Publications by authors named "Xinhui Wang"

256 Publications

Phosphorus equivalency of phytase with various evaluation indicators of meat duck.

Poult Sci 2021 Apr 27;100(11):101216. Epub 2021 Apr 27.

College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China. Electronic address:

The objective of the present experiment was to determine the efficacy and the phosphorus (P) equivalency of phytase in the corn-soybean meal-rapeseed meal diets of Cherry Valley ducks from 1 to 35 d of age. 320 ducks were randomly divided into 8 blocks of 5 cages with 8 ducks per cage. This experiment included eight treatments diets. The available P levels of I to IV treatments were respectively 0.25%, 0.32%, 0.39%, 0.46% (d 1-14) and 0.20%, 0.27%, 0.34%, 0.41% (d 15-35). And 4 levels of phytase added to low-P basal diet (treatment I) with 300, 600, 900, and 1,200 U/kg (treatment V to VIII). Among them, treatment IV was a P-adequate positive control, treatment I was a low-P negative control. The ratio of calcium (Ca) to P was 1.3:1 for all diets. The other nutritional indexes in all diets were basically the same. Ducks were provided ad libitum access to water and experimental diets. The negative control diet reduced (P < 0.05) body weight, carcase weight, eviscerated weigh, breast muscle weight, leg muscle weight, bone ash, tibia Ca and tibia P, and increasing levels of available P and supplementary phytase significantly (P < 0.05) improved the growth performance and slaughtering performance of meat ducks. Phytase supplementation at a dose of 900 U/kg in the low-P basal diet increased the growth performance of ducks to a level comparable to that of a P-adequate diet. The available P level of 0.39% (1-14 d) and 0.34% (15-35 d) could meet the nutritional needs of meat ducks for P, and the apparent P utilization rate was high, and the effective utilization effect of P was the best. In addition, with the evaluation indexes of feed intake, body weight gain, tibia ash, tibia Ca, tibia P, content of blood Ca and P, the addition of 500 U/kg phytase could release available P of 0.02%, 0.02%, 0.02%, 0.02%, 0.01%, 0.04%, and 0.03%, respectively. In the same way, the addition of 1,000 U/kg phytase could release available phosphorus of 0.14%, 0.04%, 0.04%, 0.05%, 0.02%, 0.12%, and 0.01%, respectively.
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http://dx.doi.org/10.1016/j.psj.2021.101216DOI Listing
April 2021

Ambient Air Pollution and Long-Term Trajectories of Episodic Memory Decline among Older Women in the WHIMS-ECHO Cohort.

Environ Health Perspect 2021 Sep 13;129(9):97009. Epub 2021 Sep 13.

Department of Neurology, University of Southern California, Los Angeles, California, USA.

Background: Episodic memory decline varies by age and underlying neuropathology. Whether ambient air pollution contributes to the heterogeneity of episodic memory decline in older populations remains unclear.

Objectives: We estimated associations between air pollution exposures and episodic memory decline according to pollutant, exposure time window, age, and latent class subgroups defined by episodic memory trajectories.

Methods: Participants were from the Women's Health Initiative Memory Study-Epidemiology of Cognitive Health Outcomes. Older women (; 74-92 years of age) completed annual (2008-2018) episodic memory assessments using the telephone-based California Verbal Learning Test (CVLT). We estimated 3-y average fine particulate matter [PM with an aerodynamic diameter of ()] and nitrogen dioxide () exposures at baseline and 10 y earlier (recent and remote exposures, respectively), using regionalized national universal kriging. Separate latent class mixed models were used to estimate associations between interquartile range increases in exposures and CVLT trajectories in women and , adjusting for covariates.

Results: Two latent classes were identified for women (), "slow-decliners" { [95% confidence interval (CI): , ] and "fast-decliners" [ (95% CI: , )]}. In the slow-decliner class, but not the fast-decliner class, exposures were associated with a greater decline in CVLT scores over time, with a stronger association for recent vs. remote exposures [ (95% CI: , ) per and (95% CI: , 0.01) per , respectively]. Among women (), the largest latent class comprised "steady-decliners" [ (95% CI: , )], whereas the second class, "cognitively resilient", had no decline in CVLT on average. was not associated with episodic memory decline in either class. A increase in recent was associated with nonsignificant acceleration of episodic memory decline in the -y-old fast-decliner class [ (95% CI: , 0.04)], and in the cognitively resilient class [ (95% CI: , 0.03)] and steady-decliner class [ (95% CI: , 0.05)]. Associations with recent exposure in women were stronger and statistically significant when 267 women with incident probable dementia were excluded [e.g., (95% CI: , ) for the cognitively resilient class]. In contrast with changes in CVLT over time, there were no associations between exposures and CVLT scores during follow-up in any subgroup.

Discussion: In a community-dwelling U.S. population of older women, associations between late-life exposure to ambient air pollution and episodic memory decline varied by age-related cognitive trajectories, exposure time windows, and pollutants. https://doi.org/10.1289/EHP7668.
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http://dx.doi.org/10.1289/EHP7668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437247PMC
September 2021

Yangyin Fuzheng Jiedu Prescription exerts anti-tumor immunity in hepatocellular carcinoma by alleviating exhausted T cells.

Phytomedicine 2021 Oct 19;91:153722. Epub 2021 Aug 19.

Center for Integrative Medicine, Beijing Ditan Hospital Capital Medical University, Beijing 100015, PR China. Electronic address:

Background: Yangyin Fuzheng Jiedu Prescription (YFJP), a formulated Chinese herbal medicine, has been used for several decades in the treatment of hepatocellular carcinoma (HCC). Previous studies have demonstrated its anti-tumor efficacy, but the mechanism of action remains uncharacterized. This study aims to evaluate the therapeutic effect of YFJP on H22 tumor-bearing mice.

Purpose: This study aimed to evaluate the therapeutic effect of YFJP on H22 tumor-bearing mice.

Methods: A total of 50 male H22 tumor-bearing mice were randomly divided into 6 groups and continuous administered either different doses of YFJP or cyclophosphamide (CTX) or normal saline. for 2 weeks. The tumor appearance was observed by taking photos, and the tumor volume, weight, spleen and thymus index were calculated. Morphology of tumor infiltrating lymphocytes and the CD8 T lymphocytes were detected through HE staining immunohistochemistry respectively. The frequency of CD3, CD8 T cell subsets and co-inhibitory receptors PD-1, TIGIT, Tim-3 on CD8 T cell in spleen, peripheral blood and tumor tissue was performed by flow cytometry. Meanwhile, the killing and apoptotic functions of CD8 T cells in tumor tissues were also detected by the same method. The levels of cytokines in peripheral blood were detected by Milliplex map mouse highs sensitivity T Cell kit. The expression of T cell transcription factor T-bet and Eomes in tumor tissues were observed by Western blot.

Results: We found that YFJP could effectively inhibit the solid tumor growth and spleen indexes, but showed little effect on the body weight in the established mouse model of HCC. Furthermore, we investigated the effect of YFJP on the phenotypic and functional changes of T cells. The results showed that YFJP could maintain the high ratio of CD3 and CD8 T cells in the peripheral blood, spleen, and tumor tissues while decreasing the expression of programmed cell death-1 (PD-1), T cell immunoglobulin and ITIM domain (TIGIT), T cell immunoglobulin domain and mucin domain-3 (Tim-3) in CD8 T cells, respectively. Surprisingly, PD-1/Tim-3 double-positive T cells in the peripheral blood and tumor tissues were significantly decreased. Additionally, YFJP restored the cytotoxicity of tumor-infiltrating T cells and delayed their apoptosis in H22 tumor-bearing mice. In addition, treatment with YFJP significantly decreased the expression of inflammatory and immunosuppressive cytokines (including IL-1β, IL-6, and IL-10) in the serum and tumor tissues whereas enhancing that of effector cytokines TNF-α, and IFN-γ. Moreover, T cell transcription factors T-bet increased and Eomes degraded in the tumor tissues upon YFJP treatment.

Conclusion: In conclusion, these results demonstrated that YFJP could simultaneously exert anti-tumor immune response in H22 tumor-bearing mice by alleviating T cell exhaustion and immunosuppression.
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http://dx.doi.org/10.1016/j.phymed.2021.153722DOI Listing
October 2021

Identification of effective natural PIK3CA H1047R inhibitors by computational study.

Aging (Albany NY) 2021 08 20;13(16):20246-20257. Epub 2021 Aug 20.

Department of Breast Surgery, The First Hospital of Jilin University, Changchun, China.

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with a poor prognosis and a high recurrence rate. gene is frequently mutated in breast cancer, with as the hotspot mutation reported in TNBC. We used the ZINC database to screen natural compounds that could be structurally modified to develop drugs targeting the PIK3CA H1047R mutant protein in the PI3K pathway. The LibDock module showed that 2,749 compounds could strongly bind to the PIK3CA H1047R protein. Ultimately, the top 20 natural ligands with high LibDock scores were used for further analyses including assessment of ADME (absorption, distribution, metabolism, and excretion), toxicity, stability, and binding affinity. ZINC000004098448 and ZINC000014715656 were selected as the safest drug candidates with strong binding affinity to PIK3CA H1047R, no hepatotoxicity, less carcinogenicity, better plasma protein binding (PPB) properties, and enhanced intestinal permeability and absorption than the two reference drugs, PKI-402 and wortmannin. Moreover, their lower potential energies than those of PIK3CA H1047R confirmed the stability of the ligand-receptor complex under physiological conditions. ZINC000004098448 and ZINC000014715656 are thus safe and stable leads for designing drugs against PIK3CA H1047R as part of a targeted therapeutic approach for patients with TNBC.
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http://dx.doi.org/10.18632/aging.203409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436935PMC
August 2021

Application of unilateral external fixation by the "joystick technique" in the treatment of pediatric tibia shaft fractures: technical note.

J Orthop Surg Res 2021 Aug 12;16(1):493. Epub 2021 Aug 12.

Emergency, Trauma Center, The Third Hospital of Hebei Medical University, No.139 Ziqiang Road of Qiao'xi District, Shijiazhuang, 050000, Hebei, China.

Background: The aims of current study were to present the clinical outcomes in patients with pediatric tibia shaft fractures who were treated with unilateral external fixation combined with joystick for fracture reduction and describe the details of our technique.

Methods: We retrospectively analyzed the patients with pediatric tibia shaft fractures who were treated with unilateral external fixation combined with joystick for fracture reduction between July 2018 and March 2020. The clinical outcomes were evaluated.

Results: A total of 23 patients were included in the current study with the average age of 8.0 years (ranged 4-14 years). The average duration of hospital and follow-up were 5.9 days (ranged 4-8 days) and 17.4 months (ranged 8-27 months), respectively. At postoperative 3 days, the visual analog scale (VAS) score was 3.1 ± 1.43, which was significantly lower than the preoperative score of 7.3 ± 1.5. Of these, 2 cases showed redness and swelling of pin-tract and exudation at postoperative 1 month, who improved after oral antibiotics without causing fixation failure. The average time to full weight-bearing without crutches was 5.1 weeks (ranged 3-8 weeks). All patients achieved fracture healing and good functional recovery. No complications including fixation failure, reoperation, epiphyseal injury occurred, infection around implants, vessel damage, nerve damage, and limitation of joint movement were observed. The Johner-Wruh scores showed that 21 cases (91.3%) were "excellent" and 2 cases (8.7%) were "good."

Conclusions: This procedure had advantages of simple operation, minimum trauma, early recovery of lower limb function, and no risk of complications. It may provide a new choice for children with tibia shaft fractures who require surgical treatment.
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http://dx.doi.org/10.1186/s13018-021-02625-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359599PMC
August 2021

Racial/Ethnic Disparities in Alzheimer's Disease Risk: Role of Exposure to Ambient Fine Particles.

J Gerontol A Biol Sci Med Sci 2021 Aug 12. Epub 2021 Aug 12.

University of Southern California.

Background: Whether racial/ethnic disparities in Alzheimer's disease (AD) risk may be explained by ambient fine particles (PM2.5) has not been studied.

Methods: We conducted a prospective, population-based study on a cohort of Black (n=481) and White (n=6004) older women (aged 65-79) without dementia at enrollment (1995-98). Cox models accounting for competing risk were used to estimate the hazard ratio (HR) for racial/ethnic disparities in AD (1996-2010) defined by DSM-IV and the association with time-varying annual average PM2.5 (1999-2010) estimated by spatiotemporal model.

Results: Over an average follow-up of 8.3 (±3.5) years with 158 incident cases (21 in Black women), the racial disparities in AD risk (range of adjusted HRBlack women = 1.85-2.41) observed in various models could not be explained by geographic region, age, socioeconomic characteristics, lifestyle factors, cardiovascular risk factors, and hormone therapy assignment. Estimated PM2.5 exposure was higher in Black (14.38±2.21 µg/m 3) than in White (12.55±2.76 µg/m 3) women, and further adjustment for the association between PM2.5 and AD (adjusted HRPM2.5 = 1.18-1.28) slightly reduced the racial disparities by 2-6% (HRBlack women = 1.81-2.26). The observed association between PM2.5 and AD risk was ~2 times greater in Black (HRPM2.5 = 2.10-2.60) than in White (HRPM2.5 = 1.07-1.15) women (range of interaction Ps: <.01 to .01). We found similar results after further adjusting for social engagement (social strain; social support; social activity; living alone), stressful life events, WHI clinic sites, and neighborhood socioeconomic characteristics.

Conclusions: PM2.5 may contribute to racial/ethnic disparities in AD risk and its associated increase in AD risk was stronger amongst Black women.
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http://dx.doi.org/10.1093/gerona/glab231DOI Listing
August 2021

Differentially Expressed Circular Non-coding RNAs in Atherosclerotic Aortic Vessels and Their Potential Functions in Endothelial Injury.

Front Cardiovasc Med 2021 7;8:657544. Epub 2021 Jul 7.

Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics; Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China.

Circular non-coding RNA (circRNA) has a variety of biological functions. However, the expression profile and potential effects of circRNA on atherosclerosis (AS) and vascular endothelial injury have not been fully elucidated. This study aims to identify the differentially expressed circRNAs in atherosclerotic aortic vessels and predict their potential functions in endothelial injury. ApoE-/- mice were fed with high-fat diet for 12 weeks to induce AS. Atherosclerotic plaques were evaluated by H&E and Masson staining and immunohistochemistry; differentially expressed circRNAs were detected by Arraystar Circular RNA Microarray and verified by RT-PCR; the potential target mircoRNAs of circRNAs were predicted by miRanda, Tarbase, Targetscan and their expression changes were verified by RT-PCR; the potential target genes of mircoRNAs were predicted by Targetscan and verified by Western blot; the signaling pathways that they might annotate or regulate and their potential functions in vascular endothelial injury were predicted by gene enrichment analysis. Fifty two circRNAs were up-regulated more than twice and 47 circRNAs were down-regulated more than 1.5 times in AS aortic vessels. Mmmu_circRNA_36781 and 37699 were up-regulated both in AS aortic vessels and HO-treated mouse aortic endothelial cells (MAECs). The expression of miR-30d-3p and miR-140-3p, the target microRNA of circRNA_37699 and circRNA_36781, were downregulated both in AS vessels and HO-treated MAECs. On the contrary, MKK6 and TP53RK, the potential target gene of miR-140-3p and miR-30d-3p, were upregulated both in AS aortic roots and HO-treated MAECs. Besides, gene enrichment analysis showed that MAPK and PI3K-AKT signaling pathway were the most potential signaling pathways regulated by the differentially expressed circRNAs in atherosclerosis. Mmu_circRNA_36781 (circRNA ABCA1) and 37699 (circRNA KHDRBS1) were significantly up-regulated in AS aortic vessels and HO-treated MAECs. They have potential regulatory effects on atherosclerosis and vascular endothelial injury by targeting miR-30d-3p-TP53RK and miR-140-3p-MKK6 axis and their downstream signaling pathways.
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http://dx.doi.org/10.3389/fcvm.2021.657544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294331PMC
July 2021

Salidroside activates the AMP-activated protein kinase pathway to suppress non-alcoholic steatohepatitis.

Hepatology 2021 Jul 22. Epub 2021 Jul 22.

Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China.

Background & Aims: Nonalcoholic steatohepatitis (NASH) is becoming a leading cause of liver cirrhosis and hepatocellular carcinoma (HCC). Salidroside (p-hydroxyphenethyl-β-d-glucoside) has various biological and pharmacological activities, including anti-inflammatory, antioxidant and anticancer activities. However, the therapeutic effect and underlying molecular mechanism of salidroside in NASH remain to be further clarified.

Methods & Results: In this study, we found that salidroside alleviated lipid accumulation and inflammatory response in primary hepatocytes after palmitic acid/oleic acid (PO) stimulation. In addition, salidroside effectively prevented high-fat/high-cholesterol (HFHC) diet induced NASH progression by regulating glucose metabolism dysregulation, insulin resistance, lipid accumulation, inflammation and fibrosis. Mechanistically, integrated RNA sequencing and bioinformatic analysis showed that salidroside promoted AMPK signaling pathway activation in vitro and in vivo, and this finding was further verified by determining the phosphorylation levels of AMPK. Furthermore, the protective effects of salidroside on lipid accumulation and inflammation in hepatocytes and livers induced by PO- or HFHC- stimulation were blocked by AMPK interruption.

Conclusion: Our studies demonstrate that salidroside protects against metabolic stress-induced NASH progression through activation of AMPK signaling, indicating that salidroside could be a potential new drug component for NASH therapy.
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http://dx.doi.org/10.1002/hep.32066DOI Listing
July 2021

The consequences of using different epoch lengths on the classification of accelerometer based sedentary behaviour and physical activity.

PLoS One 2021 15;16(7):e0254721. Epub 2021 Jul 15.

Department of Public and Occupational Health, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Public Health research institute, Amsterdam, The Netherlands.

We examined the influence of using different epoch lengths on the classification accuracy of laboratory-controlled sedentary behaviour (SB), and free-living total time and time spent in bouts of SB and moderate-to-vigorous physical activity (MVPA), in children and adolescents. We used two studies including accelerometer-derived data of: 1) controlled activities, i.e. seven sedentary, one standing and one dancing (n = 90); 2) free-living activities (n = 902). For the controlled-activity data, we calculated percentages of time classified as SB and MVPA. For the free-living data, we calculated medians (25th-75th percentiles) of total time and time spent in bouts of SB and MVPA. Applying 8counts/5seconds, 25counts/15seconds and 100counts/60seconds for SB on controlled-activity data revealed respectively (1) 92-96%, 89-99% and 98-100% of sedentary time accurately classified as SB (activity- and age-dependent); (2) 91-98%, 88-99% and 97-100% of standing time classified as SB (age-dependent); (3) 25-37%, 20-25% and 25-38% of dancing time classified as SB (age-dependent). Using longer epochs, children's total time in SB and MVPA decreased while time accumulated in bouts of SB and MVPA accumulated in bouts increased. We conclude that a 60-second epoch seems preferable when the aim is to classify sedentary behaviour, while a shorter epoch length is needed to capture children's short bursts of MPVA. Furthermore, we should be aware that a longer epoch results in averaging of intensities to the middle category.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254721PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282067PMC
July 2021

Computational study on novel natural inhibitors targeting BCL2.

Med Oncol 2021 Jul 14;38(8):94. Epub 2021 Jul 14.

Department of Neurosurgery, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.

Ideal lead compounds and candidate drugs with inhibitory effect on BCL2 were screened from ZINC database, which laid a foundation for drug development and compound improvement of drug treatment for diffuse large B-cell lymphoma (DLCBL). Identification of potential BCL2 inhibitors by computer-aided virtual screening. Libdock was applied to 17,931 compounds and the top 20 were selected for further analysis. Selected compounds were performed absorption, distribution, metabolism, and excretion (ADME) and toxicity prediction. The binding affinity between the selected ligands and BCL2 was confirmed by Molecular docking. The new natural compounds, ZINC00000255131 and ZINC00013298233, were found to bind closely with BCL2. Furthermore, they all scored lower in ames-induced mutagenicity, rodent carcinogenicity, non-developmental toxicity potential, and cytochrome P4502D6 tolerance. Molecular dynamics simulation shows that the combinations of ZINC00000255131 and ZINC00013298233 with BCL2 in the natural environment are more stable. Two new compounds, ZINC00000255131 and ZINC00013298233, were found to be potential inhibitors of BCL2. These compounds have been proved to be safe, which is of great significance for the development and improvement of DLCBL drugs.
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http://dx.doi.org/10.1007/s12032-021-01513-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280014PMC
July 2021

TIGIT TIM-3 NK cells are correlated with NK cell exhaustion and disease progression in patients with hepatitis B virus‑related hepatocellular carcinoma.

Oncoimmunology 2021 28;10(1):1942673. Epub 2021 Jun 28.

Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

The prognosis of hepatocellular carcinoma (HCC) is extremely poor, of which hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) accounts for the majority in China. Immune checkpoint inhibitors have become an effective immunotherapy method for the treatment of HCC, but they are mainly used for T cells. NK cells play a vital role as the first line of defense against tumors. Therefore, we explored the characteristic expression pattern of immune checkpoints on NK cells of HBV-HCC patients. We analyzed the correlation between the co-expression of TIGIT and TIM-3 and the clinical progress of patients with HBV-HCC. The co-expression of TIGIT and TIM-3 on NK cells is elevated in patients with HBV-HCC. TIGITTIM-3NK cells showed exhausted phenotypic characteristics and displayed dysfunction manifested as weakened killing function, reduced cytokine production, and proliferation function. TIGITTIM-3NK cells participate in NK cells function exhaustion and are closely related to the disease progression of patients with HBV-HCC, suggesting a new target for future immunotherapy.
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http://dx.doi.org/10.1080/2162402X.2021.1942673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244763PMC
August 2021

A new Ti-based IMAC nanohybrid with high hydrophilicity and enhanced absorption capacity for the selective enrichment of phosphopeptides.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 Aug 29;1179:122851. Epub 2021 Jun 29.

College of Life Sciences, Nanjing Normal University, Nanjing 210023, China. Electronic address:

Ti-based immobilized metal affinity chromatography (IMAC) nanomaterial has shown high potential in phosphoproteome mass-spectrometric (MS) analysis. However, the limited surface area and poor solubility will greatly restrict its use in phosphoproteome research. To overcome these two key drawbacks, a novel Ti-based IMAC nanomaterial was prepared by Ti-bonded β-cyclodextrin (β-CD) anchored on the surface of carbon nanotubes (CNTs) (denoted as COOH-CNTs-CD-Ti) and successfully applied as a biofunctional adsorbent for selectively enriching trace phosphopeptides. In the selective enrichment process, CNTs provided greater surface area for the absorption of phosphopeptides, while β-CD also offered a greater opportunity for the interaction between phosphopeptides and Ti. COOH-CNTs-CD-Ti with the aforementioned properities exhibited higher selectivity for phosphopeptides from the standard protein digests, the tryptic digests of nonfat milk and human serum, showing a great selective enrichment capability towards complex biological samples.
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http://dx.doi.org/10.1016/j.jchromb.2021.122851DOI Listing
August 2021

Synthesis and Characterization of Hyperbranched and Organosilicone Modified Waterborne Polyurethane Acrylates Photosensitive Resin.

Polymers (Basel) 2021 Jun 22;13(13). Epub 2021 Jun 22.

College of Marine Science and Biological Engineering, Qingdao University of Science & Technology, Qingdao 266042, China.

A new type of waterborne polyurethane acrylate was synthesized for use as a UV curing coating. The N,N-dihydroxy methyl ethyl-3-Methyl aminopropanoate monomer was first prepared via adding reactions of methyl acrylate and diethanol amine with methyl alcohol as the solvent. Then, the hyperbranched prepolymer was obtained by addition of trimethylolpropane with toluenesulfonic acid as catalyst and N,N-dimethyl formamide as solvent. The resulting hyperbranched and organosilicone modified waterborne polyurethane acrylates was synthesized through the mixed reaction of prepolymer and Hydroxy silicone oil, polyethylene glycol-1000, toluene diisocynate, dimethylolpropionic acid, 1,2-propylene glycol, hydroxyethyl acrylate, and triethylamine with dibutyltin dilaurate as the catalyst. The molecular structures were characterized by FT-IR and H NMR spectroscopy and GPC analysis and the thermal stability was studied by using TGA. Moreover, the influence of contemodnt of hydroxyl silicone oil, dimethylolpropionic acid, polyethylene glycol-1000, and prepolymer to various of properties such as glossiness, hardness, adhesive force, abrasion resistance, water absorption, elongation at break and tensile strength of films were analyzed. The temperature and catalyst dosage impact on percent conversion of isocyanate group (-NCO) were also studied. It was proven that the best dosage of hydroxyl silicone oil and dimethylolpropionic acid were 4.6%, the dosage of polyethylene glycol-1000 was 50%, and the amount of hyperbranched prepolymer was 0.5%, which could make the film achieve the optimum properties. The percent conversion of isocyanate group (-NCO) was maximum when reacting two hours at 80 °C with 0.2% catalyst.
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http://dx.doi.org/10.3390/polym13132039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271574PMC
June 2021

Genetic support of a causal relationship between iron status and type 2 diabetes: a Mendelian randomization study.

J Clin Endocrinol Metab 2021 Jun 19. Epub 2021 Jun 19.

The Fourth Affiliated Hospital, School of Public Health, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China.

Context: Iron overload is a known risk factor for type 2 diabetes (T2D); however, both iron overload and iron deficiency have been associated with metabolic disorders in observational studies.

Objective: Using Mendelian randomization (MR), we assessed how genetically predicted systemic iron status affected T2D risk.

Design And Methods: A two-sample MR analysis was used to obtain a causal estimate. We selected genetic variants strongly associated (P < 5×10 -8) with four biomarkers of systemic iron status from a study involving 48,972 subjects performed by the Genetics of Iron Status consortium and applied these biomarkers to the T2D case-control study (74,124 cases and 824,006 controls) performed by the Diabetes Genetics Replication and Meta-analysis consortium. The simple median, weighted median, MR-Egger, MR analysis using mixture-model, weighted allele scores, and MR based on Bayesian model averaging approaches were used for the sensitivity analysis.

Results: Genetically instrumented serum iron (OR: 1.07; 95% CI: 1.02-1.12), ferritin (OR: 1.19; 95% CI: 1.08-1.32), and transferrin saturation (OR: 1.06; 95% CI: 1.02-1.09) were positively associated with T2D. In contrast, genetically instrumented transferrin, a marker of reduced iron status, was inversely associated with T2D (OR: 0.91; 95% CI: 0.87-0.96).

Conclusions: Genetic evidence supports a causal link between increased systemic iron status and increased T2D risk. Further studies involving various ethnic backgrounds based on individual-level data and studies regarding the underlying mechanism are warranted for reducing the risk of T2D.
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http://dx.doi.org/10.1210/clinem/dgab454DOI Listing
June 2021

Dictionary learning constrained direct parametric estimation in dynamic myocardial perfusion PET.

IEEE Trans Med Imaging 2021 Jun 14;PP. Epub 2021 Jun 14.

In myocardial perfusion imaging with dynamic positron emission tomography (PET), direct parametric reconstruction from the projection data allows accurate modeling of the Poisson noise in the projection domain to provide more reliable estimate of the parametric images. In this study, we propose to incorporate a superior denoiser to efficiently suppress the unfavorable noise propagation during the direct reconstruction. The dictionary learning (DL) based sparse representation serves as a regularization term to constrain the intermediate K1 estimation. We rewrite the DL regularizer into a voxel-separable form to facilitate the decoupling of a DL penalized curve fitting from the reconstruction of dynamic frames. The nonlinear fitting is then solved by a damped Newton method with uniform initialization. Using simulated and patient 82Rb dynamic PET data, we study the performance of the proposed DL direct algorithm and quantitatively compare it with the indirect method with or without post-filtering, the direct reconstruction without regularization, and the quadratic penalty regularized direct algorithm. The DL regularized direct reconstruction achieves improved noise versus bias performance in the reconstructed K1 images as well as superior recovery of reduced myocardial blood flow defect. The dictionary learned from a 3D self-created hollow sphere image yields comparable results to those using the dictionary learned from the corresponding MR image. The uniform initialization has been shown to converge to similar K1 estimation to the result from initializing with the indirect reconstruction. To summarize, we demonstrate the potential of the proposed DL constrained direct parametric reconstruction in improving quantitative dynamic PET imaging.
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http://dx.doi.org/10.1109/TMI.2021.3089112DOI Listing
June 2021

Causal association of childhood obesity with cancer risk in adulthood: A Mendelian randomization study.

Int J Cancer 2021 10 1;149(7):1421-1425. Epub 2021 Jun 1.

College of Pharmacy, Faculty of Medicine, Hangzhou Normal University, Hangzhou, China.

In observational studies of children and adolescents, higher body weight has been associated with distinct disease outcomes, including cancer, in adulthood. Therefore, we performed a two-sample Mendelian randomization (MR) study to evaluate the causal effect of childhood obesity on long-term cancer risk. Single-nucleotide polymorphisms associated with higher childhood body mass index (BMI) from large-scale genome-wide association studies were used as genetic instruments. Summary-level data for 24 site-specific cancers were obtained from UK Biobank. We found that a 1-SD increase in childhood BMI (kg/m ) was significantly associated with a 60% increase in risk of pancreatic cancer (odds ratio [OR]: 1.60; 95% confidence interval [CI]: 1.12-2.28; P < 0.01) and a 47% increase in risk of esophageal cancer (OR: 1.47; 95% CI: 1.09-1.97; P < 0.01) in adults. In contrast, there was an inverse association of genetic predisposition to childhood obesity with throat (OR: 0.46; 95% CI: 0.27-0.79; P < 0.01) and breast cancer (OR: 0.77; 95% CI: 0.64-0.94; P < 0.01) in adult life. For the other 20 cancers studied, no statistically significant association was observed. Our MR analyses found causal effects of childhood obesity on several cancers. Maintaining a healthy weight should be emphasized during childhood and adolescence to prevent cancer risk later in life.
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http://dx.doi.org/10.1002/ijc.33691DOI Listing
October 2021

High TIL, HLA, and Immune Checkpoint Expression in Conventional High-Grade and Dedifferentiated Chondrosarcoma and Poor Clinical Course of the Disease.

Front Oncol 2021 12;11:598001. Epub 2021 Apr 12.

Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Purpose: The aim of this study was to characterize chondrosarcoma tumor infiltration by immune cells and the expression of immunologically relevant molecules. This information may contribute to our understanding of the role of immunological events in the pathogenesis of chondrosarcoma and to the rational design of immunotherapeutic strategies.

Patients And Methods: A tissue microarray (TMA) containing 52 conventional and 24 dedifferentiated chondrosarcoma specimens was analyzed by immunohistochemical staining for the expression of parameters associated with tumor antigen-specific immune responses, namely, CD4 and CD8 tumor infiltrating lymphocytes (TILs) and the expression of HLA class I heavy chain, beta-2 microglobulin (β2m), HLA class II and immune checkpoint molecules, B7-H3 and PD-1/PD-L1. The results were correlated with histopathological characteristics and the clinical course of the disease.

Results: CD8 TILs were present in 21% of the conventional and 90% of the dedifferentiated chondrosarcoma tumors tested. B7-H3 was expressed in 69% of the conventional and 96% of the dedifferentiated chondrosarcoma tumors tested. PD-1 and PD-L1 were expressed 53% and 33% respectively of the dedifferentiated tumors tested. PD-L1 expression was associated with shorter time to metastasis.

Conclusion: The tumor infiltration by lymphocytes suggests that chondrosarcoma is immunogenic. Defects in HLA class I antigen and expression of the checkpoint molecules B7-H3 and PD-1/PD-L1 suggest that tumor cells utilize escape mechanisms to avoid immune recognition and destruction. This data implies that chondrosarcoma will benefit from strategies that enhance the immunogenicity of tumor antigens and/or counteract the escape mechanisms.
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http://dx.doi.org/10.3389/fonc.2021.598001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071983PMC
April 2021

Improved low-dose positron emission tomography image reconstruction using deep learned prior.

Phys Med Biol 2021 May 20;66(11). Epub 2021 May 20.

MinFound Medical Systems Co., Ltd., Hangzhou, People's Republic of China.

Positron emission tomography (PET) is a promising medical imaging technology that provides non-invasive and quantitative measurement of biochemical process in the human bodies. PET image reconstruction is challenging due to the ill-poseness of the inverse problem. With lower statistics caused by the limited detected photons, low-dose PET imaging leads to noisy reconstructed images with much quality degradation. Recently, deep neural networks (DNN) have been widely used in computer vision tasks and attracted growing interests in medical imaging. In this paper, we proposed a maximum(MAP) reconstruction algorithm incorporating a convolutional neural network (CNN) representation in the formation of the prior. Rather than using the CNN in post-processing, we embedded the neural network in the reconstruction framework for image representation. Using the simulated data, we first quantitatively evaluated our proposed method in terms of the noise-bias tradeoff, and compared with the filtered maximum likelihood (ML), the conventional MAP, and the CNN post-processing methods. In addition to the simulation experiments, the proposed method was further quantitatively validated on the acquired patient brain and body data with the tradeoff between noise and contrast. The results demonstrated that the proposed CNN-MAP method improved noise-bias tradeoff compared with the filtered ML, the conventional MAP, and the CNN post-processing methods in the simulation study. For the patient study, the CNN-MAP method achieved better noise-contrast tradeoff over the other three methods. The quantitative enhancements indicate the potential value of the proposed CNN-MAP method in low-dose PET imaging.
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http://dx.doi.org/10.1088/1361-6560/abfa36DOI Listing
May 2021

A Pan-Histone Deacetylase Inhibitor Enhances the Antitumor Activity of B7-H3-Specific CAR T Cells in Solid Tumors.

Clin Cancer Res 2021 Jul 2;27(13):3757-3771. Epub 2021 Apr 2.

Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Purpose: The limited efficacy of chimeric antigen receptor (CAR) T-cell therapies with solid malignancies prompted us to test whether epigenetic therapy could enhance the antitumor activity of B7-H3.CAR T cells with several solid cancer types.

Experimental Design: We evaluated B7-H3 expression in many human solid cancer and normal tissue samples. The efficacy of the combinatorial therapy with B7-H3.CAR T cells and the deacetylase inhibitor SAHA with several solid cancer types and the potential underlying mechanisms were characterized with and experiments.

Results: B7-H3 is expressed in most of the human solid tumor samples tested, but exhibits a restricted expression in normal tissues. B7-H3.CAR T cells selectively killed B7-H3 expressing human cancer cell lines . A low dose of SAHA upregulated B7-H3 expression in several types of solid cancer cells at the transcriptional level and B7-H3.CAR expression on human transgenic T-cell membrane. In contrast, the expression of immunosuppressive molecules, such as CTLA-4 and TET2, by T cells was downregulated upon SAHA treatment. A low dose of SAHA significantly enhanced the antitumor activity of B7-H3.CAR T cells with solid cancers and , including orthotopic patient-derived xenograft and metastatic models treated with autologous CAR T-cell infusions.

Conclusions: Our results show that our novel strategy which combines SAHA and B7-H3.CAR T cells enhances their therapeutic efficacy with solid cancers and justify its translation to a clinical setting.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-2487DOI Listing
July 2021

Utilization of NaP zeolite synthesized with different silicon species and NaAlO from coal fly ash for the adsorption of Rhodamine B.

J Hazard Mater 2021 Aug 12;415:125627. Epub 2021 Mar 12.

Heilongjiang Key Laboratory of Oil & Gas Chemical Technology, Northeast Petroleum University, Daqing 163318, PR China; Education Ministry Key Lab of Resource Chemistry, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, PR China.

NaP zeolite was successfully synthesized by using various commercial silicon sources and NaAlO extracted from coal fly ash as raw materials. Multiple characterization methods were employed to investigate the effect of silicon sources on NaP zeolite. Adsorption performance and mechanism of NaP zeolite for Rhodamine B were surveyed. The product synthesized by fumed SiO at n(NaO)/n(SiO) = 0.70 presented single spherical morphology with the average grain size of 3.22 µm. The shearing of NaOH resulted in the formation of silicates with different polymerization degrees and silicates occurring in the forms of monomeric, dimeric, trimeric, long-chain, and cyclic oligomers, initiating an improvement in pore structure and morphology. The introduction of dynamic crystallization mode (with the rotating speed of 150 r/min) not only reduced grain size (from 3.22 µm to 1.78 µm) but also shortened crystallization time (from 12 h to 10 h) of NaP-fumed SiO. NaP zeolite had excellent adsorption performance for Rhodamine B with the removal rate of 98.26%. Adsorption behavior fitted well with pseudo-second-order kinetics and Langmuir isotherm adsorption equations. Adsorption process was endothermic and feasible. NaP zeolite had good regeneration and alkali resistance capacities. Adsorption manners mainly contained pore filling, electrostatic attraction, and hydrogen bonding, focused on physisorption.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125627DOI Listing
August 2021

Spatial variability of soil nutrients in seasonal rivers: A case study from the Guo River Basin, China.

PLoS One 2021 16;16(3):e0248655. Epub 2021 Mar 16.

The College of Environment and Planning, Henan University, Kaifeng, China.

Agricultural non-point source pollution refers that substance such as nitrogen and phosphorus cause water environment pollution through surface runoff and underground leakage in agricultural production activities. Water environment pollution related to agricultural non-point source pollution in the Huaihe River Basin is becoming more and more prominent. Therefore, it is necessary to analyze the characteristic of soil nutrient in cultivated land and explore the spatial variation and influencing factors of soil nutrients at the watershed scale. A total of 239 topsoil samples were collected from the Guo river basin, and the related factors of soil organic matter (SOM), total carbon (TC), total nitrogen (TN), total phosphorous (TP), total potassium (TK) and potential of hydrogen (PH) were studied by using descriptive statistics and geostatistical methods. The results showed that TK and PH were weak variation, while SOM, TC, TN and TP were medium variation. Soil pH, TP, TK, TC and SOM had moderate spatial variability, which was caused by both random factors and structural factors such as soil texture, soil type, fertilization and local ecological restoration management. Soil TN showed a strong spatial correlation, mainly due to soil texture and soil type. If the recommended fertilization amount is still given based on the average value of soil nutrients ignoring the spatial heterogeneity, it will not only affect crop production efficiency and fertilizer utilization, but may also cause greater environmental pollution. This study can provide a theoretical basis for the management of agro-ecological environments throughout the basin area.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248655PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963053PMC
March 2021

Smart transformable nanomedicines for cancer therapy.

Biomaterials 2021 04 2;271:120737. Epub 2021 Mar 2.

Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, PR China. Electronic address:

Despite that great progression has been made in nanoparticulate drug delivery systems (nano-DDS), multiple drug delivery dilemmas still impair the delivery efficiency of nanomedicines. Rational design of smart transformable nano-DDS based on the in vivo drug delivery process represents a promising strategy for overcoming delivery obstacle of nano-DDS. In recent years, tremendous efforts have been devoted to developing smart transformable anticancer nanomedicines. Herein, we provide a review to outline the advances in this emerging field. First, smart size-reducible nanoparticles (NPs) for deep tumor penetration are summarized, including carrier degradation-induced, protonation-triggered and photobleaching-induced size reduction. Second, emerging transformable nanostructures for various therapeutic applications are discussed, including prolonging tumor retention, reversing drug-resistance, inhibiting tumor metastasis, preventing tumor recurrence and non-pharmaceutical therapy. Third, shell-detachable nanocarriers are introduced, focusing on chemical bonds breaking-initiated, charge repulsion-mediated and exogenous stimuli-triggered shell detachment approaches. Finally, the future perspectives and challenges of transformable nanomedicines in clinical cancer therapy are highlighted.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120737DOI Listing
April 2021

A prognostic nomogram based on LASSO Cox regression in patients with alpha-fetoprotein-negative hepatocellular carcinoma following non-surgical therapy.

BMC Cancer 2021 Mar 8;21(1):246. Epub 2021 Mar 8.

Center for Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, People's Republic of China.

Background: Alpha-fetoprotein-negative hepatocellular carcinoma (AFP-NHCC) (< 8.78 ng/mL) have special clinicopathologic characteristics and prognosis. The aim of this study was to apply a new method to establish and validate a new model for predicting the prognosis of patients with AFP-NHCC.

Methods: A total of 410 AFP-negative patients with clinical diagnosed with HCC following non-surgical therapy as a primary cohort; 148 patients with AFP-NHCC following non-surgical therapy as an independent validation cohort. In primary cohort, independent factors for overall survival (OS) by LASSO Cox regression were all contained into the nomogram1; by Forward Stepwise Cox regression were all contained into the nomogram2. Nomograms performance and discriminative power were assessed with concordance index (C-index) values, area under curve (AUC), Calibration curve and decision curve analyses (DCA). The results were validated in the validation cohort.

Results: The C-index of nomogram1was 0.708 (95%CI: 0.673-0.743), which was superior to nomogram2 (0.706) and traditional modes (0.606-0.629). The AUC of nomogram1 was 0.736 (95%CI: 0.690-0.778). In the validation cohort, the nomogram1 still gave good discrimination (C-index: 0.752, 95%CI: 0.691-0.813; AUC: 0.784, 95%CI: 0.709-0.847). The calibration curve for probability of OS showed good homogeneity between prediction by nomogram1 and actual observation. DCA demonstrated that nomogram1 was clinically useful. Moreover, patients were divided into three distinct risk groups for OS by the nomogram1: low-risk group, middle-risk group and high-risk group, respectively.

Conclusions: Novel nomogram based on LASSO Cox regression presents more accurate and useful prognostic prediction for patients with AFP-NHCC following non-surgical therapy. This model could help patients with AFP-NHCC following non-surgical therapy facilitate a personalized prognostic evaluation.
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http://dx.doi.org/10.1186/s12885-021-07916-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938545PMC
March 2021

Effects of starter culture inoculation on microbial community diversity and food safety of Chinese Cantonese sausages by high-throughput sequencing.

J Food Sci Technol 2021 Mar 26;58(3):931-939. Epub 2020 Jun 26.

Chengdu Agricultural College, Chengdu, 611130 Sichuan Province China.

Effects of starter culture composed of , , and at the ratios (w/w) of 1:1:1:1 on bacterial community diversity and food safety of Chinese Cantonese sausages were demonstrated by high-throughput sequencing technology. At genus level, spoilage organisms and pathogenic bacteria such as spp., spp., spp., spp. accounted for 54.13%, 10.01%, 6.94% and 5.35% of bacterial in the initial fermentation of spontaneous sausage, and the dominant bacteria of spp. reached 84.61% on day 20. Accordingly, the total proportion of spp., spp. and spp. were present higher than 98% during fermentation in fermented sausage by starter culture inoculation, and spp. was dominant genus and increased from 53.53 to 74.09% during whole fermentation process. Moreover, the histamine accumulation was lower 84.17% in sausage fermented by starter culture inoculation than that of spontaneous sausage, suggesting that starter culture could decrease histamine accumulation of sausages significantly (< 0.01). These results revealed that the starter culture inoculation was conducive to improve the microbial quality and food safety of Chinese Cantonese sausages.
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http://dx.doi.org/10.1007/s13197-020-04607-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884565PMC
March 2021

Targeting Radiation-Resistant Prostate Cancer Stem Cells by B7-H3 CAR T Cells.

Mol Cancer Ther 2021 03;20(3):577-588

Division of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

Radiotherapy (RT) is a key treatment for prostate cancer. However, RT resistance can contribute to treatment failure. Prostate cancer stem cells (PCSCs) are radioresistant. We recently found that fractionated irradiation (FIR) upregulates expression of the immune checkpoint B7-H3 (CD276) on PCSCs and bulk cells in each prostate cancer cell line tested. These findings prompted us to investigate whether B7-H3 targeting chimeric antigen receptor (CAR) T cells, which may abrogate function of an immune checkpoint and mediate lysis of targeted cells, can target RT-resistant PCSCs and . B7-H3 expression is naturally higher on PCSCs than bulk prostate cancer cells and cytotoxicity of B7-H3 CAR T cells to PCSCs is more potent than to bulk prostate cancer cells. Furthermore, FIR significantly upregulates B7-H3 expression on PCSCs and bulk prostate cancer cells. The duration of FIR or single-dose irradiation-induced further upregulation of B7-H3 on bulk prostate cancer cells and PCSCs lasts for up to 3 days. B7-H3 CAR T-cell cytotoxicity against FIR-resistant PCSCs at a low effector to target ratio of 1:1 was assessed by flow cytometry and sphere formation assays. Further upregulation of B7-H3 expression by FIR made PCSCs even more sensitive to B7-H3 CAR T-cell-mediated killing. Consequently, the FIR and B7-H3 CAR T-cell therapy combination is much more effective than FIR or CAR T cells alone in growth inhibition of hormone-insensitive prostate cancer xenografts in immunodeficient mice. Our work provides a sound basis for further development of this unique combinatorial model of RT and B7-H3 CAR T-cell therapy for prostate cancer. SIGNIFICANCE: We demonstrate that FIR significantly upregulates B7-H3 expression by RT-resistant PCSCs and bulk cells; cytotoxicity of B7-H3 CAR T cells to FIR-treated PCSCs is potent and results in significantly improved antitumor efficacy in mice.
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http://dx.doi.org/10.1158/1535-7163.MCT-20-0446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952034PMC
March 2021

Gab2 deficiency suppresses high-fat diet-induced obesity by reducing adipose tissue inflammation and increasing brown adipose function in mice.

Cell Death Dis 2021 02 26;12(2):212. Epub 2021 Feb 26.

School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Xiamen University, 361005, Xiamen, Fujian, China.

Obesity is caused by a long-term imbalance between energy intake and consumption and is regulated by multiple signals. This study investigated the effect of signaling scaffolding protein Gab2 on obesity and its relevant regulation mechanism. Gab2 knockout (KO) and wild-type (WT) mice were fed with a standard diet (SD) or high-fat diet (HFD) for 12 weeks. The results showed that the a high-fat diet-induced Gab2 expression in adipose tissues, but deletion of Gab2 attenuated weight gain and improved glucose tolerance in mice fed with a high-fat diet. White adipose tissue and systemic inflammations were reduced in HFD-fed Gab2 deficiency mice. Gab2 deficiency increased the expression of Ucp1 and other thermogenic genes in brown adipose tissue. Furthermore, the regulation of Gab2 on the mature differentiation and function of adipocytes was investigated in vitro using primary or immortalized brown preadipocytes. The expression of brown fat-selective genes was found to be elevated in differentiated adipocytes without Gab2. The mechanism of Gab2 regulating Ucp1 expression in brown adipocytes involved with its downstream PI3K (p85)-Akt-FoxO1 signaling pathway. Our research suggests that deletion of Gab2 suppresses diet-induced obesity by multiple pathways and Gab2 may be a novel therapeutic target for the treatment of obesity and associated complications.
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http://dx.doi.org/10.1038/s41419-021-03519-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910586PMC
February 2021

Transcatheter closure of coronary artery fistula draining into left ventricle: a long-term study.

Rev Esp Cardiol (Engl Ed) 2021 08 21;74(8):721-723. Epub 2021 Feb 21.

Department of Structural Heart Disease, Cardiovascular Institute and Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

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http://dx.doi.org/10.1016/j.rec.2021.01.008DOI Listing
August 2021

Targeting cancer stem cells by disulfiram and copper sensitizes radioresistant chondrosarcoma to radiation.

Cancer Lett 2021 05 11;505:37-48. Epub 2021 Feb 11.

Division of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA. Electronic address:

Overcoming the radiosensitivity of chondrosarcoma (CS), the second most common primary bone tumor, is needed. Radioresistance is attributed to cancer stem cells (CSCs) in many malignancies. Disulfiram (DSF), an FDA-approved anti-alcoholism drug, complexed with Cu (DSF/Cu) can radiosensitize epithelial CSCs. This prompted us to investigate the radiosensitizing effect of DSF/Cu on CS CSCs (CCSCs). The radiosensitizing effects of DSF/Cu on CCSCs were investigated in vitro using cell lines SW1353 and CS-1. Stemness was identified independently by flow cytometry for CCSCs (ALDHCD133), sphere-forming ability, and Western blot analysis of stemness gene protein expression. The radiosensitizing effect of DSF/Cu was studied in an orthotopic CS xenograft mouse model by analyzing xenograft growth and residual xenografts for stemness. CCSCs were found to be resistant to single-dose (IR) and fractionated irradiation (FIR). IR and FIR increased CS stemness. Combined with DSF/Cu in vitro and in vivo, IR and FIR eliminated CS stemness. RT + DSF/Cu was safer and more effective than either RT ± DSF in inhibiting growth of orthotopic CS xenografts. In conclusion, DSF/Cu radiosensitizes CCSCs. These results can be translated into clinical trials for CS patients requiring RT for improved outcomes.
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http://dx.doi.org/10.1016/j.canlet.2021.02.002DOI Listing
May 2021

Mass Spectrometry Guided Discovery and Design of Novel Asperphenamate Analogs From Reveals an Extraordinary NRPS Flexibility.

Front Microbiol 2020 15;11:618730. Epub 2021 Jan 15.

Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark.

Asperphenamate is a small peptide natural product that has gained much interest due to its antitumor activity. In the recent years numerous bioactive synthetic asperphenamate analogs have been reported, whereas only a handful of natural analogs either of microbial or plant origin has been discovered. Herein we describe a UHPLC-HRMS/MS and amino acid supplement approach for discovery and design of novel asperphenamate analogs. Chemical analysis of , a prolific producer of asperphenamate, revealed three previously described and two novel asperphenamate analogs produced in significant amounts, suggesting a potential for biosynthesis of further asperphenamate analogs by varying the amino acid availability. Subsequent growth on proteogenic and non-proteogenic amino acid enriched media, revealed a series of novel asperphenamate analogs, including single or double amino acid exchange, as well as benzoic acid exchange for nicotinic acid, with the latter observed from a natural source for the first time. In total, 22 new asperphenamate analogs were characterized by HRMS/MS, with one additionally confirmed by isolation and NMR structure elucidation. This study indicates an extraordinary nonribosomal peptide synthetase (NRPS) flexibility based on substrate availability, and therefore the potential for manipulating and designing novel peptide natural products in filamentous fungi.
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http://dx.doi.org/10.3389/fmicb.2020.618730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843940PMC
January 2021

Pulmonary MRI Radiomics and Machine Learning: Effect of Intralesional Heterogeneity on Classification of Lesion.

Acad Radiol 2021 Jan 22. Epub 2021 Jan 22.

School of Electronic and Information Engineering, Beijing Jiaotong University, Shangyuan Village No 3 in Haidian, Beijing, China.

Rationale And Objectives: To investigate the effect of intralesional heterogeneity on differentiating benign and malignant pulmonary lesions, quantitative magnetic resonance imaging (MRI) radiomics, and machine learning methods were adopted.

Materials And Methods: A total of 176 patients with multiparametric MRI were involved in this exploratory study. To investigate the effect of intralesional heterogeneity on lesion classification, a radiomics model called tumor heterogeneity model was developed and compared to the conventional radiomics model based on the entire tumor. In tumor heterogeneity model, each lesion was divided into five sublesions depending on the spatial location through clustering algorithm. From the five sublesions in multi-parametric MRI sequences, 1100 radiomics features were extracted. The recursive feature elimination method was employed to select features and support vector machine classifier was used to distinguish benign and malignant lesion. The performance of classification was evaluated with the receiver operating characteristic curve and the area under the curve (AUC) was the figure of merit. The 3-fold cross-validation (CV) with and without nesting was used to validate the model, respectively.

Results: The tumor heterogeneity model (AUC = 0.74 ± 0.04 and 0.90 ± 0.03, CV with and without nesting, respectively) outperforms conventional model (AUC = 0.68 ± 0.04 and 0.87 ± 0.03). The difference between the two models is statistically significant (p = 0.03) for lesions greater than 18.80 cm.

Conclusion: Intralesional heterogeneity influences the classification of pulmonary lesions. The tumor heterogeneity model tends to perform better than conventional radiomics model.
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http://dx.doi.org/10.1016/j.acra.2020.12.020DOI Listing
January 2021
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