors that are ferried to the nucleus by nuclear transport shuttles importins/karyopherins. We studied the impact of simultaneously targeting two of these shuttles, importin alpha 5 (Imp α5) and importin beta 1 (Imp β1), with a cell-penetrating Nuclear Transport Modifier (NTM) in a mouse model of polymicrobial sepsis. NTM reduced nuclear import of stress-responsive transcription factors nuclear factor kappa B, signal transducer and activator of transcription 1 alpha, and activator protein 1 in liver, which was also protected from sepsis-associated metabolic changes. Strikingly, NTM without antimicrobial therapy improved bacterial clearance in blood, spleen, and lungs, wherein a 700-fold reduction in bacterial burden was achieved while production of proinflammatory cytokines and chemokines in blood plasma was suppressed. Furthermore, NTM significantly improved thrombocytopenia, a prominent sign of microvascular injury in sepsis, inhibited neutrophil infiltration in the liver, decreased L-selectin, and normalized plasma levels of E-selectin and P-selectin, indicating reduced microvascular injury. Importantly, NTM combined with antimicrobial therapy extended the median time to death from 42 to 83 hours and increased survival from 30% to 55% (p = 0.022) as compared to antimicrobial therapy alone. This study documents the fundamental role of nuclear signaling mediated by Imp α5 and Imp β1 in the mechanism of polymicrobial sepsis and highlights the potential for targeting nuclear transport as an adjunctive therapy in sepsis management. [ABSTRACT FROM AUTHOR]

This paper models the prevalence of antibodies to Borrelia burgdorferi in domestic dogs in the United States using climate, geographic, and societal factors. We then use this model to forecast the prevalence of antibodies to B. burgdorferi in dogs for 2016. The data available for this study consists of 11,937,925 B. burgdorferi serologic test results collected at the county level within the 48 contiguous United States from 2011-2015. Using the serologic data, a baseline B. burgdorferi antibody prevalence map was constructed through the use of spatial smoothing techniques after temporal aggregation; i.e., head-banging and Kriging. In addition, several covariates purported to be associated with B. burgdorferi prevalence were collected on the same spatio-temporal granularity, and include forestation, elevation, water coverage, temperature, relative humidity, precipitation, population density, and median household income. A Bayesian spatio-temporal conditional autoregressive (CAR) model was used to analyze these data, for the purposes of identifying significant risk factors and for constructing disease forecasts. The fidelity of the forecasting technique was assessed using historical data, and a Lyme disease forecast for dogs in 2016 was constructed. The correlation between the county level model and baseline B. burgdorferi antibody prevalence estimates from 2011 to 2015 is 0.894, illustrating that the Bayesian spatio-temporal CAR model provides a good fit to these data. The fidelity of the forecasting technique was assessed in the usual fashion; i.e., the 2011-2014 data was used to forecast the 2015 county level prevalence, with comparisons between observed and predicted being made. The weighted (to acknowledge sample size) correlation between 2015 county level observed prevalence and 2015 forecasted prevalence is 0.978. A forecast for the prevalence of B. burgdorferi antibodies in domestic dogs in 2016 is also provided. The forecast presented from this model can be used to alert veterinarians in areas likely to see above average B. burgdorferi antibody prevalence in dogs in the upcoming year. In addition, because dogs and humans can be exposed to ticks in similar habitats, these data may ultimately prove useful in predicting areas where human Lyme disease risk may emerge. [ABSTRACT FROM AUTHOR]

Vibrio mimicus is a pathogen that causes ascites disease in fish. We have previously demonstrated that the outer membrane protein U (OmpU) is an important adhesin in V. mimicus. Here eight specific OmpU-binding phage clones, which presented three different OmpU-binding peptides (designated P1, P2, P3), were screened from a commercially available phage displayed 12-mer peptide library using rOmpU protein as target. Then, synthetic OmpU-binding peptides were measured for their adhesion antagonistic activity and binding affinity via adhesion inhibition test and non-competitive ELISA, respectively. The results showed that after co-incubated with the mixture of rOmpU and P3, visible green fluorescence could be observed on the epithelioma papulosum cyprinidi (EPC) cells surface; while the EPC cells co-incubated with the mixture of rOmpU and P1/P2 exhibited little green fluorescence. The average adhesion number of V. mimicus 04–14 isolate before and after treatment with peptide was 21.4 ± 1.5, 20.8 ± 0.8 (irrelevant peptide), 20.2 ± 0.5 (P3), 5.1 ± 0.7 (P1) and 3.4 ± 0.8 (P2), respectively. There was a significant decrease in the adhesive level of 04–14 isolate treated with P1/ P2 compared to the untreated isolate (p<0.01). The affinity constants of P1 and P2 were (6.17 ± 0.19) × 108 L/mol and (1.24 ± 0.56) × 109 L/mol, respectively. Furthermore, protective effects of P1 and P2 on grass carps challenged with V. mimicus were preliminary detected. It was found there was delayed death of fish in the groups treated with P1/P2, and the survival rate of challenged fish improved with the increase of the dose of adhesion antagonistic peptide. Taken together, two novel OmpU-binding peptides, which possessed adhesion antagonistic activity, high affinity and a certain degree of antibacterial activity against V. mimicus, were screened and identified. [ABSTRACT FROM AUTHOR]

Objective: The impact of hepatitis B virus (HBV) preS/S-gene mutations on occult HBV infection (OBI) is not fully understood. This study characterized multiple novel HBV preS/S-gene mutants obtained from an OBI patient. Methods: PreS/S-gene mutants were analyzed by clonal sequencing. Viral replication and expression were analyzed by transfecting HBV genomic recombinants into HepG2 cells. Results: Twenty-one preS/S-gene mutants were cloned from four sequential serum samples, including 13 mutants that were not previously documented: (1) sI/T126V+sG145R; (2) preS1 nt 3014−3198 deletion; (3) preS1 nt 3046−3177 deletion; (4) preS1 nt 3046−3177 deletion+s115−116 “INGTST” insertion; (5) preS1 nt 3046−3177 deletion+s115−116 “INGTST” insertion+sG145R; (6) preS1 nt 3115−3123 deletion+sQ129N; (7) preS1 nt 3115−3123 deletion+s126−127 “RPCMNCTI” insertion; (8) s115−116 “INGTST” insertion; (9) s115−116 “INGTST” insertion+sG145R; (10) s126−127 “RPCMNCTI” insertion; (11) preS1 nt 2848−2862 deletion+preS2 initiation codon M→I; (12) s122−123 “KSTGLCK” insertion+sQ129N; and (13) preS2 initiation codon M→I+s131−133TSM→NST. The proportion of preS1 nt 3046−3177 deletion and preS2 initiation codon M→I+s131−133TSM→NST mutants increased in the viral pool with prolonged disease. The 13 novel OBI-related mutants showed a 51.2−99.9% decrease in HBsAg levels compared with that of the wild type. Additional N-glycosylation-associated mutations, sQ129N and s131−133TSM→NST, but not s126−127 “RPCMNCTI,” greatly attenuated anti-HBs binding to HBsAg. Compared with the wild type, replication and surface antigen promoter II activity of the preS1 nt 3046−3177 deletion mutant decreased by 43.3% and 97.0%, respectively. Conclusion: PreS/S-gene mutations may play coordinated roles in the presentation of OBI and might be associated with disease progression. This has implications for HBV diagnosis and vaccine improvement. [ABSTRACT FROM AUTHOR]

For centuries, mulberry leaf has been used in traditional Chinese medicine for the treatment of diabetes. This study aims to test the prevention effects of a proprietary mulberry leaf extract (MLE) and a formula consisting of MLE, fenugreek seed extract, and cinnamon cassia extract (MLEF) on insulin resistance development in animals. MLE was refined to contain 5% 1-deoxynojirimycin by weight. MLEF was formulated by mixing MLE with cinnamon cassia extract and fenugreek seed extract at a 6:5:3 ratio (by weight). First, the acute toxicity effects of MLE on ICR mice were examined at 5 g/kg BW dose. Second, two groups of normal rats were administrated with water or 150 mg/kg BW MLE per day for 29 days to evaluate MLE’s effect on normal animals. Third, to examine the effects of MLE and MLEF on model animals, sixty SD rats were divided into five groups, namely, (1) normal, (2) model, (3) high-dose MLE (75 mg/kg BW) treatment; (4) low-dose MLE (15 mg/kg BW) treatment; and (5) MLEF (35 mg/kg BW) treatment. On the second week, rats in groups (2)-(5) were switched to high-energy diet for three weeks. Afterward, the rats were injected (ip) with a single dose of 105 mg/kg BW alloxan. After four more days, fasting blood glucose, post-prandial blood glucose, serum insulin, cholesterol, and triglyceride levels were measured. Last, liver lysates from animals were screened with 650 antibodies for changes in the expression or phosphorylation levels of signaling proteins. The results were further validated by Western blot analysis. We found that the maximum tolerance dose of MLE was greater than 5 g/kg in mice. The MLE at a 150 mg/kg BW dose showed no effect on fast blood glucose levels in normal rats. The MLE at a 75 mg/kg BW dose and MLEF at a 35 mg/kg BW dose, significantly (p < 0.05) reduced fast blood glucose levels in rats with impaired glucose and lipid metabolism. In total, 34 proteins with significant changes in expression and phosphorylation levels were identified. The changes of JNK, IRS1, and PDK1 were confirmed by western blot analysis. In conclusion, this study demonstrated the potential protective effects of MLE and MLEF against hyperglycemia induced by high-energy diet and toxic chemicals in rats for the first time. The most likely mechanism is the promotion of IRS1 phosphorylation, which leads to insulin sensitivity restoration. [ABSTRACT FROM AUTHOR]

Pollen-mediated gene flow (PMGF) is the main mode of transgene flow in flowering plants. The study of pollen and gene flow of transgenic wheat can help to establish the corresponding strategy for preventing transgene escape and contamination between compatible genotypes in wheat. To investigate the pollen dispersal and gene flow frequency in various directions and distances around the pollen source and detect the association between frequency of transgene flow and pollen density from transgenic wheat, a concentric circle design was adopted to conduct a field experiment using transgenic wheat with resistance to wheat yellow mosaic virus (WYMV) as the pollen donor and dwarf male-sterile wheat as the pollen receptor. The results showed that the pollen and gene flow of transgenic wheat varied significantly among the different compass sectors. A higher pollen density and gene flow frequency was observed in the downwind SW and W sectors, with average frequencies of transgene flow of 26.37 and 23.69% respectively. The pollen and gene flow of transgenic wheat declined dramatically with increasing distance from its source. Most of the pollen grains concentrated within 5 m and only a few pollen grains were detected beyond 30 m. The percentage of transgene flow was the highest where adjacent to the pollen source, with an average of 48.24% for all eight compass directions at 0 m distance. Transgene flow was reduced to 50% and 95% between 1.61 to 3.15 m, and 10.71 to 20.93 m, respectively. Our results suggest that climate conditions, especially wind direction, may significantly affect pollen dispersal and gene flow of wheat. The isolation-by-distance model is one of the most effective methods for achieving stringent transgene confinement in wheat. The frequency of transgene flow is directly correlated with the relative density of GM pollen grains in air currents, and pollen competition may be a major factor influencing transgene flow. [ABSTRACT FROM AUTHOR]

Sleep alleviates Alzheimer’s disease (AD)-related neuropathological processes, whereas sleep disturbance in AD patients is associated with elevated peripheral inflammatory cytokine levels. In the present study, we assessed interleukin (IL)-1β and APOEε4 polymorphisms for association with susceptibility of sleep disturbances in AD patients. A total of 123 pretreated AD patients and 120 age-, gender- and education level-matched healthy controls were recruited for two consecutive full-night polysomnography and measurement of Epworth Sleepiness Scale (ESS) scores for sleep-wake disturbance. Their genomic DNA was analyzed for IL-1β and APOEε4 SNPs using ligase detection reaction (LDR) technology. Blood levels of IL-1β, IL-6, and tumor necrosis factor alpha (TNF-α) were measured using ELISA after lipopolysaccharide (LPS) stimulation. The odds ratio and 95% confidence interval for genotype-specific risk were calculated using an unconditional logistic regression model and adjusted by age, gender, educational levels, body mass index (BMI), and activities of daily living (ADL). Compared to the non-APOEε4/ε4 genotype, APOEε4/ε4 significantly increased the risk of AD (APOEε4/ε4 vs. non-APOEε4/ε4, adjusted OR = 4.33, 95% CI = 1.33–14.10, p = 0.015). Compared to the IL-1β CC genotype (-31), the TT genotype significantly increased the risk of AD (TT vs. CC, adjusted OR = 1.72, 95% CI = 1.13–2.61, p = 0.010). AD patients carrying the APOEε4 allele and the IL-1β TT genotype showed less time in bed, longer sleep latency and REM latency, more awakenings, and a lower SWS percentage than those carrying CC/CT combined genotypes. In addition, blood IL-1β levels were significantly greater in AD patients carrying both the APOEε4 allele and the IL-1β-31TT genotype than in those carrying the APOEε4 allele and the -31 TC or CC genotype. In conclusion, this study provides the first evidence indicating that the IL-1β-31TT genotype and homozygous APOEε4 combined are associated with increased risk of developing AD with sleep disturbance. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the changes of intraocular pressure (IOP) induced by 3-diopter (3 D) accommodation in progressing myopes, stable myopes and emmetropes. Design: Cross-sectional study. Participants: 318 subjects including 270 myopes and 48 emmetropes. Methods: 195 progressing myopes, 75 stable myopes and 48 emmetropes participated in this study. All subjects had their IOP measured using iCare rebound tonometer while accommodative stimuli of 0 D and 3 D were presented. Main Outcome Measures: IOP values without accommodation and with 3 D accommodation were measured in all subjects. Baseline IOPs and IOP changes were compared within and between groups. Results: There was no significant difference in IOPs between progressing myopes, stable myopes and emmetropes when no accommodation was induced (17.47±3.46, 16.62±2.98 and 16.80±3.62 respectively, p>0.05). IOP experienced an insignificantly slight decrease after 3 D accommodation in three groups (mean change -0.19±2.16, -0.03±1.68 and -0.39±2.65 respectively, p>0.05). Subgroup analysis showed in progressing myopic group, IOP of children (<18 years old) declined with accommodation while IOP of adults (≥18 years) increased, and the difference was statistically significant (p = 0.008). However, after excluding the age factor, accommodation induced IOP changes of high progressing myopes (≤-6 D), low, moderate and non-myopes (>-6 D) was not significantly different after Bonferroni correction (p = 0.838). Conclusions: Although no difference was detected between the baseline IOPs and accommodation induced IOP changes in progressing myopes, stable myopes and emmetropes, this study found accommodation could cause transient IOP elevation in adult progressing myopes. [ABSTRACT FROM AUTHOR]

Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections have emerged as the most common therapeutic approach for the management of diabetic macular edema (DME). Despite their proven superiority over other interventions, there is a paucity of data regarding the relative effectiveness of anti-VEGF agents in treating DME diagnosed with different patterns of optical coherence tomography (OCT). In this regard, we conducted a systematic review and comparative analysis of the therapeutic efficacy of intravitreal bevacizumab, ranibizumab, aflibercept, and conbercept in the management of DME with diffuse retinal thickening (DRT), cystoid macular edema (CME), and serous retinal detachment (SRD) patterns identified using OCT. Our study encompassed a comprehensive search of PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Wan Fang Data from their inception until January 25, 2023. The network meta-analysis involved the inclusion of 1606 patients from 20 retrospective studies with a moderate risk of bias but no evidence of publication bias. The DRT group had the highest increase in best-corrected visual acuity (BCVA) with anti-VEGF, while the SRD group had the greatest reduction in Central Macular Thickness (CMT). Furthermore, conbercept, ranibizumab, and bevacizumab, respectively, showed the best treatment outcomes for patients with DRT, CME, and SRD in terms of improvement in BCVA. And, conbercept exhibited the highest reduction in CMT in the DRT, CME, and SRD groups. In conclusion, our study highlights the efficacy of anti-VEGF agents in the management of DME and provides valuable insights into the selection of anti-VEGF agents tailored to the individual needs of patients. [ABSTRACT FROM AUTHOR]

In daily life, mobility requires walking while performing a cognitive or upper-extremity motor task. Although previous studies have evaluated the effects of dual tasks on gait performance, few studies have evaluated cortical activation and its association with gait disturbance during dual tasks. In this study, we simultaneously assessed gait performance and cerebral oxygenation in the bilateral prefrontal cortices (PFC), premotor cortices (PMC), and supplemental motor areas (SMA), using functional near-infrared spectroscopy, in 17 young adults performing dual tasks. Each participant was evaluated while performing normal-pace walking (NW), walking while performing a cognitive task (WCT), and walking while performing a motor task (WMT). Our results indicated that the left PFC exhibited the strongest and most sustained activation during WCT, and that NW and WMT were associated with minor increases in oxygenation levels during their initial phases. We observed increased activation in channels in the SMA and PMC during WCT and WMT. Gait data indicated that WCT and WMT both caused reductions in walking speed, but these reductions resulted from differing alterations in gait properties. WCT was associated with significant changes in cadence, stride time, and stride length, whereas WMT was associated with reductions in stride length only. During dual-task activities, increased activation of the PMC and SMA correlated with declines in gait performance, indicating a control mechanism for maintaining gait performance during dual tasks. Thus, the regulatory effects of cortical activation on gait behavior enable a second task to be performed while walking. [ABSTRACT FROM AUTHOR]

Background: Fur is an important genetically-determined characteristic of domestic rabbits; rabbit furs are of great economic value. We used the Solexa sequencing technology to assess gene expression in skin tissues from full-sib Rex rabbits of different phenotypes in order to explore the molecular mechanisms associated with fur determination. Methodology/Principal Findings: Transcriptome analysis included de novo assembly, gene function identification, and gene function classification and enrichment. We obtained 74,032,912 and 71,126,891 short reads of 100 nt, which were assembled into 377,618 unique sequences by Trinity strategy (N50=680 nt). Based on BLAST results with known proteins, 50,228 sequences were identified at a cut-off E-value ≥ 10-5. Using Blast to Gene Ontology (GO), Clusters of Orthologous Groups (KOG) and Kyoto Encyclopedia of Genes and Genomes (KEGG), we obtained several genes with important protein functions. A total of 308 differentially expressed genes were obtained by transcriptome analysis of plaice and un-plaice phenotype animals; 209 additional differentially expressed genes were not found in any database. These genes included 49 that were only expressed in plaice skin rabbits. The novel genes may play important roles during skin growth and development. In addition, 99 known differentially expressed genes were assigned to PI3K-Akt signaling, focal adhesion, and ECM-receptor interactin, among others. Growth factors play a role in skin growth and development by regulating these signaling pathways. We confirmed the altered expression levels of seven target genes by qRT-PCR. And chosen a key gene for SNP to found the differentially between plaice and un-plaice phenotypes rabbit. Conclusions/Significance: The rabbit transcriptome profiling data provide new insights in understanding the molecular mechanisms underlying rabbit skin growth and development. [ABSTRACT FROM AUTHOR]

Gastric cancer is one of the most common malignancies and has a high rate of metastasis. We hypothesize that NME2 (Nucleoside Diphosphate Kinase 2), which has previously been considered as an anti-metastatic gene, plays a role in the invasiveness of gastric cancer cells. Using a tissue chip technology and immunohistochemistry, we demonstrated that NME2 expression was associated with levels of differentiation of gastric cancer cells and their metastasis into the lymph nodes. When the NME2 gene product was over-expressed by ;in vitro stable transfection, cells from BGC823 and MKN45 gastric cancer cell lines had reduced rates of proliferation, migration, and invasion through the collagen matrix, suggesting an inhibitory activity of NME2 in the propagation and invasion of gastric cancer. NME2 could, therefore, severe as a risk marker for gastric cancer invasiveness and a potential new target for gene therapy to enhance or induce NME2 expression. [ABSTRACT FROM AUTHOR]

Louse borne typhus (also called epidemic typhus) was one of man's major scourges, and epidemics of the disease can be reignited when social, economic, or political systems are disrupted. The fear of a bioterrorist attack using the etiologic agent of typhus, Rickettsia prowazekii, was a reality. An attenuated typhus vaccine, R. prowazekii Madrid E strain, was observed to revert to virulence as demonstrated by isolation of the virulent revertant Evir strain from animals which were inoculated with Madrid E strain. The mechanism of the mutation in R. prowazekii that affects the virulence of the vaccine was not known. We sequenced the genome of the virulent revertant Evir strain and compared its genome sequence with the genome sequences of its parental strain, Madrid E. We found that only a single nucleotide in the entire genome was different between the vaccine strain Madrid E and its virulent revertant strain Evir. The mutation is a single nucleotide insertion in the methyltransferase gene (also known as PR028) in the vaccine strain that inactivated the gene. We also confirmed that the vaccine strain E did not cause fever in guinea pigs and the virulent revertant strain Evir caused fever in guinea pigs. We concluded that a single nucleotide insertion in the methyltransferase gene of R. prowazekii attenuated the R. prowazekii vaccine strain E. This suggested that an irreversible insertion or deletion mutation in the methyl transferase gene of R. prowazekii is required for Madrid E to be considered a safe vaccine. [ABSTRACT FROM AUTHOR]

Background: Ketosis-prone diabetes (KPDM) is new-onset diabetic ketoacidosis without precipitating factors in non-type 1 diabetic patients; after management, some are withdrawn from exogenous insulin, although determining factors remain unclear. Methods: Twenty KPDM patients and twelve type 1 diabetic patients (T1DM), evaluated at baseline, 12 and 24 months with/without insulin maintenance underwent a standardized mixed-meal tolerance test (MMTT) for 2 h. Results: At baseline, triglyceride and C3 were higher during MMTT in KPDM vs. T1DM (p<0.0001) with no differences in non-esterified fatty acids (NEFA) while Acylation Stimulating Protein (ASP) tended to be higher. Within 12 months, 11 KPDM were withdrawn from insulin treatment (KPDM-ins), while 9 were maintained (KPDM+ins). NEFA was lower in KPDM-ins vs. KPDM+ins at baseline (p = 0.0006), 12 months (p<0.0001) and 24 months (p<0.0001) during MMTT. NEFA in KPDM-ins decreased over 30–120 minutes (p<0.05), but not in KPDM+ins. Overall, C3 was higher in KPDM-ins vs KPDM+ins at 12 months (p = 0.0081) and 24 months (p = 0.0019), while ASP was lower at baseline (p = 0.0024) and 12 months (p = 0.0281), with a decrease in ASP/C3 ratio. Conclusions: Notwithstanding greater adiposity in KPDM-ins, greater NEFA decreases and lower ASP levels during MMTT suggest better insulin and ASP sensitivity in these patients. [ABSTRACT FROM AUTHOR]

β-lactam antibiotics are widely used in clinic. Filamentous fungus Acremonium chrysogenum is an important industrial fungus for the production of CPC, one of the major precursors of β-lactam antibiotics. Although its fermentation yield has been bred significantly over the past decades, little is known regarding molecular changes between the industrial strain and the wild type strain. This limits the possibility to improve CPC production further by molecular breeding. Comparative transcriptome is a powerful tool to understand the molecular mechanisms of CPC industrial high yield producer compared to wild type. A total of 57 million clean sequencing reads with an average length of 100 bp were generated from Illumina sequencing platform. 22,878 sequences were assembled. Among the assembled unigenes, 9502 were annotated and 1989 annotated sequences were assigned to 121 pathways by searching against the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) database. Furthermore, we compared the transcriptome differences between a high-yield and a wild-type strain during fermentation. A total of 4329 unigenes with significantly different transcription level were identified, among which 1737 were up-regulated and 2592 were down-regulated. 24 pathways were subsequently determined which involve glycerolipid metabolism, galactose metabolism, and pyrimidine metabolism. We also examined the transcription levels of 18 identified genes, including 11 up-regulated genes and 7 down-regulated genes using reverse transcription quantitative -PCR (RT-qPCR). The results of RT-qPCR were consistent with the Illumina sequencing. In this study, the Illumina sequencing provides the most comprehensive sequences for gene expression profile of Acremonium chrysogenum and allows de novo transcriptome assembly while lacking genome information. Comparative analysis of RNA-seq data reveals the complexity of the transcriptome in the fermentation of different yield strains. This is an important public information platform which could be used to accelerate the research to improve CPC production in Acremonium chrysogenum. [ABSTRACT FROM AUTHOR]

Recent studies provide convincing evidence that a combined immunohistochemical or fluorescence in situ hybridization (FISH) score of MYC, BCL2, BCL6 proteins and MYC translocations predicted outcome in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, by far, all these researches are based on Western populations. Therefore, we investigate the prognostic relevance of MYC-, BCL2- and BCL6-rearrangements and protein expression by immunohistochemistry and FISH from 336 de novo DLBCL, NOS treated with CHOP or R-CHOP. Breaks in MYC and BCL6, and fusion in IGH/BCL2 were detected in 9.7%, 20.0%, and 11.1% of the cases, respectively, and were not significantly associated with clinical outcomes. Protein overexpression of MYC (≥40%), BCL2 (≥70%) and BCL6 (≥50%) was encountered in 51%, 51% and 36% of the tumors, respectively. On the basis of MYC, BCL2 and BCL6 expression, double-hit scores (DHSs) and triple-hit score (THS) were assigned to all patients with DLBCL. Patients with high MYC/BCL2 DHS, high MYC/BCL6 DHS and high THS had multiple adverse prognostic factors including high LDH level, poor performance status, advanced clinical stage, high International Prognostic Index (IPI) score, and non-germinal center B-cell. In univariate analysis, high MYC/BCL2 DHS, high MYC/BCL6 DHS and high THS were associated with inferior OS and PFS in both CHOP and R-CHOP cohorts (P<0.05). The highly significant correlations with OS and PFS were maintained in multivariate models that controlled for IPI (P<0.05). DLBCLs with high DHSs and high THS share the clinical features and poor prognosis of double-hit lymphoma (P>0.05). These data together suggest that the immunohistochemical DHSs and THS defined a large subset of DLBCLs with double-hit biology and was strongly associated with poor outcome in patients treated with R-CHOP or CHOP. [ABSTRACT FROM AUTHOR]

Background: Mounting evidence indicates that elevated serum uric acid may increase the incidence of chronic kidney disease (CKD). Our goal was to systematically evaluate longitudinal cohort studies for the association of serum uric acid levels and incident CKD. Methods: We searched electronic databases and the reference lists of relevant articles. The primary outcome was incident CKD, which was defined as an eGFR less than 60 mL/min/1.73 m2 at the follow-up examination. Study-specific risk estimates were combined using random-effects models. The included studies were stratified into subgroups, and meta-regression analyses were performed. Results: Fifteen unique cohorts with a total of 99,205 individuals and 3,492 incident CKD cases were included. The relative risk of CKD was 1.22 (95% CI 1.16–1.28, I2 = 65.9%) per 1 mg/dL serum uric level increment. This positive association was consistently observed in subgroups stratified according to most of the study-level characteristics. The observed positive association was more pronounced among group with a mean age <60 years (RR 1.26, 95% CI 1.21–1.31), and low-level heterogeneity was observed in the findings for this age group (I2 = 46.4%, P = 0.022). However, no association was observed among studies with a mean age≥60 years (RR 1.04, 95% CI 0.96–1.13), and no evidence of heterogeneity was evident among the studies (I2 = 0%, P = 0.409). This mean age-related difference in the association between serum uric acid levels and CKD was significant (P = 0.004). The sensitivity analysis results were consistent when the analyses were restricted to studies that controlled for proteinuria and metabolic syndrome. Conclusions: Our meta-analysis demonstrated a positive association between serum uric acid levels and risk of CKD in middle-aged patients independent of established metabolic risk factors. Future randomized, high-quality clinical trials are warranted to determine whether lowering uric acid levels is beneficial in CKD. [ABSTRACT FROM AUTHOR]

CITED2 was identified as a cardiac transcription factor which is essential to the heart development. Cited2-deficient mice showed cardiac malformations, adrenal agenesis and neural crest defects. To explore the potential impact of mutations in CITED2 on congenital heart disease (CHD) in humans, we screened the coding region of CITED2 in a total of 700 Chinese people with congenital heart disease and 250 healthy individuals as controls. We found five potential disease-causing mutations, p.P140S, p.S183L, p.S196G, p.Ser161delAGC and p. Ser192_Gly193delAGCGGC. Two mammalian two-hybrid assays showed that the last four mutations significantly affected the interaction between p300CH1 and CITED2 or HIF1A. Further studies showed that four CITED2 mutations recovered the promoter activity of VEGF by decreasing its competitiveness with HIF1A for binding to p300CH1 and three mutations decreased the consociation of TFAP2C and CITED2 in the transactivation of PITX2C. Both VEGF and PITX2C play very important roles in cardiac development. In conclusion, we demonstrated that CITED2 has a potential causative impact on congenital heart disease. [ABSTRACT FROM AUTHOR]

NRP1 as multifunctional non-tyrosine-kinase receptors play critical roles in tumor progression. MicroRNAs (miRNAs) are an important class of pervasive genes that are involved in a variety of biological functions, particularly cancer. It remains unclear whether miRNAs can regulate the expression of NRP1. The goal of this study was to identify miRNAs that could inhibit the growth, invasion and metastasis of gastric cancer by targeting NRP1 expression. We found that miR-338 expression was reduced in gastric cancer cell lines and in gastric cancer tissues. Moreover, we found that miR-338 inhibited gastric cancer cell migration, invasion, proliferation and promoted apoptosis by targeting NRP1 expression. As an upstream regulator of NRP1, miR-338 directly targets NRP1. The forced expression of miR-338 inhibited the phosphorylation of Erk1/2, P38 MAPK and Akt; however, the expression of phosphorylated Erk1/2, P38 MAPK and Akt was restored by the overexpression of NRP1. In AGS cells infected with miR-338 or transfected with SiNRP1, the protein levels of fibronectin, vimentin, N-cadherin and SNAIL were decreased, but the expression of E-cadherin was increased. The expression of mesenchymal markers in miR-338-expressing cells was restored to normal levels by the restoration of NRP1 expression. In vivo, miR-338 also decreased tumor growth and suppressed D-MVA by targeting NRP1. Therefore, we conclude that miR-338 acts as a novel tumor suppressor gene in gastric cancer. miR-338 can decrease migratory, invasive, proliferative and apoptotic behaviors, as well as gastric cancer EMT, by attenuating the expression of NRP1. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficiency and safety of the transperitoneal approaches with retroperitoneal approaches in laparoscopic partial nephrectomy for renal cell carcinoma and provide evidence-based medicine support for clinical treatment. Methods: A systematic computer search of PUBMED, EMBASE, and the Cochrane Library was executed to identify retrospective observational and prospective randomized controlled trials studies that compared the outcomes of the two approaches in laparoscopic partial nephrectomy. Two reviewers independently screened, extracted, and evaluated the included studies and executed statistical analysis by using software STATA 12.0. Outcomes of interest included perioperative and postoperative variables, surgical complications and oncological variables. Results: There were 8 studies assessed transperitoneal laparoscopic partial nephrectomy (TLPN) versus retroperitoneal laparoscopic partial nephrectomy (RLPN) were included. RLPN had a shorter operating time (SMD = 1.001,95%confidence interval[CI] 0.609–1.393,P<0.001), a lower estimated blood loss (SMD = 0.403,95%CI 0.015–0.791,P = 0.042) and a shorter length of hospital stay (WMD = 0.936 DAYS,95%CI 0.609–1.263,P<0.001) than TLPN. There were no significant differences between the transperitoneal and retroperitoneal approaches in other outcomes of interest. Conclusions: This meta-analysis indicates that, in appropriately selected patients, especially patients with intraperitoneal procedures history or posteriorly located renal tumors, the RLPN can shorten the operation time, reduce the estimated blood loss and shorten the length of hospital stay. RLPN may be equally safe and be faster compared with the TLPN. [ABSTRACT FROM AUTHOR]

Background and Aims: The American Heart Association has recently established seven ideal cardiovascular health metrics for cardiovascular health promotion and disease reduction (i.e., non-smoking, normal body mass index, physically active, healthy diet, and normal levels of cholesterol, blood pressure and fasting blood glucose). The present study seeks to evaluate how well these metrics predict mortality from all causes and cardiovascular diseases in adult Chinese living in a northern industrial city. Methods and Results: Data of 95,429 adults who participated in the Kailuan cohort study from June 2006 to October 2007 was analyzed. All participants underwent questionnaire assessment, clinical examination, laboratory assessments and were followed up biannually. During a median follow-up of 4.02 years, 1,843 deaths occurred, with 597 deaths resulting from cardiovascular diseases. Lower mortality rates from all causes and cardiovascular diseases were observed among the subjects who met a higher number of the ideal health metrics. Compared to the participants who met none or one ideal health metric, those meeting ≥5 ideal health metrics had a lower risk of all-cause mortality by 30% (adjusted hazard ratio, 0.70; 95% confidence interval, 0.56–0.88) and a lower risk of mortality from cardiovascular diseases by 39% (adjusted hazard ratio, 0.61; 95% confidence interval, 0.41–0.89) . Four metrics (smoking status, physical activity, blood pressure and fasting blood glucose) were significantly associated with all-cause mortality. Three metrics (physical activity, blood pressure and fasting blood glucose) were significantly associated with mortality from cardiovascular diseases. Conclusion: The number of ideal health metrics is negatively associated with mortality rates from all causes and cardiovascular diseases among adults in a Northern Chinese industrial city. The data supports the AHA recommendation of ideal health metrics for adults from Northern China. [ABSTRACT FROM AUTHOR]

Background and Aims: Lamivudine (LAM) is still widely used for anti-HBV therapy in China. The study aimed to clarify whether a newly-found rtM204Q mutation from patients was associated with the drug resistance. Methods: HBV complete reverse-transcriptase region was screened by direct sequencing and verified by clonal sequencing. Replication-competent plasmids containing patient-derived 1.1mer mutant or wild-type viral genome were constructed and transfected into HepG2 cells. After cultured with or without serially-diluted antiviral drugs, intracellular HBV replicative intermediates were quantitated for calculating the 50% effective concentration of drug (EC50). Results: A total of 12,000 serum samples of 9,830 patients with chronic HBV infection were screened. rtM204Q mutation was detected in seven LAM-refractory patients. By contrast, rtM204I/rtM204V mutations were detected in 2,502 patients' samples. The rtM204Q emerged either alone or in concomitance with rtM204I/rtM204V, and all were accompanied with virologic breakthrough in clinical course. Clonal sequencing verified that rtM204Q mutant was predominant in viral quasispecies of these samples. Phenotypic analysis showed that rtM204Q mutant had 89.9% of replication capacity and 76-fold increased LAM EC50 of the concomitant wild-type strain. By contrast, rtM204I mutant in the sample had lower replication capacity and higher LAM resistance (46.3% and 1396-fold increased LAM EC50 of the wild-type strain) compared to rtM204Q mutant. rtM204Q mutant was susceptible to adefovir dipivoxil (ADV) in vitro and ADV/ADV+LAM rescue therapy in clinic. Conclusion: rtM204Q is suggested to be a novel LAM-resistance-associated mutation. It conferred a moderate resistance with higher competent natural replication capacity compared to rtM204I mutation. [ABSTRACT FROM AUTHOR]

Ehrlichia chaffeensis is an obligately intracellular bacterium that resides and multiplies within cytoplasmic vacuoles of phagocytes. The Ehrlichia-containing vacuole (ECV) does not fuse with lysosomes, an essential condition for Ehrlichia to survive inside phagocytes, but the mechanism of inhibiting the fusion of the phagosome with lysosomes is not clear. Understanding the ECV molecular composition may decipher the mechanism by which Ehrlichia inhibits phagosome-lysosome fusion. In this study, we obtained highly purified ECVs from E. chaffeensis-infected DH82 cells by sucrose density gradient centrifugation and analyzed their composition by mass spectrometry-based proteomics. The ECV composition was compared with that of phagolysosomes containing latex beads. Lysosomal proteins such as cathepsin D, cathepsin S, and lysosomal acid phosphatase were not detected in E. chaffeensis phagosome preparations. Some small GTPases, involved in membrane dynamics and phagocytic trafficking, were detected in ECVs. A notable finding was that Rab7, a late endosomal marker, was consistently detected in E. chaffeensis phagosomes by mass spectrometry. Confocal microscopy confirmed that E. chaffeensis phagosomes contained Rab7 and were acidified at approximately pH 5.2, suggesting that the E. chaffeensis vacuole was an acidified late endosomal compartment. Our results also demonstrated by mass spectrometry and immunofluorescence analysis that Ehrlichia morulae were not associated with the autophagic pathway. Ehrlichia chaffeensis did not inhibit phagosomes containing latex beads from fusing with lysosomes in infected cells. We concluded that the E. chaffeensis vacuole was a late endosome and E. chaffeensis might inhibit phagosome-lysosome fusion by modifying its vacuolar membrane composition, rather than by regulating the expression of host genes involved in trafficking. [ABSTRACT FROM AUTHOR]

Background: Finding a specific agent is useful for early detection of tumor. Angiotensin II type 1 receptor (AT1R) was reported to be elevated in a variety of tumors and participate in tumor progression. The aim of our study was to evaluate whether 131I-anti-AT1R monoclonal antibody (mAb) is an efficient imaging reporter for the detection of hepatocellular carcinoma. Methodology/Principal Findings: AT1R mAb or isotype IgG was radioiodinated with 131I and the radiochemical purity and stability of the two imaging agents and the affinity of 131I-anti-AT1R mAb against AT1R were measured. 3.7 MBq 131I-anti-AT1R mAb or isotype 131I-IgG was intravenously injected to mice with hepatocellular carcinoma through tail vein, and then the whole-body autoradiography and biodistribution of the two imaging agents and the pharmacokinetics of 131I-anti-AT1R mAb were studied. 131I-anti-AT1R mAb and 131I-IgG were successfully radioiodinated and both maintained more stable in serum than in saline. The 131I-anti-AT1R mAb group showed much clearer whole-body images for observing hepatocellular carcinoma than the 131I-IgG group. The biodistributions of the two imaging agents suggested that hepatocellular carcinoma tissue uptook more 131I-anti-AT1R mAb than other tissues (%ID/g = 1.82±0.40 and T/NT ratio = 7.67±0.64 at 48 h), whereas hepatocellular carcinoma tissue did not selectively uptake 131I-IgG (%ID/g = 0.42±0.06 and T/NT ratio = 1.33±0.08 at 48 h). The pharmacokinetics of 131I-anti-AT1R mAb was in accordance with the two-compartment model, with a rapid distribution phase and a slow decline phase. These results were further verified by real-time RT-PCR, immunohistochemistry staining and Western blot. Conclusions/Significance: 131I-anti-AT1R mAb may be a potential target for early detection of tumor. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) genotypes and subgenotypes may vary in geographical distribution and virological features. Previous investigations, including ours, showed that HBV genotypes B and C were respectively predominant in South and North China, while genotypes A and D were infrequently detected and genotype G was not found. In this study, a novel A/C/G intergenotype was identified in patients with chronic HBV infection in Guilin, a city in southern China. Initial phylogenetic analysis based on the S gene suggested the HBV recombinant to be genotype G. However, extended genotyping based on the entire HBV genome indicated it to be an A/C/G intergenotype with a closer relation to genotype C. Breakpoint analysis using the SIMPLOT program revealed that the recombinant had a recombination with a arrangement of genotypes A, G, A and C fragments. Compared with the HBV recombinants harboring one or two genotype G fragments found in Asian countries, this Guilin recombinant was highly similar to the Vietnam (98–99%) and Long An recombinants (96–99%), but had a relatively low similarity to the Thailand one (89%). Unlike those with the typical genotype G of HBV, the patients with the Guilin recombinant were seropositive for HBeAg. Moreover, a relatively high HBV DNA viral load (>2×106 IU/ml) was detected in the patients, and the analysis of viral replication capacity showed that the Guilin recombinant strains had a competent replication capacity similar to genotypes B and C strains. These findings can aid in not only the clarification of the phylogenetic origin of the HBV recombinants with the genotype G fragment found in Asian countries, but also the understanding of the virological properties of these complicated HBV recombinants. [ABSTRACT FROM AUTHOR]

Methotrexate (MTX) is a key agent for the treatment of childhood acute lymphoblastic leukemia (ALL). Increased MTX plasma concentrations are associated with a higher risk of adverse drug effects. ATP-binding cassette subfamily C member 2 (ABCC2) is important for excretion of MTX and its toxic metabolite. The ABCC2 −24C>T polymorphism (rs717620) reportedly contributes to variability of MTX kinetics. In the present study, we assessed the association between the ABCC2 −24C>T polymorphism and methotrexate (MTX) toxicities in childhood ALL patients treated with high-dose MTX. A total of 112 Han Chinese ALL patients were treated with high-dose MTX according to the ALL-Berlin-Frankfurt-Muenster 2000 protocol. Our results showed that presence of the −24T allele in ABCC2 gene led to significantly higher MTX plasma concentrations at 48 hours after the start of infusion, which would strengthen over repeated MTX infusion. The −24T allele in ABCC2 gene was significantly associated with higher risks of high-grade hematologic (leucopenia, anemia, and thrombocytopenia) and non-hematologic (gastrointestinal and mucosal damage/oral mucositis) MTX toxicities. This study provides the first evidence that the −24T allele in ABCC2 gene is associated with the severity of MTX toxicities, which add fresh insights into clinical application of high-dose MTX and individualization of MTX treatment. [ABSTRACT FROM AUTHOR]

SH2B1 is an SH2 and PH domain-containing adaptor protein. Genetic deletion of SH2B1 results in obesity, type 2 diabetes, and fatty liver diseases in mice. Mutations in SH2B1 are linked to obesity in humans. SH2B1 in the brain controls energy balance and body weight at least in part by enhancing leptin sensitivity in the hypothalamus. SH2B1 in peripheral tissues also regulates glucose and lipid metabolism, presumably by enhancing insulin sensitivity in peripheral metabolically-active tissues. However, the function of SH2B1 in individual peripheral tissues is unknown. Here we generated and metabolically characterized hepatocyte-specific SH2B1 knockout (HKO) mice. Blood glucose and plasma insulin levels, glucose tolerance, and insulin tolerance were similar between HKO, albumin-Cre, and SH2B1f/f mice fed either a normal chow diet or a high fat diet (HFD). Adult-onset deletion of SH2B1 in the liver either alone or in combination with whole body SH2B2 knockout also did not exacerbate HFD-induced insulin resistance and glucose intolerance. Adult-onset, but not embryonic, deletion of SH2B1 in the liver attenuated HFD-induced hepatic steatosis. In agreement, adult-onset deletion of hepatic SH2B1 decreased the expression of diacylglycerol acyltransferase-2 (DGAT2) and increased the expression of adipose triglyceride lipase (ATGL). Furthermore, deletion of liver SH2B1 in SH2B2 null mice attenuated very low-density lipoprotein (VLDL) secretion. These data indicate that hepatic SH2B1 is not required for the maintenance of normal insulin sensitivity and glucose metabolism; however, it regulates liver triacylglycerol synthesis, lipolysis, and VLDL secretion. [ABSTRACT FROM AUTHOR]

Background and Aims: Interferon-gamma induced protein 10 (IP-10) was suggested to be involved in liver injury in viral hepatitis. This study aimed to investigate the impact of the single nucleotide polymorphisms (SNP) G-201A (rs1439490) in IP-10 gene on disease progression of hepatitis B virus (HBV) infection. Methods: The -201 SNP in IP-10 promoter was genotyped from 577 patients with different illness categories and 275 health controls; In vitro IP-10 promoter activity was compared between haplotype GG and AA homozygotes using luciferase reporter system in HepG2 cells. In vivo expression of IP-10 was compared between patients with -201 AA genotype and GG genotype. Results: The detected frequency of G-201A SNP was 17.8%, 25.3%, 26.6%, and 13.8% for patients with acute hepatitis B (AHB), patients with mild chronic hepatitis B (CHB-M), patients with severe chronic hepatitis B (CHB-S), and health controls, respectively. In vitro IP-10 promoter-driven luciferase activity in pGL3-Enhancer-201A transfected HepG2 cells was 1.43-fold higher than that in pGL3-Enhancer-201G transfected HepG2 cells (P<0.01). In vivo IP-10 transcriptional expression of peripheral blood mononuclear cells was 1.38-fold higher in patients with -201 AA genotype than in patients with -201 GG genotype (P<0.01). Conclusion: G-201A in promoter region of IP-10 gene was associated with liver disease progression in patients with HBV infection through up-regulating IP-10 expression. [ABSTRACT FROM AUTHOR]

Various types of marine-continental transitional facies are present in the gas-bearing shales of the southeastern Sichuan Basin. A review of the different lithological assemblages in these rocks is important for assessing the likely shale gas content and the development of the storage space. This study of the lithological assemblages of the Permian Longtan Formation in the southeastern Sichuan Basin at Well X1 used core observations, optical thin-section observations, Ar-ion polishing, scanning electron microscopy, and nitrogen adsorption tests to compare and analyze storage space types and pore structures in the shale to determine the sedimentary paleoenvironment, petromineralogy, and organic content. The marine-continental transitional facies in the study area were deposited in a warm climate that favored enrichment by organic matter. The kerogen is type II2-III (average vitrinite reflectance 2.66%), which is within the favorable thermal maturity range for the presence of shale gas. The lithology mainly consists of shale, siltstone, and limestone (with bioclasts), as well as a coal seam. The lithological development divides the Longtan Formation into lower (swamp), middle (tidal flat/lagoon), and upper (delta) sub-members. From lower to upper divisions, the lithofacies evolved from silty shale to clay shale and then to shale intercalated with siltstone or calcareous layers. The proportions of intergranular and dissolution pores in the clay minerals decrease gradually from lower to upper sub-members, and pore size sizes also tend to decrease. Relatively large-diameter pores and microfractures occur in the inorganic matter in the lowest sub-member. Quartz and clay are the main constituents of the shale, respectively contributing to the specific surface area and specific pore volume of the reservoir space. [ABSTRACT FROM AUTHOR]

Background: Although it is well established that a higher body weight is protective against osteoporosis, the effects of body fat and fat distribution on bone mineral density (BMD) after adjustment for body weight remains uncertain. Objective: To examine the relationship between body fat and fat distribution and BMD beyond its weight-bearing effect in middle-aged Chinese adults. Method: The study had a community-based cross-sectional design and involved 1,767 women and 698 men aged 50–75 years. The BMD of the lumbar spine, total hip, and whole body, and the fat mass (FM) and percentage fat mass (%FM) of the total body and segments of the body were measured by dual-energy X-ray absorptiometry. General information on the participants was collected using structured questionnaire interviews. Result: After adjusting for potential confounders, an analysis of covariance showed the weight-adjusted (WA-) total FM (or %FM) to be negatively associated with BMD in all of the studied sites (P<0.05) in both women and men. The unfavorable effects of WA-total FM were generally more substantial in men than in women, and the whole body was the most sensitive site related to FM, followed by the total hip and the lumbar spine, in both genders. The mean BMD of the lumbar spine, total hip, and whole body was 3.93%, 3.01%, and 3.65% (in women) and 5.02%, 5.57%, 6.03% (in men) lower in the highest quartile (vs. lowest quartile) according to the WA-total FM (all p<0.05). Similar results were noted among the groups for WA-total FM%. In women, abdominal fat had the most unfavorable association with BMD, whereas in men it was limb fat. Conclusion: FM (or %FM) is inversely associated with BMD beyond its weight-bearing effect. Abdominal fat in women and limb fat in men seems to have the greatest effect on BMD. [ABSTRACT FROM AUTHOR]