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Abstract Incidence of liver cancer as one of the most common cancers worldwide and become the significant contributor for the mortality among cancer patients. The disease burden, risk factors, and trends in incidence and mortality of liver cancer globally was described subsequently estimated the projections of liver cancer incidence or mortality by 2040. Data regarding age-standardized incidence and mortality rates for liver cancer was obtained from multiple databases, including GLOBOCAN 2020, CI5 volumes I–XI, WHO mortality database, and Global Burden of Disease (GBD)-2019. Concentrating on worldwide variations, this thorough analysis offers insights into patterns of incidence and mortality based on gender and age. Our findings encompass significant indicators, including age-standardized rates (ASRs), average annual percentage change (AAPC), and future projections extending up to the year 2040. Liver cancer holds the sixth position in terms of most frequently diagnosed cancers and stands as the sixth leading cause of cancer-related deaths worldwide in 2020, accounting for 905,677 new cases and 782,000 fatalities. Additionally, liver cancer contributed to 12,528,421 age-standardized disability-adjusted life years (DALYs), with an age-standardized DALYs rate of 161.92 in 2019 worldwide. The age-specific incidence rates exhibited significant variations across different regions, showing a fivefold difference in males and females. A significant increase in incidence was observed in North Europe and Asia, while North African countries reported a higher mortality burden (ASR, 10 per 100,000) compared to developed countries. Since last few years, the incidence and mortality rates have increased and attained Annual Average Percentage Change (AAPC) incidence rate of 7.7 (95% CI 3.9–11.6) for men and the highest AAPC mortality rate of 12.2 (95% CI 9.5–15.0) for women. In 2019, Western Europe emerged as the high-risk region for DALYs related to smoking and alcohol consumption, while high-income North America carried a high risk for DALYs associated with a high body-mass index. The projected trend indicates a surge in new liver cancer incident cases, expected to rise from around 905,347 to an estimated 1,392,474 by 2040. This study described the evidence pertinent to higher incidence trends in liver cancer, particularly among both young and older adults, encompassing males and females, as well as those who are HIV-infected and HBsAg positive. A significant rise in the young population poses a significant public health concern that warrants attention from healthcare professionals to prioritize the promotion of health awareness and the development of effective cancer prevention strategies, particularly in many developing countries.

BackgroundIn recent years, there have been frequent reports of human infection with H5N6 avian influenza. However, the fundamental characteristics of the disease remain unclear. This paper conducts a systematic review to explore the epidemiological features of the disease, aiming to provide a foundation for epidemic prevention and control and to serve as a reference for clinical diagnosis.MethodA systematic search was performed in PubMed, Web of Science, CNKI, Wanfang and gray literature up to November 15, 2023. All articles were about the epidemic features of the H5N6 subtype of avian influenza, written in English or Chinese.ResultsThis review encompasses 24 documented outbreaks of human H5N6 avian influenza, exclusively reported in southern China. The age range of cases spanned from under 2 years old to 81 years old. The incubation period ranged from 1 to 13 days, with a mean of 4.3 days. Among the 24 cases, 22 individuals had a documented history of contact with poultry. Of the 23 cases with available prognosis data, 12 resulted in fatalities, yielding a significant fatality rate of 52.2%. A noteworthy observation is that all cases with a history of contact with sick and dead poultry resulted in fatalities, and the difference in fatality rates between this group and others was statistically significant (χ2 = 7.441, p = 0.014). This study identified a total of 888 close contacts, none of whom demonstrated infection.ConclusionThis study represents a comprehensive summary of the epidemiological characteristics of human H5N6 avian influenza. Significantly, it sheds light on the incubation period of the disease and underscores a potential elevated risk of mortality among patients with a history of contact with sick and dead poultry.

Abstract AIFM2 is a crucial NADH oxidase involved in the regulation of cytosolic NAD+. However, the role of AIFM2 in the progression of human cancers remains largely unexplored. Here, we elucidated the clinical implications, biological functions, and molecular mechanisms of AIFM2 in hepatocellular carcinoma (HCC). We found that AIFM2 is significantly upregulated in HCC, which is most probably caused by DNA hypomethylation and downregulation of miR-150-5p. High expression of AIFM2 is markedly associated with poor survival in patients with HCC. Knockdown of AIFM2 significantly impaired, while forced expression of AIFM2 enhanced the metastasis of HCC both in vitro and in vivo. Mechanistically, increased mitochondrial biogenesis and oxidative phosphorylation by activation of SIRT1/PGC-1α signaling contributed to the promotion of metastasis by AIFM2 in HCC. In conclusion, AIFM2 upregulation plays a crucial role in the promotion of HCC metastasis by activating SIRT1/PGC-1α signaling, which strongly suggests that AIFM2 could be targeted for the treatment of HCC.

Objective: Hemodynamic monitoring plays a crucial way in guiding the clinical decision-making process for the management of critically ill neonates. Noninvasive hemodynamic monitoring is characterized by continuous, convenient, and accurate assessment, presenting a viable option for implementation in neonatal intensive care units (NICU). This review article summarizes the research advancements made in noninvasive hemodynamic monitoring and electronic cardiometry (EC) applications in neonates, providing valuable reference resource for studies in the field of hemodynamic monitoring. Mechanism: The clinical significance of hemodynamic monitoring in neonates is first introduced and followed by a comprehensive description of both invasive and noninvasive techniques employed in hemodynamic monitoring. Furthermore, the research progress of EC in neonates is discussed, focusing particularly on its feasibility and accuracy. Finally, the application and influencing factors of EC in diverse diseases, encompassing neonatal conditions, are presented. Findings in Brief: Due to the risks associated with invasive cardiac output monitoring, noninvasive or minimally invasive alternative techniques are needed for hemodynamic monitoring. In recent years, noninvasive and minimally invasive techniques, such as ultrasound cardiac output monitor (USCOM) and impedance cardiography have been utilized. EC, as an impedance-based monitoring, facilitates noninvasive and real-time assessment of hemodynamic parameters. The integration of EC enables real-time and continuous monitoring of dynamic changes in cardiac and vascular functions in patients, thereby assisting in clinical evaluation and guiding the clinical decision-making. Conclusion: EC is a noninvasive, highly sensitive, and accurate monitoring technique that holds important guiding significance in clinical practice.

The continuous gas displacement in unconsolidated sandstone gas reservoirs will necessarily result in the pore structure and rock permeability variations, which cannot be neglected in the gas development process. However, the variations have not been comprehensively addressed yet, especially for the rock structure in pore scale. This work presented the quantitative results of pore structure in microscale and permeability variations during gas displacement in unconsolidated sandstone reservoirs through computed tomography (CT) reconstruction analysis. The results indicated that a more than 3% increase in porosity after gas displacement resulted from the enlargement of the pore and throat with a diameter of more than 20 μm and 3 μm, respectively, owing to the release and migration of clay and fine particles, in spite of the distribution frequency decline of both pore and throat with a small diameter. The pore connectivity would be enhanced by the increase of the connected pores as well as the enlargement of the pore and throat sizes. However, the pore-throat coordination number could only change with slight improvement. In terms of permeability and relative permeability changes with pore structure, the improvement of permeability after gas displacement was higher than that of porosity, and the continuous gas displacement would broaden gas-water flow region and lower irreducible water saturation and residual gas saturation, and then, the equal phase relative permeability point would shift to the right. These investigations will contribute to more accurate reserve evaluation and productivity prediction.

Empathy involves both empathic ability and empathic motivation. An important topic has been how to measure empathic ability and motivation simultaneously in both clinical and non-clinical samples and across different cultures. The Empathy Components Questionnaire (ECQ) is a self-report questionnaire that measures empathic ability and motivation in a questionnaire. The current study aimed to validate the Mandarin Chinese version of the ECQ (ECQ-Chinese) in three Chinese samples. In study 1, a total of 538 Chinese participants (Sample 1) completed the ECQ-Chinese via an online survey, and existing measures of empathy and related constructs which were used for criterion validity. In study 2, a total of 104 participants (Sample 2) were recruited again from sample 1 and completed the ECQ-Chinese three weeks later to investigate test-retest reliability. In study 3, a further 324 participants (Sample 3) completed the ECQ-Chinese for confirmatory factor analysis. The results showed that the ECQ-Chinese has a good internal consistency reliability, split-half reliability, and criterion validity (Study 1), and a good test-retest reliability (Study 2). Further, Study 3 found that a 22-item ECQ-Chinese consisting of five subscales had a good construct validity, convergence validity and discriminate validity, demonstrating it to be a suitable tool for the measurement of empathic ability and motivation in Chinese samples and to carry out cross-cultural studies of empathy and its components.

Background: Anatomy is a required course for all medicine-related industries. In recent decades, the teaching quality and effect of anatomy have been compromised by factors including a decrease in human body specimens, dampened enthusiasm for the discipline, reduced teaching hours of anatomy, scale expansion of medical education, and obstacles in performing field autopsies and observations. Methods: Based on China's digitalized visible human research achievements, this article extracts the boundary information of anatomic structures from tomographic images, constructs threedimensional (3D) digital anatomical models with authentic texture information, and develops an anatomy assistive teaching system for teachers and students based on the knowledge points of anatomy, to meet the anatomy teaching requirements of different majors at various levels. Results: This scientific, complete, and holistic system has produced over 6000 3D digital anatomical models, 5000 anatomy knowledge points, 50 anatomical operation videos, and 150 micro demonstration classes, with teaching contents for different majors and levels, such as systematic anatomy, topographic anatomy, sectional anatomy, anatomy of motion, and virtual anatomical operation table. Ranging from network terminals, desktops, touchscreen 3D displays, desktops, and projection 3D volumetric displays to augmented reality, its diversified interactive forms meet the requirements for a learning environment in different settings. Conclusions: With multiple teaching and learning links covered, such as teaching environment, teaching resources, instructional slides, autonomous learning, and learning effect evaluation, this novel teaching system serves as a vital component and a necessary resource in anatomy teaching and functions as an important supplement to traditional anatomy teaching. Applied and promoted in most medical colleges and schools in China, this system has been recognized and approved by anatomy teachers and students, and plays a positive role in guaranteeing the effect and quality of anatomy teaching.

With the deep application of artificial intelligence and big data in education, adaptive learning has become a new research hotspot in online education. Based on the systematic review of the connotation and research progress of adaptive learning, a new definition of adaptive learning is given. By literature analysis, this paper points out the challenges faced by adaptive learning research, such as the lack of cognition of brain and technology, the bottleneck of the model of emotion domain, the separation of education and technology, the security of data management and the risk of privacy leakage. These challenges can be summarized into two aspects: one is mechanical issues, the other is safety issues. Different from traditional research perspectives, the paper opens a new research window, and puts forward countermeasures from the perspectives of cognitive principles, zone of proximal development theory in technology, breakthrough in the emotional domain model, learning data management and privacy security. In view of the centralization of learning data management nowadays, the concept of code chain and the decentralized management mode based on code chain are proposed. Different from the traditional adaptive learning recommendation technology, a new adaptive learning pulling model is proposed.

Abstract NOXA, a BH3-only proapoptotic protein involved in regulating cell death decisions, is highly expressed but short-lived in colorectal cancer (CRC). Neddylated cullin-5 (CUL5)-mediated ubiquitination and degradation of NOXA is crucial to prevent its overaccumulation and maintain an appropriate action time. However, how this process is manipulated by CRC cells commonly exposed to oxidative stress remain unknown. The peroxiredoxin PRDX1, a conceivable antioxidant overexpressed in CRC tissues, has been shown to inhibit apoptosis and TRAF6 ubiquitin-ligase activity. In this study, we found that PRDX1 inhibits CRC cell apoptosis by downregulating NOXA. Mechanistically, PRDX1 promotes NOXA ubiquitination and degradation, which completely depend on CUL5 neddylation. Further studies have demonstrated that PRDX1 oligomers bind with both the Nedd8-conjugating enzyme UBE2F and CUL5 and that this tricomplex is critical for CUL5 neddylation, since silencing PRDX1 or inhibiting PRDX1 oligomerization greatly dampens CUL5 neddylation and NOXA degradation. An increase in reactive oxygen species (ROS) is not only a hallmark of cancer cells but also the leading driving force for PRDX1 oligomerization. As shown in our study, although ROS play a role in upregulating NOXA mRNA transcription, ROS scavenging in CRC cells by N-acetyl-L-cysteine (NAC) can significantly reduce CUL5 neddylation and extend the NOXA protein half-life. Therefore, in CRC, PRDX1 plays a key role in maintaining intracellular homeostasis under conditions of high metabolic activity by reinforcing UBE2F-CUL5-mediated degradation of NOXA, which is also evidenced in the resistance of CRC cells to etoposide treatment. Based on these findings, targeting PRDX1 could be an effective strategy to overcome the resistance of CRC to DNA damage-inducing chemotherapeutics.

BackgroundIn this study, we enrolled 862 patients with Crohn’s disease (CD) in China to investigate the correlation between serum vitamin D (SVD) and serum lipids, inflammatory biomarkers, and important clinical parameters.Materials and Methods25(OH)D was measured by LS/MS/MS. Correlation analysis, chi-square tests, and logistic regression analysis were performed to determine the correlations between vitamin D and potential risk factors when vitamin D levels were lower than 10 ng/mL or 20 ng/mL.ResultsThe incidence of severe vitamin D deficiency (SVD < 10 ng/mL) in patients with CD was significantly higher than that in healthy controls (28.9 vs. 9.5%). Multinomial logistic regression analysis showed that penetrating disease [odds ratio (OR) = 2.18], low levels of high-density lipoprotein cholesterol (HDL) (OR = 1.91), high erythrocyte sedimentation rate (OR = 1.73), and platelet count (PLT) (OR = 2.71) were regarded as predictors of severe vitamin D deficiency, while only PLT (OR = 1.90) and HDL (OR = 1.76) were considered as predictors of mild vitamin D deficiency (SVD 10–20 ng/mL).ConclusionOur results confirm a higher incidence of severe vitamin D deficiency in patients with CD in China and show that vitamin D deficiency could result from the combined effects of penetrating disease, inflammation, and low levels of HDL.

Abstract Background Stroke is the leading cause of long-term motor disability and cognitive impairment. Recently, neurogenesis has become an attractive strategy for the chronic recovery of stroke. It is important to understand the molecular mechanism that promotes neural stem cell (NSC) neurogenesis for future NSC-based therapies. Our previous study showed that Momordica charantia polysaccharides (MCPs) exerted neuroprotective effects on stroke via their anti-oxidant and anti-inflammation activities. However, it remains unknown whether MCPs promote NSC neurogenesis after cerebral ischemic/reperfusion injury (IRI). Methods We investigated MCPs’ function in differentiation of neural stem cells (NSCs) in vivo and in vitro experiments. Based on a middle cerebral artery occlusion (MCAO) rat model, the effect of MCPs on neuronal differentiation after MCAO was analyzed. Primary NSCs and neural stem cell line C17.2 were cultured and subjected to glutamate stimulation to establish the cell model of IRI. We evaluated the effect of MCPs on NSC differentiation in IRI cell model by Western blot and immunofluorescence staining. The SIRT1 activity of NSCs post glutamate stimulation was also evaluated by CELL SIRT1 COLORIMETRY ASSAY KIT. In addition, molecular mechanism was clarified by employing the activator and inhibitor of SIRT1. Results MCPs had no effects on the differentiation of neural stem cells under physiological conditions while shifted NSC differentiation potential from the gliogenic to neurogenic lineage under pathological conditions. Activation of SIRT1 with MCPs was responsible for the neuronal differentiation of C17.2-NSCs. The neuronal differentiation effect of MCPs was attributed to upregulation SIRT1-mediated deacetylation of β-catenin. MCP-induced deacetylation via SIRT1 promoted nuclear accumulation of β-catenin in NSCs. Conclusion Our findings indicate that the deacetylation of β-catenin by SIRT1 represents a critical mechanism of action of MCPs in promoting NSC neuronal differentiation. It provides an improved understanding of molecular mechanism underlying neuroprotective effects of MCPs in IRI, indicating its potential role on treating ischemic stroke especially chronic recovery.

Abstract Background Interleukin-17A (IL-17) is an evolutionary conserved cytokine and best known for its role in boosting immune response. However, recent clinical researches showed that abundant IL-17 in tumor microenvironment was often associated with poor prognosis and reduced cytotoxic T cell infiltration. These contradictory phenomena suggest that IL-17 may have unique target cells in tumor microenvironment which switch its biological consequences from pro-inflammatory to anti-inflammatory. Mesenchymal stem/stromal cells (MSCs) are a major component of the tumor microenvironment. Upon cytokine stimulation, MSCs can express a plenary of inhibitory molecules, playing a critical role in tumor development and progression. Therefore, we aim to investigate the role of IL-17 in MSC-mediated immunosuppression. Results We found IFNγ and TNFα, two major cytokines in tumor microenvironment, could induce programmed death-ligand 1 (PD-L1) expression in MSCs. Interestingly, IL-17 has a synergistic effect with IFNγ and TNFα in elevating PD-L1 expression in MSCs. The presence of IL-17 empowered MSCs with strong immunosuppression abilities and enabled MSCs to promote tumor progression in a PD-L1 dependent manner. The upregulated PD-L1 expression in MSCs was due to the accumulation of nitric oxide (NO). On one hand, NO donor could mimic the effects of IL-17 on MSCs; on the other hand, IL-17 failed to enhance PD-L1 expression in inducible nitric oxide synthase (iNOS) deficient MSCs or with iNOS inhibitor presence. Conclusions Our study demonstrates that IL-17 can significantly increase the expression of PD-L1 by MSCs through iNOS induction. This IL-17-MSCs-PD-L1 axis shapes the immunosuppressive tumor microenvironment and facilitates tumor progression.

Interleaved practice (i.e., exemplars from different categories are intermixed within blocks) has been shown to enhance induction performance compared to blocked practice (i.e., exemplars from the same category are presented sequentially). The main aim of the present study was to examine explanations of why interleaved practice produces this benefit in category induction (known as the interleaving effect). We also evaluated two hypotheses, the attention attenuation hypothesis and the discriminative-contrast hypothesis, by collecting data on participants’ fixation on exemplars, provided by eye-tracking data, and manipulating the degree of discriminative-contrast. In Experiments 1 and 2, participants were instructed to learn the style of 12 new artists in blocked and interleaved practice in fixed-paced and self-paced learning conditions, respectively. We examined fixation durations for six positions (temporal sequence of exemplars presented in each block) using eye-tracking. The results of the two experiments, based on eye-tracking data, suggested that attention attenuation may not be the primary mechanism underlying the interleaving effect in category induction. In Experiment 3, we manipulated the degree of discriminative-contrast to examine the impact on the interleaving effect in category induction. The results showed that the main effect of the degree of discriminative-contrast was significant, and performance in the high-contrast condition was significantly better than those in the medium-contrast and low-contrast conditions. Thus, the current results support the discriminative-contrast hypothesis rather than the attention attenuation hypothesis.

Abstract Background Nicotinamide N-methyltransferase (NNMT) is overexpressed in various human tumors and involved in the development and progression of several carcinomas. In breast cancer, NNMT was found to be overexpressed in several cell lines. However, the clinical relevance of NNMT in breast cancer is not yet clear. Methods NNMT expression in breast carcinoma was examined by immunohistochemistry, and then, its relationship with patient clinicopathological characteristics was analyzed. The effects of NNMT on chemoresistance in breast cancer cells were assessed by cell viability, colony formation, and apoptosis assay. The NNMT, SIRT1, p53, and acetyl-p53 proteins, which are involved in NNMT-related chemoresistance, were examined by Western blotting. The SIRT1 mRNA was examined by real-time PCR, and its activity was measured by using the SIRT1 deacetylase fluorometric reagent kit. Results NNMT expression was significantly higher (53.9%) in breast carcinoma than in paracancerous tissues (10.0%) and breast hyperplasia (13.3%). A high level of NNMT expression correlated with poor survival and chemotherapy response in breast cancer patients who received chemotherapy. Ectopic overexpression of NNMT significantly inhibited the apoptotic cell death and suppression of colony formation induced by adriamycin and paclitaxel. Mechanistic studies revealed that NNMT overexpression increased SIRT1 expression and promoted its activity. Either inhibition of SIRT1 by EX527 or knockdown of SIRT1 by siRNA could reverse NNMT-mediated resistance to adriamycin and paclitaxel, which suggests that SIRT1 plays a critical role in NNMT-related chemoresistance in breast cancer. Conclusions The results of this study demonstrate a novel correlation between the NNMT expression level and patient survival, suggesting that NNMT has the potential to become a new prognostic biomarker to predict the treatment outcomes of the clinical chemotherapy in breast cancer. Moreover, targeting NNMT or downstream SIRT1 may represent a new therapeutic approach to improve the efficacy of breast cancer chemotherapy.

With the rapid growth of the Internet, the scale of graphs has increased dramatically, which poses special challenges in representing both web graphs and social network graphs. In the adjacency matrix of web and social network graphs, only a very small proportion of the elements is “1” s. Furthermore, we find that using the aggregation of scattered 1 s to form a high density of adjacency matrices is beneficial to the compression of storage space. Based on these findings, we propose the DGC-K2-tree compression approach based on K2-tree, which can greatly increase the density of 1 s among the existing algorithms and adequately compress the blank area in the adjacency matrix. Then, we design a query algorithm for this mechanism to support the operation on the graph. The experimental results show that compared with the state-of-the-art algorithms, including the K2-tree based on a diagonal clustering mechanism (K2-BDC), the K2-tree, Re-Pair, and LZ78, our approach achieves better compression ratio and shorter time consumption. In terms of storage efficiency, our approach reduces the space by an average of 34.07% compared to the best performing algorithm K2-BDC. In terms of query efficiency, our approach reduces the time by an average of 80.63% compared to the best performing algorithm LZ78.

Class imbalance is a serious problem that plagues the semantic segmentation task in urban remote sensing images. Since large object classes dominate the segmentation task, small object classes are usually suppressed, so the solutions based on optimizing the overall accuracy are often unsatisfactory. In the light of the class imbalance of the semantic segmentation in urban remote sensing images, we developed the concept of the Down-sampling Block (DownBlock) for obtaining context information and the Up-sampling Block (UpBlock) for restoring the original resolution. We proposed an end-to-end deep convolutional neural network (DenseU-Net) architecture for pixel-wise urban remote sensing image segmentation. The main idea of the DenseU-Net is to connect convolutional neural network features through cascade operations and use its symmetrical structure to fuse the detail features in shallow layers and the abstract semantic features in deep layers. A focal loss function weighted by the median frequency balancing (MFB_Focalloss) is proposed; the accuracy of the small object classes and the overall accuracy are improved effectively with our approach. Our experiments were based on the 2016 ISPRS Vaihingen 2D semantic labeling dataset and demonstrated the following outcomes. In the case where boundary pixels were considered (GT), MFB_Focalloss achieved a good overall segmentation performance using the same U-Net model, and the F1-score of the small object class “car” was improved by 9.28% compared with the cross-entropy loss function. Using the same MFB_Focalloss loss function, the overall accuracy of the DenseU-Net was better than that of U-Net, where the F1-score of the “car” class was 6.71% higher. Finally, without any post-processing, the DenseU-Net+MFB_Focalloss achieved the overall accuracy of 85.63%, and the F1-score of the “car” class was 83.23%, which is superior to HSN+OI+WBP both numerically and visually.

To date, the protracted pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had widespread ramifications for the economy, politics, public health, etc. Based on the current situation, definitively stopping the spread of the virus is infeasible in many countries. This does not mean that populations should ignore the pandemic; instead, normal life needs to be balanced with disease prevention and control. This paper highlights the use of Internet of Things (IoT) for the prevention and control of coronavirus disease (COVID-19) in enclosed spaces. The proposed booking algorithm is able to control the gathering of crowds in specific regions. K-nearest neighbors (KNN) is utilized for the implementation of a navigation system with a congestion control strategy and global path planning capabilities. Furthermore, a risk assessment model is designed based on a “Sliding Window-Timer” algorithm, providing an infection risk assessment for individuals in potential contact with patients.

We study the planar symmetric central configurations of the 1 + 4-body problem where the symmetry axis does not contain any infinitesimal masses. Under certain assumptions, we find analytically some central configurations for suitable positive masses and also get some numerical results of symmetric central configurations where infinitesimal masses are not necessarily equal.

A Correction to this paper has been published: https://doi.org/10.1038/s41419-021-03656-1

Abstract In this note, we try to generalize the classical Cauchy-Lipschitz-Picard theorem on the global existence and uniqueness for the Cauchy initial value problem of the ordinary differential equation with global Lipschitz condition, and we try to weaken the global Lipschitz condition. We can also get the global existence and uniqueness.

Osteoblasts and adipocytes are derived from a common precursor, mesenchymal stem cells (MSCs). Alterations in the normal fate of differentiating MSCs are involved in the development of obesity and osteoporosis. Here, we report that viable motheaten (mev) mice, which are deficient in the SH2-domain-containing phosphatase-1 (SHP1), develop osteoporosis spontaneously. Consistently, MSCs from mev/mev mice exhibit significantly reduced osteogenic potential and greatly increased adipogenic potential. When MSCs were transplanted into nude mice, SHP1-deficient MSCs resulted in diminished bone formation compared with wild-type MSCs. SHP1 was found to bind to GSK3β and suppress its kinase activity by dephosphorylating pY216, thus resulting in β-catenin stabilization. Mice, in which SHP1 was deleted in MSCs using SHP1fl/flDermo1-cre, displayed significantly decreased bone mass and increased adipose tissue. Taken together, these results suggest a possible role for SHP1 in controlling tissue homeostasis through modulation of MSC differentiation via Wnt signaling regulation.

Postpubescent females may have negative mood or premenstrual syndrome during the menstrual cycle; with the emotional and physical symptoms interfering with their quality of life. Little is known about the relationship of dietary behaviors and dietary antioxidant intake with negative mood or premenstrual syndrome in university students in China; so we explored the relationship between negative mood and dietary behavior in female university students during the three menstrual cycle phases. Random sampling was used to enroll 88 individuals from a university in Guangzhou; China in the study. Data were collected using self-administered questionnaires. Descriptive statistics and multiple logistic regression analyses were performed. During the menstrual phase, tea, black coffee and carbonated beverage intake was higher in the group with a high negative affect scale score than in the low score group (p < 0.05). Likewise; during the premenstrual phase, fresh fruit (banana and red Chinese dates) intake was higher in the group with a high negative affect scale score than in the low-score group (p < 0.05). The logistic regression analysis results showed that negative mood was positively associated with tea, coffee, and carbonated beverage intake during the menstrual phase (β = 0.21, p = 0.0453, odds ratio = 1.23), and negative mood was positively associated with banana and red Chinese dates intake during the premenstrual phase (β = 0.59, p = 0.0172, odds ratio = 1.81). Our results suggest that negative mood may be associated with diet and specific food in university postpubescent females.

Fluency influences grammaticality judgments of visually presented strings in artificial grammar learning (AGL). Of many potential sources that engender fluency, symmetry is considered to be an important factor. However, symmetry may function differently for visual and auditory stimuli, which present computationally different problems. Thus, the current study aimed to examine whether objectively manipulating fluency by speeding up perception (i.e., manipulating the inter-stimulus interval, ISI, between each syllable of a string) influenced judgments of tonal strings; and thus how symmetry-based fluency might influence judgments. In Experiment 1, with only a test phase, participants were required to give their preference ratings of tonal strings as a measurement of fluency. In experiment 2, participants were instructed to make grammaticality judgments after being incidentally trained on tonal symmetry. Results of Experiment 1 showed that tonal strings with shorter ISI were liked more than those with longer ISI while such difference was not found between symmetric and asymmetric strings without training. Additionally, Experiment 2 found both main effects of symmetry and ISI as well as an interaction. In particular, only asymmetric strings were more likely to be judged as grammatical when they were presented at a shorter ISI. Taken together, participants were sensitive to the fluency induced by the manipulation of ISI and sensitive to symmetry only after training. In sum, we conclude that objective speed influenced grammaticality judgments, implicit learning of tonal symmetry resulted in enhanced fluency, and that fluency may serve as a basis for grammaticality judgments.

Data insufficiency has become the primary factor affecting research on income disparity in China. To resolve this issue, this paper explores Chinese income distribution and income inequality using distribution functions. First, it examines 20 sets of grouped data on family income between 2005 and 2012 by the China Yearbook of Household Surveys, 2013, and compares the fitting effects of eight distribution functions. The results show that the generalized beta distribution of the second kind has a high fitting to the income distribution of urban and rural residents in China. Next, these results are used to calculate the Chinese Gini ratio, which is then compared with the findings of relevant studies. Finally, this paper discusses the influence of urbanization on income inequality in China and suggests that accelerating urbanization can play an important role in narrowing the income gap of Chinese residents.

Although a growing number of empirical studies have revealed that activating mate-related motives might exert a specific set of consequences for human cognition and behaviors, such as attention and memory, little is known about whether mate-related motives affect self-regulated learning. The present study examined the effects of mate-related motives (mate-search and mate-guarding) on study-time allocation to faces varying in attractiveness. In two experiments, participants in mate-related priming conditions (Experiment 1: mate-search; Experiment 2: mate-guarding) or control conditions studied 20 female faces (10 highly attractive, 10 less attractive) during a self-paced study task, and then were given a yes/no face recognition task. The finding of Experiment 1 showed that activating a mate-search motive led the male participants to allocate more time to highly attractive female faces (i.e., perceived potential mates) than to less attractive ones. In Experiment 2, female participants in the mate-guarding priming condition spent more time studying highly attractive female faces (i.e., perceived potential rivals) than less attractive ones, compared to participants in the control condition. These findings illustrate the highly specific consequences of mate-related motives on study-time allocation, and highlight the value of exploring human cognition and motivation within evolutionary and self-regulated learning frameworks.

Berberine, one of the major constituents of Chinese herb Rhizoma coptidis, has been demonstrated to lower blood glucose, blood lipid, and body weight in patients with type 2 diabetes mellitus. The anti-obesity effect of berberine has been attributed to its anti-adipogenic activity. However, the underlying molecular mechanism remains largely unknown. In the present study, we found that berberine significantly suppressed the expressions of CCAAT/enhancer-binding protein (C/EBP)α, peroxisome proliferators-activated receptor γ2 (PPARγ2), and other adipogenic genes in the process of adipogenesis. Berberine decreased cAMP-response element-binding protein (CREB) phosphorylation and C/EBPβ expression at the early stage of 3T3-L1 preadipocyte differentiation. In addition, CREB phosphorylation and C/EBPβ expression induced by 3-isobutyl-1-methylxanthine (IBMX) and forskolin were also attenuated by berberine. The binding activities of cAMP responsive element (CRE) stimulated by IBMX and forskolin were inhibited by berberine. The binding of phosphorylated CREB to the promoter of C/EBPβ was abrogated by berberine after the induction of preadipocyte differentiation. These results suggest that berberine blocks adipogenesis mainly via suppressing CREB activity, which leads to a decrease in C/EBPβ-triggered transcriptional cascades.

This work reports the chemical and light extinction characteristics of the atmospheric particles collected from January to November 2014 in suburban Nanjing. Size-segregated measurement results showed that more than 80% of the major aerosol components were concentrated in PM2.5. The concentration of PM2.5 was highest in winter and lowest in autumn. Specifically, K+ concentration peaked in late spring indicating heavy influences from straw burning, while sulfate concentration was highest in summer and its daytime concentration was also higher than its nighttime concentration, both reflecting a significant role of photochemical production. Nevertheless, except for sulfate, all other components had higher concentrations during nighttime, signifying the role of unfavorable meteorological conditions in exacerbating the air pollution. The IMPROVE formula was employed, which can reconstruct the PM2.5 mass and light extinction well. The light extinction was mainly contributed by (NH4)2SO4 and NH4NO3 (together 58.3%). Mass concentrations of all PM2.5 components increased significantly with the increase of pollution levels, but nitrate increased most rapidly; correspondingly, the contribution of nitrate to light extinction also increased quickly when pollution became heavy. Such results were different from those observed in Beijing-Tianjin-Hebei where sulfate increased most quickly. Our results thus highlight that reduction of vehicular NO2 is likely a priority for air quality improvement in Nanjing. Back trajectory analysis showed the dominance of the local air mass and the one from Huanghai, yet the air mass originated from Bohai, and passed though Shandong and north of Jiangsu province could deliver highly-polluted air to Nanjing, as well.

Many studies show that the relationship among income inequality, poverty, and income mobility needs to be further discussed. Meanwhile, some researches on Distribution Function offer new perspective and methods to analyze this issue. First, this paper expresses the relationship among the Gini coefficient, poverty ratio, and income mobility of 5 common Distribution Functions through math deduction; this finding cannot be found in relevant literatures. Furthermore, an empirical research result proves that the income distribution of urban residents in the period from 2005 to 2010 fits Log-Logistic Distribution. On the basis of the above analysis and empirical data, the paper explores the relations of income inequality, poverty, and income mobility of urban residents and draws some useful conclusions.

We use Jacobi's necessary condition for the variational minimizer to study the periodic solution for spatial restricted N+1-body problems with a zero mass on the vertical axis of the plane for N equal masses. We prove that the minimizer of the Lagrangian action on the anti-T/2 or odd symmetric loop space must be a nonconstant periodic solution for any 2≤N≤472; hence the zero mass must oscillate, so that it cannot be always in the same plane with the other bodies. This result contradicts with our intuition that the small mass should always be at the origin.

BACKGROUND: To date, the available non-invasive remedies for primary aldosteronism are not satisfactory in clinical practice. The phosphoinositide 3-kinase (PI3Ks)/protein kinase B (PKB or AKT)/mammalian target of rapamycin (mTOR) signaling pathway is essential for tumorigenesis and metastasis in many types of human tumors, including renal cancer, adrenal carcinoma and pheochromocytoma. The possibility that this pathway is also necessary for the pathogenesis of primary aldosteronism has not yet been explored. To answer this question, we investigated the activity of the PI3K/AKT/mTOR signaling pathway in normal adrenal glands (NAGs), primary aldosteronism (PA) patients and NCI-H295R cells. METHODOLOGY/PRINCIPAL FINDINGS: Between January 2005 and December 2011, we retrospectively reviewed the records of 45 patients with PA. We compared clinical characteristics (age, gender and biochemical data) and the expression of phospho-AKT (p-AKT), phospho-mTOR (p-mTOR), phospho-S6 (p-S6) and vascular endothelial growth factor (VEGF) by immunohistochemical staining and western blotting, analyzing 30 aldosterone-producing adenomas (APAs), 15 idiopathic hyperaldosteronism (IHA) tissues and 12 NAGs following nephrectomy for renal tumors (control group). Compared with the control group, most of the PA patients presented with polydipsia, polyuria, resistant hypertension, profound hypokalemia, hyperaldosteronemia and decreased plasma renin activity. Compared with normal zona glomerulosa, the levels of p-AKT, p-mTOR, p-S6 and VEGF were significantly upregulated in APA and IHA. No significant differences were found between APA and IHA in the expression of these proteins. Additionally, positive correlations existed between the plasma aldosterone levels and the expression of p-AKT and p-mTOR. In vitro studies showed that mTOR inhibitor rapamycin could inhibit cell proliferation in NCI-H295R cells in a dose- and time-dependent manner. Furthermore, this inhibitor also decreased aldosterone secretion. CONCLUSIONS: Our data suggest that the PI3K/AKT/mTOR signaling pathway, which was overactivated in APA and IHA compared with normal zona glomerulosa, may mediate aldosterone hypersecretion and participate in the development of PA.

People can implicitly learn a connection between linguistic forms and meanings, for example between specific determiners (e.g. this, that...) and the type of nouns to which they apply. Li et al (2013) recently found that transfer of form-meaning connections from a concrete domain (height) to an abstract domain (power) was achieved in a metaphor-consistent way without awareness, showing that unconscious knowledge can be abstract and flexibly deployed. The current study aims to determine whether people transfer knowledge of form-meaning connections not only from a concrete domain to an abstract one, but also vice versa, consistent with metaphor representation being bi-directional. With a similar paradigm as used by Li et al, participants learnt form- meaning connections of different domains (concrete vs. abstract) and then were tested on two kinds of generalizations (same and different domain generalization). As predicted, transfer of form-meaning connections occurred bidirectionally when structural knowledge was unconscious. Moreover, the present study also revealed that more transfer occurred between metaphorically related domains when judgment knowledge was conscious (intuition) rather than unconscious (guess). Conscious and unconscious judgment knowledge may have different functional properties.

Sensors and sensor technology have been applied in various fields such as the medical and agricultural industries. However, in the field of education, there is a scarcity of research on the use of sensor technology to analyze the teacher--student interaction process, a key factor affecting classroom efficiency. In particular, research focusing on IT classes is even scarcer. In this study, we investigate the overall status and characteristics of teacher--student interaction in the IT class using ministerial-level excellence courses. By a qualitative method, we adopt the Information-technology-based Interaction Analysis System (ITIAS) to encode the interaction behavior and use lag sequential analysis (LSA) to understand the conversion modes of interaction behavior. In addition, we analyze the participation elements, expressions, and transitions of interaction behavior. We found a trend of three-subject interaction among teachers, students, and technology. However, there exist some problems, such as technology being in the subordinate position of interaction, the lack of deep interaction between teachers and students with technology, and teachers dominating the conversion of interaction. Accordingly, we propose countermeasures for teachers and provide new ideas for the application of sensors on the interaction in the learning environment as well. [ABSTRACT FROM AUTHOR]

Abstract Background LncRNAs play essential roles in multiple tumors. However, research on genome-wide lncRNA alterations and their functions in cervical cancer (CC) is limited. This study aims to explore key lncRNAs in CC progression and uncover the molecular mechanisms involved in the development of CC. Methods In this study, we analyzed 30 tissues from CC, cervical intraepithelial neoplasia (CIN), and normal (NOR) using transcriptome sequencing and weighted gene co-expression network analysis to establish gene modules related to the NOR-CIN-CC transition. Machine learning diagnostic models were employed to investigate the role of lncRNAs in this transition. Molecular biological experiments were conducted to elucidate the potential mechanisms of CARMN in CC, with a particular focus on its transcriptional and post-transcriptional regulation of abnormal expression in CC. Results CARMN was identified as a hub gene in two modules significantly associated with the NOR-CIN-CC transition. Analysis using ten machine learning models confirmed its critical role in this progression. The results of RNA-seq, qPCR and RNAScope performed in another cohort of 83 cervical tissues all showed that CARMN was significantly downregulated in CC. CARMN significantly enhanced the interaction between Keap1 and Nrf2, leading to increased ROS levels. The elevated ROS levels suppressed the Akt/mTOR signaling pathway, leading to autophagy arrest via autophagic flux blockade. Additionally, CARMN interacted with TFAP2α to repress MAPK13 transcription, further inhibiting the MAPK cascade. A promoter SNP (rs12517403) was found to increase CC risk (OR = 1.34, 95% CI = 1.11–1.61) and reduce CARMN expression by decreasing SP1 binding. Furthermore, the RNA binding proteins that could modulate CARMN RNA stability were also determined using RNA-pulldown assay. The results demonstrated that YBX1, a component of the coding region instability determinant (CRD)-mediated mRNA stabilization complex, promoted CARMN RNA stability. DHX9, another component of complex, acted as a scaffold to bridge YBX1 and CARMN. Conclusions CARMN exerts an anti-cancer effect in CC progression by inhibiting the Akt-mTOR and MAPK signaling pathways. rs12517403 and the YBX1/DHX9 complex are key mechanisms influencing its transcription and stability in CC cells. CARMN represents a promising biomarker for CC diagnosis and therapeutic target.

Abstract Brain damage caused by acute hypoxia is associated with the physiological activities of mitochondria. Although mitochondria being dynamically regulated, our comprehensive understanding of the response of specific brain cell types to acute hypoxia remains ambiguous. Tumor necrosis factor receptor-associated protein 1 (TRAP1), a mitochondrial-based molecular chaperone, plays a role in controlling mitochondrial movements. Herein, we demonstrated that acute hypoxia significantly alters mitochondria morphology and functionality in both in vivo and in vitro brain injury experiments. Summary-data-based Mendelian Randomization (SMR) analyses revealed possible causative links between mitochondria-related genes and hypoxia injury. Advancing the protein-protein interaction network and molecular docking further elucidated the associations between TRAP1 and mitochondrial dynamics. Furthermore, it was shown that TRAP1 knockdown levels variably affected the expression of key mitochondrial dynamics proteins (DRP1, FIS1, and MFN1/2) in primary hippocampal neurons, astrocytes, and BV-2 cell, leading to changes in mitochondrial structure and function. Understanding the function of TRAP1 in altering mitochondrial physiological activity during hypoxia-induced acute brain injury could help serve as a potential therapeutic target to mitigate neurological damage.

Abstract The Ice, Cloud, and Land Elevation Satellite-2 (ICESat-2) has great potential for development due to its advantages of the use of multiple beams, low energy consumption, high repetition frequency, and high measurement sensitivity. However, the weak photon signal emitted by the photon counting lidar is susceptible to the background noise caused by the sun and the atmosphere, which can seriously affect the processing and application of laser data. This paper proposes an improved DBSCAN clustering algorithm for denoising single photon laser point clouds in mountainous areas. Firstly, a grouping method based on elevation and distance statistics is proposed to reduce the influence of terrain undulations on denoising accuracy. Finally, an automatic radius search method is put forward to determine clustering radius of each group, automatically find the optimal radius, and improve the existing DBSCAN clustering method. The method proposed in this paper is compared with the classical DBSCAN algorithm. The results show that the proposed algorithm significantly improves denoising accuracy in mountainous areas and effectively filters out most background noise. Graphical Abstract