Publications by authors named "Yuan Chen"

1,511 Publications

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Characteristics of immune and inflammatory responses among different age groups of pediatric patients with COVID-19 in China.

World J Pediatr 2021 Aug 2. Epub 2021 Aug 2.

Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Severe cases of coronavirus disease 2019 (COVID-19) among pediatric patients are more common in children less than 1 year of age. Our aim is to address the underlying role of immunity and inflammation conditions among different age groups of pediatric patients.

Methods: We recruited pediatric patients confirmed of moderate COVID-19 symptoms, admitted to Wuhan Children's Hospital from January 28th to April 1st in 2020. Patients were divided into four age groups (≤ 1, 1-6, 7-10, and 11-15 years). Demographic information, clinical characteristics, laboratory results of lymphocyte subsets test, immune and inflammation related markers were all evaluated.

Results: Analysis included 217/241 (90.0%) of patients with moderate clinical stage disease. Average recovery time of children more than 6 years old was significantly shorter than of children younger than 6 years (P = 0.001). Reduced neutrophils and increased lymphocytes were significantly most observed among patients under 1 year old (P < 0.01). CD19+ B cells were the only significantly elevated immune cells, especially among patients under 1 year old (cell proportion: n = 12, 30.0%, P < 0.001; cell count: n = 13, 32.5%, P < 0.001). While, low levels of immune related makers, such as immunoglobulin (Ig) G (P < 0.001), IgA (P < 0.001), IgM (P < 0.001) and serum complement C3c (P < 0.001), were also mostly found among patients under 1 year old, together with elevated levels of inflammation related markers, such as tumor necrosis factor γ (P = 0.007), interleukin (IL)-10 (P = 0.011), IL-6 (P = 0.008), lactate dehydrogenase (P < 0.001), and procalcitonin (P = 0.007).

Conclusion: The higher rate of severe cases and long course of COVID-19 among children under 1 year old may be due to the lower production of antibodies and serum complements of in this age group.
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http://dx.doi.org/10.1007/s12519-021-00440-1DOI Listing
August 2021

Metabolomics profiling for identification of potential biomarkers in chickens infected with avian leukosis virus subgroup J (ALV-J).

Res Vet Sci 2021 Jul 25;139:166-171. Epub 2021 Jul 25.

Guangdong Laboratory Animal Monitoring Institute, Guangdong Key Laboratory of Laboratory Animals, Guangzhou 510633, China.

There are currently no vaccines or effective drugs to prevent the disorders caused by avian leukosis virus subgroup J (ALV-J). Hence, it is critical to identify potential biomarkers in ALV-J-infected chickens to prevent ALV-J-induced disorders. We hypothesized that ALV-J infection alters metabolic profile in chickens. In the present study, a nontargeted metabolomics approach based on liquid chromatography coupled with mass spectrometry (LC-MS) was used to find differential metabolites in plasma samples from ALV-J-infected chickens and healthy controls. The parametric statistical test (Student's t-test) and fold change analysis were used for univariate analysis. Multivariate statistical analyses included principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA). The levels of methyl bromide, pyraclonil, hexaflumuron, lythidathion, 3-phosphoglycerol-glutathione, bis-4-nitrophenyl phosphate, 4-ketocyclophosphamide, oxidized photinus luciferin, phenyl sulfate, and aryl sulfate significantly decreased, whereas the levels of 2-methylthiobenzothiazole, irinotecan, methadone, 3-o-ethyl-l-ascorbic acid, and o-acetylneuraminic acid markedly increased in ALV-J-infected chickens as compared to those in healthy controls. These data provide metabolic evidence and potential biomarkers for ALV-J-induced alterations in plasma metabolism.
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http://dx.doi.org/10.1016/j.rvsc.2021.07.026DOI Listing
July 2021

Ultrahigh Rate Capability and Lifespan MnCo2O4/Ni-MOF Electrode for High Performance Battery-Type Supercapacitor.

Chemistry 2021 Jul 31. Epub 2021 Jul 31.

Northwest Normal University, College of Chemistry and Chemical Engineering, Anning East Road 967, 730070, Lanzhou, CHINA.

MnCo2O4 is derived from a Co/Mn bimetallic MOF. Then Ni-MOF is directly grown on the surface of the obtained MnCo2O4 to form a nano-flower structure with small balls. Big surface area, abundant active sites of MnCo2O4 and porosity of Ni-MOF allow the prepared MnCo2O4/Ni-MOF composition material to deliver an excellent electrochemical performance. At the same time, appropriate thermal treatment temperature of the MnCo2O4 precursor is also very important for controlling the morphology of the obtained MnCo2O4 and electrochemical performances of the resulted composition material including electric conductivity, specific capacitance and rate performance. The prepared MnCo2O4-600/Ni-MOF shows an ultrahigh rate performance (when the current density increases from 1 to 10 A·g-1, the capacitance retention rate is as high as 93.41%) and good cycle stability (the assembled asymmetric supercapacitor advice delivers a capacitance retention rate of 94.74% after 20,000 charge and discharge cycles) as well as a relatively high specific capacitance. These excellent electrochemical properties indicate that MnCo2O4/Ni-MOF has a good application prospect in the market.
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http://dx.doi.org/10.1002/chem.202102008DOI Listing
July 2021

Baicalin Rescues Cognitive Dysfunction, Mitigates Neurodegeneration, and Exerts Anti-Epileptic Effects Through Activating TLR4/MYD88/Caspase-3 Pathway in Rats.

Drug Des Devel Ther 2021 20;15:3163-3180. Epub 2021 Jul 20.

Pediatrics, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050051, People's Republic of China.

Purpose: This study aims to evaluate the beneficial effects of anti-epileptic mechanisms of baicalin (BA) on cognitive dysfunction and neurodegeneration in pentylenetetrazol (PTZ)-induced epileptic rats.

Methods: First, PTZ-induced epileptic rats were administered intraperitoneally a sub-convulsive dose of PTZ (40 mg/kg) daily, and the seizure susceptibility (the degree of seizures and latency) was evaluated using Racine's criterion. Then, classical behavioral experiments were performed to test whether BA ameliorated cognitive dysfunction. Neurodegeneration was assessed using Fluoro Jade-B (FJB), and NeuN staining was used to determine whether BA offered a neuroprotective role. After BA had been proven to possess anti-epileptic effects, its possible mechanisms were analyzed through network pharmacology. Finally, the key targets for predictive mechanisms were experimentally verified.

Results: The epileptic model was successfully established, and BA had anti-epileptic effects. Epileptic rats displayed significant cognitive dysfunction, and BA markedly ameliorated cognitive dysfunction. Further, we also discovered that BA treatment mitigated neurodegeneration of the hippocampus CA3 regions, thereby ameliorated cognitive dysfunction of epileptic rats. Subsequent network pharmacology analysis was implemented to reveal a possible mechanism of BA in the anti-epileptic process and the TLR4/MYD88/Caspase-3 pathway was predicted. Finally, experimental studies showed that BA exerted an anti-epileptic effect by activating the TLR4/MYD88/Caspase-3 pathway in PTZ-induced epileptic rats.

Conclusion: In conclusion, BA had a protective effect against PTZ-induced seizures. BA improved cognitive dysfunction and exerted a neuroprotective action. The anti-epileptic effects of BA may be potentially through activation of the TLR4/MYD88/Caspase-3 pathway.
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http://dx.doi.org/10.2147/DDDT.S314076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312624PMC
July 2021

Synthesis, molecular docking and mosquitocidal efficacy of lawsone and its derivatives against the dengue vector Aedes aegypti L. (Diptera: Culicidae).

Med Chem 2021 Jul 27. Epub 2021 Jul 27.

State Key Laboratory of Subtropical Silviculture, Zhejiang A&F University, Hangzhou 311300, China.

Background: Aedes aegypti is the primary dengue vector, a significant public health problem in many countries. Controlling the growth of Ae. aegypti is the biggest challenge in the mosquito control program, and there is a need for finding bioactive molecules to control Ae. aegypti in order to prevent dengue virus transmission.

Objective: To assess the mosquitocidal property of lawsone and its 3-methyl-4H-chromen-3-yl-1-phenylbenzo[6,7]chromeno[2,3,c]pyrazole-dione derivatives (6a-6h) against various life stages of Ae. aegypti. Besides, to study the mode of action of the active compound by molecular docking and histopathological analysis.

Methods: All derivatives were synthesized from the reaction between 2-hydroxy-1,4-naphthoquinone, chromene-3-carbaldehyde, and 1-phenyl-3-methyl-pyrazol-5-one by using one pot sequential multicomponent reaction. The mosquito life stages were subjected to diverse concentrations ranging from 1.25, 2.5, 5.0, and 10 ppm for lawsone and its derivatives. The structure of all synthesized compounds was characterized by spectroscopic analysis. Docking analysis was performed using autodock tools. Midgut sections of Ae. aegypti larvae were analyzed for histopathological effects.

Results: Among the nine compounds screened, derivative 6e showed the highest mortality on Ae. aegypti life stages. The analyzed LC50 and LC90 results of derivative 6e were 3.01, 5.87 ppm, and 3.41, 6.28 ppm on larvae and pupae of Ae. aegypti, respectively. In the ovicidal assay, the derivative 6e recorded 47.2% egg mortality after 96-hour post-exposure to 10 ppm concentration. In molecular docking analysis, the derivative 6e confirmed strong binding interaction (-9.09 kcal/mol and -10.17 kcal/mol) with VAL 60 and HIS 62 of acetylcholinesterase 1 (AChE1) model and LYS 255, LYS 263 of kynurenine aminotransferase of Ae. aegypti, respectively. The histopathological results showed that the derivative 6e affected the columnar epithelial cells (CC) and peritrophic membrane (pM).

Conclusion: The derivative 6e is highly effective in the life stages of Ae. aegypti mosquito and it could be used in the integrated mosquito management programme.
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http://dx.doi.org/10.2174/1573406417666210727121654DOI Listing
July 2021

Recombinase Polymerase Amplification Assay for Simultaneous Detection of Maize Chlorotic Mottle Virus and Sugarcane Mosaic Virus in Maize.

ACS Omega 2021 Jul 6;6(28):18008-18013. Epub 2021 Jul 6.

College of Plant Protection, Shenyang Agricultural University, Shenyang, Liaoning 110866, China.

Maize chlorotic mottle virus (MCMV) can cause maize lethal necrosis (MLN) when coinfected with potyvirids, such as sugarcane mosaic virus (SCMV), maize dwarf mosaic virus, or wheat streak mosaic virus. MLN is often caused by coinfection of MCMV and SCMV, which has been reported in China and several countries of Africa. In this study, a recombinase polymerase amplification (RPA) assay was established for simultaneous detection of MCMV and SCMV in maize. The RPA assay can be completed within 30 min at 38 °C. The primers for the RPA assay were specific since no crossreaction was detected with other selected viruses that infected maize in China. The detection limit of the RPA method was 10 copies μL, which was about 10-fold more sensitive than that of the conventional PCR method. Moreover, the RPA assay can be successfully applied to detect maize samples collected in the field. These results demonstrated that the established RPA assay is a rapid and efficient method to conduct simultaneous detection of MCMV and SCMV, which provides an alternative technology for MLN diagnosis.
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http://dx.doi.org/10.1021/acsomega.1c01767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295995PMC
July 2021

Recombinase Polymerase Amplification Assay for Simultaneous Detection of Maize Chlorotic Mottle Virus and Sugarcane Mosaic Virus in Maize.

ACS Omega 2021 Jul 6;6(28):18008-18013. Epub 2021 Jul 6.

College of Plant Protection, Shenyang Agricultural University, Shenyang, Liaoning 110866, China.

Maize chlorotic mottle virus (MCMV) can cause maize lethal necrosis (MLN) when coinfected with potyvirids, such as sugarcane mosaic virus (SCMV), maize dwarf mosaic virus, or wheat streak mosaic virus. MLN is often caused by coinfection of MCMV and SCMV, which has been reported in China and several countries of Africa. In this study, a recombinase polymerase amplification (RPA) assay was established for simultaneous detection of MCMV and SCMV in maize. The RPA assay can be completed within 30 min at 38 °C. The primers for the RPA assay were specific since no crossreaction was detected with other selected viruses that infected maize in China. The detection limit of the RPA method was 10 copies μL, which was about 10-fold more sensitive than that of the conventional PCR method. Moreover, the RPA assay can be successfully applied to detect maize samples collected in the field. These results demonstrated that the established RPA assay is a rapid and efficient method to conduct simultaneous detection of MCMV and SCMV, which provides an alternative technology for MLN diagnosis.
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http://dx.doi.org/10.1021/acsomega.1c01767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295995PMC
July 2021

Evaluation of Immediate Implantation and Provisionalization Combined with Guided Bone Regeneration by a Flap Approach in the Maxillary Esthetic Zone: A Retrospective Controlled Study.

Materials (Basel) 2021 Jul 12;14(14). Epub 2021 Jul 12.

State Key Laboratory of Oral Diseases, Department of Implant Dentistry, West China School/Hospital of Stomatology, Sichuan University, Chengdu, China.

The aim of this research was too compare the thickness change of labial contour and bone tissues, as well as some biological complications of immediate implantation with and without immediate provisionalization for a single anterior maxilla presenting a vertical defect on labial bone with the need of guided bone regeneration (GBR) by a flap approach. A total of 40 single implants were placed in 40 patients into fresh extraction sockets of the anterior maxilla with a vertical defect on the labial bone (<4 mm). Simultaneously, GBR was conducted at the sites by a flap approach, and the implants were given immediate or delayed provisionalization. The thickness change of bone tissues during six-month evaluation and labial contour during three and six-month follow-up were measured. Complications such as implant and restoration survival rates, infection as well as wound exposure were also evaluated at six months postoperatively. After six months, the mean thickness losses in labial bone were 0.9040, 0.8050, 0.7165, 0.5285 and 0.5335 mm at five different sites in immediate provisionalization group, and 0.8780, 0.8605, 0.7560, 0.5900 and 0.6300 mm, respectively, in delayed provisionalization group, showing no significant difference between the groups at all measurement sites. Although the labial contour changes of the two groups were similar at most sites, the values at 1 and 2 mm above the implant neck remained significantly lower in the immediate provisionalization group at three and six months postoperatively. No complications occurred during the follow-up time. Based on the limitation of this study, the immediate implantation combined with GBR, flap operation and immediate provisionalization obtained acceptable outcomes for a single anterior maxilla with vertical defect on the labial bone, but more long-term research with a larger sample are urgently needed in the future.
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http://dx.doi.org/10.3390/ma14143874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307239PMC
July 2021

Physicochemical Characterization and Biopharmaceutical Evaluation of ZWF: A Novel Anticancer Drug for the Treatment of Non-small Cell Lung Cancer.

AAPS PharmSciTech 2021 Jul 23;22(6):207. Epub 2021 Jul 23.

Key Laboratory of Drug-Targeting and Drug Delivery Systems of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, People's Republic of China.

The orally available novel small molecule drug ZWF is under preclinical development for an anticancer purpose. The present study aimed to assess the viability of developing ZWF as a form of oral formulation for clinical application based on the principles of biopharmaceutics and pharmacokinetics. The crucial physicochemical properties of ZWF were determined by in vitro assays. The in situ gastrointestinal absorption characteristics and in vivo pharmacokinetic behaviors of ZWF in rats were characterized. The solubility of ZWF showed a highly pH-dependent profile, decreasing from 25,392.89 to 20.48 μg/mL as the solution pH increased from 1.0 to 5.8. In PBS with a pH of 1.0 to 5.8, the LogP value of ZWF ranged from -2.35 to 2.20 and was gradually increased as the pH value increased. ZWF was partially absorbed in the stomach, and the favorable absorption sites were the duodenum, jejunum, and ileum. Pharmacokinetic studies showed that the AUC and C values of ZWF after its oral administration as a suspension prepared with 0.5% CMC-Na were increased by 18.97% and 40% than that with normal saline, providing a model oral formulation of ZWF with ideal bioavailability and system exposure in rats. From the perspective of oral absorption, ZWF possessed appealing qualities as a drug candidate and could be prepared as an oral preparation for clinical application. The present study has established a fundamental foundation for the development and quality evaluation of the ZWF oral formulations.
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http://dx.doi.org/10.1208/s12249-021-02084-wDOI Listing
July 2021

Baicalin ameliorates chronic unpredictable mild stress-induced depression through the BDNF/ERK/CREB signaling pathway.

Behav Brain Res 2021 Jul 16;414:113463. Epub 2021 Jul 16.

Hebei Key Laboratory of Turbidity, Hebei Academy of Chinese Medicine Sciences, Shijiazhuang, Hebei, 050011, China. Electronic address:

Brain-derived neurotrophic factor (BDNF) can activate the extracellular regulated protein kinase (ERK)/cAMP response element binding protein (CREB) cascade revealing an important role in antidepressant effects. Here, we studied the neuroprotective effect of baicalin (BA) in mice with chronic unpredictable mild stress (CUMS)-induced via a BDNF/ERK/CREB signaling pathway. Depression was induced via six weeks of CUMS in male ICR mice, and drug therapy was given simultaneously for the last three weeks. Cognitive dysfunctions were then evaluated via sucrose preference test (SPT), open field test (OFT), Morris water maze test (MWM), tail suspension test (TST), and novelty suppressed feeding test (NSF). Western blot and real-time PCR were then used to detect the relative expression of ERK, CREB, p-ERK, and p-CREB. Integrated optical density (IOD) tests of p-ERK and p-CREB were then evaluated via immunofluorescence. The behavior results showed that the cognitive dysfunctions increased in the CUMS group versus the control (CON) group (p < 0.01). There were decreases in fluoxetine (FLU) and BA groups (p < 0.05, p < 0.01). The protein ratios of p-ERK/ERK, p-CREB/CREB and ERK mRNA, and CREB mRNA expression decreased in the CUMS group (p < 0.01) and markedly increased in the FLU and BA groups (p < 0.05, p < 0.01). The IOD value of the p-ERK and p-CREB in the CUMS group was decreased versus the CON group (p < 0.01), and these changes were improved via BA and FLU treatment (p < 0.05, p < 0.01). This study indicated that BA can improve cognitive functions and has antidepressant effects in mice, which may be associated with activation of the BDNF/ERK/CREB signaling pathway in the hippocampus.
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http://dx.doi.org/10.1016/j.bbr.2021.113463DOI Listing
July 2021

Collaborative Equilibrium Coupling of Catalytic DNA Nanostructures Enables Programmable Detection of SARS-CoV-2.

Adv Sci (Weinh) 2021 Jul 18:e2101155. Epub 2021 Jul 18.

Institute for Health Innovation & Technology, National University of Singapore, Singapore, 117599, Singapore.

Accessible and adaptable nucleic acid diagnostics remains a critical challenge in managing the evolving COVID-19 pandemic. Here, an integrated molecular nanotechnology that enables direct and programmable detection of SARS-CoV-2 RNA targets in native patient specimens is reported. Termed synergistic coupling of responsive equilibrium in enzymatic network (SCREEN), the technology leverages tunable, catalytic molecular nanostructures to establish an interconnected, collaborative architecture. SCREEN mimics the extraordinary organization and functionality of cellular signaling cascades. Through programmable enzyme-DNA nanostructures, SCREEN activates upon interaction with different RNA targets to initiate multi-enzyme catalysis; through system-wide favorable equilibrium shifting, SCREEN directly transduces a single target binding into an amplified electrical signal. To establish collaborative equilibrium coupling in the architecture, a computational model that simulates all reactions to predict overall performance and optimize assay configuration is developed. The developed platform achieves direct and sensitive RNA detection (approaching single-copy detection), fast response (assay reaction is completed within 30 min at room temperature), and robust programmability (across different genetic loci of SARS-CoV-2). When clinically evaluated, the technology demonstrates robust and direct detection in clinical swab lysates to accurately diagnose COVID-19 patients.
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http://dx.doi.org/10.1002/advs.202101155DOI Listing
July 2021

Mouse Spexin: (II) Functional Role as a Satiety Factor inhibiting Food Intake by Regulatory Actions Within the Hypothalamus.

Front Endocrinol (Lausanne) 2021 2;12:681647. Epub 2021 Jul 2.

School of Biological Sciences, The University of Hong Kong, Hong Kong, Hong Kong.

Spexin (SPX) is a pleiotropic peptide with highly conserved protein sequence from fish to mammals and its biological actions are mediated by GalR2/GalR3 receptors expressed in target tissues. Recently, SPX has been confirmed to be a novel satiety factor in fish species but whether the peptide has a similar function in mammals is still unclear. Using the mouse as a model, the functional role of SPX in feeding control and the mechanisms involved were investigated. After food intake, serum SPX in mice could be up-regulated with elevations of transcript expression and tissue content of SPX in the glandular stomach but not in other tissues examined. As revealed by immunohistochemical staining, food intake also intensified SPX signals in the major cell types forming the gastric glands (including the foveolar cells, parietal cells, and chief cells) within the gastric mucosa of glandular stomach. Furthermore, IP injection of SPX was effective in reducing food intake with parallel attenuation in transcript expression of NPY, AgRP, NPY type 5 receptor (NPY5R), and ghrelin receptor (GHSR) in the hypothalamus, and these inhibitory effects could be blocked by GalR3 but not GalR2 antagonism. In agreement with the central actions of SPX, similar inhibition on feeding and hypothalamic expression of NPY, AgRP, NPY5R, and GHSR could also be noted with ICV injection of SPX. In the same study, in contrast to the drop in NPY5R and GHSR, SPX treatment could induce parallel rises of transcript expression of leptin receptor (LepR) and melanocortin 4 receptor (MC4R) in the hypothalamus. These findings, as a whole, suggest that the role of SPX as a satiety factor is well conserved in the mouse. Apparently, food intake can induce SPX production in glandular stomach and contribute to the postprandial rise of SPX in circulation. Through GalR3 activation, this SPX signal can act within the hypothalamus to trigger feedback inhibition on feeding by differential modulation of feeding regulators (NPY and AgRP) and their receptors (NPY5R, GHSR, LepR, and MC4R) involved in the feeding circuitry within the CNS.
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http://dx.doi.org/10.3389/fendo.2021.681647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283969PMC
July 2021

Comprehensive Analysis of Monocarboxylate Transporter 4 (MCT4) expression in breast cancer prognosis and immune infiltration via integrated bioinformatics analysis.

Bioengineered 2021 Dec;12(1):3850-3863

Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Lactate blunts the anticancer immune response in breast cancer (BC). However, little is known about the exact effect of lactate transporters such as monocarboxylate transporter 4 (MCT4) on immunotherapy. In this study, we investigated the expression status and prognostic value of MCT4 in BC through large-scale transcriptome data. Our results showed that MCT4 was overexpressed in BC, particularly in the basal-like molecular subtype. Overexpression of MCT4 was significantly correlated with high BC lesion grade and poor prognosis. Enrichment analysis indicated that the MCT4-related genes were involved in immune- and metabolism-related bioprocesses, such as myeloid leukocyte activation, the adaptive immune system, and catabolic process. We also found that the expression of MCT4 in BC lesions was associated with immune cell infiltration and glycolytic rate-limiting enzymes like pyruvate kinase M2 (PKM2) and hexokinases-3 (HK3). Our observations indicate that MCT4 may play a pivotal role in the maintenance of the tumor immune microenvironment (TIME) through metabolic reprogramming. The enzymes of the glycolysis pathway (MCT4, PKM2, and HK3) may thus serve as new targets to modulate the TIME and enhance immunotherapy efficiency.[Figure: see text].
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http://dx.doi.org/10.1080/21655979.2021.1951928DOI Listing
December 2021

Sugar-sweetened beverage, artificially sweetened beverage and sugar intake and colorectal cancer survival.

Br J Cancer 2021 Jul 15. Epub 2021 Jul 15.

Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA.

Background: The influence of a high sugar diet on colorectal cancer (CRC) survival is unclear.

Methods: Among 1463 stage I-III CRC patients from the Nurses' Health Study and Health Professionals Follow-up Study, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC-specific and all-cause mortality in relation to intake of post-diagnosis sugar-sweetened beverages (SSB), artificially sweetened beverages (ASB), fruit juice, fructose and other sugars.

Results: Over a median 8.0 years, 781 cases died (173 CRC-specific deaths). Multivariable-adjusted HRs for post-diagnosis intake and CRC-specific mortality were 1.21 (95% CI: 0.87-1.68) per 1 serving SSBs per day (serving/day) and 1.24 (95% CI: 0.95-1.63) per 20 grams fructose per day. Significant positive associations for CRC-specific mortality were primarily observed ≤5 years from diagnosis (HR per 1 serving/day of SSBs = 1.59, 95% CI: 1.06-2.38). Significant inverse associations were observed between ASBs and CRC-specific and all-cause mortality (HR for ≥5 versus <1 serving/week = 0.44, 95% CI: 0.26-0.75 and 0.70, 95% CI: 0.55-0.89, respectively).

Conclusions: Higher post-diagnosis intake of SSBs and sugars may be associated with higher CRC-specific mortality, but only up to 5 years from diagnosis, when more deaths were due to CRC. The inverse association between ASBs and CRC-specific mortality warrants further examination.
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http://dx.doi.org/10.1038/s41416-021-01487-7DOI Listing
July 2021

The shrinking behavior, mechanism and anti-shrinkage resolution of an electrospun PLGA membrane.

J Mater Chem B 2021 Jul;9(29):5861-5868

Research Center for Nano-Biomaterials, Analytical and Testing Center, Sichuan University, Chengdu 610064, China.

The deformation shrinkage of a poly(lactide-co-glycolide) (PLGA) fibrous material seriously affects its biomedical application. To demonstrate the underlying shrinking mechanism and to find a method to prevent the shrinkage of an electrospun PLGA membrane, we investigated the shrinking behavior of PLGA electrospun membranes under various test conditions and discussed the underlying shrinking mechanism. The results indicated that the shrinkage of the electrospun PLGA membrane was mainly regulated by the glass transition of its polymer fiber; the temperature and liquid environment were found to be the two main factors leading to the shrinkage of the electrospun PLGA membrane through affecting its glass transition. Then a heat stretching (HS) technique was proposed by us to stabilize the electrospun PLGA membrane. After HS treatment, the glass transition temperature (Tg) of the electrospun PLGA membrane could increase from 48.38 °C to 54.55 °C. Our results indicated that the HS-treated membranes could maintain a high area percentage of 90.89 ± 2.27% and 84.78 ± 3.36% after immersion respectively in PBS and blood at 37 °C for 2 hours. Further experiments confirmed that the HS technique could also stabilize the dimensional structure of the electrospun PDLLA membrane in PBS and blood at 37 °C. This study provides an effective strategy for preventing the shrinkage of electrospun polyester biomaterials in a physiological environment that may benefit both the material structural stability and the in vivo biological performance.
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http://dx.doi.org/10.1039/d1tb00734cDOI Listing
July 2021

The Experiences of Community-dwelling older adults during the COVID-19 Lockdown in Wuhan: A qualitative study.

J Adv Nurs 2021 Jul 14. Epub 2021 Jul 14.

School of Nursing, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Aims: To explore the experiences of community-dwelling older adults in Wuhan during the coronavirus disease 2019 lockdown.

Design: An empirical phenomenological approach was used to conduct a qualitative study.

Methods: We performed semi-structured, in-depth telephone interviews between July 24 and August 2, 2020. A purposive sample of 18 participants (≥65 years old) who lived in Wuhan during the lockdown was recruited, including both infected and uninfected people. Data summarization and theme categories refinement were performed following Colaizzi's phenomenological approach.

Results: Four main theme categories emerged. First, the 'Challenges' posed by the epidemic. Older adults were challenged with barriers in seeing a doctor and daily life inconveniences. And they experienced negative emotions, whether infected or not. The second domain was 'multi-dimensional support', which helped older people went through the difficult period. The third domain was 'resilience amid challenges'. Although they experienced physical and psychological distress, most of them could self-adjust and achieve transcendence from the unique experience. Lastly, the remaining impact after the epidemic affected older adults. Some still had mental burdens, while others thought they have benefited from the quarantine time (e.g. regular diet, learning new skills).

Conclusion: The epidemic and lockdown of the city brought significant physical and mental challenges to community-dwelling older adults. Active adaptation and multifaceted support helped them through this period. However, the mental burdens after the epidemic still require attention. These experiences would provide guidelines for the protection of vulnerable populations during public health emergencies.

Impact: The results of the study suggested that certain social dynamics and individual behaviours helped the elderly to better cope with the stressful lockdown period. The findings in this study provided guidelines on how to reduce the negative effects on older adults during the pandemic and enlighten studies concerning the well-being of older adults or other vulnerable people in future crises.
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http://dx.doi.org/10.1111/jan.14978DOI Listing
July 2021

Novel TNC-PDGFD fusion in fibrosarcomatous dermatofibrosarcoma protuberans: a case report.

Diagn Pathol 2021 Jul 13;16(1):63. Epub 2021 Jul 13.

Department of Pathology, Laboratory Medicine Center, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, 158 Shangtang Road, Gongshu District, Hangzhou, 310014, Zhejiang, China.

Background: Dermatofibrosarcoma protuberans (DFSP) is a superficial fibroblastic tumor characterized by high rate of local recurrence and low metastatic potential. Fibrosarcomatous transformation can rarely arise in DFSP either de novo or as recurrent, which represents a form of tumor progression and carries an increased risk of metastasis over classic DFSP. Cytogenetically, DFSP is characterized by a recurrent unbalanced chromosome translocation t (17;22)(q22;q13), leading to the formation of COL1A1-PDGFB fusion transcript that is present in more than 90% of cases. Alternative fusions involving the PDGFD with partners of COL6A3 or EMILIN2 have recently been documented in less than 2% of cases. Herein, we report a DFSP with fibrosarcomtous morphology harboring a novel TNC-PDGFD fusion.

Case Presentation: A 54-year-old female presented with a slowly growing mass in the right thigh. Excision demonstrated a 2-cm ovoid, well-circumscribed, gray-white, mass. Microscopic examination revealed a partially encapsulated subcutaneous nodule without dermal connection. The neoplasm was composed of cellular and fairly uniform spindle cells with brisk mitoses, arranged in elongated fascicles and herringbone patterns, with focal collagenized stroma. The neoplastic cells were positive for CD34 and smooth muscle actin. Fluorescence in-situ hybridization analyses showed negative for COL1A1-PDGFB fusion as well as NTRK1/2/3 rearrangements. A subsequent RNA sequencing detected an in-frame fusion between exon 15 of TNC and exon 6 of PDGFD. This fusion was further confirmed by nested reverse transcription polymerase chain reaction amplification followed by Sanger sequencing. A diagnosis of fibrosarcomatous DFSP was rendered and the patient was in good status at a follow-up of 12 months after the operation.

Conclusions: We report a fibrosarcomatous DFSP with novel TNC-PDGFD fusion, which adds to the pathologic and genetic spectrum of PDGFD-rearranged DFSP.
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http://dx.doi.org/10.1186/s13000-021-01123-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276425PMC
July 2021

The measurement of Cobb angle based on spine X-ray images using multi-scale convolutional neural network.

Phys Eng Sci Med 2021 Jul 12. Epub 2021 Jul 12.

NuVasive, San Diego, CA, 92121, USA.

Adolescent idiopathic scoliosis (AIS) is a structural spinal deformity mainly in the coronal plane and is among the most frequent deformities in children, adolescents, and young adults, with an overall prevalence of 0.47-5.2%. The Cobb angle is an objective measure to determine the progression of deformity and plays a critical role in the planning of surgical treatment. However, existing studies suggested that Cobb angle measurement is susceptible to inter- and intra-observer variability, as well as a high variability in the definition of the end vertebra. In this study, we proposed an automatic method for the spine vertebrae segmentation using Deeplab V3+, a powerful tool that has shown success in the image segmentation of other anatomical regions but spine, and Cobb angle measurement. The segmentation performance was compared to existing mainstay neural networks. Compared to U-Net, Residual U-Net and Dilated U-Net, our method using Deeplab V3+ showed the best performance in the Dice Similarity Coefficient (DSC), accuracy, sensitivity and Jaccard Index. An excellent correlation in the final Cobb angle calculation was achieved between the smallest distance point (SDP) method and two experts (> 0.95), with a small error in the angle estimation compared (MAE < 3°). The proposed method could provide a potential tool for the automatic estimation of the Cobb angle to improve the efficiency and accuracy of the treatment workflow for AIS.
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http://dx.doi.org/10.1007/s13246-021-01032-zDOI Listing
July 2021

Rice Root Hair Phenotypes Imaged by Cryo-SEM.

Bio Protoc 2021 Jun 5;11(11):e4037. Epub 2021 Jun 5.

Research Centre for Plant RNA Signaling, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 311121, China.

Cryo-scanning electron microscopy (cryo-SEM) was first introduced for scientific use in the 1980s. Since then, cryo-SEM has become a routine technique for studying the surfaces and internal structures of biological samples with a high water content. In contrast to traditional SEM, cryo-SEM requires no sample pretreatment processes; thus, we can obtain the most authentic images of the sample shape and structure. Cryo-SEM has two main steps: cryoprocessing of samples and scanning electron microscopy (SEM) observation. The cryoprocessing step includes preparation of the cooled slushing station, cooling of the preparation chamber, sample preparation, and sputtering. The sample is then transferred to an SEM cold stage for observation. We used cryo-SEM to study rice root hair tissues, but the methods and protocols can be applied to other root systems. This protocol optimizes the two key operation steps of reducing the humidity in the growth chamber and previewing the samples before sputtering and can more quickly obtain high-quality images.
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http://dx.doi.org/10.21769/BioProtoc.4037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249913PMC
June 2021

Impulsivity in cocaine users compared to matched controls: Effects of sex and preferred route of cocaine use.

Drug Alcohol Depend 2021 Jul 2;226:108840. Epub 2021 Jul 2.

Division on Substance Use Disorders, New York State Psychiatric Institute and Department of Psychiatry, Columbia University Vagelos College of Physicians and Surgeons and Columbia University Irving Medical Center, 1051 Riverside Drive, New York, NY, 10032, USA.

Background: Impulsivity has been identified as playing a role in cocaine use. The purpose of this study was to explore self-report measures of impulsivity in large groups of male and female cocaine users and matched controls and to determine if differences in impulsivity measures within a group of cocaine users related to self-reported money spent on cocaine and route of cocaine use.

Methods: Eight self-report impulsivity measures yielding 34 subscales were obtained in 230 cocaine users (180 M, 50 F) and a matched group of 119 healthy controls (89 M, 30 F). Correlational analysis of the questionnaires revealed 2 factors: Impulsive Action (Factor 1) consisting of many traditional impulsivity measures and Thrill-seeking (Factor 2) consisting of delay discounting, sensation and thrill seeking.

Results: Sex influenced within group comparisons. Impulsive Action scores did not vary as a function of sex within either group. But, male controls and male cocaine users had greater Thrill-seeking scores than females within the same group. Sex also influenced between group comparisons. Male cocaine users had greater Impulsive Action scores while female cocaine users had greater Thrill-seeking scores than their sex-matched controls. Among cocaine users, individuals who preferred insufflating ("snorting") cocaine had greater Thrill-seeking scores and lower Impulsive Action scores than individuals who preferred smoking cocaine. Individuals who insufflate cocaine also spent less money on cocaine.

Conclusions: Greater Impulsive Action scores in males and Thrill-seeking scores in females were associated with cocaine use relative to controls.
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http://dx.doi.org/10.1016/j.drugalcdep.2021.108840DOI Listing
July 2021

Synthesis and Luminescence Properties of Two-Electron Bimetallic Cu-Ag and Cu-Au Nanoclusters via Copper Hydride Precursors.

Inorg Chem 2021 Jul 8;60(14):10799-10807. Epub 2021 Jul 8.

Department of Chemistry, National Dong Hwa University, No. 1, Sec. 2, Da Hsueh Road, Shoufeng, Hualien, Taiwan 974301, R.O.C.

The synthesis, structural characteristics, and photophysical properties of luminescent Cu-rich bimetallic superatomic clusters [[email protected](SCNPr)(C≡CPh)] (), [[email protected]{SP(OR)}(C≡CPh)] (), ( = Pr; = Pr), [[email protected]{SP(CHPh)}(C≡CPh)] (), and [[email protected]{SP(OPr)}(C≡CPh)] () were studied. Compositionally uniform clusters - were isolated from the reaction of dithiolato-stabilized, polyhydrido copper clusters with phenylacetylene in the presence of heterometal salts. By using X-ray diffraction, the structures of , , , and were able to be determined. ESI-mass spectrometry and elemental analysis confirmed their compositions and purity. The structural characteristics of these clusters are similar with respect to displaying gold (or silver)-centered Cu cuboctahedra surrounded by six dithiocarbamate/dithiophosph(in)ate and four alkynyl ligands. The doping of Au and Ag atoms into the polyhydrido copper nanoclusters significantly enhances their PL quantum yields from [email protected] (0.58%) to [email protected] (55%) at ambient temperature in solution. In addition, the electrochemical properties of the new alloys were investigated by cyclic voltammetry.
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http://dx.doi.org/10.1021/acs.inorgchem.1c01489DOI Listing
July 2021

Multilevel Chirality Transfer from Amino Acid Derivatives to Circularly Polarized Luminescence-Active Nanoparticles in Aqueous Medium.

Chemistry 2021 Jul 7. Epub 2021 Jul 7.

Jiangsu Key Laboratory of Advanced Organic Materials School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, P.R. China.

Chirality at different levels is widely observed in nature, but the clue to connect it all together, and the way chirality transfers among different levels are still obscure. Herein, a l-/d-lysine-based self-assembly system was constructed, in which two-step chirality transfer among three different levels was observed in aqueous solution. The chirality originated from the point chirality of amino acid derivatives l-/d-PyLys hydrochloride, and was transferred to the planar conformational chirality of water-soluble pillar[5]arene pR-/pS-WP5. Then, with the aid of pR-/pS-WP5, nanoparticles were formed that exhibited L-/R-handed circularly polarized luminescence with a dissymmetry factor of up to ±0.001, arising from pyrene chiral excimers. This multilevel chirality transfer not only provides a perspective to trace potential clues, and to pursue certain ways by which the chirality transfers, but also offers a strategy to create controllable CPL emission in aqueous media.
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http://dx.doi.org/10.1002/chem.202100458DOI Listing
July 2021

Metabolic Reprogramming of Colorectal Cancer Cells and the Microenvironment: Implication for Therapy.

Int J Mol Sci 2021 Jun 10;22(12). Epub 2021 Jun 10.

Section Pathology of the Institute of Forensic Medicine, University Hospital Jena, Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany.

Colorectal carcinoma (CRC) is one of the most frequently diagnosed carcinomas and one of the leading causes of cancer-related death worldwide. Metabolic reprogramming, a hallmark of cancer, is closely related to the initiation and progression of carcinomas, including CRC. Accumulating evidence shows that activation of oncogenic pathways and loss of tumor suppressor genes regulate the metabolic reprogramming that is mainly involved in glycolysis, glutaminolysis, one-carbon metabolism and lipid metabolism. The abnormal metabolic program provides tumor cells with abundant energy, nutrients and redox requirements to support their malignant growth and metastasis, which is accompanied by impaired metabolic flexibility in the tumor microenvironment (TME) and dysbiosis of the gut microbiota. The metabolic crosstalk between the tumor cells, the components of the TME and the intestinal microbiota further facilitates CRC cell proliferation, invasion and metastasis and leads to therapy resistance. Hence, to target the dysregulated tumor metabolism, the TME and the gut microbiota, novel preventive and therapeutic applications are required. In this review, the dysregulation of metabolic programs, molecular pathways, the TME and the intestinal microbiota in CRC is addressed. Possible therapeutic strategies, including metabolic inhibition and immune therapy in CRC, as well as modulation of the aberrant intestinal microbiota, are discussed.
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http://dx.doi.org/10.3390/ijms22126262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230539PMC
June 2021

Bevacizumab biosimilar LY01008 compared with bevacizumab (Avastin) as first-line treatment for Chinese patients with unresectable, metastatic, or recurrent non-squamous non-small-cell lung cancer: A multicenter, randomized, double-blinded, phase III trial.

Cancer Commun (Lond) 2021 Jun 29. Epub 2021 Jun 29.

Respiratory Department, Taizhou Hospital of Zhejiang Province, Taizhou, Zhejiang, 317000, P. R. China.

Background: Previous studies have demonstrated the preclinical pharmacological and toxicological consistency, and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab (Avastin). This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first-line treatment of Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC).

Methods: Stage IIIB-IV NSCLC patients with evaluable lesions, good physical status, and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin (combined treatment) for 4-6 cycles, followed by maintenance monotherapy with LY01008 until disease progression, intolerable toxicity, or death. The primary endpoint was objective response rate (ORR) in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 confirmed by independent radiological review committees (IRRC). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. This study was registered in ClinicalTrials.gov (NCT03533127).

Results: Between December 15 , 2017, and May 15 , 2019, a total of 649 patients were randomized to the LY01008 (n = 324) or Avastin (n = 325) group. As of September 25 , 2019 for primary endpoint analysis, 589 patients received ORR evaluation, with a median number of combined treatment cycles of 5 (range 1-6) and median duration of treatment of 3.0 (range 0.0-5.1) months. ORR of response-evaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%, respectively. The stratified ORR ratio was 0.91 (90% CI 0.80-1.04, within the prespecified equivalence margin of 0.75-1.33). Up to May 15 , 2020, with a median follow-up of 13.6 (range 0.8-28.4) months, no notable differences in DCR, median DoR, median PFS, median OS, and 1-year OS rate were observed between the LY01008 and Avastin groups. There were no clinically meaningful differences in safety and immunogenicity across treatment groups.

Conclusions: LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC. LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable, metastatic, or recurrent non-squamous NSCLC patients in the first-line setting.
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http://dx.doi.org/10.1002/cac2.12179DOI Listing
June 2021

Evaluation of phenolic composition and antioxidant properties of different varieties of Chinese citrus.

Food Chem 2021 Jun 19;364:130413. Epub 2021 Jun 19.

Fujian Academy of Agricultural Sciences, Fuzhou 350003, China. Electronic address:

Citrus peels have health-promoting effects and are a rich source of antioxidant substances. This study evaluated the compositions of phenolic compounds and antioxidant activities in the peels of 52 citrus varieties with consistent planting time and management. The highest levels of total phenols (72.95 ± 37.60 mg/g DW) and total flavonoids (71.43 ± 37.64 mg/g DW) were found in mandarin. The highest phenolic acid content (18.78 ± 0.38 mg/g DW), dominated by protocatechuic acid, was found in kumquat. The antioxidant potency composite index was 6.23-94.56, suggesting mandarin varieties HJ, TWPG, TTPG, AY28, BZH and TCJC had the highest antioxidant activity. Statistics analysis indicated phenolic compounds and antioxidant activity were positively correlated. Principal component analysis and hierarchical cluster analysis suggested a strong relationship between phenolic compound composition and genetic background. This study indicated significant differences in the biological properties of various types of citrus peels; which are valuable for future utilization and research of citrus peels.
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http://dx.doi.org/10.1016/j.foodchem.2021.130413DOI Listing
June 2021

A phase 1, randomized study to evaluate safety, tolerability, and pharmacokinetics of GDC-3280, a potential novel anti-fibrotic small molecule, in healthy subjects.

Pulm Pharmacol Ther 2021 Jun 21;69:102051. Epub 2021 Jun 21.

Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA. Electronic address:

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease. Although anti-fibrotic treatments, such as pirfenidone, are available that reduce the rate of disease progression, these medications have limitations in tolerability, and IPF patients still have poor prognoses. GDC-3280, an orally available small molecule that was designed to improve upon pirfenidone's activity, has anti-fibrotic activity in animal models. This first-in-human, phase 1 trial evaluated GDC-3280 to determine its safety, tolerability, and pharmacokinetics (PK).

Methods: Single and multiple ascending-doses of GDC-3280 were administered to healthy volunteers in two parts. Part A consisted of 6 treatment groups, each receiving a single, oral dose of GDC-3280 (25-1600 mg) or placebo in the fasted state. Part A also assessed the effect of food and coadministration of a proton pump inhibitor (rabeprazole) on the tolerability and PK of single doses of 400- and 800-mg GDC-3280. Part B consisted of 3 treatment groups who received either 200- or 275-mg GDC-3280 twice daily or 525-mg once daily after a low-fat meal for 7 days. The trial monitored treatment-emergent adverse events (TEAEs) and assessed the pharmacokinetics of GDC-3280 in blood and urine samples.

Results: Fifty-six subjects (42 GDC-3280, 14 placebo) in Part A and 24 subjects (18 GDC-3280, 6 placebo) in Part B received treatment. No deaths, serious adverse events, or dose-limiting adverse events occurred, and no subjects withdrew due to a TEAE. In both Parts A and B, most TEAEs were mild. The most frequent TEAEs in Part A were headache and nausea. TEAEs occurred more often when GDC-3280 was administered with food. Pretreatment and coadministration with rabeprazole had no effect on GDC-3280 tolerability. In Part B, the most frequent TEAEs were nausea, dizziness, nasal congestion, and cough. Transient, treatment-related increases in serum creatinine occurred at doses greater than 400 mg in Part A (12%-18% from baseline) and after multiple doses in each group in Part B (20%-34% from baseline). GDC-3280 was generally readily absorbed with a median t < 4.0 h following single- or repeat-dose oral administration. In Part A, less-than-dose-proportional increases in systemic exposure occurred, and in Part B, dose-proportional increases occurred within the dose range tested. At doses of 200 mg or lower, more than 50%-70% of orally administered doses were recovered in urine as unchanged GDC-3280 when subjects received a single dose of GDC-3280, suggesting renal excretion is one of the major routes of elimination. Administration of single doses of 400- and 800-mg GDC-3280 after a meal caused statistically significant increases in exposure due to increased rates of absorption compared to the fasted state. Pretreatment and coadministration of rabeprazole dosing led to decreases in exposure compared to GDC-3280 alone, indicating a weak drug-drug interaction. Following repeat dose administration, steady-state plasma concentrations of GDC-3280 were achieved within 2 days with an apparent terminal half-life (t) between 5 and 6 h.

Conclusions: Single and multiple doses of GDC-3280 were generally well tolerated, with acceptable safety and pharmacokinetic profiles that support twice-daily, oral administration with food in future clinical trials.
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http://dx.doi.org/10.1016/j.pupt.2021.102051DOI Listing
June 2021

Once-daily savolitinib in Chinese patients with pulmonary sarcomatoid carcinomas and other non-small-cell lung cancers harbouring MET exon 14 skipping alterations: a multicentre, single-arm, open-label, phase 2 study.

Lancet Respir Med 2021 Jun 21. Epub 2021 Jun 21.

Hutchison MediPharma, Shanghai, China.

Background: Savolitinib is a selective MET tyrosine-kinase inhibitor. We investigated the activity and safety of savolitinib in patients with pulmonary sarcomatoid carcinoma and other non-small-cell lung cancer (NSCLC) subtypes positive for MET exon 14 skipping alterations (METex14-positive).

Methods: We did a multicentre, single-arm, open-label, phase 2 study across 32 hospitals in China. Eligible patients were 18 years or older with locally advanced or metastatic METex14-positive pulmonary sarcomatoid carcinoma or other NSCLC subtypes, had either presented with disease progression or toxicity intolerance towards one or more standard treatments or were deemed clinically unsuitable for standard treatment, were MET inhibitor-naive, and had measurable disease. Patients received either 600 mg (bodyweight ≥50 kg) or 400 mg (bodyweight <50 kg) of oral savolitinib once daily until disease progression, death, intolerable toxicity, initiation of other anti-tumour therapy, non-compliance, patient withdrawal, or patient discontinuation. Radiographic tumour evaluation was done at baseline, every 6 weeks within 1 year of the first dose, and every 12 weeks thereafter. The primary endpoint was objective response rate, defined as the proportion of patients with confirmed complete or partial responses by independent review committee (IRC) assessment. The primary endpoint was assessed in the tumour response evaluable set, which comprised all treated patients with a measurable lesion at baseline and at least one adequate scheduled post-baseline tumour assessment or the presence of radiological disease progression, with a sensitivity analysis done in the full analysis set, which comprised all patients who received at least one dose of savolitinib. Safety was also evaluated in the full analysis set. This study is registered with ClinicalTrials.gov, NCT02897479, and recruitment is complete, with treatment and follow-up ongoing.

Findings: From Nov 8, 2016, to Aug 3, 2020, 84 patients with METex14 skipping alterations were screened for eligibility, of whom 70 were enrolled, received savolitinib, and comprised the full analysis set. The IRC-assessed tumour response evaluable set comprised 61 patients. At a median follow-up of 17·6 months (IQR 14·2-24·4), the IRC-assessed objective response rate was 49·2% (36·1-62·3; 30 of 61 patients) in the tumour response evaluable set and 42·9% (95% CI 31·1-55·3; 30 of 70 patients) in the full analysis set. All 70 patients reported at least one treatment-related adverse event. Treatment-related adverse events of grade 3 or more occurred in 32 (46%) patients, the most frequent of which were increased aspartate aminotransferase (n=9), increased alanine aminotransferase (n=7), and peripheral oedema (n=6). Treatment-related serious adverse events occurred in 17 (24%) patients, the most common being abnormal hepatic function (n=3) and hypersensitivity (n=2). One death due to tumour lysis syndrome in a patient with pulmonary sarcomatoid carcinoma was assessed to be probably related to savolitinib by the investigator.

Interpretation: Savolitinib yielded promising activity and had an acceptable safety profile in patients with pulmonary sarcomatoid carcinoma and other NSCLC subtypes positive for METex14 skipping alterations. Savolitinib could therefore be a novel treatment option in this population.

Funding: Hutchison MediPharma and AstraZeneca.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S2213-2600(21)00084-9DOI Listing
June 2021

Porous 2D and 3D Covalent Organic Frameworks with Dimensionality-Dependent Photocatalytic Activity in Promoting Radical Ring-Opening Polymerization.

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

School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules and State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai, 200240, China.

Dimensionality is a fundamental parameter to modulate the properties of solid materials by tuning electronic structures. Covalent organic frameworks (COFs) are a prominent class of porous crystalline materials, but the study of dimensional dependence on their physicochemical properties is still lacking. Herein we illustrate photocatalytic performances of N,N-diaryl dihydrophenazine (PN)-based COFs are heavily dependent on the structural dimensionality. Six isostructural imine-bonded 2D-PN COFs and one 3D-PN COF were prepared. All can be heterogeneous photocatalysts to promote radical ring-opening polymerization of vinylcyclopropanes (VCPs), which typically produces polymers with a combination of linear (l) and cyclic (c) repeat units. The 2D-PN COFs have much higher catalytic activity than the 3D-PN COF, allowing the efficient synthesis of poly(VCPs) with controlled molecular weight, low dispersity and high l/c selectivity (up to 97 %). The improved performance can be ascribed to the 2D structure which has a larger internal surface area, more catalytically active sites, higher photosensitizing ability and photoinduced electron transfer efficiency.
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http://dx.doi.org/10.1002/anie.202107915DOI Listing
June 2021
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