Publications by authors named "Chao Chen"

2,148 Publications

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Assessment of Neonatal Intensive Care Unit Practices, Morbidity, and Mortality Among Very Preterm Infants in China.

JAMA Netw Open 2021 Aug 2;4(8):e2118904. Epub 2021 Aug 2.

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

Importance: The Chinese Neonatal Network was established in 2018 and maintains a standardized national clinical database of very preterm or very low-birth-weight infants in tertiary neonatal intensive care units (NICUs) throughout China. National-level data on outcomes and care practices of very preterm infants (VPIs) in China are lacking.

Objective: To assess the care practices in NICUs and outcomes among VPIs in China.

Design, Setting, And Participants: A cohort study was conducted comprising 57 tertiary hospitals from 25 provinces throughout China. All infants with gestational age (GA) less than 32 weeks who were admitted to the 57 NICUs between January 1 and December 31, 2019, were included.

Main Outcomes And Measures: Care practices, morbidities, and survival were the primary outcomes of the study. Major morbidities included bronchopulmonary dysplasia, severe intraventricular hemorrhage (grade ≥3) and/or periventricular leukomalacia, necrotizing enterocolitis (stage ≥2), sepsis, and severe retinopathy of prematurity (stage ≥3).

Results: A total of 9552 VPIs were included, with mean (SD) GA of 29.5 (1.7) weeks and mean (SD) birth weight of 1321 (321) g; 5404 infants (56.6%) were male. Antenatal corticosteroids were used in 75.6% (6505 of 8601) of VPIs, and 54.8% (5211 of 9503)were born through cesarean delivery. In the delivery room, 12.1% of VPIs received continuous positive airway pressure and 26.7% (2378 or 8923) were intubated. Surfactant was prescribed for 52.7% of the infants, and postnatal dexamethasone was prescribed to 9.5% (636 of 6675) of the infants. A total of 85.5% (8171) of the infants received complete care, and 14.5% (1381) were discharged against medical advice. The incidences of the major morbidities were bronchopulmonary dysplasia, 29.2% (2379 of 8148); severe intraventricular hemorrhage and/or periventricular leukomalacia, 10.4% (745 of 7189); necrotizing enterocolitis, 4.9% (403 of 8171 ); sepsis, 9.4% (764 of 8171); and severe retinopathy of prematurity, 4.3% (296 of 6851) among infants who received complete care. Among VPIs with complete care, 95.4% (7792 of 8171) survived: 65.6% (155 of 236) at 25 weeks' or less GA, 89.0% (880 of 988) at 26 to 27 weeks' GA, 94.9% (2635 of 2755)at 28 to 29 weeks' GA, and 98.3% (4122 of 4192) at 30 to 31 weeks' GA. Only 57.2% (4677 of 8171) of infants survived without major morbidity: 10.5% (25 of 236) at 25 weeks' or less GA, 26.8% (48 of 179) at 26 to 27 weeks' GA, 51.1% (1409 of 2755) at 28 to 29 weeks' GA, and 69.3% (2904 of 4192) at 30 to 31 weeks' GA. Among all infants admitted, the survival rate was 87.6% (8370 of 9552)and survival without major morbidities was 51.8% (4947 of 9552).

Conclusions And Relevance: The findings of this study suggest that survival and survival without major morbidity of VPIs in Chinese NICUs have improved but remain lower than in high-income countries. Comprehensive and targeted quality improvement efforts are needed to provide complete care for all VPIs, optimize obstetrical and neonatal care practices, and improve outcomes.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.18904DOI Listing
August 2021

Tetravalent SARS-CoV-2 Neutralizing Antibodies Show Enhanced Potency and Resistance to Escape Mutations.

J Mol Biol 2021 Jul 27:167177. Epub 2021 Jul 27.

The Donnelly Centre, University of Toronto, Toronto, Canada. Electronic address:

Neutralizing antibodies (nAbs) hold promise as therapeutics against COVID-19. Here, we describe protein engineering and modular design principles that have led to the development of synthetic bivalent and tetravalent nAbs against SARS-CoV-2. The best nAb targets the host receptor binding site of the viral S-protein and tetravalent versions block entry with a potency exceeding bivalent nAbs by an order of magnitude. Structural studies show that both the bivalent and tetravalent nAbs can make multivalent interactions with a single S-protein trimer, consistent with the avidity and potency of these molecules. Significantly, we show that the tetravalent nAbs show increased tolerance to potential virus escape mutants and an emerging variant of concern. Bivalent and tetravalent nAbs can be produced at large-scale and are as stable and specific as approved antibody drugs. Our results provide a general framework for enhancing antiviral therapies against COVID-19 and related viral threats, and our strategy can be applied to virtually any antibody drug.
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http://dx.doi.org/10.1016/j.jmb.2021.167177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316672PMC
July 2021

Long Noncoding RNA NONHSAT079852.2 Contributes to GBM Recurrence by Functioning as a ceRNA for has-mir-10401-3p to Facilitate HSPA1A Upregulation.

Front Oncol 2021 8;11:636632. Epub 2021 Jul 8.

College of Life Sciences, Northwest University, Xian, China.

Glioblastoma multiforme (GBM) is the most common brain malignancy and major cause of high mortality in patients with GBM, and its high recurrence rate is its most prominent feature. However, the pathobiological mechanisms involved in recurrent GBM remain largely unknown. Here, whole-transcriptome sequencing (RNA-sequencing, RNA-Seq) was used in characterizing the expression profile of recurrent GBM, and the aim was to identify crucial biomarkers that contribute to GBM relapse. Differentially expressed RNAs in three recurrent GBM tissues compared with three primary GBM tissues were identified through RNA-Seq. The function and mechanism of a candidate long noncoding RNA (lncRNA) in the progression and recurrence of GBM were elucidated by performing comprehensive bioinformatics analyses, such as functional enrichment analysis, protein-protein interaction prediction, and lncRNA-miRNA-mRNA regulatory network construction, and a series of assays. As the most significantly upregulated gene identified in recurrent GBM, HSPA1A is mainly related to antigen presentation and the MAPK signaling pathway, as indicated by functional enrichment analysis. HSPA1A was predicted as the target gene of the lncRNA NONHSAT079852.2. qRT-PCR revealed that NONHSAT079852.2 was significantly elevated in recurrent GBM relative to that in primary GBM, and high NONHSAT079852.2 expression was associated with the poor overall survival rates of patients with GBM. The knockdown of NONHSAT079852.2 successfully induced tumor cell apoptosis, inhibited the proliferation, migration, invasion and the expression level of HSPA1A in glioma cells. NONHSAT079852.2 was identified to be a sponge for hsa-miR-10401-3p through luciferase reporter assay. Moreover, HSPA1A was targeted and regulated by hsa-miR-10401-3p. Collectively, the results suggested that NONHSAT079852.2 acts as a sponge of hsa-mir-10401-3p and thereby enhances HSPA1A expression, promotes tumor cell proliferation and invasion, and leads to the progression and recurrence of GBM. This study will provide new insight into the regulatory mechanisms of NONHSAT079852.2-mediated competing endogenous RNA in the pathogenesis of recurrent GBM and evidence of the potential of lncRNAs as diagnostic biomarkers or potential therapeutic targets.
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http://dx.doi.org/10.3389/fonc.2021.636632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297974PMC
July 2021

Hypoxia-Responsive Gene Editing to Reduce Tumor Thermal Tolerance for Mild-Photothermal Therapy.

Angew Chem Int Ed Engl 2021 Jul 23. Epub 2021 Jul 23.

Nanjing University, College of Engineering and Applied Sciences, State Key Laboratory of Analytical Chemistry for Life Science, CHINA.

Near-infrared (NIR)-light-triggered photothermal therapy (PTT) is usually associated with an undesirable heating damage to normal organs nearby due to its high temperature (>50 o C) for available tumor ablation. Achieving PTT strategies at a relatively low temperature therefore demonstrates tremendous value to clinic. Here, we construct a hypoxia-responsive gold nanorods (AuNRs)-based nanocomposite of CRISPR-Cas9 for mild-photothermal therapy via tumor-targeted gene editing. AuNRs are modified with azobenzene-4, 4'-dicarboxylic acid (p-AZO) to achieve on-demand release of CRISPR-Cas9 using hypoxia-responsive azo bonds. In the hypoxic tumor microenvironment, the azo groups of APACPs are selectively reduced by the overexpression of reductases, leading to the release of Cas9 and subsequent gene editing. Owing to the knockout of Hsp90α for reducing thermal-resistance of cancer cells, highly effective tumor ablation both in vitro and in vivo was achieved with APACPs under mild PTT. This strategy provides a promising method for gene editing targeting tumor microenvironments, and opens a possibility to improve the therapeutic effect and minimize the side effects.
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http://dx.doi.org/10.1002/anie.202107036DOI Listing
July 2021

[Risk factors and their predictive value for intensive care unit acquired weakness in patients with sepsis].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2021 Jun;33(6):648-653

Department of Critical Care Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou 450003, Henan, China. Corresponding author: Qin Bingyu, Email:

Objective: To explore the risk factors of intensive care unit acquired weakness (ICUAW) in patients with sepsis, and to evaluate the predictive value of each risk factor for ICUAW.

Methods: A case control study was conducted, 60 septic patients admitted to the intensive care unit (ICU) of Henan Provincial People's Hospital from October 20, 2020 to February 20, 2021 were enrolled. The patients were divided into two groups: sepsis ICUAW group and sepsis non-ICUAW group. The data of gender, age, body mass index (BMI), acute physiology and chronic health evaluation II (APACHE II) score, complications, mechanical ventilation, duration of ICUAW, length of stay in ICU, fasting blood glucose, blood lactic acid (Lac), procalcitonin (PCT), C-reactive protein (CRP), sequential organ failure assessment (SOFA) score, outcome, antimicrobial agent, glucocorticoid, sedatives and analgesics drugs and vasoactive drugs were collected. Risk factors were screened by univariate Logistic regression analysis, and odds ratio (OR) was adjusted by multivariate binary logistic regression, P < 0.05 was considered as independent risk factors. Finally, the receiver operating characteristic curve (ROC curve) was drawn to analyze the predictive value of independent risk factors.

Results: The APACHE II score of the sepsis ICUAW group was significantly higher than that of the sepsis non-ICUAW group (23.05±8.17 vs. 15.33±4.89, P < 0.05), the total length of stay in the ICU was significantly longer than that of the sepsis non-ICUAW group (days: 15.1±9.2 vs. 8.5±3.4, P < 0.05), the improvement rate of patients was significantly lower than that of the sepsis non-ICUAW group [45.0% (9/20) vs. 95.0% (38/40), P < 0.05]. After univariate Logistic regression and multicollinearity test analysis, 7 factors including APACHE II score, average SOFA score, blood lactic acid, proportion of mechanical ventilation, sedatives and analgesics drugs, type of antibiotics and type of vasoactive drugs were included in the binary Logistic regression model [OR: 1.21, 2.05, 2.26, 0.21, 1.54, 2.07, 1.38, 95% confidence interval (95%CI): 1.09-1.35, 1.42-2.94, 1.12-4.57, 0.05-0.66, 1.03-2.29, 1.27-3.37, 0.96-2.00, all P < 0.05]. Hosmer-Lemchaw test P = 0.901, and the correct percentage of prediction was 85%, indicating good model fit. Multivariate binary Logistic regression analysis showed that APACHE II score and average SOFA score were independent risk factors for the occurrence of ICUAW in septic patients (APACHE II score: OR = 1.17, 95%CI was 1.004-1.376, P = 0.044; average SOFA score: OR = 1.86, 95%CI was 1.157-2.981, P = 0.01). ROC curve analysis showed that the mean value of APACHE II score, average SOFA score and their combined detection had a certain predictive value for the occurrence of ICUAW in sepsis patients, areas under ROC curve (AUC) were 0.787, 0.881, 0.905, 95%CI was 0.646-0.928, 0.791-0.972, 0.828-0.982, all P < 0.05. When the cut-off value was 19.500, 6.225, 0.375, the sensitivity was 75%, 90%, 90%, and the specificity were 80%, 80%, 85%, respectively.

Conclusions: APACHE II score and average SOFA score can be used as independent risk factors for the occurrence of ICUAW in sepsis, and their combined predictive value is better than that of individual index.
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http://dx.doi.org/10.3760/cma.j.cn121430-20210329-00459DOI Listing
June 2021

Endovascular treatment of vertebro-vertebral arteriovenous fistula in neurofibromatosis type I: A report of two cases and literature review with a focus on endovascular treatment.

Clin Neurol Neurosurg 2021 Jul 14;207:106806. Epub 2021 Jul 14.

Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai, China. Electronic address:

Vertebro-Vertebral arteriovenous fistula (VV-AVF) associated with neurofibromatosis Type I (NF-1) is rare. We presented two female NF-1 patients with a diagnosis of VV-AVF treated with endovascular approach. The fistula was completely obliterated with balloon assisted embolization and covered stent separately and VA patency was preserved in both cases. Reviewing the literature with a focus on endovascular treatment, endovascular occlusion of VV-AVF in NF-1 patients is safe and effective. To preserve the parent VA patency and obliterate the fistula simultaneously is challenging generally, but feasible in some cases.
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http://dx.doi.org/10.1016/j.clineuro.2021.106806DOI Listing
July 2021

PAX6 upstream antisense RNA (PAUPAR) inhibits colorectal cancer progression through modulation of the microRNA (miR)-17-5p / zinc finger protein 750 (ZNF750) axis.

Bioengineered 2021 Dec;12(1):3886-3899

Department of Gastrointestinal Surgery, Huizhou Municipal Central Hospital, Huizhou, Guangdong, China.

Researchers have demonstrated that long non-coding RNAs (lncRNAs) are vital in colorectal cancer (CRC) progression. Here, we aimed to explore the function of lncRNA PAX6 upstream antisense RNA (PAUPAR) in the development of CRC. In the present study, PAUPAR and microRNA (miR)-17-5p expression levels in CRC tissues and cells were examined using quantitative real-time polymerase chain reaction (qRT-PCR). Western blot analysis was adopted to examine ZNF750 expression at the protein level in CRC cells. CRC cell proliferation was examined by colony formation experiment and 5-Bromo-2-deoxyUridine (BrdU) experiment. CRC cell migration and invasion were assessed by Transwell experiments. Apoptosis was measured using the TUNEL experiment. The targeting relationship between PAUPAR and miR-17-5p was confirmed using dual-luciferase reporter gene and RNA immunoprecipitation (RIP) experiments. We demonstrated that PAUPAR was markedly down-modulated in CRC, and its low expression was significantly related to increased T stage and local lymph node metastasis. Knockdown of PAUPAR enhanced CRC cell proliferation, migration and invasion, and restrained apoptosis relative to controls, whereas PAUPAR overexpression caused the opposite effects. Moreover, rescue experiments showed that miR-17-5p inhibitor could reverse the role of PAUPAR knockdown on the malignant phenotypes of CRC cells. Additionally, PAUPAR could positively regulate the expression of ZNF750 via repressing miR-17-5p. Taken together, these findings suggest that PAUPAR/miR-17-5p/ZNF750 axis is a novel mechanism implicated in CRC progression.
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http://dx.doi.org/10.1080/21655979.2021.1940071DOI Listing
December 2021

Prognostic factors for ovarian metastases in colorectal cancer patients.

World J Surg Oncol 2021 Jul 20;19(1):220. Epub 2021 Jul 20.

Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, the Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, Zhejiang Province, 310009, People's Republic of China.

Purpose: The aim of this study was to analyze prognostic factors for ovarian metastases (OM) in colorectal cancer (CRC) using data from a Chinese center. In addition, the study aimed at developing a new clinical scoring system for prognosis of OM of CRC patients after surgery.

Patients And Methods: Data of CRC patients with OM were collected from a single Chinese institution (n = 67). Kaplan-Meier analysis was used to evaluate cumulative survival of patients. Factors associated with prognosis of overall survival (OS) were explored using Cox's proportional hazard regression models. A scoring system to determine effectiveness of prognosis was developed.

Results: Median OS values for patients with or without surgery were 22 and 7 months, respectively. Size of OM, number of OM, peritoneal metastasis (PM), Peritoneal cancer index (PCI), and completeness of cytoreduction (CC) were associated with OS of patients through univariate analysis. Multivariate analysis using a Cox regression model showed that only CC was an independent predictor for OS. Three variables (the size of OM >15cm, PCI ≥ 10, and carcinoembryonic antigen (CEA) >30 ng/mL) assigned one point each were used to develop a risk score. The resulting score was used for prognosis of OS.

Conclusion: Surgical treatment of metastatic sites is effective and safe for CRC patients with OM. CC-0 is recommended for improved prognosis. The scoring system developed in this study is effective for prediction of OS of patients after surgery.
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http://dx.doi.org/10.1186/s12957-021-02305-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293531PMC
July 2021

Dynamics of sediment phosphorus affected by mobile aeration: Pilot-scale simulation study in a hypereutrophic pond.

J Environ Manage 2021 Jul 16;297:113297. Epub 2021 Jul 16.

Chengdu Academy of Agricultural and Forestry Science, Chengdu, 610000, China.

Controlling the release of phosphorus (P) in sediments is important to prevent eutrophication and harmful algal blooms in water bodies. Here we explored the effect of mobile aerators on the control of P release from sediments in a eutrophic pond. The dissolved oxygen in the water body recovered significantly after six months of aeration, becoming 4.2-5.8 times higher than in the control. The pH and Eh values at the sediment-water interface considerably increased, while the concentration of soluble reactive phosphorus (SRP) in pore water significantly decreased, resulting in the alteration of SRP fluxes from 1.69 mg/m d to -53.49 mg/m d. Moreover, the inert P in sediments increased by 5.2% of the total P at the end of the study compared with the initial state, and the calcium-bound phosphorus (HCl-P) increased by 96.6%. However, although aeration reduced the concentration of SRP in the water column, the total P concentration was 2.45 times higher than that of the control, and the content of redox-sensitive P (BD-P) in the sediment also increased by 200%. Overall, although mobile aeration can maintain the microenvironment of the sediment interface and increase the inert P content in the sediment to reduce the P flux, it cannot reduce the risk of release of mobile P.
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http://dx.doi.org/10.1016/j.jenvman.2021.113297DOI Listing
July 2021

NDMA formation during ozonation of metformin: Roles of ozone and hydroxyl radicals.

Sci Total Environ 2021 Jul 13;796:149010. Epub 2021 Jul 13.

State Key Joint Laboratory of Environment Simulation and Pollution Control, School of Environment, Tsinghua University, Beijing 100084, China. Electronic address:

Metformin, a high-consumed pharmaceutical for diabetes, has been reported to generate carcinogenic nitroso-dimethylamine (NDMA) during treatment of its containing wastewater. However, whether it would produce NDMA during ozonation or not is unclear, let alone discriminate roles of ozone (O) and hydroxyl radicals (OH). In this paper, effects of ozonation on NDMA formation from metformin were investigated, roles of O and OH were also distinguished by adding tert-butyl alcohol (tBA) as OH scavenger. Moreover, various influencing factors and reaction mechanisms were demonstrated. The results indicated that NDMA could be directly formed from metformin during ozonation, the addition of OH scavenger significantly enhanced its formation (0-46.2 ng/L vs 0-139.1 ng/L). The formation of NDMA by O and OH was more affected by bromide and HCO than those with only O; while the impacts of pH and sulphate on the latter were more notable. No matter without/with tBA in the solution, the formed NDMA during ozonation of metformin increased with raising pH (from 5 to 9) and achieved the maximum 69.6 ng/L and 235.9 ng/L at pH 9, respectively; small amount of bromide (0.1 μM) promoted NDMA production, high levels of bromide (10 μM) inhibited its formation; the existence of HCO enhanced the amounts of NDMA from 44.5 to 73.5 ng/L (raised by 65.2%) by O and OH and from 102.9 to 130 ng/L with only O (raised by 26.3%); with the addition of sulphate, NDMA concentration raised by 43.8% by O and OH, while the value was high up to 134.6% with only O. Based on the result of UPLC-Q-TOF and density functional theory, the oxidation intermediates were identified and possible transformation pathways of metformin during ozonation were proposed. The findings in this paper would provide reference when treating metformin-containing water in future.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149010DOI Listing
July 2021

[Retracted] Connecting endoplasmic reticulum stress to autophagy through IRE1/JNK/beclin‑1 in breast cancer cells.

Int J Mol Med 2021 Aug 19;48(2). Epub 2021 Jul 19.

Faculty of Pharmacy, Bengbu Medical College, Anhui Engineering Technology Research Center of Biochemical Pharmaceuticals, Bengbu, Anhui 233030, P.R. China.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that possible anomalies were associated with data shown in Fig. 4B, C and E, and western blotting data shown in Fig. 5, such that it was difficult to interpret the presented results as having originated from discrete experiments performed in two breast cancer cell lines (MCF‑7 and MDA‑MB‑231). After having investigated the matter internally, the Editor of has decided that this paper should be retracted from the Journal on account of a lack of confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory response. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in International Journal of Molecular Medicine 34: 772-781, 2014; DOI: 10.3892/ijmm.2014.1822].
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http://dx.doi.org/10.3892/ijmm.2021.4997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262653PMC
August 2021

Single-molecule FRET and conformational analysis of beta-arrestin-1 through genetic code expansion and a Se-click reaction.

Chem Sci 2021 Jul 31;12(26):9114-9123. Epub 2021 May 31.

Institute of Biophysics, Chinese Academy of Sciences Chaoyang District Beijing 100101 China.

Single-molecule Förster resonance energy transfer (smFRET) is a powerful tool for investigating the dynamic properties of biomacromolecules. However, the success of protein smFRET relies on the precise and efficient labeling of two or more fluorophores on the protein of interest (POI), which has remained highly challenging, particularly for large membrane protein complexes. Here, we demonstrate the site-selective incorporation of a novel unnatural amino acid (2-amino-3-(4-hydroselenophenyl) propanoic acid, SeF) through genetic expansion followed by a Se-click reaction to conjugate the Bodipy593 fluorophore on calmodulin (CaM) and β-arrestin-1 (βarr1). Using this strategy, we monitored the subtle but functionally important conformational change of βarr1 upon activation by the G-protein coupled receptor (GPCR) through smFRET for the first time. Our new method has broad applications for the site-specific labeling and smFRET measurement of membrane protein complexes, and the elucidation of their dynamic properties such as transducer protein selection.
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http://dx.doi.org/10.1039/d1sc02653dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261736PMC
July 2021

Evaluation of area under the concentration curve adjusted by the terminal-phase as a metric to reduce the impact of variability in bioequivalence testing.

Br J Clin Pharmacol 2021 Jul 16. Epub 2021 Jul 16.

GSK.

Aim: To quantify the utility of a terminal-phase adjusted area under the concentration curve method in increasing the probability of a correct and conclusive outcome of a bioequivalence (BE) trial for highly variable drugs when clearance (CL) varies more than the volume of distribution (V).

Methods: Data from a large population of subjects were generated with variability in CL and V, and used to simulate a two-period, two-sequence crossover BE trial. The 90% confidence interval for formulation comparison was determined following BE assessment using the area under the concentration curve (AUC) ratio test, and the proposed terminal-phase adjusted AUC ratio test. An outcome of bioequivalent, non-bioequivalent or inconclusive was then assigned according to predefined BE limits.

Results: When CL is more variable than V, the proposed approach would enhance the probability of correctly assigning bioequivalent or non-bioequivalent and reduce the risk of an inconclusive trial. For a hypothetical drug with between-subject variability of 35% for CL and 10% for V, when the true test-reference ratio of bioavailability is 1.15, a cross-over study of n=14 subjects analyzed by the proposed method would have 80% or 20% probability of claiming bioequivalent or non-bioequivalent, compared to 22%, 46% or 32% probability of claiming bioequivalent, non-bioequivalent or inconclusive using the standard AUC ratio test.

Conclusions: The terminal-phase adjusted AUC ratio test represents a simple and readily applicable approach to enhance the BE assessment of drug products when CL varies more than V.
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http://dx.doi.org/10.1111/bcp.14986DOI Listing
July 2021

Controlled CRISPR-Cas9 Ribonucleoprotein Delivery for Sensitized Photothermal Therapy.

Small 2021 Jul 16:e2101155. Epub 2021 Jul 16.

Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, 210023, China.

Manipulation of CRISPR delivery for stimuli-responsive gene editing is crucial for cancer therapeutics through maximizing efficacy and minimizing side-effects. However, realizing controlled gene editing for synergistic combination therapy remains a key challenge. Here, a near-infrared (NIR) light-triggered thermo-responsive copper sulfide (CuS) multifunctional nanotherapeutic platform is constructed to achieve controlled release of CRISPR-Cas9 ribonucleoprotein (RNP) and doxorubicin for tumor synergistic combination therapy involving in gene therapy, mild-photothermal therapy (PTT), and chemotherapy. The semiconductor CuS serves as a "photothermal converter" and can stably convert NIR light (808 nm) into local thermal effect to provide photothermal stimulation. The double-strand formed between CuS nanoparticle-linked DNA fragments and single-guide RNA is employed as a controlled element in response to photothermal stimulation for controlled gene editing and drug release. Hsp90α, one subunit of heat shock protein 90 (Hsp90), is targeted by Cas9 RNP to reduce tumor heat tolerance for enhanced mild-PTT effects (≈43 °C). Significant synergistic therapy efficacy can be observed by twice NIR light irradiation both in vitro and in vivo, compared to PTT alone. Overall, this exogenously controlled method provides a versatile strategy for controlled gene editing and drug release with potentially synergistic combination therapy.
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http://dx.doi.org/10.1002/smll.202101155DOI Listing
July 2021

Circulating endothelial microparticles: a promising biomarker of acute kidney injury after cardiac surgery with cardiopulmonary bypass.

Ann Transl Med 2021 May;9(9):786

Division of Cardiac Surgery, Heart Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Background: Current diagnostic strategies for acute kidney injury (AKI) after cardiac surgery with cardiopulmonary bypass (CPB) are nonspecific and limited. Previously, we demonstrated that circulating microparticles (MPs) in patients with valve heart disease (VHD) and congenital heart diseases (CHD) induce endothelial dysfunction and neutrophil chemotaxis, which may result in kidney injury. We also found that circulating MPs increase after cardiac surgery with CPB and are related to cardiac function. However, the relationship between circulating MPs and AKI after CPB is unknown.

Methods: Eighty-five patients undergoing cardiac surgery with CPB were enrolled. Patients were divided into AKI and non-AKI groups based on the serum creatinine levels at 12 h and 3 d post-CPB. Circulating MPs were isolated from plasma, and their levels including its subtypes were detected by flow cytometer. Independent risk factors for the CPB-associated AKI (CPB-AKI) were determined by multivariate logistic regression analysis. Receiver operating characteristic (ROC) analysis was used to measure the prognostic potential of CPB-AKI.

Results: The morbidity of AKI at 12 h and 3 d after cardiac surgery with CPB was 40% and 31.76%, respectively. The concentrations of total MPs and platelet-derived MPs (PMP) remained unchanged at 12 h and then increased at 3 d post-CPB, while that of endothelial-derived MPs (EMP) increased at both time points. In patients with AKI, PMP and EMP were elevated compared with the patients without AKI. However, no significant change was detected on monocyte-derived MPs (MMP) at 12 h and 3 d post-CPB. The logistic regression analysis showed that EMP was the independent risk factor for AKI both at 12 h and 3 d post-CPB. The area under ROC for the concentrations of EMP at 12 h and 3 d post-CPB was 0.86 and 0.91, with the specificity up to 0.88 and 0.91, respectively.

Conclusions: Circulating EMP may serve as a potential biomarker of AKI after cardiac surgery with CPB.
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http://dx.doi.org/10.21037/atm-20-7828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246187PMC
May 2021

Melatonin Improves Cotton Salt Tolerance by Regulating ROS Scavenging System and Ca Signal Transduction.

Front Plant Sci 2021 28;12:693690. Epub 2021 Jun 28.

State Key Laboratory of Cotton Biology/Institute of Cotton Research of Chinese Academy of Agricultural Sciences/Research Base, Zhengzhou University/Key Laboratory for Cotton Genetic Improvement, MOA, Anyang, China.

As one of the cash crops, cotton is facing the threat of abiotic stress during its growth and development. It has been reported that melatonin is involved in plant defense against salt stress, but whether melatonin can improve cotton salt tolerance and its molecular mechanism remain unclear. We investigated the role of melatonin in cotton salt tolerance by silencing melatonin synthesis gene and exogenous melatonin application in upland cotton. In this study, applicating of melatonin can improve salt tolerance of cotton seedlings. The content of endogenous melatonin was different in cotton varieties with different salt tolerance. The inhibition of melatonin biosynthesis related genes and endogenous melatonin content in cotton resulted in the decrease of antioxidant enzyme activity, Ca content and salt tolerance of cotton. To explore the protective mechanism of exogenous melatonin against salt stress by RNA-seq analysis. Melatonin played an important role in the resistance of cotton to salt stress, improved the salt tolerance of cotton by regulating antioxidant enzymes, transcription factors, plant hormones, signal molecules and Ca signal transduction. This study proposed a regulatory network for melatonin to regulate cotton's response to salt stress, which provided a theoretical basis for improving cotton's salt tolerance.
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http://dx.doi.org/10.3389/fpls.2021.693690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273866PMC
June 2021

Mechanistic insight into different adsorption of norfloxacin on microplastics in simulated natural water and real surface water.

Environ Pollut 2021 Sep 5;284:117537. Epub 2021 Jun 5.

Institute of Ecological and Environmental Sciences, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China.

Microplastics (MPs) as carriers of various contaminants have attracted more attentions in water environments. However, the interactions between typical MPs and norfloxacin (NOR) in natural water environments were still not systematically studied. In this study, the adsorption of NOR onto four typical types of MPs (polyethylene (PE), polypropylene (PP), polystyrene (PS), and polyvinyl chloride (PVC)) was investigated in simulated natural water and real surface water, and the adsorption mechanisms were deeply explored to provide fundamental understandings of the MPs-NOR complicated pollution. The results showed that the kinetics of NOR onto all MPs obeyed pseudo-second-order model, and was greatly slowed down at lower temperature or higher salinity. The intrinsic structure and surface area of MPs played important roles in the adsorption behaviors of NOR on these four types of MPs. The adsorption isotherm of NOR onto all MPs could be well described by linear model, with the K values following the order of PVC > PS > PE > PP (i.e. 6.229-11.901 L/μg) in simulated natural water. However, in surface water the adsorption isotherms of NOR on all MPs could be well fitted by Freundlich model. For all MPs, the adsorption of NOR was quite pH-dependent due to the electrostatic interactions. Furthermore, the salinity and the presence of dissolved organic matter (DOM) had significantly hindered the NOR adsorption. More importantly, compared with adsorption behaviors in simulated natural water, the competition of coexisting substances such as cations and NOM for adsorption sites and higher water pH dramatically reduced the adsorption of NOR onto all types of MPs in Jiang'an River, with the reduction rate of 19.7-41.2%. Finally, the mechanism studies indicated that the electrostatic attractions played a key role in the adsorption of NOR onto MPs, and π-π, H-bonding, polar-polar, and Van Der Waals interactions were also involved in adsorption processes.
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http://dx.doi.org/10.1016/j.envpol.2021.117537DOI Listing
September 2021

Relationship between serum total testosterone and prostate volume in aging men.

Sci Rep 2021 Jul 8;11(1):14122. Epub 2021 Jul 8.

Department of Urology, Beijing Shijitan Hospital, Capital Medical University, 10th Tieyi Road, Haidian District, Beijing, 100038, China.

Total testosterone levels decline with age, while prostate volume and the prevalence of benign prostatic hyperplasia increase with age. We sought to investigate the correlation of serum testosterone levels with prostate volume in aging men. We analyzed clinical data obtained from 416 ostensibly healthy men who underwent routine health check-ups and recruited and collected data from these subjects 4 years later. We analyzed the correlation between prostate volume and relevant factors, as well as the correlation between changes in prostate volume and low testosterone over a 4-year period. Men with low testosterone had significantly larger prostate volume than those in the normal testosterone group (26.86 ± 8.75 vs. 24.06 ± 6.77 P = 0.02), and subjects with low testosterone had significantly higher levels of obesity-related factors, including waist circumference, body mass index, and insulin (all P < 0.001). After adjustment for age, testosterone level was negatively correlated with prostate volume (P = 0.004), and prostate volume and 4-year changes in prostate volume were associated with low testosterone. With increased testosterone level, prostate volume showed a significant linear decreasing trend. These findings provide evidence of the relationship between testosterone and prostate volume. Additional large studies are needed to confirm these preliminary results.
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http://dx.doi.org/10.1038/s41598-021-93728-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266836PMC
July 2021

L₁ Sparsity-Regularized Attention Multiple-Instance Network for Hyperspectral Target Detection.

IEEE Trans Cybern 2021 Jul 8;PP. Epub 2021 Jul 8.

Attention-based deep multiple-instance learning (MIL) has been applied to many machine-learning tasks with imprecise training labels. It is also appealing in hyperspectral target detection, which only requires the label of an area containing some targets, relaxing the effort of labeling the individual pixel in the scene. This article proposes an L1 sparsity-regularized attention multiple-instance neural network (L1-attention MINN) for hyperspectral target detection with imprecise labels that enforces the discrimination of false-positive instances from positively labeled bags. The sparsity constraint applied to the attention estimated for the positive training bags strictly complies with the definition of MIL and maintains better discriminative ability. The proposed algorithm has been evaluated on both simulated and real-field hyperspectral (subpixel) target detection tasks, where advanced performance has been achieved over the state-of-the-art comparisons, showing the effectiveness of the proposed method for target detection from imprecisely labeled hyperspectral data.
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http://dx.doi.org/10.1109/TCYB.2021.3087662DOI Listing
July 2021

3D Laparoscopy-Assisted Operation to Adult Intussusceptions During Perioperative Period of Liver Transplantation: Case Report and Literature Review.

Front Surg 2021 21;8:647767. Epub 2021 Jun 21.

Department of Gastrointestinal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Adult intussusception during the perioperative period is defined as an extremely rare condition, especially when it emerges within short intervals of laparotomy, which may be explained as an unphysiological peristaltic function of the bowel without any lead points. Accurate diagnosis and therapeutic schedule predict a satisfactory outcome. Here, we introduce the case of a 32-year-old man who had symptoms of abdominal pain, no gas emission, and defecation shortly after liver transplantation. Intussusception was definitely diagnosed by abdominal CT, and then reduction was operated successfully by three-dimensional laparoscopy-assisted operation. There were no other complaints, and no secondary lesions were detected during the postoperative rehabilitation process in the hospital and over a follow-up period of 6 months. Relevant literature has been summarized subsequently. A promising minimally invasive surgery along with minimal secondary trauma was presented by laparoscopy in this rare case, providing the potential remedy for perioperative intussusception in the adult.
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http://dx.doi.org/10.3389/fsurg.2021.647767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256994PMC
June 2021

Attention-Guided Discriminative Region Localization and Label Distribution Learning for Bone Age Assessment.

IEEE J Biomed Health Inform 2021 Jul 7;PP. Epub 2021 Jul 7.

Bone age assessment (BAA) is clinically important as it can be used to diagnose endocrine and metabolic disorders during child development. Existing deep learning based methods for classifying bone age use the global image as input, or exploit local information by annotating extra bounding boxes or key points. However, training with the global image underutilizes discriminative local information, while providing extra annotations is expensive and subjective. In this paper, we propose an attention-guided approach to automatically localize the discriminative regions for BAA without any extra annotations. Specifically, we first train a classification model to learn the attention maps of the discriminative regions, finding the hand region, the most discriminative region (the carpal bones), and the next most discriminative region (the metacarpal bones). Guided by those attention maps, we then crop the informative local regions from the original image and aggregate different regions for BAA. Instead of taking BAA as a general regression task, which is suboptimal due to the label ambiguity problem in the age label space, we propose using joint age distribution learning and expectation regression, which makes use of the ordinal relationship among hand images with different individual ages and leads to more robust age estimation. Extensive experiments are conducted on the RSNA pediatric bone age data set. {\color{red} Without using extra manual} annotations, our method achieves competitive results compared with existing state-of-the-art deep learning-based methods that require manual annotation. Code is available at \url{https://github.com/chenchao666/Bone-Age-Assessment}.
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http://dx.doi.org/10.1109/JBHI.2021.3095128DOI Listing
July 2021

Development and validation of ultra-high performance supercritical fluid chromatography method for quantitative determination of six compounds in Guizhi Fuling capsule and tablet samples.

J Sep Sci 2021 Jul 2. Epub 2021 Jul 2.

School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, 529020, PR China.

A fast and simple ultra-high performance supercritical fluid chromatography method has been developed for the determination of six analytes, namely (paeonol, coumarin, cinnamic alcohol, cinnamic acid, paeoniflorin, and amygdalin) in Guizhi Fuling capsule and tablet samples. The influence of the key chromatographic parameters for the separation purposes was evaluated. The optimal column was Trefoil CEL1 column. The optimal mobile phase was a gradient mixture of carbon dioxide and methanol at flow rate of 1.0 mL/min. The back pressure of the system was set to 1.38 × 10  Pa and the temperature to 45°C. The six compounds were separated within 11 min by the proposed ultra-high performance supercritical fluid chromatography method with satisfactory resolution. Method validation confirmed that the procedure is accurate with the recovery rates from 87.04 to 104.30%, intraday precision values less than 4.81% and interday precision less than 5.22%, and linear with R higher than 0.9967. Therefore, this work provides a simple and novel method for the simultaneous analysis of six compounds in Guizhi Fuling capsule and tablet samples.
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http://dx.doi.org/10.1002/jssc.202100181DOI Listing
July 2021

Different Types of Minor Blood Group Incompatibility Causing Haemolytic Disease of Neonates in one of the National Children's Medical Centre in China.

J Blood Med 2021 25;12:497-504. Epub 2021 Jun 25.

Neonatal Department, Children's Hospital of Fudan University, Shanghai, 201102, People's Republic of China.

Purpose: To review the neonatal cases with different types of minor blood group incompatible haemolytic diseases in China, and to improve the clinical understanding and management.

Materials And Methods: Seven cases from January, 1st, 2013 to December 31st, 2019 were searched out and reviewed retrospectively. All clinical data and laboratory findings were collected.

Results: There were totally seven cases enrolled including three cases of MNS, three of Diego, and one of Kidd combined with Rh, anti-RhE incompatibility. Among the seven cases, two had intrauterine transfusion, two underwent exchange transfusion, five received intravenous immune globulin, five cases developed anaemia, and three of them had transfusion. But among them, only four were found to have positive antibody screening and three were confirmed HDN with antibody types antenatally.

Conclusion: The clinical presentation is diverse. Antibody screening followed by the technique of peak systolic velocity in the fetal middle cerebral artery (MCA-PSV) helps to filter out the severe cases.
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http://dx.doi.org/10.2147/JBM.S303633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240843PMC
June 2021

Ultrasound-on-chip platform for medical imaging, analysis, and collective intelligence.

Proc Natl Acad Sci U S A 2021 Jul;118(27)

Butterfly Network, Inc., Guilford, CT 06437.

Over the past half-century, ultrasound imaging has become a key technology for assessing an ever-widening range of medical conditions at all stages of life. Despite ultrasound's proven value, expensive systems that require domain expertise in image acquisition and interpretation have limited its broad adoption. The proliferation of portable and low-cost ultrasound imaging can improve global health and also enable broad clinical and academic studies with great impact on the fields of medicine. Here, we describe the design of a complete ultrasound-on-chip, the first to be cleared by the Food and Drug Administration for 13 indications, comprising a two-dimensional array of silicon-based microelectromechanical systems (MEMS) ultrasonic sensors directly integrated into complementary metal-oxide-semiconductor-based control and processing electronics to enable an inexpensive whole-body imaging probe. The fabrication and design of the transducer array with on-chip analog and digital circuits, having an operating power consumption of 3 W or less, are described, in which approximately 9,000 seven-level feedback-based pulsers are individually addressable to each MEMS element and more than 11,000 amplifiers, more than 1,100 analog-to-digital converters, and more than 1 trillion operations per second are implemented. We quantify the measured performance and the ability to image areas of the body that traditionally takes three separate probes. Additionally, two applications of this platform are described-augmented reality assistance that guides the user in the acquisition of diagnostic-quality images of the heart and algorithms that automate the measurement of cardiac ejection fraction, an indicator of heart health.
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http://dx.doi.org/10.1073/pnas.2019339118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271708PMC
July 2021

Effects of maslinic acid on cardiac function in ischemia-reperfusion injury rats.

J Investig Med 2021 Jun 30. Epub 2021 Jun 30.

Cardiovascular Department Ⅴ, Cangzhou Central Hospital, Cangzhou, China.

Maslinic acid (MA), a pentacyclic triterpenoid, has been reported to exert broad pharmacological properties. However, it is still unclear whether MA exhibits protective effects against ischemia/reperfusion (I/R) injury. Herein, we aimed to investigate the effects of MA on I/R injury and its underlying mechanisms. A rat model of I/R injury was established and administrated with MA by intraperitoneal injection. Cardiac function was assessed with a color ultrasound diagnosis system and PowerLab system. The levels of oxidative stress-related and I/R-related biomarkers were evaluated by using commercial kits. Apoptosis-related biomarkers and sirtuin (SIRT)1/AMP-activated protein kinase (AMPK) signaling proteins were determined by using quantitative reverse transcription PCR and western blotting, respectively. Treatment with MA improved cardiac performance and cardiac hemodynamic parameters in the I/R injury rat model. Besides, treatment with MA (20 mg/kg) ameliorated I/R injury-related biomarkers in serum. Interestingly, treatment with MA (20 mg/kg) also regulated myocardial apoptosis and inhibited oxidative-stress in left ventricular tissue. Mechanistic studies demonstrated that MA upregulated SIRT1 and AMPK phosphorylation in the left ventricular tissue. In summary, MA exerted protective effects against the impairments of cardiac function in I/R injury rats by the regulation of SIRT1/AMPK signaling pathways.
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http://dx.doi.org/10.1136/jim-2021-001927DOI Listing
June 2021

Genome-wide identification and expression analysis of Raffinose synthetase family in cotton.

BMC Bioinformatics 2021 Jun 29;22(1):356. Epub 2021 Jun 29.

College of Agriculture / Xinjiang Agricultural University / Xinjiang Research Base, State Key Laboratory of Cotton Biology, Urumqi, 830052, Xinjiang, China.

Background: The Raffinose synthetase (RAFS) genes superfamily is critical for the synthesis of raffinose, which accumulates in plant leaves under abiotic stress. However, it remains unclear whether RAFS contributes to resistance to abiotic stress in plants, specifically in the Gossypium species.

Results: In this study, we identified 74 RAFS genes from G. hirsutum, G. barbadense, G. arboreum and G. raimondii by using a series of bioinformatic methods. Phylogenetic analysis showed that the RAFS gene family in the four Gossypium species could be divided into four major clades; the relatively uniform distribution of the gene number in each species ranged from 12 to 25 based on species ploidy, most likely resulting from an ancient whole-genome polyploidization. Gene motif analysis showed that the RAFS gene structure was relatively conservative. Promoter analysis for cis-regulatory elements showed that some RAFS genes might be regulated by gibberellins and abscisic acid, which might influence their expression levels. Moreover, we further examined the functions of RAFS under cold, heat, salt and drought stress conditions, based on the expression profile and co-expression network of RAFS genes in Gossypium species. Transcriptome analysis suggested that RAFS genes in clade III are highly expressed in organs such as seed, root, cotyledon, ovule and fiber, and under abiotic stress in particular, indicating the involvement of genes belonging to clade III in resistance to abiotic stress. Gene co-expressed network analysis showed that GhRFS2A-GhRFS6A, GhRFS6D, GhRFS7D and GhRFS8A-GhRFS11A were key genes, with high expression levels under salt, drought, cold and heat stress.

Conclusion: The findings may provide insights into the evolutionary relationships and expression patterns of RAFS genes in Gossypium species and a theoretical basis for the identification of stress resistance materials in cotton.
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http://dx.doi.org/10.1186/s12859-021-04276-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243485PMC
June 2021

Reducing hyperactivated BAP1 attenuates mutant ASXL1-driven myeloid malignancies in human haematopoietic cells.

Cancer Lett 2021 Jun 26;519:78-90. Epub 2021 Jun 26.

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China. Electronic address:

Additional sex combs-like 1 (ASXL1) is frequently mutated in a variety of myeloid malignancies, resulting in expression of a C-terminal-truncated ASXL1 protein that confers gain of function on the ASXL1-BAP1 deubiquitinase (DUB) complex. Several studies have reported that hyperactivity of BRCA-1-associated protein 1 (BAP1) in deubiquitinating mono-ubiquitinated histone H2AK119 is one of the critical molecular mechanisms in ASXL1 mutation-driven myeloid malignancies in mice. In this study, we found that human haematopoietic stem and progenitor cells (HSPCs) overexpressing truncated ASXL1 (ASXL1) developed an MDS-like phenotype similar to that induced by overexpression of BAP1. We then used shRNAs targeting BAP1 in ASXL1-overexpressing HSPCs and primary leukaemia cells with ASXL1 mutation, demonstrating that reduced BAP1 expression can partially rescue the pathological consequences. RNA sequencing and chromatin immunoprecipitation coupled with quantitative PCR analyses revealed that reduced BAP1 expression suppressed upregulation of the transcription factors AP-1 and EGR1/2, as well as myeloid dysplasia-associated genes, by retarding H2AK119Ub removal caused by ASXL1 mutation. This study indicates that targeting the hyperactive ASXL1-BAP1 DUB complex can attenuate mutant ASXL1-driven myeloid malignancies in human.
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http://dx.doi.org/10.1016/j.canlet.2021.06.019DOI Listing
June 2021

Coordinated β-glucosidase activity with the cellulosome is effective for enhanced lignocellulose saccharification.

Bioresour Technol 2021 Oct 23;337:125441. Epub 2021 Jun 23.

CAS Key Laboratory of Biofuels, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, PR China; Shandong Provincial Key Laboratory of Synthetic Biology, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, PR China; Shandong Engineering Laboratory for Single Cell Oil, Qingdao Engineering Laboratory for Single Cell Oil, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, PR China; Dalian National Laboratory for Clean Energy, Qingdao 266101, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China. Electronic address:

Consolidated bio-saccharification (CBS) technology employs cellulosome-producing bacterial cells, rather than fungal cellulases, as biocatalysts for cost-effective production of lignocellulosic sugars. Extracellular β-glucosidase (BGL) expression in the whole-cell arsenal is indispensable, due to severe cellobiose inhibition of the cellulosome. However, high-level BGL expression in Clostridium thermocellum is challenging, and the optimal BGL production level for efficient cellulose saccharification is currently unknown. Herein, we obtained new CBS biocatalysts by transforming BGL-expressing plasmids into C. thermocellum, which produced abundant BGL proteins and hydrolyzed cellulose effectively. The optimal ratio of extracellular BGL-to-cellulosome activity was determined to be in a range of 5.5 to 21.6. Despite the critical impact of BGL, both excessive BGL expression and its assembly on the cellulosome via type I cohesin-dockerin interaction led to reduced cellulosomal activity, which further confirmed the importance of coordinated BGL expression with the cellulosome. This study will further promote industrial CBS application in lignocellulose conversion.
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http://dx.doi.org/10.1016/j.biortech.2021.125441DOI Listing
October 2021

Sensitive and selective detection of chromium (VI) based on two-dimensional luminescence metal organic framework nanosheets via the mechanism integrating chemical oxidation-reduction and inner filter effect.

J Hazard Mater 2021 Jun 22;419:126443. Epub 2021 Jun 22.

Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research (Ministry of Education, China), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha 410081, PR China.

Two-dimensional luminescence metal organic framework nanosheets (LMOF) named NH-CuMOFs were synthesized using Cu (II) nodes coordinated with negatively charged 2-aminoterephthalic acid (NH-BDC) via a bottom-up strategy, which were first used as the fluorescent probes for the detection of chromium Cr (VI). The nanosheets possess stable fluorescence with the maximum emission wavelength of 436 nm at excitation of 338 nm that can be effectively quenched by hexavalent chromium Cr (VI). The NH-CuMOFs nanosheets show superior advantage over the linker of NH-BDC for the excellent selectivity to Cr (Ⅵ) without the interferences of other metal ions. The mechanism investigation suggested that the sensitive detection of Cr (VI) was attributed to the chemical oxidation-reduction (redox) reaction and internal filtration effect (IFE) between Cr (VI) and NH-CuMOFs nanosheets. Based on this mechanism, the quantitation of Cr (VI) was realized in the linear range of 0.1-20 μM with a detection limit of 18 nM. Moreover, the detection of Cr (VI) in real samples was also conducted with good recovery. This work provides an optical sensing nanoplatform for heavy metal ions based on two-dimensional LMOFs via a novel mechanism integrating chemical redox reaction and IFE, which may promise broad application prospect for two-dimensional luminescence nanosheets.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126443DOI Listing
June 2021

Comparative study of the reorganization in bilateral motor and sensory cortices after spinal cord hemisection in mice.

Neuroreport 2021 Jun 22. Epub 2021 Jun 22.

Department of Orthopaedics Department of Plastic and Reconstructive surgery, General Hospital of Chinese PLA Department of Anesthesiology, District Hospital of Shun Yi, Beijing Department of Neuroscience, Shenzhen Bay Laboratory, Shenzhen Department of Pediatric Surgery, General Hospital of Chinese PLA, Beijing, People's Republic of China.

Objective: The effects of spinal cord injury (SCI) on sensorimotor cortex plasticity have not been well studied. Therefore, to explore the reorganization after SCI, we dynamically monitored postsynaptic dendritic spines of pyramidal neurons in vivo.

Methods: Thy1-YFP transgenic mice were randomly divided into two groups: the control and SCI group. We then opened the spinal vertebral plates of all mice and sectioned one-half of the spinal cord in SCI group. The relevant areas were imaged bilaterally at 0, 3, 14 and 28 days post-SCI. The rates of elimination, formation and stable spines were evaluated.

Results: At the early stage, the rate of stable and elimination spines experienced a similar change trend. But the rate of formation spines in the contralateral sensory cortex was significantly increased after SCI compared with those in the control group. At the late stage, spines of three types remodeled very differently between the sensory and motor cortex. Compared with those in the control group, spines in the bilateral sensory cortex demonstrated obvious differences in the rate of stable and elimination spines but not formation spines, while spines in the motor cortex, especially in the contralateral cortex increased significantly in the rate of formation after SCI. As for survival rate, differences mainly appeared in time frame instead of cortex type or region.

Conclusions: The dendritic spines in hindlimb representation area of the sensorimotor cortex experienced bilaterally remodeling after SCI. And those spines in the sensory and motor cortex experienced great but different change trends after SCI.
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http://dx.doi.org/10.1097/WNR.0000000000001694DOI Listing
June 2021
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