Publications by authors named "Yin Zhang"

854 Publications

Clinical characteristics of anti-isoleucyl-tRNA synthetase antibody associated syndrome and comparison with different patient cohorts.

Clin Exp Rheumatol 2021 Jun 8. Epub 2021 Jun 8.

Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China.

Objectives: This study aimed to analyse the clinical features of anti-isoleucyl-tRNA synthetase (OJ) antibodies in Chinese patients and to compare with previously published cohorts. We reviewed the clinical data of anti-OJ antibody positive patients, including their long-term follow-up.

Results: Anti-OJ antibodies were present in 10 of 1269 (0.8%) patients with idiopathic inflammatory myopathies (IIMs), and 10/320 (3.1%) patients with anti-synthetase syndrome (ASS). Of the anti-OJ antibody-positive patients, 90% had interstitial lung disease (ILD), of whom three (30%) developed rapidly progressive ILD (RP-ILD). Half (50%) of the patients were febrile and developed myocardial involvement; 40% of patients experienced myositis, mechanic's hands and arthritis. Compared to the anti-Jo-1 group, the levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in the anti-OJ antibody-positive group were higher (p<0.05). From a review of the literature regarding the clinical features of anti-OJ, fever was more common in the eastern cohort (41.7% vs. 8.3%, p=0.002), whereas patients in western countries were more likely to develop arthritis (20.9% vs. 58.1%, p=0.001). With complete follow-up of the present cohort, 80% improved with treatment, including one patient who underwent lung transplant.

Conclusions: The anti-OJ antibody occurred infrequently in Chinese patients, ILD was the major clinical feature, but myocardial injury was also a prominent associated complication. Anti-OJ positive patients were responsive to treatment.
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June 2021

PERK Signaling Controls Myoblast Differentiation by Regulating MicroRNA Networks.

Front Cell Dev Biol 2021 28;9:670435. Epub 2021 May 28.

MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.

The unfolded protein response (UPR) plays important roles in various cells that have a high demand for protein folding, which are involved in the process of cell differentiation and development. Here, we separately knocked down the three sensors of the UPR in myoblasts and found that PERK knockdown led to a marked transformation in myoblasts from a fusiform to a rounded morphology, which suggests that PERK is required for early myoblast differentiation. Interestingly, knocking down PERK induced reprogramming of C2C12 myoblasts into stem-like cells by altering the miRNA networks associated with differentiation and stemness maintenance, and the PERK-ATF4 signaling pathway transactivated muscle differentiation-associated miRNAs in the early stage of myoblast differentiation. Furthermore, we identified Ppp1cc as a direct target gene of miR-128 regulated by the PERK signaling pathway and showed that its repression is critical for a feedback loop that regulates the activity of UPR-associated signaling pathways, leading to cell migration, cell fusion, endoplasmic reticulum expansion, and myotube formation during myoblast differentiation. Subsequently, we found that the RNA-binding protein ARPP21, encoded by the host gene of miR-128-2, antagonized miR-128 activity by competing with it to bind to the 3' untranslated region (UTR) of Ppp1cc to maintain the balance of the differentiation state. Together, these results reveal the crucial role of PERK signaling in myoblast maintenance and differentiation and identify the mechanism underlying the role of UPR signaling as a major regulator of miRNA networks during early differentiation of myoblasts.
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http://dx.doi.org/10.3389/fcell.2021.670435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193987PMC
May 2021

Bioinspired Soft Robotic Fingers with Sequential Motion Based on Tendon-Driven Mechanisms.

Soft Robot 2021 Jun 11. Epub 2021 Jun 11.

School of Aeronautics and Astronautics, Sichuan University, Chengdu, China.

The conformability is yet a challenge for most soft robotic grippers due to the continuous motion and deformation of these machines under external force. Herein, inspired by the movement mechanism of human fingers, we propose a novel tendon-driven soft robotic finger with a preprogrammed bending configuration and a human finger like sequential motion that can be obtained by matching the stiffness gradient of the finger joints with three-dimensional (3D) printing technology. The contents of this article are organized as follows. First, the effect of the anisotropy caused by 3D printing filling direction on the mechanical property is investigated by tensile test. Then, kinematic, stiffness, and fingertip trajectory models are established to analyze the influence of the cross-section thickness and width on the bending and bearing capacity of the finger joint. Furthermore, several experiments are conducted on a self-built experimental platform to evaluate the advantages of sequential motion induced by stiffness gradients. Results reveal that soft robotic fingers with sequential motion show excellent conformability on the object surfaces with various curvatures and outperform nonsequential motion fingers with larger envelop range. Without changing motion trajectories of the fingertip, the deformability of the finger can be tuned by adjusting only the stiffness of the joint. Besides, a two-finger gripper is developed, which presents the capability of grasping objects with different shapes and weights in practical applications. The sequential motion mechanism proposed in this study shows promising potential in soft grippers and robotic design.
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http://dx.doi.org/10.1089/soro.2021.0009DOI Listing
June 2021

Relationship Between High-Sensitivity C-Reactive Protein and Long-Term Outcomes in Elderly Patients With 3-Vessel Disease.

Angiology 2021 Jun 10:33197211021195. Epub 2021 Jun 10.

34736Fuwai Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People's Republic of China.

The prognostic value of high-sensitivity C-reactive protein (hsCRP) in complex coronary artery disease has not been fully established. We aimed to determine the association between hsCRP and long-term outcomes in elderly patients with 3-vessel disease (TVD). From April 2004 to February 2011, 3069 patients aged ≥65 years with TVD were consecutively enrolled and received medical treatment alone, percutaneous coronary intervention, or coronary artery bypass grafting. The patients were divided into 2 groups according to their hsCRP levels: <3.00 mg/L (62.1%) and ≥3.00 mg/L (37.9%). The mean age was 71 ± 4 years. The high hsCRP group had more risk factors and more frequently received conservative treatment than the low hsCRP group. During a median follow-up period of 6.2 years, elevated hsCRP was significantly associated with increased all-cause death (19.5% vs 29.6%, < .001), cardiac death (9.4% vs 15.2%, = .001), and major adverse cardiovascular and cerebrovascular events (34.1% vs 42.5%, = .001). Multivariable Cox regression analyses revealed that hsCRP was an independent predictor for all of these events. Combining hsCRP with Synergy between PCI with TAXUS and Cardiac Surgery score II further improved the predictive power of the score. The relationship between hsCRP and mortality was relatively consistent across subgroups. Overall, hsCRP could prove useful for risk prediction in elderly patients.
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http://dx.doi.org/10.1177/00033197211021195DOI Listing
June 2021

A reconstructed porous copper surface promotes selectivity and efficiency toward C products by electrocatalytic CO reduction.

Chem Sci 2020 May 19;11(39):10698-10704. Epub 2020 May 19.

CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology Beijing 100190 P. R. China

Electrocatalytic synthesis of multicarbon (C) products from CO reduction suffers from poor selectivity and low energy efficiency. Herein, a facile oxidation-reduction cycling method is adopted to reconstruct the Cu electrode surface with the help of halide anions. The surface composed of entangled Cu nanowires with hierarchical pores is synthesized in the presence of I, exhibiting a C faradaic efficiency (FE) of 80% at -1.09 V RHE. A partial current density of 21 mA cm is achieved with a C half-cell power conversion efficiency (PCE) of 39% on this electrode. Such high selective C production is found to mainly originate from CO intermediate enrichment inside hierarchical pores rather than the surface lattice effect of the Cu electrode.
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http://dx.doi.org/10.1039/d0sc01202eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162280PMC
May 2020

Comparison of a new predictive model with other critical scores for predicting in-hospital mortality among children with pneumonia-related bacteremia.

J Investig Med 2021 Jun 3. Epub 2021 Jun 3.

Department of Respiratory Disease, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders. Chongqing Key Laboratory of Pediatrics, Chongqing, China

Prediction of mortality in children with pneumonia-related bacteremia is necessary for providing timely care and treatment. This study aims to develop and validate a nomogram and compare it with Pediatric Risk of Mortality III (PRISM III), Brighton Pediatric Early Warning Score (Brighton PEWS) and Pediatric Critical Illness Score (PCIS), which are widely used in predicting in-hospital mortality in children with pneumonia-related bacteremia. This retrospective study collected clinical data of hospitalized children with pneumonia-related bacteremia in Chongqing, China (January 2013-May 2019). The nomogram was built using multivariate logistic regression analysis. The nomogram was compared with PRISM III, PEWS and PCIS in accuracy and clinical benefits in predicting in-hospital mortality in children with pneumonia-related bacteremia. A total of 242 children were included. The nomogram including time to first positivity of blood cultures (TTFP), serum albumin (ALB) and lactate dehydrogenase (LDH) was established. The area under the receiver operating characteristic curve of the nomogram was 0.84 (95% CI 0.77 to 0.91) in the training set and 0.82 (95% CI 0.71 to 0.93) in the validating set. Good consistency was observed between the predictions and the actual observations, and the decision curve analysis showed that the nomogram was clinically useful. The results showed that the nomogram significantly performed better than the three critical scores. In conclusion, a nomogram-illustrated model incorporating TTFP, ALB and LDH for predicting in-hospital mortality in children with pneumonia-related bacteremia at the early stage was established and validated. It performed better than PRISM III, PEWS and PCIS.
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http://dx.doi.org/10.1136/jim-2020-001688DOI Listing
June 2021

Mitomycin C Inhibits Esophageal Fibrosis by Regulating Cell Apoptosis and Autophagy via lncRNA-ATB and miR-200b.

Front Mol Biosci 2021 17;8:675757. Epub 2021 May 17.

Department of Gastroenterology, The Third Affiliated Hospital of Soochow University, Changzhou, China.

Benign esophageal strictures (BESs) frequently results from esophageal fibrosis. The transformation of fibroblasts into fibrocyte is an important cause of fibrosis. The treatment of fibrosis is challenging. Some previous studies have indicated the antifibrotic effect of mitomycin C (MMC). However, the mechanism of action of MMC and its optimal dose for treatment remains unclear. In the present study, the role of MMC in fighting fibrosis and its mechanism was investigated. Human esophageal fibroblast cells (HEFs)were treated without or with MMC, at 2, 5, 10 μg/ml, combining with mimic lncRNA-ATB, miR-200b inhibitor, rapamycin (RAPA), and 3-Methyladenine (3-MA). The cell viability, and cell apoptosis were evaluated. In addition, expression of apoptosis related proteins (caspase8 and caspase3), autophagy related proteins (LC3II and ATG5) and fibrosis related proteins (α-SMA collagen-1 and TGF-β) were also evaluated. Furthermore, autophagosome was observed by transmission electron microscope. Results showed that the expression of lncRNA-ATB was down-regulated and miR-200b was up-regulated after treated with MMC. And MMC induced cell apoptosis and inhibited cell autophagy. On the other hand, RAPA, mimic lncRNA-ATB and miR-200b inhibitor reduced fibrogenic effect of MMC on HEFs. Collectively, this study suggests that MMC inhibited esophageal fibrosis by regulating cell apoptosis and autophagy via downregulating lncRNA-ATB and upregulating miR-200b.
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http://dx.doi.org/10.3389/fmolb.2021.675757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165251PMC
May 2021

SP1-induced lncRNA ZFPM2 antisense RNA 1 (ZFPM2-AS1) aggravates glioma progression via the miR-515-5p/Superoxide dismutase 2 (SOD2) axis.

Bioengineered 2021 Dec;12(1):2299-2310

Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University.

Glioma is a common life-threatening tumor with high malignancy and high invasiveness. LncRNA ZFPM2 antisense RNA 1 (ZFPM2-AS1) was confirmed to be implicated in numerous tumors, while its biological function and mechanism have not been thoroughly understood in glioma. The gene expression was measured by RT-qPCR. Cell proliferation, cell cycle, and cell apoptosis of glioma cells were validated by CCK-8, colony formation, flow cytometry and TUNEL assays. The effect of ZFPM2-AS1 on tumor growth was verified by assay. The exploration on ZFPM2-AS1-mediated mechanism was carried out via ChIP, luciferase reporter, and RIP assays. In the present study, ZFPM2-AS1 was demonstrated as a highly-expressed lncRNA in glioma tissues and cells. ZFPM2-AS1 silencing suppressed cell proliferation and cell cycle, but facilitated cell apoptosis. In addition, the inhibitive effect of silenced ZFPM2-AS1 was also observed in tumor growth. Furthermore, we found that SP1 interacted with ZFPM2-AS1 promoter to transcriptionally activate ZFPM2-AS1 expression. Moreover, ZFPM2-AS1 was identified as a competing endogenous RNA (ceRNA) for miR-515-5p to target SOD2. Rescue assays verified that SOD2 overexpression partially abolished the suppressive impact of ZFPM2-AS1 silencing on glioma cell growth. In conclusion, this study corroborated the regulatory mechanism of SP1/ZFPM2-AS1/miR-515-5p/SOD2 axis in glioma, indicating that targeting ZFPM2-AS1 might be an effective way to treat glioma.
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http://dx.doi.org/10.1080/21655979.2021.1934241DOI Listing
December 2021

Construction of Z-scheme g-CN / MnO /GO ternary photocatalyst with enhanced photodegradation ability of tetracycline hydrochloride under visible light radiation.

Environ Res 2021 May 29;200:111427. Epub 2021 May 29.

School of Hydraulic Engineering, Changsha University of Science & Technology, Changsha, 410114, PR China.

A facile wet-chemical method was adopted to synthesize g-CN/MnO/GO heterojunction photocatalyst for visible-light photodegradation of tetracycline hydrochloride (TC). The addition of MnO and GO increased the absorption of visible light and the specific surface area of the photocatalyst. The results of photoluminescence, electrochemical impedance spectroscopy, and photocurrent response indicated that CMG-10 had the lowest electron-hole recombination probability, which was beneficial for the photocatalytic reaction. The ternary photocatalyst exhibited enhanced photoelectric performance and superior photocatalytic activity with 91.4% removal of TC (10 mg/L) under a mere 60 min visible light illumination, which showed enhanced photocatalytic degradation when compared with binary (CM, 77.95%; CG, 78.83%) and single (CN, 55.5%; MnO, 36.41%) photocatalysts. A pH of 6 was optimal for the CMG-10 photocatalytic degradation of TC, and the optimal photocatalyst dosage was 0.5 g/L. Common coexisting ions influenced the removal of TC by influencing the production of active species. The catalyst is stable and reusable with only a 10% reduction in removal efficiency after four cycles. According to the active species analysis, the Z-scheme mechanism was a charge transfer behavior in the composite photocatalyst, which could prevent the recombination of photogenerated carriers. This study presents a photocatalytic approach to the effective removal of TC from water bodies, which provides practical implications to advance the use of photocatalytic technology in the restoration of aqueous environmental pollution.
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http://dx.doi.org/10.1016/j.envres.2021.111427DOI Listing
May 2021

The effects of combined environmental factors on the intestinal flora of mice based on ground simulation experiments.

Sci Rep 2021 May 31;11(1):11373. Epub 2021 May 31.

Department of General Surgery, Strategic Support Force Medical Center, Chaoyang District, Beijing, 100101, China.

The composition and function of intestinal microbial communities are important for human health. However, these intestinal floras are sensitive to changes in the environment. Adverse changes to intestinal flora can affect the health of astronauts, resulting in difficulties in implementing space missions. We randomly divided mice into three groups and placed each group in either a normal environment, simulated microgravity environment or a combined effects environment, which included simulated microgravity, low pressure and noise. Fecal samples of the mice were collected for follow-up analysis based on metagenomics technology. With the influence of different space environmental factors, the species composition at the phylum and genus levels were significantly affected by the combined effects environment, especially the abundance of the Firmicutes and Bacteroidetes. Furthermore, screening was conducted to identify biomarkers that could be regarded as environmental markers. And there have also been some noticeable changes in the function of intestinal floras. Moreover, the abundance of antibiotic resistance genes (ARGs) was also found to be changed under different environmental conditions, such as bacitracin and vancomycin. The combined effects environment could significantly affect the species composition, function, and the expression of ARGs of intestinal flora of mice which may provide a theoretical basis for space medical supervision and healthcare.
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http://dx.doi.org/10.1038/s41598-021-91077-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166921PMC
May 2021

Analogs of imine resveratrol alleviate oxidative stress-induced neurotoxicity in PC12 cells via activation of Nrf2.

FEBS Open Bio 2021 May 31. Epub 2021 May 31.

Zhejiang Chinese Medical University, Hangzhou, 310057, PR China.

Oxidative stress is closely associated with neurodegenerative, cardiovascular and metabolic diseases. Resveratrol and related compounds have shown great potential as antioxidants via either direct scavenging of abundant reactive oxygen species (ROS) or activation of the Keap1-Nrf2-ARE pathway. Herein, we evaluated imine resveratrol analogs (IRAs) for their neuroprotective effects against ROS in PC12 cells, which are a commonly employed model system for studies of neuronal development and function. We identified that IRA-3 (4-[[(4-hydroxyphenyl)methylene]amino]-phenol) was more potent than resveratrol at rescuing PC12 cells from H O -induced oxidative damage, exhibiting a recovery percentage of 60.4% at 50 μM. Our findings suggest that the neuroprotective effect of IRA-3 was achieved via multiple routes, including direct scavenging of ROS, rescue of endogenous antioxidants and activation of the Keap1-Nrf2-ARE pathway. Our results suggest that IRA-3 may have potential for development into a possible treatment for neurodegenerative diseases.
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http://dx.doi.org/10.1002/2211-5463.13209DOI Listing
May 2021

Analysis on the risk of respiratory virus transmission by air conditioning system operation based on experimental evidence.

Environ Sci Pollut Res Int 2021 May 29. Epub 2021 May 29.

MOE Key Laboratory of Deep Earth Science and Engineering, College of Architecture and Environment, Sichuan University, Chengdu, China.

It is important to know whether SARS-CoV-2 is spread through the air conditioning systems. Taking the central air conditioning system as an example, we analyze the mechanism and potential health risk of respiratory virus transmission in air-conditioned rooms and propose a method to study the risk of virus transmission in central air conditioning systems by investigating the data from medical experiments. The virus carrying capacity and the decay characteristics of indoor pathogen droplets are studied in this research. Additionally, the effects of air temperature and relative humidity on the virus survival in the air or on surfaces are investigated. The removal efficiency of infectious droplet nuclei by using an air conditioning filter was then determined. Thus, the transmission risk during the operation of the centralized air conditioning system is evaluated. The results show that the indoor temperature and humidity are controlled in the range of 20-25 °C and 40-70% by central air conditioning during the epidemic period, which not only benefits the health and comfort of residents, but also weakens the vitality of the virus. The larger the droplet size, the longer the viruses survive. Since the filter efficiency of the air conditioning filter increases with the increase in particle size, increasing the number of air changes of the circulating air volume can accelerate the removal of potential pathogen particles. Therefore, scientific operation of centralized air conditioning systems during the epidemic period has more advantages than disadvantages.
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http://dx.doi.org/10.1007/s11356-021-14495-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164484PMC
May 2021

Possible involvement of the Hedgehog and PDPK1-Akt pathways in the growth and migration of small-cell lung cancer.

J Int Med Res 2021 May;49(5):3000605211016562

Department of Respiratory Medicine, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.

Background: Small-cell lung cancer (SCLC) accounts for approximately 15% to 20% of all lung cancers, and it is the leading cause of tumor-related deaths globally. This study explored the molecular mechanisms underlying the development of SCLC.

Methods: The correlations of phosphoinositide-dependent kinase-1 (PDPK1), p-Akt, and Hedgehog expression with patient characteristics were analyzed using SCLC specimens, and their expression was measured in BEAS-2B cells (control) and the SCLC cell lines H82, H69, H446, H146, and H526. Transfection experiments were performed to inhibit or activate gene expression in cells. We then measured the proliferation and migration of H146 cells.

Results: PDPK1, p-Akt, and Hedgehog expression was significantly higher in SCLC tissues, and their expression was correlated with patient characteristics. p-Akt expression was significantly correlated with Hedgehog expression. In H146 cells, PDPK1 and p-Akt were significantly upregulated. Silencing of PDPK1 or Akt and inhibition of Hedgehog significantly inhibited the proliferation and migration of H146 cells. PDPK1 and Akt affected Hedgehog expression, but Hedgehog did not affect PDPK1 or p-Akt expression.

Conclusions: The interaction between the PDPK1-Akt pathway and the Hedgehog pathway influences the prognosis, growth, and migration of SCLC.
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http://dx.doi.org/10.1177/03000605211016562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161885PMC
May 2021

Addition of low-dose sufentanil to ropivacaine for reducing shivering and visceral traction pain during cesarean section.

J Int Med Res 2021 May;49(5):3000605211017000

Department of Anesthesia, Yongchuan Hospital of Chongqing Medical University, Chongqing, China.

Objective: To investigate the efficacy of low-dose sufentanil for preventing shivering and visceral traction pain during cesarean section under spinal anesthesia.

Methods: This was a prospective, randomized, controlled study. A total of 112 full-term parturients who underwent elective caesarean delivery were randomly divided into two groups. Group R received 0.75% isobaric ropivacaine intrathecally and group RS received 0.75% isobaric ropivacaine plus 5 µg sufentanil intrathecally.

Results: There were no significant differences in the maximum sensory block time, motor block time, duration of the surgery, and heart rate, mean arterial pressure, and blood oxygen saturation before and 1, 5, and 10 minutes after spinal anesthesia, and at the end of the surgery between the two groups. Shivering was significantly more common in group R (n = 30) than in group RS (n = 8). The incidence of visceral traction pain in group R (46.43%) was significantly higher than that in group RS (14.29%). There was no significant difference in the newborns' Apgar scores between the groups.

Conclusion: Adding low-dose sufentanil to ropivacaine can significantly reduce the incidence of shivering and visceral traction pain after spinal anesthesia.
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http://dx.doi.org/10.1177/03000605211017000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161908PMC
May 2021

The Effects and Safety of Continuous Positive Airway Pressure in Children with Bronchiolitis: A Systematic Review and Meta-Analysis.

J Trop Pediatr 2021 05;67(2)

Department of Respiration Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.

Objectives: To evaluate the effects and safety of continuous positive airway pressure (CPAP) for initial respiratory management of bronchiolitis.

Methods: PubMed, EMBASE, Cochrane Library, CNKI, Wanfang data and CQ VIP were searched until 17 June 2020. Randomized controlled trials (RCTs) which investigated the effect of CPAP for bronchiolitis were included.

Results: Twenty-seven RCTs met the eligibility criteria. In the comparison of CPAP versus standard oxygen therapy, CPAP can reduce the length of stay (LOS) in hospital, respiratory rate (RR), PaCO2, heart rate, mechanical ventilation and increase PaO2, but the SpO2 and PH were not improved. In the comparison of CPAP versus high-flow nasal cannula, CPAP can reduce treatment failure, but the PICU LOS, Incidence of intubation, RR, Modified Woods Clinical Asthma Score were not decreased. Treatment failure may be less in helmet comparing with the mask though there was no quantitative analysis.

Conclusion: CPAP for the initial respiratory management significantly benefit children with bronchiolitis, the delivery of CPAP by helmet may be a better choice. More high-quality research is needed to confirm the conclusion.
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http://dx.doi.org/10.1093/tropej/fmaa128DOI Listing
May 2021

Improvement of tacrolimus production in Streptomyces tsukubaensis by mutagenesis and optimization of fermentation medium using Plackett-Burman design combined with response surface methodology.

Biotechnol Lett 2021 May 22. Epub 2021 May 22.

Fujian Provincial Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Fuzhou, 350007, China.

Objective: This study was conducted to enhance the production of tacrolimus in Streptomyces tsukubaensis by strain mutagenesis and optimization of the fermentation medium.

Results: A high tacrolimus producing strain S. tsukubaensis FIM-16-06 was obtained by ultraviolet mutagenesis coupled with atmospheric and room temperature plasma mutagenesis.Then, nine variables were screened using Plackett-Burman experimental design, in which soluble starch, peptone and Tween 80 showed significantly affected tacrolimus production. Further studies were carried out employing central composite design to elucidate the mutual interaction between the variables and to work out optimal fermentation medium composition for tacrolimus production. The optimum fermentation medium was found to contain 61.61 g/L of soluble starch, 20.61 g/L of peptone and 30.79 g/L of Tween 80. In the optimized medium, the production of tacrolimus reached 1293 mg/L in shake-flask culture, and reached 1522 mg/L while the scaled-up fermentation was conducted in a 1000 L fermenter, which was about 3.7 times higher than that in the original medium.

Conclusions: Combining compound mutation with rational medium optimization is an effective approach for improving tacrolimus production, and the optimized fermentation medium could be efficiently used for industrial production.
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http://dx.doi.org/10.1007/s10529-021-03144-8DOI Listing
May 2021

Novel Mutations in Chinese Patients with Multiple Osteochondromas Identified Using Whole Exome Sequencing.

Genet Test Mol Biomarkers 2021 May;25(5):361-367

The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Multiple osteochondromas (MO) are an autosomal-dominant disease characterized by the growth of multiple cartilage-capped prominences in the growth plate region of the metaphysis in long and flat bones. To detect genetic mutations related to MO, a three-generation Chinese family with MO was evaluated using whole exome sequencing for mutation screening. The candidate pathogenic mutation was validated by Sanger sequencing. A novel frameshift (NM_000401.3:c.1321del:p.Leu441TrpfsTer28) in exon 8 of the exotosin 2 () gene was identified in two affected individuals. Codons 441 and 468 in the gene are highly conserved among vertebrates as demonstrated by multiple sequence alignment. The c.1321 del C resulted in an amino acid change at codon 441, which generated a premature stop codon at position 468, causing complete loss of the glycosyltransferase domain. A novel frameshift mutation c.1321delC detected in the gene may help in prenatal genetic screening and early diagnosis of MO.
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http://dx.doi.org/10.1089/gtmb.2020.0317DOI Listing
May 2021

Microchemomechanical devices using DNA hybridization.

Proc Natl Acad Sci U S A 2021 May;118(21)

Department of Physics, New York University, New York, NY 10003;

The programmability of DNA oligonucleotides has led to sophisticated DNA nanotechnology and considerable research on DNA nanomachines powered by DNA hybridization. Here, we investigate an extension of this technology to the micrometer-colloidal scale, in which observations and measurements can be made in real time/space using optical microscopy and holographic optical tweezers. We use semirigid DNA origami structures, hinges with mechanical advantage, self-assembled into a nine-hinge, accordion-like chemomechanical device, with one end anchored to a substrate and a colloidal bead attached to the other end. Pulling the bead converts the mechanical energy into chemical energy stored by unzipping the DNA that bridges the hinge. Releasing the bead returns this energy in rapid (>20 μm/s) motion of the bead. Force-extension curves yield energy storage/retrieval in these devices that is very high. We also demonstrate remote activation and sensing-pulling the bead enables binding at a distant site. This work opens the door to easily designed and constructed micromechanical devices that bridge the molecular and colloidal/cellular scales.
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http://dx.doi.org/10.1073/pnas.2023508118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166185PMC
May 2021

SSBER: removing batch effect for single-cell RNA sequencing data.

Authors:
Yin Zhang Fei Wang

BMC Bioinformatics 2021 May 14;22(1):249. Epub 2021 May 14.

Shanghai Key Lab of Intelligent Information Processing, Shanghai, China.

Background: With the continuous maturity of sequencing technology, different laboratories or different sequencing platforms have generated a large amount of single-cell transcriptome sequencing data for the same or different tissues. Due to batch effects and high dimensions of scRNA data, downstream analysis often faces challenges. Although a number of algorithms and tools have been proposed for removing batch effects, the current mainstream algorithms have faced the problem of data overcorrection when the cell type composition varies greatly between batches.

Results: In this paper, we propose a novel method named SSBER by utilizing biological prior knowledge to guide the correction, aiming to solve the problem of poor batch-effect correction when the cell type composition differs greatly between batches.

Conclusions: SSBER effectively solves the above problems and outperforms other algorithms when the cell type structure among batches or distribution of cell population varies considerably, or some similar cell types exist across batches.
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http://dx.doi.org/10.1186/s12859-021-04165-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120905PMC
May 2021

Structure validation of oxidized poly (2-hydroxyethyl acrylate) with multiple aldehyde groups and its application for collagen modification.

R Soc Open Sci 2021 Feb 17;8(2):201892. Epub 2021 Feb 17.

College of Food and Biological Engineering, Sichuan Key Laboratory of Meat Processing, Chengdu University, Chengdu, Sichuan 610106, People's Republic of China.

The structural characteristic of oxidized poly (2-hydroxyethyl acrylate) (OP) was confirmed by high-performance liquid chromatography, gel permeation chromatography and hydroxylamine hydrochloride titration. The results demonstrated that OP prepared through 2,2,6,6-tetramethylpiperidine-1-oxyl-mediated oxidation of poly (2-hydroxyethyl acrylate) was featured by multiple aldehyde groups on its side chain, with no free formaldehyde produced during the oxidation process. The computational simulation for the electrophilic reactivity of OP molecule showed that the reactivity of the aldehyde groups in OP with the amino groups of collagen was comparable to that of glutaraldehyde. In this study, OP was chosen as a collagen modifier to investigate the modification effects on the secondary structure, aggregation behaviour and thermal stability of collagen. The covalent cross-linking occurred between the aldehyde groups of OP and the amino groups of collagen under alkaline condition. The covalent binding between OP and collagen was strengthened with the increasing reaction pH and OP dosage, and the triple helix of collagen was altered to some degree. Furthermore, OP promoted the intense aggregation of collagen and enhanced the thermal stability of collagen. This work provides guidance for preparing novel collagen modifier with multiple aldehyde groups.
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http://dx.doi.org/10.1098/rsos.201892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074665PMC
February 2021

Biomedical named entity recognition using BERT in the machine reading comprehension framework.

J Biomed Inform 2021 Jun 6;118:103799. Epub 2021 May 6.

School of Computer Science and Technology, Dalian University of Technology, Dalian 116024, China.

Recognition of biomedical entities from literature is a challenging research focus, which is the foundation for extracting a large amount of biomedical knowledge existing in unstructured texts into structured formats. Using the sequence labeling framework to implement biomedical named entity recognition (BioNER) is currently a conventional method. This method, however, often cannot take full advantage of the semantic information in the dataset, and the performance is not always satisfactory. In this work, instead of treating the BioNER task as a sequence labeling problem, we formulate it as a machine reading comprehension (MRC) problem. This formulation can introduce more prior knowledge utilizing well-designed queries, and no longer need decoding processes such as conditional random fields (CRF). We conduct experiments on six BioNER datasets, and the experimental results demonstrate the effectiveness of our method. Our method achieves state-of-the-art (SOTA) performance on the BC4CHEMD, BC5CDR-Chem, BC5CDR-Disease, NCBI-Disease, BC2GM and JNLPBA datasets, achieving F1-scores of 92.92%, 94.19%, 87.83%, 90.04%, 85.48% and 78.93%, respectively.
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http://dx.doi.org/10.1016/j.jbi.2021.103799DOI Listing
June 2021

The significant sex-biased expression pattern of Sp-Wnt4 provides novel insights into the ovarian development of mud crab (Scylla Paramamosain).

Int J Biol Macromol 2021 May 3;183:490-501. Epub 2021 May 3.

Guangdong Provincial Key Laboratory of Marine Biotechnology, Shantou University, Shantou 515063, China; STU-UMT Joint Shellfish Research Laboratory, Shantou University, Shantou 515063, China. Electronic address:

The wingless-type MMTV integration site family member-4 (Wnt4), a member of the wingless-related integration site (Wnt) family, is widely accepted as a key regulator of ovarian development in mammals. In this study, a full-length cDNA of Wnt4 (designated as Sp-Wnt4) was cloned, characterized, and functionally studied in mud crab (Scylla paramamosain). The full-length cDNA of Sp-Wnt4 consists of 2659 bp with an open reading frame (ORF) encoding 359 amino acids, a 907 bp 5'-UTR and a 672 bp 3'-UTR. Sp-Wnt4 contains 25 cysteine (Cys) residues and three potential N-glycosylation sites. Sp-Wnt4 protein shared the highest identity (98.9%) to the Wnt4 protein of Portunus trituberculatus. The phylogenetic tree showed that Sp-Wnt4 and Wnt4 protein of Malacostracan crustaceans clustered together, indicating that they had a close genetic distance. Sp-Wnt4 was expressed at a higher level in the ovary compared to other tissues, with the highest expression level at the third stage (O-III) of the ovarian development (P < 0.05). A downward trend was observed in the expression level of Sp-Wnt4 from the embryo stage to crablet stages (P < 0.05). After unilateral eyestalk ablation, the expression level of Sp-Wnt4 significantly increased in testis (14-fold) and downregulated (3.1-fold) in the gill (P < 0.05) of females. In situ hybridization (ISH) assay revealed that Sp-Wnt4 transcripts were mainly localized in the cytoplasm of oocyte cells. These findings showed that Sp-Wnt4 play crucial roles in the ovarian development of S. paramamosain. In conclusion, our study provides novel insights into the evolution and roles of the Wnt4 gene.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.04.186DOI Listing
May 2021

Characterization of umami compounds in bone meal hydrolysate.

J Food Sci 2021 Jun 4;86(6):2264-2275. Epub 2021 May 4.

State Key Laboratory of Bioreactor Engineering, R&D Center of Separation and Extraction Technology in Fermentation Industry, East China University of Science and Technology, Shanghai, China.

The objective of this research was to identify and characterize the chemical compounds that exhibited monosodium glutamate (MSG)-like taste in the hydrolyzed bone meal produced by using flavourzyme. The free amino acids and peptides in the bone meal hydrolysate were analyzed. The results showed that the glutamic acid and the aspartic acid in the bone meal increased by 13.1 times and 14.2 times, respectively, after the flavourzyme hydrolysis. The peptides' isolation identified six MSG-like peptides in the hydrolysate, including APGPVGPAG, DAINWPTPGEIAH, FLGDEETVR, GVDEATIIEILTK, PAGPVGPVG, and VAPEEHPTL, which should contribute to the taste. The human sensory evaluation results indicated that the six peptides showed MSG-like taste, and the electronic tongue analysis indicated that the six peptides showed sourness, saltiness, bitterness, and astringency. The findings of this study demonstrated that the MSG-like taste of the bone meal hydrolysate should be attributed to the generation of MSG-like amino acids and peptides from the flavourzyme hydrolysis. PRACTICAL APPLICATION: The manuscript describes the umami compounds in the bone meal hydrolysate. The findings from this study should further confirm the feasibility of using bone meal to prepare meat-flavor essence and provide a better understanding of preparing bio-source flavoring peptides, which is very important to the artificial meat development and gene breeding.
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http://dx.doi.org/10.1111/1750-3841.15751DOI Listing
June 2021

Binding mechanism and functional evaluation of quercetin 3-rhamnoside on lipase.

Food Chem 2021 Oct 28;359:129960. Epub 2021 Apr 28.

College of Chemical Engineering, Sichuan University, Chengdu 610010, China.

The interaction between lipase and quercetin 3-rhamnoside was studied by fluorescence spectroscopy, enzyme kinetics, and molecular dynamics simulation. The results showed that quercetin 3-rhamnoside had a strong quenching effect on the intrinsic fluorescence of lipase. The binding constant decreased with increasing temperature, and the number of binding sites approached 1. Thermodynamic parameters indicated that hydrogen bonding and van der Waals forces are the dominant forces when the interaction occurs. Circular dichroism spectroscopy and infrared spectroscopy proved that the ligand perturbed the structure of lipase. Enzyme kinetics results showed that quercetin 3-rhamnoside inhibited lipase, and the inhibitory effect was dose-dependent. Molecular dynamics simulation further explained the interaction mechanism and inhibitory effect. This study confirmed the inhibitory effect of quercetin 3-rhamnoside on lipase explained their binding mechanism, which will contribute to guiding the development of fat-reducing functional foods.
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http://dx.doi.org/10.1016/j.foodchem.2021.129960DOI Listing
October 2021

A Novel Clinical Nomogram to Predict Transient Symptomatic Associated with Infarction: The ABCD3-SLOPE Score.

Biomed Res Int 2021 14;2021:5597155. Epub 2021 Apr 14.

Educational Office, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Background: It is hard to differentiate transient symptoms associated with infarction (TSI) from transient ischemic stroke (TIA) without MRI in the early onset. However, they have distinct clinical outcomes and respond differently to therapeutics. Therefore, we aimed to develop a risk prediction model based on the clinical features to identify TSI.

Methods: We enrolled 230 consecutive patients with transient neurologic deficit in the Department of Neurology, Tongji University Affiliated Tenth People's Hospital from March 2014 to October 2019. All the patients were assigned into TIA group (DWI-negative) or TSI group (DWI-positive) based on MRI conducted within five days of onset. We summarized the clinical characteristics of TSI by univariate and multivariate analyses. And then, we developed and validated a nomogram to identify TSI by the logistic regression equation.

Results: Of the 230 patients, 41.3% were diagnosed with TSI. According to the multivariate analysis, four independent risk factors, including smoking history, low-density lipoprotein cholesterol, brain natriuretic peptide precursor, and ABCD3 score, were incorporated into a nomogram. We developed a predictive model named ABCD3-SLOPE. The calibration curve showed good agreement between nomogram prediction and observation. The concordance index (C-index) of the nomogram for TSI prediction was 0.77 (95% confidence interval, 0.70-0.83), and it was well-calibrated.

Conclusions: Smoking history, low-density lipoprotein cholesterol, brain natriuretic peptide precursor, and ABCD3 score were reliable risk factors for TSI. ABCD3-SLOPE was a potential tool to quantify the likelihood of TSI.
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http://dx.doi.org/10.1155/2021/5597155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062161PMC
June 2021

Comparison of children receiving emergent sepsis care by mode of arrival.

Am J Emerg Med 2021 Apr 21;47:217-222. Epub 2021 Apr 21.

Department of Pediatrics, University of Cincinnati, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45249, United States of America. Electronic address:

Objective: To determine if differences in patient characteristics, treatments, and outcomes exist between children with sepsis who arrive by emergency medical services (EMS) versus their own mode of transport (self-transport).

Methods: Retrospective cohort study of patients who presented to the Emergency Department (ED) of two large children's hospitals and treated for sepsis from November 2013 to June 2017. Presentation, ED treatment, and outcomes, primarily time to first bolus and first parental antibiotic, were compared between those transported via EMS versus patients who were self-transported.

Results: Of the 1813 children treated in the ED for sepsis, 1452 were self-transported and 361 were transported via EMS. The EMS group were more frequently male, of black race, and publicly insured than the self-transport group. The EMS group was more likely to have a critical triage category, receive initial care in the resuscitation suite (51.9 vs. 22%), have hypotension at ED presentation (14.4 vs. 5.4%), lactate >2.0 mmol/L (60.6 vs. 40.8%), vasoactive agents initiated in the ED (8.9 vs. 4.9%), and to be intubated in the ED (14.4 vs. 2.8%). The median time to first IV fluid bolus was faster in the EMS group (36 vs. 57 min). Using Cox LASSO to adjust for potential covariates, time to fluids remained faster for the EMS group (HR 1.26, 95% CI 1.12, 1.42). Time to antibiotics, ICU LOS, 3- or 30-day mortality rates did not differ, yet median hospital LOS was significantly longer in those transported by EMS versus self-transported (6.5 vs. 5.3 days).

Conclusions: Children with sepsis transported by EMS are a sicker population of children than those self-transported on arrival and had longer hospital stays. EMS transport was associated with earlier in-hospital fluid resuscitation but no difference in time to first antibiotic. Improved prehospital recognition and care is needed to promote adherence to both prehospital and hospital-based sepsis resuscitation benchmarks.
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http://dx.doi.org/10.1016/j.ajem.2021.04.053DOI Listing
April 2021

A Fast Multi-Locus Ridge Regression Algorithm for High-Dimensional Genome-Wide Association Studies.

Front Genet 2021 29;12:649196. Epub 2021 Mar 29.

College of Finance, Nanjing Agricultural University, Nanjing, China.

The mixed linear model (MLM) has been widely used in genome-wide association study (GWAS) to dissect quantitative traits in human, animal, and plant genetics. Most methodologies consider all single nucleotide polymorphism (SNP) effects as random effects under the MLM framework, which fail to detect the joint minor effect of multiple genetic markers on a trait. Therefore, polygenes with minor effects remain largely unexplored in today's big data era. In this study, we developed a new algorithm under the MLM framework, which is called the fast multi-locus ridge regression (FastRR) algorithm. The FastRR algorithm first whitens the covariance matrix of the polygenic matrix K and environmental noise, then selects potentially related SNPs among large scale markers, which have a high correlation with the target trait, and finally analyzes the subset variables using a multi-locus deshrinking ridge regression for true quantitative trait nucleotide (QTN) detection. Results from the analyses of both simulated and real data show that the FastRR algorithm is more powerful for both large and small QTN detection, more accurate in QTN effect estimation, and has more stable results under various polygenic backgrounds. Moreover, compared with existing methods, the FastRR algorithm has the advantage of high computing speed. In conclusion, the FastRR algorithm provides an alternative algorithm for multi-locus GWAS in high dimensional genomic datasets.
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http://dx.doi.org/10.3389/fgene.2021.649196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041068PMC
March 2021

Efficacy and safety of traditional Chinese medicine on treating oligomenorrhea: a systematic review and meta-analysis.

Ann Palliat Med 2021 Mar 24. Epub 2021 Mar 24.

Department of Traditional Chinese Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.

Background: Oligomenorrhea is one of the most frequent gynecologic complaints that interferes with women's life quality. Treatment using traditional Chinese medicine (TCM) is a preferred alternative therapy for oligomenorrhea. However, systematic reviews (SRs) evaluating the efficacy of TCM treatments for oligomenorrhea remain absent. The present SR and meta-analysis aimed to evaluate the efficacy and safety of TCM treatment for oligomenorrhea.

Methods: Randomized controlled trials (RCTs) published in English and Chinese were retrieved by searching in the databases in October 2019, including PubMed, Cochrane Library, EMBASE, Sinomed, CNKI, VIP, and WanFang databases. Quantitative analyses and quality assessments were then conducted based on abstracted data. This study protocol is registered PROSPERO, number CRD42018095660.

Results: A total of 26 eligible RCTs involving 2,389 patients were included in our analysis. Overall, we observed an effect of increasing menstrual blood volumes owing to using TCM treatments plus bio-medicine (BM) (n=649; MD, 12.05; 95% CI: 5.23 to 18.87; P<0.00001; I2 =96%). Besides, TCM combined with BM yielded a significant prolongation in menstrual periods (MD, 1.20; 95% CI: 0.78 to 1.62; P<0.00001; I 2 =76%), and had potential improvements on enhancing effectiveness rates, increasing endometrial thickness, and raising the levels of estradiol (E2) and progesterone (P). Concerning adverse events (AEs), no significant difference was found in either group. The quality of evidence was relatively low.

Conclusions: This study seems to support the potential effect of TCM on treating oligomenorrhea. However, the relatively low quality of prior studies calls for future RCTs to further assess the efficacy of TCM on treating oligomenorrhea using rigorous designs.
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http://dx.doi.org/10.21037/apm-20-825DOI Listing
March 2021

MEX3A promotes development and progression of breast cancer through regulation of PIK3CA.

Exp Cell Res 2021 Jul 1;404(1):112580. Epub 2021 Apr 1.

Department of General Surgery, The Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China. Electronic address:

Breast cancer has been identified as the most common malignant tumors among women and the morbidity of breast cancer is still increasing rapidly. MEX3A possesses important functions in the regulation of mRNAs and may be involved in a variety of human diseases including cancer, whose relationship with breast cancer is still not clear. In this study, MEX3A was identified as a potential promotor in breast cancer, whose expression was strongly higher in breast cancer tissues than normal tissues. The in vitro experiments showed that MEX3A is capable of promoting the development of breast cancer through stimulating cell proliferation, inhibiting cell apoptosis, arresting cell cycle and promoting cell migration. The functions of MEX3A were also verified in vivo. Furthermore, a combination of genechip analysis and Ingenuity pathway analysis (IPA) identified PIK3CA as a potential downstream target of MEX3A, knockdown of which executes similar inhibitory effects on breast cancer and could alleviate MEX3A-induced progression of breast cancer. In conclusion, our study unveiled, as the first time, MEX3A as a tumor promotor for breast cancer, whose function was carried out probably through the regulation of PIK3CA.
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http://dx.doi.org/10.1016/j.yexcr.2021.112580DOI Listing
July 2021