Tartaric acid ameliorates experimental non-alcoholic fatty liver disease by activating the AMP-activated protein kinase signaling pathway.

Tartaric acid (TA) has been shown beneficial effects on blood pressure and lipid levels. However, its effect on non-alcoholic fatty liver disease (NAFLD) remains unknown. This study aimed to investigate the role of TA in experimental NAFLD. Mice were fed a Western diet for 8 weeks, followed by administration of TA or a vehicle for an additional 12 weeks while continuing on the Western diet. Blood biochemistry including transaminases and glucose tolerance test and liver tissue RNA sequencing (RNA-seq), lipid content, and histology were investigated. The HepG2 cell line was used to explore the mechanism by which TA regulates lipid metabolism. We found that TA significantly improved weight gain, insulin resistance, hepatic steatosis, inflammation and fibrosis in Western diet-fed mice. By comparing gene expression differences, we found that TA affects pathways related to lipid metabolism, inflammatory response, and fibrosis. Furthermore, TA effectively reduced oleic acid-induced lipid accumulation in HepG2 cells and downregulated the genes associated with fatty acid synthesis, which were enriched in the AMP-activated protein kinase (AMPK) signaling pathway. TA also enhanced the phosphorylation of AMPK which could be reverted by the AMPK inhibitor Compound C in HepG2 cells. Our study suggests that TA improves experimental NAFLD by activating the AMPK signaling pathway. These findings indicate that TA may serve as a potential therapy for the human NAFLD.

Oregano essential oil encapsulated in zein-pectin-chitosan nanoparticles to improve the storage quality of Harbin red sausage.

In this study, the effect of oregano essential oil loaded in zein-pectin-chitosan (Zein-PC-CS-OEO) nanoparticles on the quality of Harbin red sausage during storage was examined. Zein-PC-CS-OEO nanoparticles exhibit the better encapsulation efficiency, antioxidant and antibacterial properties than these of other prepared nanoparticles, which were subsequently incorporated into Harbin red sausage with different concentrations. The physicochemical properties, bacterial community structure, and flavor characteristics of the Harbin red sausage were determined. Both thiobarbituric acid values and the growth of dominant spoilage bacteria in Harbin red sausage are inhibited by Zein-PC-CS-OEO nanoparticles, while the total aerobic bacteria count is reduced. These results indicate that the storage quality of Harbin red sausage is improved by Zein-PC-CS-OEO nanoparticles. It is worth noting that the shelf life of Harbin red sausage supplemented with 0.1 % Zein-PC-CS-OEO nanoparticles is extended to 9 d, and the flavor characteristics of which are better maintained. This study provides a new approach to extend the application of essential oil and improve the storage quality of Harbin red sausage.

BAG5 regulates HSPA8-mediated protein folding required for sperm head-tail coupling apparatus assembly.

Teratozoospermia is a significant cause of male infertility, but the pathogenic mechanism of acephalic spermatozoa syndrome (ASS), one of the most severe teratozoospermia, remains elusive. We previously reported Spermatogenesis Associated 6 (SPATA6) as the component of the sperm head-tail coupling apparatus (HTCA) required for normal assembly of the sperm head-tail conjunction, but the underlying molecular mechanism has not been explored. Here, we find that the co-chaperone protein BAG5, expressed in step 9-16 spermatids, is essential for sperm HTCA assembly. BAG5-deficient male mice show abnormal assembly of HTCA, leading to ASS and male infertility, phenocopying SPATA6-deficient mice. In vivo and in vitro experiments demonstrate that SPATA6, cargo transport-related myosin proteins (MYO5A and MYL6) and dynein proteins (DYNLT1, DCTN1, and DNAL1) are misfolded upon BAG5 depletion. Mechanistically, we find that BAG5 forms a complex with HSPA8 and promotes the folding of SPATA6 by enhancing HSPA8's affinity for substrate proteins. Collectively, our findings reveal a novel protein-regulated network in sperm formation in which BAG5 governs the assembly of the HTCA by activating the protein-folding function of HSPA8.

Physiological responses of low- and high-cadmium accumulating Robinia pseudoacacia-rhizobium symbioses to cadmium stress.

The role of rhizobia in alleviating cadmium (Cd) stress in woody legumes is still unclear. Therefore, two types of black locust (Robinia pseudoacacia L.) with high and low Cd accumulation abilities were selected from 11 genotypes in China, and the effects of rhizobium (Mesorhizobium huakuii GP1T11) inoculation on the growth, CO2 and H2O gas exchange parameters, Cd accumulation, and the absorption of mineral elements of the high (SX) and low Cd-accumulator (HB) were compared. The results showed that rhizobium-inoculation significantly increased biomass, shoot Cd contents, Cd accumulation, root-to-shoot translocation factor (TF) and the absorption and accumulation of mineral elements in both SX and HB. Rhizobium-inoculation increased chlorophyll a and carotenoid contents, and the intercellular carbon dioxide concentrations in HB plants. Under Cd exposure, the high-accumulator SX exhibited a significant decrease in photosynthetic CO2 fixation (Pn) and an enhanced accumulation of Cd in leaves, but coped with Cd exposure by increasing chlorophyll synthesis, regulating stomatal aperture (Gs), controlling transpiration (Tr), and increasing the absorption and accumulation of mineral elements. In contrast, the low-accumulator HB was more sensitive to Cd exposure despite preferential accumulation of Cd in roots, with decreased chlorophyll and carotenoid contents, but significantly increased root biomass. Compared to the low-accumulator HB, non-inoculated Cd-exposed SX plants had higher chlorophyll contents, and rhizobium-inoculated Cd-exposed SX plants had higher Pn, Tr, and Gs as well as higher levels of P, K, Fe, Ca, Zn, and Cu. In conclusion, the high- and low-Cd-accumulator exhibited different physiological responses to Cd exposure. Overall, rhizobium-inoculation of black locust promoted the growth and heavy metal absorption, providing an effective strategy for the phytoremediation of heavy metal-contaminated soils by this woody legume.

Quantitative assessment of bone marrow infiltration and characterization of tumor burden using dual-layer spectral CT in patients with multiple myeloma.

BACKGROUND: The aim of the study was to evaluate whether virtual calcium subtraction (VNCa) image extracted from dual-layer spectral CT could estimate bone marrow (BM) infiltration with MRI as the reference standard and characterize tumor burden in patients with multiple myeloma (MM). PATIENTS AND METHODS: Forty-seven patients with newly diagnosed MM were retrospectively enrolled. They had undergone whole-body low-dose dual-layer spectral CT (DLCT) and whole-body MRI within one week. VNCa images with calcium-suppressed (CaSupp) indices ranging from 25 to 95 at an interval of 10 and apparent diffusion coefficient (ADC) maps were quantitatively analyzed on vertebral bodies L1-L5 at the central slice of images. The optimal combination was selected by correlation analysis between CT numbers and ADC values. Then, it was used to characterize tumor burden by correlation analysis and receiver operating characteristic (ROC) curves analysis, including plasma cell infiltration rate (PCIR), high serum-free light chains (SFLC) ratio and the high-risk cytogenetic (HRC) status. RESULTS: The most significant quantitative correlation between CT numbers of VNCa images and ADC values could be found at CaSupp index 85 for averaged L1-L5 (r = 0.612, p < 0.001). It allowed quantitative evaluation of PCIR (r = 0.835, p < 0.001). It could also anticipate high SFLC ratio and the HRC status with area under the curve (AUC) of 0.876 and 0.760, respectively. CONCLUSIONS: The VNCa measurements of averaged L1-L5 showed the highest correlation with ADC at CaSupp index 85. It could therefore be used as additional imaging biomarker for non-invasive assessment of tumor burden if ADC is not feasible.

Contrast Agent Reflux in Transvaginal 4-D Hysterosalpingo-Contrast Sonography: Influencing Factors and Coping Strategies.

ABSTRACT: Transvaginal 4-D hysterosalpingo-contrast sonography (TV 4-D HyCoSy) plays an important role in the detection and diagnosis of clinical female infertility. The purposes of this study were to analyze the influencing factors of TV 4murD HyCoSy complicated with contrast agent reflux and to provide evidence for clinical diagnosis and treatment. Female patients diagnosed as infertility by transvaginal hysterosalpingography from January 2021 to December 2022 were included. The characteristics of patients with and without contrast agent reflux were evaluated. Pearson correlation and logistic regression were conducted to analyze the related factors affecting the occurrence of contrast reflux. A total of 416 patients undergoing TV 4-D HyCoSy were included, and the incidence of contrast agent reflux in patients undergoing TV 4-D HyCoSy was 38.94%. Pearson correlation analysis results indicated that history of uterine cavity operation ( r = 0.556), adenomyosis of uterus ( r = 0.584), examination on less than 5 days after menstruation ( r = 0.602), endometrial thickness ( r = 0.566), and endometrial polyps ( r = 0.575) are all correlated with contrast agent reflux in patients undergoing 4-D HyCoSy (all P < 0.05). Logistic regression analysis showed that history of uterine cavity operation (odds ratio [OR], 1.109; 95% confidence interval [CI], 1.012-1.872), adenomyosis of uterus (OR, 2.026; 95% CI, 1.864-2.425), examination on less than 5 days after menstruation (OR, 2.465; 95% CI, 2.118-2.851), endometrial thickness less than 6 mm (OR, 2.866; 95% CI, 2.095-2.957), and endometrial polyps (OR, 1.587; 95% CI, 1.137-1.744) were the influencing factors of contrast agent reflux in patients undergoing (all P < 0.05). The incidence of contrast agent reflux in TV 4-D HyCoSy is high, and there are many influencing factors. Clinical medical workers should take early measures based on these influencing factors to reduce the contrast agent reflux.

Repopulating Kupffer cells originate directly from hematopoietic stem cells.

BACKGROUND: Kupffer cells (KCs) originate from yolk-sac progenitors before birth. Throughout adulthood, they self-maintain independently from the input of circulating monocytes (MOs) at a steady state and are replenished within 2 weeks after having been depleted, but the origin of repopulating KCs in adults remains unclear. The current paradigm dictates that repopulating KCs originate from preexisting KCs or monocytes, but there remains a lack of fate-mapping evidence. METHODS: We first traced the fate of preexisting KCs and that of monocytic cells with tissue-resident macrophage-specific and monocytic cell-specific fate-mapping mouse models, respectively. Secondly, we performed genetic lineage tracing to determine the type of progenitor cells involved in response to KC-depletion in mice. Finally, we traced the fate of hematopoietic stem cells (HSCs) in an HSC-specific fate-mapping mouse model, in the context of chronic liver inflammation induced by repeated carbon tetrachloride treatment. RESULTS: By using fate-mapping mouse models, we found no evidence that repopulating KCs originate from preexisting KCs or MOs and found that in response to KC-depletion, HSCs proliferated in the bone marrow, mobilized into the blood, adoptively transferred into the liver and differentiated into KCs. Then, in the chronic liver inflammation context, we confirmed that repopulating KCs originated directly from HSCs. CONCLUSION: Taken together, these findings provided in vivo fate-mapping evidence that repopulating KCs originate directly from HSCs, which presents a completely novel understanding of the cellular origin of repopulating KCs and shedding light on the divergent roles of KCs in liver homeostasis and diseases.

Associations of Lifestyle Patterns With Overweight and Depressive Symptoms Among United States Emerging Adults With Different Employment Statuses.

Objective: To identify lifestyle patterns in emerging adults and examine the association of lifestyle patterns with overweight and depression. Methods: Data was from the National Health and Nutrition Examination Survey between 2011 and 2018. A latent class analysis (LCA) was conducted with 2,268 US emerging adults based on sedentary behavior, moderate-to-vigorous physical activity, diet, sleep, alcohol drinking, and cigarette smoking. The associations of lifestyle groups with overweight and depression were examined by logistic regression and were further stratified by employment status. Results: The LCA results favored a four-class solution: "unhealthy but non-substance use" (59%), "healthy but sleepless and drinking" (12%), "unhealthy lifestyle" (15%), and "healthy but sedentary" group (14%). Compared to the "unhealthy lifestyle" group, participants in the "unhealthy but non-substance use" (coef. = -1.44, SE = 0.27; OR = 0.40, 95% CI [0.26, 0.61]), "healthy but sleepless and drinking" (coef. = -1.49, SE = 0.35; OR = 0.38, 95% CI [0.20, 0.72]), and "healthy but sedentary" (coef. = -1.97, SE = 0.34; OR = 0.29, 95% CI [0.14, 0.57]) groups had lower depression severity and reported fewer depressive symptoms. Moreover, lifestyle groups and health outcomes showed different relationships among employed and unemployed participants. Conclusion: This study found that the combinations of lifestyle behaviors had synergistic effects on mental health, and such effects differed by employment status.

Tyrosine phosphorylation of IRF3 by BLK facilitates its sufficient activation and innate antiviral response.

Viral infection triggers the activation of transcription factor IRF3, and its activity is precisely regulated for robust antiviral immune response and effective pathogen clearance. However, how full activation of IRF3 is achieved has not been well defined. Herein, we identified BLK as a key kinase that positively modulates IRF3-dependent signaling cascades and executes a pre-eminent antiviral effect. BLK deficiency attenuates RNA or DNA virus-induced ISRE activation, interferon production and the cellular antiviral response in human and murine cells, whereas overexpression of BLK has the opposite effects. BLK-deficient mice exhibit lower serum cytokine levels and higher lethality after VSV infection. Moreover, BLK deficiency impairs the secretion of downstream antiviral cytokines and promotes Senecavirus A (SVA) proliferation, thereby supporting SVA-induced oncolysis in an in vivo xenograft tumor model. Mechanistically, viral infection triggers BLK autophosphorylation at tyrosine 309. Subsequently, activated BLK directly binds and phosphorylates IRF3 at tyrosine 107, which further promotes TBK1-induced IRF3 S386 and S396 phosphorylation, facilitating sufficient IRF3 activation and downstream antiviral response. Collectively, our findings suggest that targeting BLK enhances viral clearance via specifically regulating IRF3 phosphorylation by a previously undefined mechanism.

Synthesis of geopolymer using municipal solid waste incineration fly ash and steel slag: Hydration properties and immobilization of heavy metals.

In this study, a novel method for the disposal of municipal solid waste incineration fly ash (MSWIFA) was proposed. By applying geopolymer technology, steel slag (SS) and MSWIFA were used together as precursors to synthesize a cementitious material with sufficient strength that is useable in construction. The effects of the dosages of SS and alkaline activator on the properties of the geopolymer were investigated. Compressive testing was used to characterize the mechanical properties of the geopolymer. X-ray diffraction (XRD), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) were used for microscopic analysis. Leaching tests were performed to assess the immobilization effect of the geopolymer on heavy metals. The results showed that the compressive strength of the geopolymer reached 23.03 MPa at 56 d with 20% SS and 11% Na2O admixture. Highly polymerized hydration products, such as C-(A)-S-H gels and N-A-S-H gels, contributed to the compact microstructure, which provided mechanical strength and limited the migration and leaching of heavy metals in the geopolymer matrix. In terms of the results, this work is significant for the development of MSWIFA management.

Transcriptome analysis reveals key transcription factors and pathways of polian vesicle associated with cell proliferation in Vibrio splendidus-challenged Apostichopus japonicus.

Polian vesicle is thought to produce coelomocytes and contribute to the sea cucumber's immune system. Our previous work has indicated that polian vesicle was responsible for cell proliferation at 72 h post pathogenic challenge. However, the transcription factors related to the activation of effector factors and the molecular process behind this remained unknown. In this study, to reveal the early functions of polian vesicle in response to the microbe, a comparative transcriptome sequencing of polian vesicle in V. splendidus-challenged Apostichopus japonicus, including normal group (PV 0 h), pathogen challenging for 6 h (PV 6 h) and 12 h (PV 12 h) was performed. Compared PV 0 h to PV 6 h, PV 0 h to PV 12 h, and PV 6 h to PV 12 h, we found 69, 211, and 175 differentially expressed genes (DEGs), respectively. KEGG enrichment analysis revealed the DEGs, including several transcription factors such as fos, FOS-FOX, ATF2, egr1, KLF2, and Notch3 between PV 6 h and PV 12 h were consistently enriched in MAPK, Apelin and Notch3 signaling pathways related to cell proliferation compared with that in PV 0 h. Important DEGs involved in cell growth were chosen, and their expression patterns were almost the same as the transcriptome profile analysis by qPCR. Protein interaction network analysis indicated that two DEGs of fos and egr1 were probably significant as key candidate genes controlling cell proliferation and differentiation in polian vesicle after pathogenic infection in A. japonicus. Overall, our analysis demonstrates that polian vesicles may play an essential role in regulating proliferation via transcription factors-mediated signaling pathway in A. japonicus and provide new insights into hematopoietic modulation of polian vesicles in response to pathogen infection.

Neuro death through autophagy via the acetylation of FoxO1 by SIRT2 in the hippocampus of mice in a autism spectrum disorder mice model.

Autism Spectrum Disorder (ASD) is a series of complex neurodevelopmental disorders, which can affect children's social, behavioral and communication abilities. A member of the Sirtuins family of NAD + dependent deacetylases called SIRT2 could regulate the inflammation progress during stress, but the relevant mechanism has not been clearly defined. In the present study, the ASD model of wild type and SIRT2 knock out mice was established to evaluate the impact on the homeostasis of neurons in the hippocampus using western blotting, immunofluorescence and Nissl staining. The results showed that the amplification of neuronal richness was significantly decreased and neuroinflammation increased in the hippocampus following ASD due to autophagy, caused by enhancing the acetylation of FoxO1 using SIRT2 gene deletion and indicating this should be the target for ASD or other psychological stress treatment.

MITOCHONDRIA: The dual function of the transient receptor potential melastatin 2 channels from cytomembrane to mitochondria.

Mitochondria are closely related to oxidative stress and play an important role in maintaining cell functional homeostasis and meeting cell energy demand. The transient receptor potential melastatin 2 (TRPM2) channel affects the occurrence and progression of diseases by regulating mitochondrial function. TRPM2 channel promotes Ca2+ influx to affect 18 kDa translocator protein (TSPO), mitochondrial membrane potential (MMP), reactive oxygen species (ROS), adenosine triphosphate (ATP) production, and mitochondrial autophagy. The mechanism of Ca2+ influx into the mitochondria by TRPM2 is abundant. Interestingly, the TRPM2 channel inhibits the production of mitochondrial ROS in cancer cells and promotes the production of mitochondrial ROS in normal cells, which induces cell death in normal cells but proliferation in cancer cells. TRPM2 can be a potential target for the treatment of various diseases due to its role as a molecular link between mitochondria and Ca2+ signals.

Chloride intracellular channel 1 promotes esophageal squamous cell carcinoma proliferation via mTOR signalling.

OBJECTIVES: To investigate the clinical significance of Chloride Intracellular Channel 1 (CLIC1) expression in esophageal squamous cell carcinoma (ESCC) and its functional contribution and molecular mechanisms to the progression of ESCC. METHODS: CLIC1 expression was analyzed by immunohistochemistry (IHC) in a cohort of 86 ESCC tissue specimens and paired normal adjacent esophageal tissues. Associations between clinicopathological features of ESCC and CLIC1 expression were determined. In vitro analyses examined CLIC1 expression in the ESCC cell lines KYSE150 and TE1 using RT-PCR and Western blotting. The downstream pathways of CLIC1 were detected by lentiviral shRNA knockdown and subsequent proteomic analyses. CLIC1 siRNA knockdown was performed in ESCC cell lines KYSE150 and TE1 and the functional effects of CLIC1 on the growth and proliferation of ESCC cells were evaluated combined with cell viability and colony formation assays; the mTOR signaling pathway-related proteins were detected by Western blotting based on the previous proteomic data. RESULTS: CLIC1 expression was significantly increased in ex vivo ESCC tissues compared with corresponding normal tissues, and the up-regulation was associated with clinical tumor node metastasis (TNM) classifications. Knockdown of CLIC1 inhibited in vitro cell proliferation of ESCC cell lines KYSE150 and TE1. CLIC1 knockdown down-regulated the protein expression of p-mTOR and the downstream targets Rictor and p-4EBP1 in both KYSE150 and TE1 cell lines. And the CLIC1 knockdown induced inhibition of cell proliferation on ESCC cells could be rescued by mTOR overexpression. CONCLUSIONS: CLIC1 expression increases during esophageal carcinogenesis and it may functionally contribute to the progression of ESCC through growth promotion effects by promoting the mTOR and downstream signaling pathway. CLIC1 therefore constitutes a candidate molecular biomarker of ESCC.

Exposure to metals and the disruption of sex hormones in 6-19 years old children: An exploration of mixture effects.

BACKGROUND: Individual metals have been linked to sex hormones disruption, but the associations of metals mixture are rarely examined among children. METHODS: A total of 1060 participants of 6-19-year-old who participated in the National Health and Nutrition Examination Survey (2013-2016) were included. Eighteen metals were quantified in the whole blood and urine. Sex hormones were measured in serum, including total testosterone (TT), estradiol (E2), and sex hormone binding globulin (SHBG). In addition, free androgen index (FAI) and the ratio of TT to E2 were calculated. Bayesian kernel machine regression and latent class analysis were performed to assess the associations of metals mixture and exposure patterns of metals at varied levels with sex hormones while adjusting for selected covariates. All analyses were conducted by sex-age and sex-puberty groups to explore the potential sex-dimorphic effects. RESULTS: Exposure to metals mixture was associated with elevated levels of FAI and E2 among 12-19 years old girls. Moreover, the exposure pattern of metals that was characterized by high levels of blood and urinary cadmium, blood manganese, and urinary cobalt was associated with elevated E2 and reduced TT/E2 levels among girls of 12-19 years old. However, the associations of metals mixture with sex hormones were overall nonsignificant among boys. Nevertheless, metals exposure pattern that was characterized by high levels of blood lead, urinary barium, strontium, and lead but comparatively low levels of the other metals was consistently associated with reduced levels of FAI and E2 but elevated levels of TT/E2 and SHBG among boys of 12-19 years old. CONCLUSION: Metals mixture and exposure patterns that were dominated by high levels of certain metals were associated with sex hormones imbalance among 12-19 years old children in a sex-dimorphic pattern, with the identified individual metals that drove the associations of metals mixture varied by sex.

Cistanche tubulosa phenylethanoid glycosides suppressed adipogenesis in 3T3-L1 adipocytes and improved obesity and insulin resistance in high-fat diet induced obese mice.

BACKGROUND: Cistanche tubulosa is an editable and medicinal traditional Chinese herb and phenylethanoid glycosides are its major components, which have shown various beneficial effects such as anti-tumor, anti-oxidant and neuroprotective activities. However, the anti-obesity effect of C. tubulosa phenylethanoid glycosides (CTPG) and their regulatory effect on gut microbiota are still unclear. In the present study, we investigated its anti-obesity effect and regulatory effect on gut microbiota by 3T3-L1 cell model and obesity mouse model. METHODS: 3T3-L1 adipocytes were used to evaluate CTPG effects on adipogenesis and lipids accumulation. Insulin resistant 3T3-L1 cells were induced and used to measure CTPG effects on glucose consumption and insulin sensitivity. High-fat diet (HFD)-induced C57BL/6 obese mice were used to investigate CTPG effects on fat deposition, glucose and lipid metabolism, insulin resistance and intestinal microorganism. RESULTS: In vitro data showed that CTPG significantly decreased the triglyceride (TG) and non-esterified fatty acid (NEFA) contents of the differentiated 3T3-L1 adipocytes in a concentration-dependent manner without cytotoxicity, and high concentration (100 µg/ml) of CTPG treatment dramatically suppressed the level of monocyte chemoattractant protein-1 (MCP-1) in 3T3-L1 mature adipocytes. Meanwhile, CTPG increased glucose consumption and decreased NEFA level in insulin resistant 3T3-L1 cells. We further found that CTPG protected mice from the development of obesity by inhibiting the expansion of adipose tissue and adipocyte hypertrophy, and improved hepatic steatosis by activating AMPKα to reduce hepatic fat accumulation. CTPG ameliorated HFD-induced hyperinsulinemia, hyperglycemia, inflammation and insulin resistance by activating IRS1/Akt/GLUT4 insulin signaling pathway in white adipose tissue. Moreover, gut microbiota structure and metabolic functions in HFD-induced obese mice was changed by CTPG, especially short chain fatty acids-producing bacteria including Blautia, Roseburia, Butyrivibrio and Bacteriodes were significantly increased by CTPG treatment. CONCLUSIONS: CTPG effectively suppressed adipogenesis and lipid accumulation in 3T3-L1 adipocytes and ameliorated HFD-induced obesity and insulin resistance through activating AMPKα and IRS1/AKT/GLUT4 signaling pathway and regulating the composition and metabolic functions of gut microbiota.

Prognostic factors for IB2-IIIB cervical cancer patients treated by radiation therapy with high-dose-rate brachytherapy in a single-institution study.

Purpose: To evaluate the efficacy of radiotherapy in locally advanced cervical cancer, and to determine the factors affecting prognosis. Material and methods: Clinical data of 211 patients with cervical cancer, treated at our institution between June 2014 and February 2017 were reviewed retrospectively. All patients were treated with definitive radiotherapy and received external irradiation of 45-50.4 Gy. High-dose-rate brachytherapy (HDR-BT) of 24-36 Gy was prescribed to a high-risk clinical target volume (HR-CTV) as a local boost. All statistical analyses were performed with SPSS version 19.0 using Kaplan-Meier survival test and Cox regression analysis. Additionally, dose parameters of patients with IIIB stage treated with combined intracavitary/interstitial (IC/IS) implants were compared with IC only. Results: With a median follow-up time of 69 months, local control (LC), overall survival (OS), disease-free survival (DFS), and nodal control (NC) at 5 years were 89%, 78%, 67%, and 88%, respectively. In multivariate analysis, the major determinant of LC was the level of pre-treatment squamous cell carcinoma antigen (SCC-Ag). The predictors of shorter OS were adenocarcinoma, pre-treatment SCC-Ag, and FIGO stage. Worse DFS was associated with adenocarcinoma, pre-treatment SCC-Ag, and involved lymph nodes. The predictors for nodal failure were positive pelvic lymph nodes. Patients with IIIB treated with IC/IS brachytherapy tended to improve DFS compared with IC alone, and obtained similar HR-CTV D90 EQD2 (n = 10) and biological effective dose (BED), 91 ±6 Gy vs. 89 ±3 Gy, and 107 ±4.5 Gy vs. 107 ±5.6 Gy, whereas decreased organs at risk (OARs) doses, including rectum and bladder D2cm3 were 7.5 Gy and 7.2 Gy lower, respectively. Late grade 3-4 bladder and bowel toxicities were observed in 1.9% of patients. Conclusions: Radiation therapy carried out in our institution results in good survival, with acceptable toxicity in locally advanced cervical cancer. Different individualized therapeutic strategies should be considered for patients with high-risk factors.

A sustainable mouse karyotype created by programmed chromosome fusion.

Chromosome engineering has been attempted successfully in yeast but remains challenging in higher eukaryotes, including mammals. Here, we report programmed chromosome ligation in mice that resulted in the creation of new karyotypes in the lab. Using haploid embryonic stem cells and gene editing, we fused the two largest mouse chromosomes, chromosomes 1 and 2, and two medium-size chromosomes, chromosomes 4 and 5. Chromatin conformation and stem cell differentiation were minimally affected. However, karyotypes carrying fused chromosomes 1 and 2 resulted in arrested mitosis, polyploidization, and embryonic lethality, whereas a smaller fused chromosome composed of chromosomes 4 and 5 was able to be passed on to homozygous offspring. Our results suggest the feasibility of chromosome-level engineering in mammals.

Novel recycling application of high volume municipal solid waste incineration bottom ash (MSWIBA) into sustainable concrete.

Since municipal solid waste incineration bottom ash (MSWIBA) contains some heavy metals that are harmful to the groundwater and soil, this study proposes an effective and new approach to deal with high-volume MSWIBA. Selecting 70% MSWIBA, 10% ordinary Portland cement (OPC), 10% fly ash/ground granulated blast furnace slag (FA/GGBFS), and 1% volume of polypropylene (PP) fiber as the raw materials, this project designed and manufactured cold-bonded fiber aggregates (CBFAs) and applied them into sustainable concrete. It was found that the water absorption of CBFAs was between 12 and 14%, the bulk density was between 900 and 1100 kg/m3, and the compressive strength of single particle was greater than 1.8 MPa. And it was found that the mechanical strength and bulk density of CBFAs were positively correlated, while the mechanical strength and water absorption were negatively correlated. The leaching behaviors of CBFAs on Cu, Pb, Cd, and Cr were successfully suppressed to less than 1% of that originally from MSWIBA, which can be in line with the Chinese standards. Additionally, it is also found that the green concrete with adding GGBFS-CBFAs has higher overall fluidity and better mechanical properties than the concrete with FA-CBFAs. The mechanical properties of concrete were the best under the replacement rate of 60% of CFBAs, and the strength of green concrete added with GGBFS-CBFAs reached 96% of that of ordinary concrete. In this study, the rapid chloride ion penetration test, mercury intrusion and electron microscope tests found that the bonding effect between the CBFAs and the green concrete matrix was better, and the pore structure in the transition zone of the surrounding interface was refined. The proportion of transition pores in the pore structure was up to 59%. This shows that the concrete added with CBFAs has better resistance to chloride ion diffusion, and has some improvement on the durability. This research suggests that CBFAs including high volume MSWIBA has the potential to be successfully applied as the alternative to natural aggregates in sustainable concrete, and this can also advance waste recycling, and solidify high volume heavy metals in infrastructures.