GP-Recon: Online Monocular Neural 3D Reconstruction with Geometric Prior.

High-fidelity online 3D scene reconstruction from monocular videos continues to be challenging, especially for coherent and fine-grained geometry reconstruction. The previous learning-based online 3D reconstruction approaches with neural implicit representations have shown a promising ability for coherent scene reconstruction, but often fail to consistently reconstruct fine-grained geometric details during online reconstruction. This paper presents a new on-the-fly monocular 3D reconstruction approach, named GP-Recon, to perform high-fidelity online neural 3D reconstruction with fine-grained geometric details. We incorporate geometric prior (GP) into a scene's neural geometry learning to better capture its geometric details and, more importantly, propose an online volume rendering optimization to reconstruct and maintain geometric details during the online reconstruction task. The extensive comparisons with state-of-the-art approaches show that our GP-Recon consistently generates more accurate and complete reconstruction results with much better fine-grained details, both quantitatively and qualitatively.

Ac2-26 activated the AKT1/GSK3ß pathway to reduce cerebral neurons pyroptosis and improve cerebral function in rats after cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass (CPB) results in brain injury, which is primarily caused by inflammation. Ac2-26 protects against ischemic or hemorrhage brain injury. The present study was to explore the effect and mechanism of Ac2-26 on brain injury in CPB rats. METHODS: Forty-eight rats were randomized into sham, CPB, Ac, Ac/AKT1, Ac/GSK3ßi and Ac/AKT1/GSK3ßa groups. Rats in sham group only received anesthesia and in the other groups received standard CPB surgery. Rats in the sham and CPB groups received saline, and rats in the Ac, Ac/AKT1, Ac/GSK3ßi and Ac/AKT1/GSK3ßa groups received Ac2-26 immediately after CPB. Rats in the Ac/AKT1, Ac/GSK3ßi and Ac/AKT1/GSK3ßa groups were injected with shRNA, inhibitor and agonist of GSK3ß respectively. The neurological function score, brain edema and histological score were evaluated. The neuronal survival and hippocampal pyroptosis were assessed. The cytokines, activity of NF-κB, S100 calcium-binding protein ß(S100ß) and neuron-specific enolase (NSE), and oxidative were tested. The NLRP3, cleaved-caspase-1 and cleaved-gadermin D (GSDMD) in the brain were also detected. RESULTS: Compared to the sham group, all indicators were aggravated in rats that underwent CPB. Compared to the CPB group, Ac2-26 significantly improved neurological scores and brain edema and ameliorated pathological injury. Ac2-26 reduced the local and systemic inflammation, oxidative stress response and promoted neuronal survival. Ac2-26 reduced hippocampal pyroptosis and decreased pyroptotic proteins in brain tissue. The protection of Ac2-26 was notably lessened by shRNA and inhibitor of GSK3ß. The agonist of GSK3ß recovered the protection of Ac2-26 in presence of shRNA. CONCLUSIONS: Ac2-26 significantly improved neurological function, reduced brain injury via regulating inflammation, oxidative stress response and pyroptosis after CPB. The protective effect of Ac2-26 primarily depended on AKT1/ GSK3ß pathway.

[Health Risk Assessment of Heavy Metals in Soils of a City in Guangdong Province Based on Source Oriented and Monte Carlo Models].

Taking a city in Guangdong Province as the research area, the concentration and spatial distribution characteristics of heavy metals in the surface soil were studied to clarify the situation of soil heavy metal pollution and priority control factors, providing basic data for the prevention and control of soil heavy metal pollution in the city. The content characteristics of heavy metals in 221 soil samples in the city were analyzed, and the potential health risk assessment and source analysis were carried out through the Monte Carlo model, the potential health risk assessment (HRA) model, and the PMF receptor model. It was found that heavy metals ω(As), ω(Hg), ω(Cd), ω(Pb), ω(Cr), ω(Cu), ω(Ni), and ω(Zn) in the soil of the city were 18.16, 0.43, 1.46, 68.57, 98.34, 64.19, 26.53, and 257.32 mg·kg-1, respectively, with a moderate to high degree of variation. Except for Ni concentration, the soil concentrations of other heavy metal elements exceeded the background values of soil in Guangdong Province to a certain extent, and the concentrations of Cd and Zn exceeded the national secondary standards, resulting in severe heavy metal pollution; the main sources of heavy metals were industrial sources, and natural parent materials, lead battery manufacturing, transportation, artificial cultivation, and pesticide and fertilizer inputs also had an undeniable impact on the accumulation of heavy metals in the soil. Heavy metals in the soil had a certain degree of tolerable carcinogenic health risk for both children and adults, whereas non-carcinogenic risks could be ignored. The potential health risk of children was greater than that of adults, and the main exposure route was through oral intake. The input sources of pesticides and fertilizers and As should be the main controlling factors for the health risks of heavy metals in the city's soil, followed by mixed sources and Cr. There were differences in the spatial distribution characteristics and relative pollution levels of heavy metals, and it is necessary to deepen zoning monitoring and control, strengthen soil pollution prevention and control, and reduce human input of heavy metals in soil.

[Pollution Characteristics and Risk Assessment of Polycyclic Aromatic Hydrocarbons in Soils of Guangzhou].

In order to comprehensively study the pollution characteristics of polycyclic aromatic hydrocarbons （PAHs） in soils of Guangzhou， 222 topsoil samples were collected and analyzed. The ecological risk of soil PAHs pollution was evaluated using the effect interval low/median method （ERL/ERM） and the （BaP） toxicity equivalent method， and the health risk of soil PAHs pollution was evaluated using the lifelong cancer risk increment model. The source of PAHs was analyzed using the characteristic compound ratio method and PMF model. The results indicated that： the content of surface soil （∑16PAHs） in Guangzhou was 38-11 115 µg·kg-1， with an average of 526 µg·kg-1， and 16 types of polycyclic aromatic hydrocarbon monomers showed strong variation. There was a certain degree of ecological risk of PAHs in Guangzhou， and there was already a significant ecological risk of PAHs pollution in individual sampling points， which were generally in a state of mild pollution. Based on the results of the health risk assessment， the contribution rates of total cancer risk in both adults and children were presented as follows： skin contact > ingestion of soil > respiratory intake. The health risk of children was greater than that of adults， and the overall health risk was within an acceptable range. Source analysis showed that the main sources of soil PAHs in Guangzhou were coal （37.1%）； diesel （32%）； coking （17.3%）； and mixed sources of traffic emissions， biomass combustion， and petrochemical product volatilization （13.6%）. The overall source of soil PAHs belonged to mixed sources. The research results have enriched our understanding of the pollution status of PAHs in the surface soil of Guangzhou and are helpful in promoting soil pollution prevention and control actions.

Disease-Related Factors Associated with Acupuncture Response in Patients with Chronic Tension-Type Headache: A Secondary Analysis of A Randomized Controlled Trial.

OBJECTIVE: To explore the demographic and disease-related factors associated with acupuncture response in patients with chronic tension-type headache (CTTH). METHODS: Using data from a randomized clinical trial (218 cases) consisting of 4 weeks of baseline assessment, 8 weeks of treatment, and 24 weeks of follow-up, participants were regrouped into responders (at least a 50% reduction in monthly headache days at week 16 compared with baseline) and non-responders. Twenty-three demographic and disease-related factors associated with acupuncture response in 183 participants were analyzed by multivariable logistic regression. RESULTS: One hundred and nineteen (65.0%) participants were classified as responders. Four factors were significantly independently associated with acupuncture response, including treatment assignment, headache intensity at baseline, and 2 domains [general health (GH) and social functioning (SF)] from the 36-Item Short Form Health Survey quality of life questionnaire. Treatment assignment was associated with non-response: participants receiving true acupuncture were 3-time more likely to achieve a CTTH response than those receiving superficial acupuncture [odds ratio (OR) 0.322, 95% confidence interval (CI) 0.162 to 0.625, P=0.001]. Compared with patients with mild-intensity headache, patients with moderate-intensity headache were twice as likely to respond to acupuncture (OR 2.001, 95% CI 1.020 to 4.011, P=0.046). The likelihood of non-response increased by 4.5% with each unit increase in the GH grade (OR 0.955, 95% CI 0.917 to 0.993, P=0.024) while decreased by 3.8% with each unit increase in the SF grade (OR 1.038, 95% CI 1.009 to 1.069, P=0.011). CONCLUSIONS: Greater headache intensity, lower GH score, and higher SF score were associated with better acupuncture responses in CTTH patients. These 3 factors require independent validation as predictors of acupuncture effectiveness in CTTH.

Serine/threonine kinase 36 induced epithelial-mesenchymal transition promotes docetaxel resistance in prostate cancer.

To investigate the role and potential mechanism of serine/threonine kinase 36 (STK36) in docetaxel resistance-prostate cancer (PCa). The expression of STK36 in PCa and the correlation with clinicopathological characteristics of PCa patients were analyzed using the data from different databases and tissue microarrays. To investigate the role of STK36 on cell proliferation, invasion, and migration, STK36 was overexpressed and silenced in DU-145 and PC-3 cell lines. Cell counting kit-8 (CCK8) was used to test cell proliferation. Cell invasion and migration were detected by cell wound scratch assay and trans well, respectively. The expression profile of STK36, E-Cadherin, and Vimentin was analyzed by Western blot. Cell apoptosis was detected by the TUNEL assay. STK36 expression was upregulated in PCa tissue compared with adjacent benign PCa tissue; it was higher in patients with advanced stages compared with lower stages and was significantly correlated with decreased overall survival. Up-regulation of STK36 significantly promoted the proliferation, invasion, and migration of DU-145 and PC-3 cells and compensated for the suppression caused by docetaxel treatment in vitro. A striking apoptosis inhibition could be observed when dealing with docetaxel, although the apoptosis of DU-145 and PC-3 cells was not affected by the STK36 exclusive overexpression. Besides, E-Cadherin expression was restrained while the expression levels of vimentin were all enhanced. The knockdown of STK36 reversed the above process. STK36 up-regulation could accelerate the biological behavior and docetaxel resistance of PCa by epithelial-mesenchymal transition (EMT) activation. STK36 may be potentially used as a target in PCa resolvent with docetaxel.

Efficacy of Acupuncture for Chronic Spontaneous Urticaria : A Randomized Controlled Trial.

BACKGROUND: The effectiveness of acupuncture for patients with chronic spontaneous urticaria (CSU), reported in a few small-scale studies, is not convincing. OBJECTIVE: To investigate whether acupuncture leads to better effects on CSU than sham acupuncture or waitlist control. DESIGN: A multicenter, randomized, sham-controlled trial. (Chinese Clinical Trial Registry: ChiCTR1900022994). SETTING: Three teaching hospitals in China from 27 May 2019 to 30 July 2022. PARTICIPANTS: 330 participants diagnosed with CSU. INTERVENTION: Participants were randomly assigned in a 1:1:1 ratio to receive acupuncture, sham acupuncture, or waitlist control over an 8-week study period (4 weeks for treatment and another 4 weeks for follow-up). MEASUREMENTS: The primary outcome was the mean change from baseline in the Weekly Urticaria Activity Score (UAS7) at week 4. Secondary outcomes included itch severity scores, self-rated improvement, and Dermatology Life Quality Index scores. RESULTS: The mean change in UAS7 (range, 0 to 42) for acupuncture from baseline (mean score, 23.5 [95% CI, 21.8 to 25.2]) to week 4 (mean score, 15.3 [CI, 13.6 to 16.9]) was -8.2 (CI, -9.9 to -6.6). The mean changes in UAS7 for sham acupuncture and waitlist control from baseline (mean scores, 21.9 [CI, 20.2 to 23.6] and 22.1 [CI, 20.4 to 23.8], respectively) to week 4 (mean scores, 17.8 [CI, 16.1 to 19.5] and 20.0 [CI, 18.3 to 21.6], respectively) were -4.1 (CI, -5.8 to -2.4) and -2.2 (CI, -3.8 to -0.5), respectively. The mean differences between acupuncture and sham acupuncture and waitlist control were -4.1 (CI, -6.5 to -1.8) and -6.1 (CI, -8.4 to -3.7), respectively, which did not meet the threshold for minimal clinically important difference. Fifteen participants (13.6%) in the acupuncture group and none in the other groups reported adverse events. Adverse events were mild or transient. LIMITATION: Lack of complete blinding, self-reported outcomes, limited generalizability because antihistamine use was disallowed, and short follow-up period. CONCLUSION: Compared with sham acupuncture and waitlist control, acupuncture produced a greater improvement in UAS7, although the difference from control was not clinically significant. Increased adverse events were mild or transient. PRIMARY FUNDING SOURCE: The National Key R&D Program of China and the Science and Technology Department of Sichuan Province.

Silencing METTL14 alleviates liver injury in non-alcoholic fatty liver disease by regulating mitochondrial homeostasis.

Mitochondrial dysfunction is an important pathogenic factor in non-alcoholic fatty liver disease (NAFLD). Methyltransferase-like 14 (METTL14) has been implicated in mitochondrial fission processes. This research aimed to investigate the mechanism of METTL14 in the mitochondrial function of NAFLD. We first established NAFLD mouse models and cell models, recording body and liver weights and examining pathological changes in liver tissues. Subsequently, serum levels of liver function indices (aspartate aminotransferase [AST], alanine aminotransferase [ALT], total cholesterol [TC], and triglycerides [TG]), inflammatory markers (tumor necrosis factor-alpha [TNF-α], interleukin [IL]-6, and IL-1ß), and mitochondrial dysfunction indicators (fission 1 protein [Fis1], dynamin-related protein 1 [Drp1], mitofusin 2 [Mfn2], SID1 transmembrane family member 2 [SIDT2], and mitochondrial membrane potential [MMP]) in the liver and cells were evaluated. The N6-methyladenosine (m6A) modification level of primary microRNA (pri-miRNA) and m6A enrichment on pri-miR-34a were quantified. Co-immunoprecipitation and dual-luciferase reporter gene assays were utilized to validate gene interactions. Our findings revealed highly elevated METTL14 expression in NAFLD mouse and cell models. Silencing METTL14 reduced weight gain and mitigated adverse liver function indices, inflammation, hepatic steatosis, and structural damage in NAFLD mice. It also led to a decrease in Fis1/Drp1 levels and an increase in MMP/Mfn2 in the liver and cells. Moreover, METTL14 increased the m6A level, promoting the binding of DiGeorge syndrome critical region 8 (DGCR8) to pri-miR-34a, which enhanced miR-34a-5p expression. Databases and dual-luciferase reporter gene assays indicated that miR-34a-5p could suppress SIDT2 expression. The overexpression of miR-34a-5p or inhibition of SIDT2 expression negated the alleviative effects of METTL14 silencing on mitochondrial homeostasis imbalance. In conclusion, METTL14, through m6A modification, modulates the miR-34a-5p/SIDT2 axis, impairing mitochondrial homeostasis in NAFLD.

Prognostic implications of the EGFR polymorphism rs763317 and clinical variables among young Chinese lung cancer population.

The 5-year survival rate for patients with lung cancer, the world's second most frequent malignant tumor, is less than 20%, and its prognosis cannot be clearly predicted. Our aim was to analyze the epidermal growth factor receptor (EGFR) rs763317 (G>A) single nucleotide polymorphism and its association with prognosis in Chinese Han lung cancer patients. 839 patients with primary lung cancer were recruited, and genomic DNA was extracted and genotyped by SNPscan. Kaplan-Meier technique and multivariate Cox proportional hazards model were used to analyze the association between prognosis and EGFR polymorphism rs763317. A significant association after stratification by age, significantly increased lung cancer risk was associated with the AA homozygous genotype of rs763317 (adjusted hazard ratio = 2.53, 95% CI: 1.31-4.88, p=0.005), and conferred a poor survival for lung cancer patients (MST: median survival time: 13.6 months) compared with GG genotype (MST: 41.5 months), and in the recessive model AA genotype (AA vs. GG + GA; adjusted hazard ratio = 2.57, 95% CI: 1.34-4.93, p=0.004) who were young (<60 years) had a significantly increased risk of death. The EGFR polymorphism rs763617 might serve as a significant genetic marker for predicting the prognosis of lung cancer.

IRE1α: from the function to the potential therapeutic target in atherosclerosis.

Inositol requiring enzyme 1 (IRE1) is generally thought to control the most conserved pathway in the unfolded protein response (UPR). Two isoforms of IRE1, IRE1α and IRE1ß, have been reported in mammals. IRE1α is a ubiquitously expressed protein whose knockout shows marked lethality. In contrast, the expression of IRE1ß is exclusively restricted in the epithelial cells of the respiratory and gastrointestinal tracts, and IRE1ß-knockout mice are phenotypically normal. As research continues to deepen, IRE1α was showed to be tightly linked to inflammation, lipid metabolism regulation, cell death and so on. Growing evidence also suggests an important role for IRE1α in promoting atherosclerosis (AS) progression and acute cardiovascular events through disrupting lipid metabolism balance, facilitating cells apoptosis, accelerating inflammatory responses and promoting foam cell formation. In addition, IRE1α was recognized as novel potential therapeutic target in AS prevention. This review provides some clues about the relationship between IRE1α and AS, hoping to contribute to further understanding roles of IRE1α in atherogenesis and to be helpful for the design of novel efficacious therapeutics agents targeting IRE1α-related pathways.

Assessment of ecological resilience in Nanchang based on "risk-connectivity-potential".

With the rapid development of urban construction, land for construction continues to expand and the ecological land is shrinking. There are various risks and degradation phenomena. The evaluation of urban ecological resilience thus becomes particularly important. From the perspective of urbanization-induced landscape changes, we evaluated the ecological resilience level of Nanchang from 2005 to 2020 by means of "risk-connectivity-potential" model, spatial autocorrelation model and kernel density assessment, as well as its spatial-temporal variations. The results showed that from 2005 to 2020, the spatial pattern of risk, connectivity, and potential subsystems in the study area was stable, with significant differences. The ecological risk was high in the middle and low in the east and west, while the spatial distribution of connectivity and ecological potential was opposite to the ecological risk, showing a pattern of low in the middle and high in the east and west. The overall level of ecological resilience was not high, with medium and low resilience levels as the main body. The low level continued to grow, and high value areas gradually decreased. The "high-high" cluster type of ecological resilience was decreasing, while the "low-low" cluster type was gradually increasing. Results of Kernel density assessment showed that the overall resilience level of Nanchang had little change, with obvious spatial difference. The number and distribution of different landscape types should be adjusted according to the characteristics of the ecological resilience level of different regions, in combination with the urban planning layout. The connectivity and agglomeration of spatial distribution of different landscape types should be changed to achieve the optimization and improvement of the overall regional ecological resilience level. The results could provide a theoretical basis for urban spatial planning and layout.

[Mammalian DMRTs: Structure, function and relationship with cancer].

DMRT, a gene family related to sexual determination, encodes a large group of transcription factors (DMRTs) with the double-sex and mab-3 (DM) domain (except for DMRT8), which is able to bind to and regulate DNAs. Current studies have shown that the DMRT gene family plays a critical role in the development of sexual organs (such as gender differentiation, gonadal development, germ cell development, etc.) as well as extrasexual organs (such as musculocartilage development, nervous system development, etc.). Additionally, it has been suggested that DMRTs may be involved in the cancer development and progression (such as prostate cancer, breast cancer, lung cancer, etc.). This review summarizes the research progress about the mammalian DMRTs' structure, function and its critical role in cancer development, progression and therapy (mainly in human and mice), which suggests that DMRT gene could be a candidate gene in the study of tumor formation and therapeutic strategy.

Applying OHSA to Detect Road Accident Blackspots.

With increasing numbers of crashes and injuries, understanding traffic accident spatial patterns and identifying blackspots is critical to improve overall road safety. This study aims at detecting blackspots using optimized hot spot analysis (OHSA). Traffic accidents were classified by their participants and severity to explore the relationship between blackspots and different types of accidents. Based on the outputs of incremental spatial autocorrelation, OHSA was then implemented on different types of accidents. Finally, the performance of OHSA in evaluating the road safety level of the proposed RBT index are examined using a binary correlation analysis (i.e., R2 = 0.89). The results show that: (1) The optimal scale distance varies from 0.6 km to 2.8 km and is influenced by the distance of the travel mode. (2) Central cities, with 54.6% of the total accidents, experiences more rigorous challenges regarding traffic safety than satellite cities. (3) There are many types of black spots in vulnerable communities, but in some specific areas, there are only black spots of non-motor vehicle accidents. Considering the practical significance of the above results, policy makers and traffic engineers are expected to give higher attention to central cities and vulnerable communities or prioritize the implementation of relevant optimization measures.

Acupuncture and Related Therapies for Chronic Urticaria: A Critical Overview of Systematic Reviews.

Background: Chronic urticaria (CU) can severely impair the quality of life. Acupuncture and related therapies have been widely used in the treatment of CU in China. This study aimed to summarize and critically evaluate the methodological and reporting quality of relevant systematic reviews (SRs) and present objective and comprehensive evidence on the effectiveness and safety of acupuncture and related therapies for CU. Methods: Eight electronic databases were searched from inception to October 2021 for SRs examining acupuncture and related therapies for CU, and gray literature was manually searched. Two authors independently identified SRs and extracted data. The methodological and reporting quality of these SRs were assessed by the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) tool and preferred reporting items for SRs and meta-analyses (PRISMA, 2020), respectively. In addition, the risk of bias in systematic reviews (ROBIS) was used to evaluate the risk of bias. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework was applied to evaluate the quality of evidence for outcome measures. Results: In total, 23 SRs, including a total of 11 outcome indicators, were published before October 2021. The AMSTAR-2 results showed that the methodological quality of all SRs was critically low; items 2, 3, 7, 9, 10, and 16 were found to have particularly low quality. For PRISMA, the reporting quality of the included SRs was unsatisfactory, and major reporting flaws were observed in the search strategy, synthesis method, certainly assessment, reporting biases, registrations, and financial support of the included SRs. For ROBIS, 22 SRs (95.65%) had a high risk of bias. Among the 55 outcomes assessed using the GRADE framework, there were 3 (5.45%) outcomes with moderate-quality evidence, 6 (10.91%) outcomes with low-quality evidence, and 46 (83.64%) outcomes with very low-quality evidence. We found the moderate quality of evidence indicating that the total effective rate and curing rate of the acupuncture group were higher than those of the western medicine group, and the recurrence rate was lower than that of the western medicine group. Conclusions: Acupuncture and related therapies for the treatment of CU are supported by low-quality evidence-based medicine. However, considering the poor quality of these SRs, we suggest that studies with more rigorous designs, larger sample sizes, and higher methodological and reporting quality are necessary to provide stronger evidence. Registration. The protocol for this study has been registered (PROSPERO registration number: CRD42021259131).

Grim-19 plays a key role in mitochondrial steroidogenic acute regulatory protein stability and ligand-binding properties in Leydig cells.

Grim-19 (gene associated with retinoid-IFN-induced mortality 19), the essential component of complex I of mitochondrial respiratory chain, functions as a noncanonical tumor suppressor by controlling apoptosis and energy metabolism. However, additional biological actions of Grim-19 have been recently suggested in male reproduction. We investigated here the expression and functional role of Grim-19 in murine testis. Testicular Grim-19 expression was detected from mouse puberty and increased progressively thereafter, and GRIM-19 protein was observed to be expressed exclusively in interstitial Leydig cells (LCs), with a prominent mitochondrial localization. In vivo lentiviral vector-mediated knockdown of Grim-19 resulted in a significant decrease in testosterone production and triggered aberrant oxidative stress in testis, thus impairing male fertility by inducing germ cell apoptosis and oligozoospermia. The control of testicular steroidogenesis by GRIM-19 was validated using the in vivo knockdown model with isolated primary LCs and in vitro experiments with MA-10 mouse Leydig tumor cells. Mechanistically, we suggest that the negative regulation exerted by GRIM-19 deficiency-induced oxidative stress on steroidogenesis may be the result of two phenomena: a direct effect through inhibition of phosphorylation of steroidogenic acute regulatory protein (StAR) and subsequent impediment to StAR localization in mitochondria and an indirect pathway that is to facilitate the inhibiting role exerted by the extracellular matrix on the steroidogenic capacity of LCs via promotion of integrin activation. Altogether, our observations suggest that Grim-19 plays a potent role in testicular steroidogenesis and that its alterations may contribute to testosterone deficiency-related disorders linked to metabolic stress and male infertility.

Premorbid Steatohepatitis Increases the Seriousness of Dextran Sulfate Sodium-induced Ulcerative Colitis in Mice.

Background and Aims: The concurrence of nonalcoholic steatohepatitis (NASH) and ulcerative colitis (UC) is increasingly seen in clinical practice, but the underlying mechanisms remain unclear. This study aimed to develop a mouse model of the phenomenon by combining high-fat high-cholesterol diet (HFHCD)-induced NASH and dextran sulfate sodium (DSS)-induced UC, that would support mechanistic studies. Methods: Male C57BL/6 mice were randomly assigned to two groups receiving either a chow diet or HFHCD for 12 weeks of NASH modeling. The mice were the divided into four subgroups for UC modeling: (1) A control group given a chow diet with normal drinking water; (2) A colitis group given chow diet with 2% DSS in drinking water; (3) A steatohepatitis group given HFHCD with normal drinking water; and (4) A steatohepatitis + colitis group given HFHCD with 2% DSS in drinking water. Results: NASH plus UC had high mortality (58.3%). Neither NASH nor UC alone were fatal. Although DSS-induced colitis did not exacerbate histological liver injury in HFHCD-fed mice, premorbid NASH significantly increased UC-related gut injury compared with UC alone. It was characterized by a significantly shorter colon, more colonic congestion, and a higher histopathological score (p<0.05). Inflammatory (tumor necrosis factor-alpha, interleukin 1 beta, C-C motif chemokine ligand 2, and nuclear factor kappa B) and apoptotic (Bcl2, Bad, Bim, and Bax) signaling pathways were significantly altered in distal colon tissues collected from mice with steatohepatitis + colitis compared with the other experimental groups. Conclusions: Premorbid steatohepatitis significantly aggravated DSS-induced colitis and brought about a lethal phenotype. Potential links between NASH and UC pathogeneses can be investigated using this model.

ZLM-7 Blocks Breast Cancer Progression by Inhibiting MDM2 via Upregulation of 14-3-3 Sigma.

Breast cancer is one of the most prevalent malignancies with poor prognosis. Inhibition of angiogenesis is becoming a valid and evident therapeutic strategy to treat cancer. Recent studies uncovered the antiangiogenic activity of ZLM-7 (a combretastain A-4 derivative), but the regulatory mechanism is unclear. ZLM-7 treatment was applied in estrogen receptor-positive cell MCF-7, triple-negative breast cancer cell MDA-MB-231 and xenograft models. Transfections were conducted to overexpress or knockdown targeted genes. The gene and protein expressions were measured by qPCR and Western blotting assay, respectively. Cell proliferation and apoptosis were evaluated using the CCK8 method, clone formation assay and flow cytometry. We found that ZLM-7 upregulated 14-3-3 sigma expression but downregulated MDM2 expression in breast cancer cells. ZLM-7 delayed cell proliferation, promoted apoptosis and blocked cell-cycle progression in human breast cancer cells in vitro, while those effects were abolished by 14-3-3 sigma knockdown; overexpression of 14-3-3 sigma reproduced the actions of ZLM-7 on the cell cycle, which could be reversed by MDM2 overexpression. In xenograft models, ZLM-7 treatment significantly inhibited tumor growth while the inhibition was attenuated when 14-3-3 sigma was silenced. Collectively, ZLM-7 could inhibit MDM2 via upregulating 14-3-3 sigma expression, thereby blocking the breast cancer progression.

Association of maternal obesity and gestational diabetes mellitus with overweight/obesity and fatty liver risk in offspring.

BACKGROUND: Childhood obesity and fatty liver are associated with adverse outcomes such as diabetes, metabolic syndrome, and cardiovascular diseases in adulthood. It is very important to identify relevant risk factors and intervene as early as possible. At present, the relationship between maternal and offspring metabolic factors is conflicting. AIM: To estimate the association of maternal obesity and gestational diabetes mellitus (GDM) with overweight/obesity and fatty liver risk in offspring at 8 years of age. METHODS: The prospective study included mothers who all had a 75-g oral glucose tolerance test at 24-28 wk of gestation and whose offspring completed follow-up at 8 years of age. Offspring birth weight, sex, height, weight, and body mass index (BMI) were measured and calculated. FibroScan-502 examination with an M probe (Echosens, Paris, France) was prospectively conducted in offspring aged 8 years from the Shanghai Prenatal Cohort Study. RESULTS: A total of 430 mother-child pairs were included in the analysis. A total of 62 (14.2%) mothers were classified as obese, and 48 (11.1%) were classified as having GDM. The mean age of the offspring at follow-up was 8 years old. Thirty-seven (8.6%) offspring were overweight, 14 (3.3%) had obesity, and 60 (14.0%) had fatty liver. The prevalence of overweight, obesity and fatty liver in offspring increased significantly across maternal BMI quartiles (all P < 0.05). Among offspring of mothers with GDM, 12 (25.0%) were overweight, 4 (8.3%) were obese, and 12 (25.0%) had fatty liver vs. 25 (6.5%), 10 (2.6%) and 48 (12.6%), respectively, for offspring of mothers without GDM (all P < 0.05). In multiple logistic regression, after adjustment for variables, the OR for fatty liver in offspring was 8.26 (95%CI: 2.38-28.75) for maternal obesity and GDM. CONCLUSION: This study showed that maternal obesity can increase the odds of overweight/obesity and fatty liver in offspring, and GDM status also increases the odds of overweight/obesity in offspring. Weight management and glycemic control before and during pregnancy need to be highlighted in primary prevention of pediatric obesity and fatty liver.

Emerging role of m6A modification in osteogenesis of stem cells.

The differentiation of stem cells into osteoblasts is a key link in the treatment of bone defects and other orthopedic diseases. N6-methyladenosine (m6A) modification, an important post-transcriptional modification, is a methylation that occurs at the N6 site of RNA adenylate. The modification plays a regulatory role in the growth and development of biological individuals, the directional differentiation of stem cells and the occurrence of diseases. It is involved in various processes of the fate decision of stem cells. And it regulates the development and constant renewal of bone and keeps bone homeostasis by controlling and maintaining the balance between osteogenesis and adipogenesis. Meanwhile, it also affects the progress of orthopedic-associated diseases such as degenerative osteoporosis and bone tumor. In this review, we mainly summarize the new findings of three key molecules including Writers, Erasers and Readers which regulate m6A modification, and the emerging role of m6A modification in determining the fate and directed differentiation potential of stem cells, especially highlight the regulatory mechanism of osteogenic differentiation, the balance between osteogenesis and adipogenesis and the occurrence and development of bone-related diseases. It may provide some important ideas about finding new strategies to recover from bone defect and degenerative bone disease.