Publications by authors named "Ke Zhang"

1,773 Publications

  • Page 1 of 1

A Long-Circulating Vector for Aptamers Based upon Polyphosphodiester-Backboned Molecular Brushes.

Angew Chem Int Ed Engl 2022 Aug 18. Epub 2022 Aug 18.

Northeastern University, Chemistry and Chemical Biology, 360 Huntington Ave, HT 102, 02115, Boston, UNITED STATES.

Aptamers face challenges for use outside the ideal conditions in which they are developed. These difficulties are most palpable in vivo due to nuclease activities, rapid clearance, and off-target binding. Herein, we demonstrate that a polyphosphodiester-backboned molecular brush can suppress enzymatic digestion, reduce non-specific cell uptake, enable long blood circulation, and rescue the bioactivity of a conjugated aptamer in vivo. The backbone along with the aptamer is assembled via solid-phase synthesis, followed by installation of poly(ethylene glycol) (PEG) side chains using a two-step process with near-quantitative efficiency. The synthesis allows for precise control over polymer size and architecture. Consisting entirely of building blocks that are generally recognized as safe for therapeutics, this novel molecular brush is expected to provide a highly translatable route for aptamer-based therapeutics.
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http://dx.doi.org/10.1002/anie.202204576DOI Listing
August 2022

Transjugular intrahepatic portosystemic shunt with radioactive seed strand for main portal vein tumor thrombosis with cirrhotic portal hypertension.

World J Gastrointest Surg 2022 Jun;14(6):567-579

Department of Interventional Therapy, Peking University Ninth School of Clinical Medicine, Beijing Shijitan Hospital, Beijing 100038, China.

Background: Patients with hepatocellular carcinoma complicated with main portal vein tumor thrombosis (mPVTT) and cirrhotic portal hypertension (CPH) have an extremely poor prognosis, and there is a lack of a clinically effective treatment paradigm.

Aim: To evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) combined with radioactive seed strand for the treatment of mPVTT patients with CPH.

Methods: The clinical data of 83 consecutive patients who underwent TIPS combined with I seed strand placement for mPVTT and CPH from January 2015 to December 2018 were retrospectively reviewed. Procedure-related data (success rate, relief of portal vein pressure and CPH symptoms, and adverse events), PVTT response, and patient survival were assessed through a 2-year follow-up.

Results: The success rate was 100.0% without perioperative death or procedure-related severe adverse events. The mean portal vein pressure was significantly decreased after the procedure (22.25 ± 7.33 mmHg 35.12 ± 7.94 mmHg, = 20.61, < 0.001). The symptoms of CPH were all effectively relieved within 1 mo. The objective response rate of PVTT was 67.5%. During a mean follow-up of 14.5 ± 9.4 mo (range 1-37 mo), the cumulative survival rates at 6, 12 and 24 mo were 83.1%, 49.7%, and 21.8%, respectively. The median survival time was 12.0 ± 1.3 mo (95% confidence interval: 9.5-14.5). In multivariate Cox regression analysis, body mass index, Child-Pugh grade, cTNM stage, and PVTT response were independent prognostic factors ( < 0.05).

Conclusion: TIPS combined with radioactive seed strand might be effective and safe in treating mPVTT patients with CPH.
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http://dx.doi.org/10.4240/wjgs.v14.i6.567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9258232PMC
June 2022

Event-Based Atmospheric Precipitation Uncovers Significant Even and Odd Hg Isotope Anomalies Associated with the Circumpolar Vortex.

Environ Sci Technol 2022 Aug 17. Epub 2022 Aug 17.

Key Laboratory of Environmental Geochemistry, Institute of Geochemistry, Chinese Academy of Sciences, Guiyang, Guizhou 550002, People's Republic of China.

The determination of the mass-independent fractionation of even Hg isotopes (even-MIF, ΔHg) in atmospheric samples adds another intriguing feature to the Hg isotope system. Despite our lack of sufficient experimental verification and the momentary absence of a valid mechanism to explain its occurrence, even-MIF could be instrumental in understanding the cycle and deposition of atmospheric Hg. In contrast to slightly positive ΔHg values (<0.30‰) frequently observed in most atmospheric samples, large ΔHg values (up to 1.24‰) determined in precipitation from Peterborough (Ontario, Canada) stand out and could provide valuable information for the origin of the even-MIF mystery. We now report a systematic analysis of high-resolution rainfall and snowfall samples collected in winter during cold weather at Peterborough, Canada. Dissolved and particulate Hg both displayed large variations of odd-MIF (from -0.93‰ to 2.02‰ for ΔHg), which may result from long-range transportation, as the negative odd-MIF in particulate Hg is likely a result of long-distance transport of arctic atmospheric Hg(II). Dissolved Hg revealed significant even-MIF values (from 0.25‰ to 1.19‰ for ΔHg) and a negative relationship between ΔHg and ΔHg, which provide further evidence for the previously proposed conceptual model of ΔHg. Disconnected odd-MIF and even-MIF trends were detected in sequentially collected precipitation samples, which further suggests different sources or mechanisms for ΔHg and ΔHg. Particularly, the high ΔHg values highlight the transport of stratospheric Hg through a polar vortex to the sampling region, stimulating further systematic investigation. The new ΔHg data for particulate Hg add to existing information on atmospheric Hg(II) worldwide, suggesting a global distribution of Hg characterized by even-MIF in the atmosphere, and further constrain the model of atmospheric Hg deposition.
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http://dx.doi.org/10.1021/acs.est.2c02613DOI Listing
August 2022

Cell- and non-cell-autonomous AUXIN RESPONSE FACTOR3 controls meristem proliferation and phyllotactic patterns.

Plant Physiol 2022 Aug 16. Epub 2022 Aug 16.

Ministry of Education Key Laboratory of Molecular and Cellular Biology, Hebei Key Laboratory of Molecular and Cellular Biology, College of Life Sciences, Hebei Normal University, Shijiazhuang, China; Hebei Collaboration Innovation Center for Cell Signaling, Shijiazhuang, China.

In cell-cell communication, non-cell-autonomous transcription factors play vital roles in controlling plant stem cell fate. We previously reported that AUXIN RESPONSE FACTOR3 (ARF3), a member of the ARF family with critical roles in floral meristem maintenance and determinacy, has a distinct accumulation pattern that differs from the expression domain of its encoding gene in the shoot apical meristem (SAM). However, the biological meaning of this difference is obscure. Here, we demonstrate that ARF3 expression in Arabidopsis (Arabidopsis thaliana) is mainly activated at the periphery of the SAM by auxin where ARF3 cell-autonomously regulates the expression of meristem-organ boundary-specific genes, such as CUP-SHAPED COTYLEDON1-3 (CUC1-3), BLADE ON PETIOLE1-2 (BOP1-2) and TARGETS UNDER ETTIN CONTROL3 (TEC3) to regulate the arrangement of organs in regular pattern, a phenomenon referred to as phyllotaxis. We also show that ARF3 is translocated into the organizing center where it represses cytokinin activity and WUSCHEL expression to regulate meristem activity non-cell-autonomously. Therefore, ARF3 acts as a molecular link that mediates the interaction of auxin and cytokinin signaling in the SAM while coordinating the balance between meristem maintenance and organogenesis. Our findings reveal an ARF3-mediated coordination mechanism through cell-cell communication in dynamic SAM maintenance.
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http://dx.doi.org/10.1093/plphys/kiac370DOI Listing
August 2022

High-Temperature-Resistant, Clean, and Environmental-Friendly Fracturing Fluid System and Performance Evaluation of Tight Sandstone.

J Environ Public Health 2022 3;2022:5833491. Epub 2022 Aug 3.

COSL-EXPRO Testing Services (Tianjin) Co., Ltd., Tianjin 300457, China.

Hydraulic fracturing, as an oil-water well stimulation and injection technology, is particularly important in the production and stimulation of low-permeability oil and gas fields, and the performance of the fracturing fluid directly affects the success of the fracturing operation. Compared with traditional water-based fracturing fluids, clean fracturing fluids have the advantages of strong sand-carrying ability and easy gel breaking with no residue. Aiming at the problem of poor temperature resistance and shear resistance of the clean fracturing fluid, based on previous research, this paper selects a high-temperature-resistant clean fracturing fluid system and evaluates the performance of the system. The research results show that the system has better rheological properties, better sand-carrying performance, shorter gel-breaking time, and less damage to the reservoir.
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http://dx.doi.org/10.1155/2022/5833491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9365598PMC
August 2022

Presenilin-1 F105C mutation leads to tau accumulation in human neurons via the Akt/mTORC1 signaling pathway.

Cell Biosci 2022 Aug 14;12(1):131. Epub 2022 Aug 14.

Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Background: The mammalian target of rapamycin (mTOR) plays a critical role in controlling cellular homeostasis, and its dysregulation has been implicated in Alzheimer's disease (AD). Presenilin-1 (PS1) mutations account for the most common causes of familial Alzheimer's disease (FAD); however, whether PS1 mutation causes mTOR dysregulation in human neurons remains a key unresolved issue.

Methods: We generated heterozygotes and homozygotes of PS1 F105C knock-in mutation in human induced pluripotent stem cells (iPSCs) via CRISPR/Cas9/piggyback-based gene editing and differentiated them into human neurons. Secreted Aβ and tau accumulation were determined by ELISA assay, immunofluorescence staining, and western blotting analysis. mTOR signaling was evaluated by western blotting analysis, immunofluorescence staining, and co-immunoprecipitation. Autophagy/lysosome activities were determined by LC3-based assay, LysoTracker Red staining, and DQ-Red BSA staining.

Results: Through comparison among these isogenic neurons, PS1 F105C mutant neurons exhibited elevated Aβ and tau accumulation. In addition, we found that the response of mTORC1 to starvation decreases in PS1 F105C mutant neurons. The Akt/mTORC1/p70S6K signaling pathway remained active upon EBSS starvation, leading to the co-localization of the vast majority of mTOR with lysosomes. Consistently, PS1 F105C neurons displayed a significant decline in starvation-induced autophagy. Notably, Torin1, a mTOR inhibitor, could efficiently reduce prominent tau pathology that occurred in PS1 F105C neurons.

Conclusion: We demonstrate that Chinese PS1 F105C mutation causes dysregulation of mTORC1 signaling, contributing to tau accumulation in human neurons. This study on inherited FAD PS1 mutation provides unprecedented insights into our understanding of the molecular mechanisms of AD. It supports that pharmaceutical blocking of mTOR is a promising therapeutic strategy for the treatment of AD.
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http://dx.doi.org/10.1186/s13578-022-00874-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9375916PMC
August 2022

Impact of inactivated SARS-CoV-2 vaccination on embryo ploidy: a retrospective cohort study of 133 PGT-A cycles in China.

Biol Res 2022 Aug 12;55(1):26. Epub 2022 Aug 12.

Center for Reproductive Medicine, Jiangxi Maternal and Child Health Hospital, 318 Bayi Avenue, Nanchang, 330006, China.

Background: Unsubstantiated concerns have been raised on the potential correlation between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and infertility, leading to vaccine hesitancy in reproductive-aged population. Herein, we aim to evaluate the impact of inactivated SARS-CoV-2 vaccination on embryo ploidy, which is a critical indicator for embryo quality and pregnancy chance.

Methods: This was a retrospective cohort study of 133 patients who underwent preimplantation genetic testing for aneuploidy (PGT-A) cycles with next-generation sequencing technology from June 1st 2021 to March 17th 2022 at a tertiary-care medical center in China. Women fully vaccinated with two doses of Sinopharm or Sinovac inactivated vaccines (n = 66) were compared with unvaccinated women (n = 67). The primary outcome was the euploidy rate per cycle. Multivariate linear and logistic regression analyses were performed to adjust for potential confounders.

Results: The euploidy rate was similar between vaccinated and unvaccinated groups (23.2 ± 24.6% vs. 22.6 ± 25.9%, P = 0.768), with an adjusted β of 0.01 (95% confidence interval [CI]: -0.08-0.10). After frozen-thawed single euploid blastocyst transfer, the two groups were also comparable in clinical pregnancy rate (75.0% vs. 60.0%, P = 0.289), with an adjusted odds ratio of 6.21 (95% CI: 0.76-50.88). No significant associations were observed between vaccination and cycle characteristics or other laboratory and pregnancy outcomes.

Conclusions: Inactivated SARS-CoV-2 vaccination had no detrimental impact on embryo ploidy during in vitro fertilization treatment. Our finding provides further reassurance for vaccinated women who are planning to conceive. Future prospective cohort studies with larger datasets and longer follow-up are needed to confirm the conclusion.
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http://dx.doi.org/10.1186/s40659-022-00395-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9372941PMC
August 2022

A translational mouse model for investigation of the mechanism of preterm diffuse white matter injury.

Transl Pediatr 2022 Jul;11(7):1074-1084

Department of Neonatology, Children's Hospital of Fudan University, Shanghai, China.

Background: The increasing incidence of preterm birth has led to a global problem of adverse neurodevelopmental outcomes in preterm neonates as a result of brain injury. There is still a lack of models mimicking diffuse white matter injury (WMI) in preterm neonates that can be applied to transgenic mice.

Methods: The right common carotid artery of the neonatal mouse was ligated on postnatal day 3 (P3) C57BL/6 mice and followed by 80, 90, or 100 min of hypoxia using a mixture of 10%±0.2% oxygen-nitrogen. The most suitable model was chosen by characterizing the effects of this hypoxic-ischemic insult on development of myelin, glial cell conditions, and neurological outcomes by hematoxylin-eosin (HE) staining performed at postnatal day 17 (P17), western blot measuring myelin basic protein (MBP) at postnatal day 10 (P10) and P17, immunofluorescence staining of MBP-neurofilament protein heavy chain (NFH), oligodendrocyte transcription factor-2 (Olig2)-adenomatous polyposis coli clone (CC1), glial fibrillary acidic protein (GFAP) and ionic calcium linker protein (Iba-1) at P17, electron microscopy observing myelin microstructure at postnatal day 52 (P52) and behavioral testing at postnatal day 45-50 (P45-P50).

Results: The 90-min group showed neuroanatomical changes in the ipsilateral side of the brain, the 80-min group showed minor changes, and the 100-min group showed severe injury. Mice in the 90-min group subsequently showed marked activation of astrocytes, augmentation of microglia, a notable decrease in expression of MBP with a normal level of NFH, long-term cognitive dysfunction, and impairment of the myelin ultrastructure in adulthood.

Conclusions: In conclusion, a mouse model of preterm diffuse WMI rather than cystic periventricular leukomalacia was successfully achieved by ligating one of the common carotid arteries on P3 followed by 90 min of hypoxia in a mixture of 10%±0.2% oxygen-nitrogen. The attempt provides an adequate translational animal model for elucidating the underlying mechanism.
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http://dx.doi.org/10.21037/tp-22-58DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9360811PMC
July 2022

The Complement System, Aging, and Aging-Related Diseases.

Int J Mol Sci 2022 Aug 4;23(15). Epub 2022 Aug 4.

Laboratory of Molecular Genetics of Aging and Tumor, Medical School, Kunming University of Science and Technology, 727 South Jing Ming Road, Kunming 650500, China.

The complement system is a part of the immune system and consists of multiple complement components with biological functions such as defense against pathogens and immunomodulation. The complement system has three activation pathways: the classical pathway, the lectin pathway, and the alternative pathway. Increasing evidence indicates that the complement system plays a role in aging. Complement plays a role in inflammatory processes, metabolism, apoptosis, mitochondrial function, and Wnt signaling pathways. In addition, the complement system plays a significant role in aging-related diseases, including Alzheimer's disease, age-related macular degeneration, and osteoarthritis. However, the effect of complement on aging and aging-related diseases is still unclear. Thus, a better understanding of the potential relationship between complement, aging, and aging-related diseases will provide molecular targets for treating aging, while focusing on the balance of complement in during treatment. Inhibition of a single component does not result in a good outcome. In this review, we discussed the research progress and effects of complement in aging and aging-related diseases.
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http://dx.doi.org/10.3390/ijms23158689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9369321PMC
August 2022

Correlation between hepatic venous pressure gradient and portal venous pressure gradient in hepatitis B cirrhosis with different hepatic veins anatomy.

Eur J Radiol 2022 Aug 6;155:110463. Epub 2022 Aug 6.

Department of Interventional Therapy, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China. Electronic address:

Purpose: The hepatic venous pressure gradient (HVPG) has been employed as the gold standard for indicating the portal venous pressure gradient (PPG) in the diagnosis of portal hypertension (PHT). However, little has been reported on whether the HVPG can accurately estimate the PPG in patients with hepatic vein collateral shunts. We aimed to explore the correlation between the HVPG and the PPG in hepatitis B cirrhosis patients with different hepatic vein anatomies.

Methods: A total of 461 hepatitis B cirrhosis patients with portal hypertension (PHT) who were treated with a transjugular intrahepatic portosystemic shunt (TIPS) between January 2016 and June 2020 were included. All patients underwent various venous pressure measurements and balloon-occluded compression hepatic venography during the TIPS operation. Agreements were evaluated by Pearson's correlation and the Bland-Altman method. Disagreements were assessed by paired t tests.

Results: The correlation coefficient (r) values (P < 0.001) between the HVPG and the PPG of the early (151 patients, 32.8 %), middle (73 patients, 15.8 %), late (46 patients, 10.0 %), portal vein (151 patients, 32.8 %), and no lateral branch development groups (40 patients, 8.7 %) were 0.373, 0.487, 0.569, 0.690, and 0.575, respectively; the determination coefficient (R) values were 0.139, 0.238, 0.323, 0.475, and 0.330, respectively. According to the Bland-Altman method, agreement was the greatest in the portal vein development group, with the 95 % limits of agreement (95 % LoA, mean differences ± 1.96 SD) being the smallest. The differences were statistically significant (P < 0.05).

Conclusion: The correlation between the HVPG and the PPG is the worst in early lateral branch development, followed by middle development, and the influence of lateral branches becomes significantly reduced in late development. Hepatic venous collateral formation is a vital factor for underestimation of the HVPG, which is the most accurate predictor of PPG in patients with portal vein development. Patients with no collateral channel development in the hepatic vein have a higher HVPG than PPG, which is an important reason for overestimation of the HVPG.
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http://dx.doi.org/10.1016/j.ejrad.2022.110463DOI Listing
August 2022

Clinical study of factors associated with pregnancy outcomes in pregnant women with systemic lupus erythematosus in the southern China.

Arch Rheumatol 2022 Mar 18;37(1):59-66. Epub 2021 Oct 18.

Department of Research Experimental Center, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, P. R. China.

Objectives: This study aims to estimate predicted factors for maternal and fetal outcomes in Hakka pregnant women with systemic lupus erythematosus (SLE) in the southern China.

Patients And Methods: Between June 2014 and February 2020, we retrospectively analyzed the data of a total of 123 singleton pregnant women with SLE (mean age: 27.1±4.1 years; range, 19 to 39 years) who were referred to our rheumatology clinic. Demographic, clinical, and laboratory data of the patients were recorded. Adverse pregnancy outcomes (APOs) were assessed.

Results: Multivariate logistic regression analysis revealed that preeclampsia was associated with the increased odds of APOs (odds ratios [OR]=9.538, 95% confidence interval [CI]: 2.055-44.271, p=0.004), premature birth (OR=14.289, 95% CI: 3.596-56.777, p<0.001) and low birth weight (OR=8.275, 95% CI: 2.117-32.345, p=0.002). Anti-double-stranded deoxyribonucleic acid (anti-dsDNA) antibody positivity was the predictor of APOs (OR=2.165, 95% CI: 1.034-4.532, p=0.040), premature birth (OR=2.849, 95% CI: 1.220-6.657, p=0.016) and pregnancy loss (OR=3.004, 95% CI: 1.086-8.305, p=0.034). The use of hydroxychloroquine and prednisone was associated with the decreased odds of APOs (OR=0.412, 95% CI: 0.198-0.860, p=0.018) and pregnancy loss (OR=0.304, 95% CI: 0.111-0.831, p=0.020).

Conclusion: Our study results indicate that preeclampsia, anti-dsDNA antibody positivity, and the use of hydroxychloroquine and prednisone are independent predictors of pregnancy outcomes.
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http://dx.doi.org/10.46497/ArchRheumatol.2022.8870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326378PMC
March 2022

The feasibility, safety and short-term clinical efficacy of laparoscopic anterior resection of rectal cancer with left colonic artery (LCA) preservation and natural orifice specimen extraction (NOSE).

BMC Surg 2022 Aug 10;22(1):308. Epub 2022 Aug 10.

Department of Gastrointestinal Surgery, Sichuan Cancer Hospital, Chengdu, 610041, China.

Background: Natural orifice specimen extraction surgery (NOSES) has the advantages of less postoperative pain, fast bowel function recovery, reduced hospital stay and better cosmetic effects. In our centre, anterior resection of rectal cancer with preservation of the left colonic artery (LCA) was performed using NOSES. The feasibility, safety and short-term clinical efficacy of the technique were discussed.

Methods: A retrospective analysis was performed on 19 patients who underwent laparoscopic anterior resection of rectal cancer with left colonic artery preservation and natural orifice specimen extraction in the Gastrointestinal Surgery Center of Sichuan Cancer Hospital from September 2018 to December 2019. General information about the patients, perioperative data and short-term postoperative results were analysed.

Results: All operations were completed smoothly, with an average operation duration of 304.36 ± 45.04 min, intraoperative bleeding of 76.31 ± 61.12 ml, first time off bed of 14.42 ± 3.56 h, first time to anus exhaust of 15.26 ± 8.92 h, first time to liquid diet of 2.94 ± 1.12 days, and average postoperative stay of 10.21 ± 3.13 days. Two patients developed temporary intestinal obstruction, and one patient developed pulmonary infection. All of them recovered well after active supportive treatment and were successfully discharged.

Conclusion: Laparoscopic NOSES for rectal cancer with left colon artery preservation is safe and feasible, with satisfactory short-term results, and is worthy of further clinical investigation.
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http://dx.doi.org/10.1186/s12893-022-01719-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9364571PMC
August 2022

Cancer-associated fibroblasts: An emerging target against esophageal squamous cell carcinoma.

Cancer Lett 2022 Aug 7;546:215860. Epub 2022 Aug 7.

Hangzhou Cancer Institution, Affiliated Hangzhou Cancer Hospital, Zhejiang University School of Medicine, Hangzhou, 310002, China; Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China. Electronic address:

Esophageal squamous cell carcinoma (ESCC) is one of the most common human malignancies worldwide and is associated with high morbidity and mortality. More than 70% of ESCC patients are diagnosed at the intermediate or advanced stage. Concurrent chemoradiotherapy is the standard treatment regimen for patients with advanced ESCC. However, ESCC patients show a poor 5-year survival rate of around 20%. Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment and control tumor initiation and progression. CAFs create a pro-survival and immunosuppressive microenvironment by crosstalk with cancer cells. Moreover, CAFs lead the collective invasion of cancer cells of the epithelial phenotype by remodeling the extracellular matrix. In this review, we highlight the impact of CAFs on ESCC, including induction of chemo- and radio-resistance, migration, invasion, and immune escape. The origin of CAFs and the influence of ESCC cells on CAF activation are also described. Furthermore, we highlight the clinical prospects and future trends of CAFs-targeted therapies in ESCC. A better understanding of the molecular biology of CAFs may contribute to the development of novel anti-ESCC strategies.
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http://dx.doi.org/10.1016/j.canlet.2022.215860DOI Listing
August 2022

Sustained air pollution exposures, fasting plasma glucose, glycated haemoglobin, prevalence and incidence of diabetes: a nationwide study in China.

Int J Epidemiol 2022 Aug 10. Epub 2022 Aug 10.

Department of Global Health, School of Public Health, Wuhan, China.

Background: Evidence remains limited and inconsistent for the associations between sustained air pollution exposures and diabetes development. This study aimed to determine the potential effects of particulate matter with a diameter of ≤10 micrometres (PM10), particulate matter with a diameter of ≤2.5 micrometres (PM2.5) and nitrogen dioxide (NO2) on alterations of fasting plasma glucose (FPG), glycated haemoglobin (HbA1c), in particular, on prevalence and incidence of diabetes.

Methods: Cross-sectional analyses were conducted based on 9628 participants aged ≥45 years from the baseline survey (2011) of the China Health and Retirement Longitudinal Study (CHARLS), whereas cohort analyses were based on 3510 individuals without diabetes at baseline in the third survey (2015). Residences of participants were geocoded and the air pollution exposures were estimated using a satellite-based spatiotemporal model. Linear, logistic and modified Poisson regression models, adjusting for multiple confounders, were applied to assess the associations between air pollution and FPG, HbA1c, prevalence and incidence of diabetes, respectively.

Results: Associations between PM10, PM2.5 and increased levels of FPG and HbA1c were identified. The levels of FPG and HbA1c increased by 0.025 mmol/L (95% CI: 0.007, 0.044) and 0.011 mmol/L (95% CI: 0.002, 0.019), respectively, for a 10-μg/m3 increase in PM10, and the levels of FPG and HbA1c increased by 0.061 mmol/L (95% CI: 0.028, 0.096) and 0.016 mmol/L (95% CI: 0.000, 0.031), respectively, for a 10-μg/m3 increase in PM2.5. There were also positive associations between diabetes prevalence and PM2.5 and PM10. In the cohort analyses, PM10, PM2.5 and NO2 were associated with a higher incidence of diabetes.

Conclusion: Air pollution was allied to diabetes development in elderly Chinese populations. Considering the impact of the dramatic increase in the incidence and prevalence of diabetes in China, interventions to improve air quality are urgently needed.
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http://dx.doi.org/10.1093/ije/dyac162DOI Listing
August 2022

PLTP deficiency-mediated atherosclerosis regression could be related to sphinogosine-1-phosphate reduction.

Atherosclerosis 2022 Jul 15. Epub 2022 Jul 15.

SUNY Downstate Health Sciences University, Brooklyn, NY, USA; Molecular and Cellular Cardiology Program, VA New York Harbor Healthcare System, Brooklyn, NY, USA. Electronic address:

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http://dx.doi.org/10.1016/j.atherosclerosis.2022.07.007DOI Listing
July 2022

Quantitative Analysis of Routine Chemical Constituents of Tobacco Based on Thermogravimetric Analysis.

ACS Omega 2022 Aug 21;7(30):26407-26415. Epub 2022 Jul 21.

Technology Center, China Tobacco Zhejiang Industrial Co., Ltd., Hangzhou 310012, China.

As the most basic indexes to evaluate the quality of tobacco, the contents of routine chemical constituents in tobacco are mainly detected by continuous-flow analysis at present. However, this method suffers from complex operation, time consumption, and environmental pollution. Thus, it is necessary to establish a rapid accurate detection method. Herein, different from the ongoing research studies that mainly chose near-infrared spectroscopy as the information source for quantitative analysis of chemical components in tobacco, we proposed for the first time to use the thermogravimetric (TG) curve to characterize the chemical composition of tobacco. The quantitative analysis models of six routine chemical constituents in tobacco, including total sugar, reducing sugar, total nitrogen, total alkaloids, chlorine, and potassium, were established by the combination of TG curve and partial least squares algorithm. The accuracy of the model was confirmed by the value of root mean square error for prediction. The models can be used for the rapid accurate analysis of compound contents. Moreover, we performed an in-depth analysis of the chemical mechanism revealed by the result of the quantitative model, namely, the regression coefficient, which reflected the correlation degree between the six chemicals and different stages of the tobacco thermal decomposition process.
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http://dx.doi.org/10.1021/acsomega.2c02243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352168PMC
August 2022

Intramuscular Inoculation of AS02-Adjuvanted Respiratory Syncytial Virus (RSV) F Subunit Vaccine Shows Better Efficiency and Safety Than Subcutaneous Inoculation in BALB/c Mice.

Front Immunol 2022 22;13:938598. Epub 2022 Jul 22.

National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, China.

We previously explored a panel of adjuvants formulated with pre-fusion RSV-F protein and found that AS02 may be a promising candidate adjuvant for developing RSV-F subunit vaccines with improved immunogenicity and desired immune response type. In this study, we performed a head-to-head comparison of the effect of intramuscular injection to that of subcutaneous injection on the immune response and protective efficacy of recombinant RSV-F subunit vaccine with or without adjuvants (Alhydrogel, squalene-based emulsion adjuvants MF59, AS03, and AS02) in BALB/c mice. After inoculations, antigen-specific antibodies, neutralizing antibodies, antibody subtypes, cytokines, and the persistence of immune response were evaluated. Moreover, challenge tests were also performed to illustrate the possible effect of inoculation routes and adjuvant on virus clearance and histochemistry changes in the lungs of mice. The results indicated that intramuscular inoculation is a more effective and antigen dose-sparing route to enhance the immune response, although subcutaneous inoculation induced faster and stronger IgG antibodies after the initial immunization. Furthermore, adjuvant, but not immunization route, is a more critical factor to affect the humoral/cellular immune response and the immune bias. In addition, adjuvant inoculated the intramuscular route is safer than that the subcutaneous route, especially for AS02. This study highlights the importance of the adjuvant and immunization routes in the design and clinical transformation of adjuvanted vaccines. Further investigation is needed to illustrate the mechanism underlying the above difference in both efficiency and safety.
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http://dx.doi.org/10.3389/fimmu.2022.938598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354885PMC
August 2022

Mechanisms of pancreatic tumor suppression mediated by Xiang-lian pill: An integrated in silico exploration and experimental validation.

J Ethnopharmacol 2022 Aug 2;298:115586. Epub 2022 Aug 2.

Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address:

Ethnopharmacological Relevance: Xiang-lian pill, consisting of Coptis chinensis Franch. coprocessed with Tetradium ruticarpum (A.Juss.) T.G.Hartley (Yu-huang-lian) and Aucklandia lappa DC. (Mu-xiang), is traditionally used to relieve fever, abdominal pain, and gastrointestinal inflammatory symptoms observed in patients with malignancies of the gastrointestinal tract. Each of the three herbs contained in Xiang-lian pill has been indicated to have anticancer effects on a variety of cancers, but its effects on pancreatic cancer remain unexplored. The main extracts of these herbs have anti-pancreatic cancer effects, but the comprehensive mechanism of this compound prescription of Xiang-lian pill in pancreatic cancer remains to be revealed.

Aim Of The Study: To explore the main active ingredients, potential anti-pancreatic cancer targets, and related mechanisms of the Xiang-lian pill and to determine its therapeutic value in vivo.

Materials And Methods: Network pharmacology and bioinformatics analysis were applied to screen the potential effective ingredients and key targets. Liquid/gas-mass spectrometry was performed for ingredients validation. Molecular docking and the cellular thermal shift assay were performed to test the binding efficiency between ingredients and targets. A murine pancreatic cancer model was established and administered different doses of the Xiang-lian pill. Hematoxylin-eosin staining was used for histopathological observation. Immunohistochemistry and immunoblotting were conducted for target validation. In vitro studies (cell viability and clonogenicity assays) were conducted to investigate the impact of three main ingredients in Xiang-lian pill on pancreatic cancer cells. PTGS2 overexpression was performed to reversely confirm the antitumor mechanisms of rutaecarpine as a specific PTGS2 inhibitor.

Results: Xiang-lian pill suppressed pancreatic cancer growth in the dose range of 0.78-2.34g/kg with no significant toxicity. Sixteen potentially active ingredients and 26 corresponding therapeutic targets for pancreatic cancer were identified. PTGS2, PTGS1, KCNH2, PRSS1, and HSP90AA1 were the top 5 significant genes targeted by the Xiang-lian pill. Evodiamine, rutaecarpine and stigmasterol bound to PTGS2 and PTGS1 with different affinities and inhibited pancreatic cancer cell proliferation. The PTGS2-associated metabolic pathway MEK/ERK was downregulated by rutaecarpine in vitro and the Xiang-lian pill in vivo.

Conclusions: Xiang-lian pill mainly regulates inflammation, apoptosis, metastasis, and metabolism to exert an antitumor effect. The main active ingredients in Xiang-lian pill exhibit antitumor roles through directly binding to key targets in pancreatic cancer. PTGS2 mediated MEK/ERK inhibition by rutaecarpine represents a key therapeutic mechanism of Xiang-lian pill.
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http://dx.doi.org/10.1016/j.jep.2022.115586DOI Listing
August 2022

Prediction of Gene Co-expression from Chromatin Contacts with Graph Attention Network.

Bioinformatics 2022 Aug 5. Epub 2022 Aug 5.

School of Information Science and Technology, ShanghaiTech University, Shanghai, 201210, China.

Motivation: The technology of high-throughput chromatin conformation capture (Hi-C) allows genome-wide measurement of chromatin interactions. Several studies have shown statistically significant relationships between gene-gene spatial contacts and their co-expression. It is desirable to uncover epigenetic mechanisms of transcriptional regulation behind such relationships using computational modeling. Existing methods for predicting gene co-expression from Hi-C data use manual feature engineering or unsupervised learning, which either limits the prediction accuracy or lacks interpretability.

Results: To address these issues, we propose HiCoEx, a novel end-to-end framework for explainable prediction of gene co-expression from Hi-C data based on graph neural network. We apply graph attention mechanism to a gene contact network inferred from Hi-C data to distinguish the importance among different neighboring genes of each gene, and learn the gene representation to predict co-expression in a supervised and task-specific manner. Then, from the trained model, we extract the learned gene embeddings as a model interpretation to distill biological insights. Experimental results show that HiCoEx can learn gene representation from 3D genomics signals automatically to improve prediction accuracy, and make the black box model explainable by capturing some biologically meaningful patterns, e.g., in a gene contact network, the common neighbors of two central genes might contribute to the co-expression of the two central genes through sharing enhancers.

Availability: The source code is freely available at https://github.com/JieZheng-ShanghaiTech/HiCoEx.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btac535DOI Listing
August 2022

A Nomogram Based on SEER Database for Predicting Prognosis in Patients with Mucinous Ovarian Cancer: A Real-World Study.

Int J Womens Health 2022 26;14:931-943. Epub 2022 Jul 26.

Department of Obstetrics and Gynaecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People's Republic of China.

Purpose: Mucinous ovarian cancer (MOC) is a rare histological type of EOC. In order to guide the clinical diagnosis and management of MOC patients, we constructed and verified a nomogram for the estimation of overall survival in patients with MOC.

Patients And Methods: We collected 494 patients with MOC diagnosed from 2010 to 2015 in SEER database, and the following main inclusion criteria were used: (1) patients whose MOC was confirmed by pathology; (2) patients without a history of primary other cancer. Subsequently, we performed randomized grouping (6:4) and Cox hazard regression analysis in the training group. Subsequently, the nomogram was established. A variety of indicators were used to validate the prognosis value of nomogram, including the C-index, area under the receiver operating characteristic curve, calibration curve, and decision curve analysis (DCA). Moreover, Kaplan-Meier analysis was used to compare the survival results among different risk subgroups.

Results: Cox hazard regression analysis revealed that age, grade, FIGO stage and log odds of positive lymph nodes stage were independent risk factors for patients with MOC. In the training group, the C-index of the nomogram was 0.827 (95% CI: 0.791-0.863) and the areas under the curve (AUC) predicting the 1-, 3- and 5-year survival rate were 0.853 (95% CI: 0.791-0.915), 0.886 (95% CI: 0.852-0.920) and 0.815 (95% CI: 0.766-0.864), respectively. The calibration curve revealed that the nomogram of the 1-, 3- and 5-year survival rate was consistent with the actual fact. Patients with high risk had a poorer prognosis than those with low risk (P < 0.001). DCA revealed that the nomogram had the best clinical value than other classical prognostic markers. Similarly, nomogram had excellent prognostic ability in the testing group.

Conclusion: The nomogram was constructed to predict overall survival in patients with MOC, which had the significance for clinical evaluation.
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http://dx.doi.org/10.2147/IJWH.S372328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9341457PMC
July 2022

Evaluation of a Functional Single Nucleotide Polymorphism of the SARS-CoV-2 Receptor That Is Potentially Involved in Long COVID.

Front Genet 2022 18;13:931562. Epub 2022 Jul 18.

Center for Applied Bioinformatics, St. Jude Children's Research Hospital, Memphis, TN, United States.

Since the occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, SARS-CoV-2 has led to a global coronavirus disease 2019 (COVID-19) pandemic. A better understanding of the SARS-CoV-2 receptor at the genetic level would help combat COVID-19, particularly for long COVID. We performed a genetic analysis of and searched for its common potential single nucleotide polymorphisms (SNPs) with minor allele frequency >0.05 in both European and Chinese populations that would contribute to gene expression variation. We thought that the variation of the expression would be an important biological feature that would strongly affect COVID-19 symptoms, such as "brain fog", which is highlighted by the fact that ACE2 acts as a major cellular receptor for SARS-CoV-2 attachment and is highly expressed in brain tissues. Based on the human GTEx gene expression database, we found rs2106809 exhibited a significant correlation with the expression among multiple brain and artery tissues. This expression correlation was replicated in an independent European brain eQTL database, Braineac. rs2106809*G also displays significantly higher frequency in Asian populations than in Europeans and displays a protective effect ( = 0.047) against COVID-19 hospitalization when comparing hospitalized COVID-19 cases with non-hospitalized COVID-19 or SARS-CoV-2 test-negative samples with European ancestry from the UK Biobank. Furthermore, we experimentally demonstrated that rs2106809*G could upregulate the transcriptional activity of . Therefore, integrative analysis and functional experiment strongly support that SNP rs2106809 is a functional brain eQTL and its potential involvement in long COVID, which warrants further investigation.
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http://dx.doi.org/10.3389/fgene.2022.931562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9340221PMC
July 2022

Seawater intrusion induced cadmium activation via altering its distribution and transformation in paddy soil.

Chemosphere 2022 Jul 30;307(Pt 2):135805. Epub 2022 Jul 30.

National-Regional Joint Engineering Research Center for Soil Pollution Control and Remediation in South China, Guangdong Key Laboratory of Integrated Agro-environmental Pollution Control and Management, Institute of Eco-environmental and Soil Sciences, Guangdong Academy of Sciences, Guangzhou, 510650, PR China.

Seawater intrusion can cause environmental risks to paddy soils around estuaries, but the impacts on the availability of heavy metals are still unclear. River water and sea water were collected along the river of an estuary. A stirred-flow experiment was conducted to examine the Cd desorption behavior in Cd-contaminated paddy soil. While the pH increased with increasing salinity levels, more Cd was released with increasing salinity, suggesting that Cd competition by cations and complexation by anions, but not pH, dominated the release of Cd from soils. Moreover, paddy soil was incubated at different salinities under alternating redox conditions. The availability of Cd, as indicated by the diffusive gradients in thin film (DGT), became relatively high with increasing salinity levels during the initial anaerobic and later aerobic stages. The available Cd fractions substantially decreased under anaerobic condition, and then rapidly increased under aerobic condition. When oxygen was introduced into the system, Cd associated with organic matter and Fe-Mn oxides were released, and oxidative dissolution of Cd sulfides was observed, especially in the high salinity treatment. Seawater intrusion affects biogeochemical cycles and can promote rapid export of NH, Fe, and SO in paddy soils, especially in soils with high salinity. Our findings demonstrated that the high salinity content in paddy soil significantly enhanced the availability of Cd, especially during the drainage stage.
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http://dx.doi.org/10.1016/j.chemosphere.2022.135805DOI Listing
July 2022

Characteristics and phylogenetic analysis of the complete chloroplast genome of T.T.Yu & L.T.Lu (family Rosaceae).

Mitochondrial DNA B Resour 2022 25;7(7):1364-1366. Epub 2022 Jul 25.

Yunnan Branch Institute of Medicinal Plant, Chinese Academy of Medical Sciences and Peking Union Medical College, Jinghong, PR China.

T.T.Yu & L.T.Lu is a climbing shrub belonging to the Rosaceae family. It is widely distributed in the provinces of Yunnan and Guizhou in China. In this study, we sequenced the first complete chloroplast genome (cpDNA) sequence of . The results showed a genome length of 156,489 bp, which is composed of a large single-copy (LSC) of 86,103 bp, small single-copy (SSC) of 18,844 bp, and two inverted repeats of 25,771 bp each. The whole chloroplast genome encodes 131 genes, including 86 coding sequences, 37 tRNAs, and eight rRNAs. Phylogenetic analysis revealed that is closely related to and .
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http://dx.doi.org/10.1080/23802359.2022.2098859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318300PMC
July 2022

Oregano Essential Oils Mediated Intestinal Microbiota and Metabolites and Improved Growth Performance and Intestinal Barrier Function in Sheep.

Front Immunol 2022 12;13:908015. Epub 2022 Jul 12.

College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, China.

With the increased demand for safe and sustainable alternatives to growth promoting antibiotics in the livestock industry, oregano essential oils (OEO) and (LR) have been examined as alternatives to antibiotics for growth promotion and to improve animal health and performance. However, the mechanism underlying the OEO and LR mediation of sheep growth remains unknown. In this study, 16S rRNA gene sequencing and untargeted metabolomics were used to determine the role of the gut microbiota in the growth improvements observed. The potential modulating roles of intestinal microbial metabolites of OEO and LR to intestinal health were systematically explored as well. It was observed that both OEO and LR had greater average daily gain (ADG) and lower F/G ratio. Furthermore, OEO also appeared to have produced a greater amylase enzyme activity and mucin gene expression in the jejunal mucosa. It was also observed that OEO reduced serum IL-2 and TNF-β as well as mRNA levels of , toll-like receptor-4 (), and in the jejunal mucosa. Moreover, dietary OEO supplementation increased the abundances of , and , while the relative abundances of , and were enriched in LR group. Spearman's correlation analysis revealed that the abundances of , and were positively correlated with the mRNA expression of mucins. Moreover, the relative abundance of was positively correlated with amylase activity. Metabolomics analysis indicated that OEO and LR increased the levels of indole acetaldehyde and indole-3-acetic acid through the tryptophan metabolism pathway. It was observed that LR also decreased the inflammatory metabolites including tryptamine and 5-hydroxyindole-3-acetic acid. Collectively, these results suggested that OEO exerted a beneficial effect on growth performance and the mucosal barrier, affected tryptophan metabolism and improved the intestinal microbiota of sheep.
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http://dx.doi.org/10.3389/fimmu.2022.908015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314563PMC
August 2022

Polysaccharide, the Active Component of , Ameliorates Metabolic Hypertension in Rats Regulating Intestinal Flora-SCFAs-Vascular Axis.

Front Pharmacol 2022 11;13:935714. Epub 2022 Jul 11.

Zhejiang University of Technology, Hangzhou, China.

Metabolic hypertension (MH) is the most common type of hypertension worldwide because of unhealthy lifestyles, such as excessive alcohol intake and high-sugar/high-fat diets (ACHSFDs), adopted by humans. Poor diets lead to a decrease in the synthesis of short-chain fatty acids (SCFAs), which are produced by intestinal flora and transferred by G protein-coupled receptors (GPCRs), resulting in impaired gastrointestinal function, disrupted metabolic processes, increased blood pressure (BP), and ultimately, MH. It is not clear whether polysaccharide (DOPS) can mediate its effects by triggering the SCFAs-GPCR43/41 pathway. In this study, DOPS, with a content of 54.45 ± 4.23% and composition of mannose, glucose, and galacturonic acid at mass percentages of 61.28, 31.87, and 2.53%, was isolated from . It was observed that DOPS, given to rats by intragastric administration after dissolution, could lower the BP and improve the abnormal lipid metabolic processes in ACHSFD-induced MH rats. Moreover, DOPS was found to increase the production, transportation, and utilization of SCFAs, while improving the intestinal flora and strengthening the intestinal barrier, as well as increasing the intestinal levels of SCFAs and the expression of GPCR43/41. Furthermore, DOPS improved vascular endothelial function by increasing the expression of GPCR41 and endothelial nitric oxide synthase in the aorta and the nitric oxide level in the serum. However, these effects were all reversed by antibiotic use. These findings indicate that DOPS is the active component of , and it can reverse MH in rats by activating the intestinal SCFAs-GPCR43/41 pathway.
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http://dx.doi.org/10.3389/fphar.2022.935714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310040PMC
July 2022

The LIM Protein AJUBA is a Potential Oncogenic Target and Prognostic Marker in Human Cancer Pan-Cancer Analysis.

Front Cell Dev Biol 2022 11;10:921897. Epub 2022 Jul 11.

School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.

The LIM (Lin-11, Isl1, MEC-3) domain protein AJUBA is involved in multiple biological functions, and its aberrant expression is related to the occurrence and progression of various cancers. However, there are no analytical studies on AJUBA in pan-cancer. We performed a comprehensive pan-cancer analysis and explored the potential oncogenic roles of AJUBA, including gene expression, genetic mutation, protein phosphorylation, clinical diagnostic biomarker, prognosis, and AJUBA-related immune infiltration based on The Cancer Genome Atlas and Genotype-Tissue Expression databases. The results revealed that the expression of AJUBA highly correlated with poor clinical outcomes in patients with different types of cancer. Meanwhile, AJUBA expression was positively correlated with cancer-associated fibroblasts in many human cancers, such as breast invasive carcinoma, colon adenocarcinoma, brain lower-grade glioma, lung adenocarcinoma (LUAD), and ovarian serous cystadenocarcinoma (OV). Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that AJUBA is mainly involved in protein serine/threonine kinase activity, cell-cell junction, covalent chromatin modification, and Hippo signaling pathway. The pan-cancer study reveals the oncogenic roles of AJUBA and provides a comprehensive understanding of the molecular biological genetic information of AJUBA in various tumors.
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http://dx.doi.org/10.3389/fcell.2022.921897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309301PMC
July 2022

Numerical Simulation of Intelligent Fuzzy Closed-Loop Control Method for Radial-Axial Ring Rolling Process of Super-Large Rings.

Materials (Basel) 2022 Jul 21;15(14). Epub 2022 Jul 21.

Hubei Key Laboratory of Advanced Technology for Automotive Components, Wuhan University of Technology, Wuhan 430070, China.

During the radial-axial ring rolling (RARR) process of super-large rings, abnormal deformation states such as instability and out of circularity often lead to rolling termination and quality fluctuation of ring products. In this work, an intelligent fuzzy closed-loop control method for RARR process of super-large rings is proposed, i.e., the ring's offset adaptive fuzzy control (ROAFC) based on the regulation of the axial roll's rotational speed and the ring's circularity fuzzy control (RCFC) based on the regulation of the mandrel's feed speed. In addition, a recursive average filtering algorithm is added to smooth the axial roll's rotational speed and the mandrel's feed speed according to the actual situation. Using the ABAQUS/Explicit software and its subroutine VUAMP, the intelligent fuzzy controller of the ring's offset and circularity in the RARR process is designed, and the finite element (FE) model for RARR process of a Φ10 m super-large ring with an integrated intelligent fuzzy control algorithm is established. The variation laws of the ring's offset and circularity error in the RARR process are studied with regard to different control methods such as conventional planning control (CPC), ROAFC, RCFC, and comprehensive control of ROAFC combined with RCFC (ROAFC + RCFC). The results obtained show that, compared with the CPC, the ring's offset is reduced by 84.6% and the circularity error is decreased by 51.9% in the RARR process utilizing comprehensive control of ROAFC + RCFC. The research results provide methodological guidance for realizing the intelligent forming of super-large rings.
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http://dx.doi.org/10.3390/ma15145084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9323681PMC
July 2022

Transformers Improve Breast Cancer Diagnosis from Unregistered Multi-View Mammograms.

Diagnostics (Basel) 2022 Jun 25;12(7). Epub 2022 Jun 25.

School of Electrical and Computer Engineering, University of Oklahoma, Norman, OK 73019, USA.

Deep convolutional neural networks (CNNs) have been widely used in various medical imaging tasks. However, due to the intrinsic locality of convolution operations, CNNs generally cannot model long-range dependencies well, which are important for accurately identifying or mapping corresponding breast lesion features computed from unregistered multiple mammograms. This motivated us to leverage the architecture of Multi-view Vision Transformers to capture long-range relationships of multiple mammograms from the same patient in one examination. For this purpose, we employed local transformer blocks to separately learn patch relationships within four mammograms acquired from two-view (CC/MLO) of two-side (right/left) breasts. The outputs from different views and sides were concatenated and fed into global transformer blocks, to jointly learn patch relationships between four images representing two different views of the left and right breasts. To evaluate the proposed model, we retrospectively assembled a dataset involving 949 sets of mammograms, which included 470 malignant cases and 479 normal or benign cases. We trained and evaluated the model using a five-fold cross-validation method. Without any arduous preprocessing steps (e.g., optimal window cropping, chest wall or pectoral muscle removal, two-view image registration, etc.), our four-image (two-view-two-side) transformer-based model achieves case classification performance with an area under ROC curve (AUC = 0.818 ± 0.039), which significantly outperforms AUC = 0.784 ± 0.016 achieved by the state-of-the-art multi-view CNNs ( = 0.009). It also outperforms two one-view-two-side models that achieve AUC of 0.724 ± 0.013 (CC view) and 0.769 ± 0.036 (MLO view), respectively. The study demonstrates the potential of using transformers to develop high-performing computer-aided diagnosis schemes that combine four mammograms.
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http://dx.doi.org/10.3390/diagnostics12071549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320758PMC
June 2022

Clinical Benefit of Niraparib to TKI/mTORi-Resistance Metastatic ccRCC With -Frame Shift Mutation: Case Report and Literature Review.

Front Oncol 2022 6;12:927250. Epub 2022 Jul 6.

Department of Oncologic and Urologic Surgery, The 903rd People's Liberation Army (PLA) Hospital, Wenzhou Medical University, Hangzhou, China.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cancer. The top four mutant genes affecting the occurrence and progression of ccRCC are , and , respectively. Tyrosine kinase/mammalian target of rapamycin inhibitors (TKI/mTORis) with or without immunotherapy are the standard and effective therapy to metastatic ccRCC. Once TKI/mTORis fail to ccRCC, there is still a lack of other effective therapies. In this study, we reported a case in which a metastatic ccRCC patient (T2aN1M1) presented resistance after a 28-month treatment by sorafenib-axitinib-everolimus (TKI-TKI-mTORi). Subsequently, a frame shift pathogenic mutation, c.799_800del (p.Q267fs) in the exon10 of in ccRCC, was revealed by targeted sequencing. Oral administration of nilapanib (PARP inhibitor) was further given, which may provide a new therapy for TKI/mTORi-resistance metastatic ccRCC. Fortunately, a partial response has been achieved and lasted for 5 months. Since the frequency of mutations in ccRCC patients was approximately 10%-20%, as reported previously, we also tried to explore the potential mechanisms benefitting from the nilapanib. Moreover, the literature concerning mutation and associated cancers including ccRCC is reviewed.
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http://dx.doi.org/10.3389/fonc.2022.927250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9299075PMC
July 2022

Integrative Analysis From Multicenter Studies Identifies a WGCNA-Derived Cancer-Associated Fibroblast Signature for Ovarian Cancer.

Front Immunol 2022 8;13:951582. Epub 2022 Jul 8.

Department of Obstetrics and Gynaecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.

Cancer-associated fibroblasts (CAFs) are a major contributor to tumor stromal crosstalk in the tumor microenvironment (TME) and boost tumor progression by promoting angiogenesis and lymphangiogenesis. This study aimed to identify prognostic genes associated with CAFs that lead to high morbidity and mortality in ovarian cancer (OC) patients. We performed bioinformatics analysis in 16 multicenter studies (2,742 patients) and identified CAF-associated hub genes using the weighted gene co-expression network analysis (WGCNA). A machine learning methodology was used to identify COL16A1, COL5A2, GREM1, LUM, SRPX, and TIMP3 and construct a prognostic signature. Subsequently, a series of bioinformatics algorithms indicated risk stratification based on the above signature, suggesting that high-risk patients have a worse prognosis, weaker immune response, and lower tumor mutational burden (TMB) status but may be more sensitive to routine chemotherapeutic agents. Finally, we characterized prognostic markers using cell lines, immunohistochemistry, and single-cell sequencing. In conclusion, these results suggest that the CAF-related signature may be a novel pretreatment guide for anti-CAFs, and prognostic markers in CAFs may be potential therapeutic targets to inhibit OC progression.
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http://dx.doi.org/10.3389/fimmu.2022.951582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304893PMC
July 2022
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