Publications by authors named "Qian Chen"

2,153 Publications

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CD70-specific CAR T cells have potent activity against acute myeloid leukemia without HSC toxicity.

Blood 2021 Jul;138(4):318-330

Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital-Texas Children's Hospital, Houston, TX.

The prognosis of patients with acute myeloid leukemia (AML) remains dismal, highlighting the need for novel innovative treatment strategies. The application of chimeric antigen receptor (CAR) T-cell therapy to patients with AML has been limited, in particular by the lack of a tumor-specific target antigen. CD70 is a promising antigen to target AML, as it is expressed on most leukemic blasts, whereas little or no expression is detectable in normal bone marrow samples. To target CD70 on AML cells, we generated a panel of CD70-CAR T cells that contained a common single-chain variable fragment (scFv) for antigen detection, but differed in size and flexibility of the extracellular spacer and in the transmembrane and the costimulatory domains. These CD70scFv CAR T cells were compared with a CAR construct that contained human CD27, the ligand of CD70 fused to the CD3ζ chain (CD27z). The structural composition of the CAR strongly influenced expression levels, viability, expansion, and cytotoxic capacities of CD70scFv-based CAR T cells, but CD27z-CAR T cells demonstrated superior proliferation and antitumor activity in vitro and in vivo, compared with all CD70scFv-CAR T cells. Although CD70-CAR T cells recognized activated virus-specific T cells (VSTs) that expressed CD70, they did not prevent colony formation by normal hematopoietic stem cells. Thus, CD70-targeted immunotherapy is a promising new treatment strategy for patients with CD70-positive AML that does not affect normal hematopoiesis but will require monitoring of virus-specific T-cell responses.
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http://dx.doi.org/10.1182/blood.2020008221DOI Listing
July 2021

Hollow-out hydrangea-like architecture composed of CoRu/Co as an excellent electrocatalyst for oxygen evolution.

ChemSusChem 2021 Jul 29. Epub 2021 Jul 29.

Sichuan Normal University, College of Chemistry and Materials Science, Jingan Road, 610068, Chengdu, CHINA.

Developing low-cost but efficient electrocatalysts to promote the sluggish kinetics of oxygen evolution from water splitting is essential for hydrogen production. Here, a hierarchical hollow-out hydrangea-like superstructure composed of CoRu/Co is constructed through a self-template method via the morphology-controlled pyrolysis transformation of flower-like Ru-doped Co-based layered double hydroxides (LDH). The anchoring of Ru into Co-LDH is the key to the formation of well-defined hydrangea-like three-dimensional superstructure composed of CoRu/Co. The optimized CoRu/Co-M-350 with a low Ru loading of 3.0 wt% exhibits excellent oxygen evolution reaction (OER) catalytic performances with an ultralow overpotential (η10=192 mV) and an excellent stability for 100 h at 100 mA cm-2 in alkaline media, outperforming the benchmark RuO2 and most of the reported electrocatalysts. The superior morphology and structure features of CoRu/Co-M-350 provide not only abundant accessible surface sites but also fast mass/electron transfer, thereby promoting the OER catalysis. The present study provides a fire-new synthetic way for preparing highly active electrocatalyst toward OER catalysis.
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http://dx.doi.org/10.1002/cssc.202101316DOI Listing
July 2021

refMiR 142 5p inhibits cell invasion and migration by targeting DNMT1 in breast cancer.

Oncol Res 2021 Jul 28. Epub 2021 Jul 28.

Abnormal cell proliferation caused by abnormal transcription regulation mechanismseems to be one of the reasons for the progression of breast cancer and also thepathological basis. MicroRNA 142 5p (miR 142 5p) is a low expressed miRNA inbreast cancer. T he role of MKL1's regulation of DNMT1 in breast cancer cellproliferation and migration is still unclear. MKL 1 (myocardi n related transcriptionfactor A) can bind to the conserved cis regulatory element CC (A/T) 6GG (called CarGbox) in the promoter to re gulate the transcription of miR 142 5p. The expression ofmiR 142 5p and MKL 1 are positively correlated. In addition, it has been proved thatDNMT1 is the target of miR 142 5p, which inhibits the expression of DNMT1 bytargeting the 3'UTR of DNMT1, thereby forming a feedback loop and inhibiting themigration and proliferation of breast cancer. Our data provide important and novelinsights into the MKL 1/miR 142 5p/DNMT1/maspin signaling pathway, and maybecome a new idea for breast cancer diagnosis, treatment and prognosis.
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http://dx.doi.org/10.3727/096504021X16274672547967DOI Listing
July 2021

Selective Expression of a Carbazole-Phenothiazine Derivative Leads to Dual-mode AIEE, TADF and Distinctive Mechanochromism.

Chemphyschem 2021 Jul 28. Epub 2021 Jul 28.

Beijing University of Chemical Technology, College of Chemical Engineering, No. 19, Beisanhuandong Road, 100029, Beijing, CHINA.

In this article, a newly designed D-A-D' carbazole-phenothiazine derivative (CNCzPTZ) with carbazole (Cz) and phenothiazine (PTZ) as the donors and cyanophenyl fragment as the acceptor was synthesized. The selective expression of chromophores enables CNCzPTZ with solvatochromism, rare dual-mode aggregation-induced emission enhancement (AIEE) property, solid-state dual-emissions with TADF and distinctive mechanochromism. Interestingly, the selective expression of Cz and PTZ leads to the dual-mode AIEE property of CNCzPTZ with the emission band abruptly shifting from 550 nm (PTZ's ICT emission) to 500 nm (Cz's ICT emission) as the water fraction increases. In the crystal state, CNCzPTZ demonstrated dual emission bands of 478 nm (ICT emission of Cz) and 538 nm (fluorescence and TADF of PTZ) owing to the simultaneous expression of Cz and PTZ. According to the TD-DFT results, for the isolated monomer, the expression of Cz is dominated; for the dimers, the expression of PTZ is dominated. Finally, CNCzPTZ shows distinctive mechanochromic property in the solid state due to the planarization between Cz and acceptor and the damage of ordered dimers. As far as we know, it is a rare report about dual-mode AIEE and selective expression of chromophores.
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http://dx.doi.org/10.1002/cphc.202100435DOI Listing
July 2021

Sequential C-H activation enabled expedient delivery of polyfunctional arenes.

Chem Commun (Camb) 2021 Jul 23. Epub 2021 Jul 23.

School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, China.

Modular construction of polyfunctional arenes from abundant feedstocks stands as an unremitting pursue in synthetic chemistry, accelerating the discovery of drugs and materials. Herein, using the multiple C-H activation strategy with versatile imidate esters, the expedient delivery of molecular libraries of densely functionalized sulfur-containing arenes was achieved, which enabled the concise construction of biologically active molecules, such as Bipenamol.
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http://dx.doi.org/10.1039/d1cc03243gDOI Listing
July 2021

[Study on the safety and effectiveness of low-dose tranexamic acid in operation of multi-level continuous thoracic ossification of ligament flavum].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Jul;35(7):873-877

Department of Orthopedics, Affiliated Hospital of North Sichuan Medical College, Nanchong Sichuan, 637000, P.R.China.

Objective: To investigate the safety and effectiveness of low-dose tranexamic acid (TXA) in operation of multi-level continuous thoracic ossification of ligament flavum (TOLF).

Methods: A clinical data of 26 patients who underwent operation for multi-level continuous TOLF and met the selection criteria between July 2015 and January 2019 was retrospectively analyzed. Among them, 13 cases (group A) were received intravenous infusion of TXA (10 mg/kg) at 15 minutes before operation, and maintained the infusion at 1 mg/(kg·h) until the end of the operation; 13 cases (group B) were received the same dose of normal saline before and during operation. There was no significant difference in gender, age, body mass index, diseased segment, and preoperative hemoglobin, platelet count, activated partial thromboplastin time, prothrombin time, international normalized ratio (INR) between the two groups ( >0.05). The hemoglobin, platelet count, activated partial thromboplastin time, prothrombin time, INR, the number of deep vein thrombosis of the lower extremities, operation time, intraoperative blood loss, postoperative drainage volume, total blood loss, and the time of drainage tube extubation in the two groups were recorded and compared.

Results: All operations in the two groups were successfully completed. Compared with group B, the operation time and time of drainage tube extubation in group A were shortened, and the intraoperative blood loss, postoperative drainage volume, and total blood loss were reduced. The differences between the two groups were significant ( <0.05). None of the two groups received blood transfusion, and the hemoglobin level of group A at 24 hours after operation was significantly higher than that of group B ( =5.062, =0.000). The incisions in both groups healed and sutures were removed within 2 weeks after operation, and no complications occurred. There was no significant difference between the two groups in activated partial thromboplastin time, prothrombin time, INR, and platelet count at 24 hours after operation ( >0.05).

Conclusion: In multi-level continuous TOLF operation, intravenous administration of low-dose TXA can effectively reduce blood loss, shorten postoperative drainage time, and does not increase the risk of complications.
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http://dx.doi.org/10.7507/1002-1892.202101084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311222PMC
July 2021

Meloxicam Inhibited the Proliferation of LPS-Stimulated Bovine Endometrial Epithelial Cells Through Wnt/β-Catenin and PI3K/AKT Pathways.

Front Vet Sci 2021 9;8:637707. Epub 2021 Jul 9.

College of Veterinary Medicine, Yangzhou University, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China.

Meloxicam is a non-steroidal anti-inflammatory drug and has been used to relieve pain and control inflammation in cows with metritis and endometritis. Meloxicam has been found to be effective in inhibiting tissue or cell growth when it is used as an anti-inflammatory therapy. However, the influence of meloxicam on bovine endometrial regeneration has not been reported. This study was to research the effect of meloxicam (0.5 and 5 μM) on the proliferation of primary bovine endometrial epithelial cells (BEECs) stimulated by lipopolysaccharide. The cell viability, cell cycle, and cell proliferation were evaluated by Cell Counting Kit-8, flow cytometry, and cell scratch test, respectively. The mRNA transcriptions of prostaglandin-endoperoxide synthase 1 () and , Toll-like receptor 4, and proliferation factors were detected using quantitative reverse-transcription polymerase chain reaction. The activations of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Wnt/β-catenin pathways were determined using western blot and immunofluorescence. As a result, co-treatment of meloxicam and lipopolysaccharide inhibited ( < 0.05) the cell cycle progression and reduced ( < 0.05) the cell healing rate and the mRNA level of proliferation factors as compared with the cells treated with lipopolysaccharide alone. Meloxicam decreased ( < 0.05) the lipopolysaccharide-induced gene expression. Neither lipopolysaccharide nor meloxicam changed mRNA abundance ( > 0.05). Meloxicam inhibited ( < 0.05) the lipopolysaccharide-activated Wnt/β-catenin pathway by reducing ( < 0.05) the protein levels of β-catenin, c-Myc, cyclin D1, and glycogen synthase kinase-3β and prevented the lipopolysaccharide-induced β-catenin from entering the nucleus. Meloxicam suppressed ( < 0.05) the phosphorylation of PI3K and AKT. In conclusion, meloxicam alone did not influence the cell cycle progression or the cell proliferation in BEEC but caused cell cycle arrest and inhibited cell proliferation in lipopolysaccharide-stimulated BEEC. This inhibitory effect of meloxicam was probably mediated by Wnt/β-catenin and PI3K/AKT pathways.
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http://dx.doi.org/10.3389/fvets.2021.637707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299055PMC
July 2021

TRPV1 Antagonist Prevents Neonatal Sevoflurane-Induced Synaptic Abnormality and Cognitive Impairment in Mice Through Regulating the Src/Cofilin Signaling Pathway.

Front Cell Dev Biol 2021 7;9:684516. Epub 2021 Jul 7.

Department of Anesthesiology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China.

Long-term neurodevelopmental disorders following neonatal anesthesia have been reported both in young animals and in children. The activation of transient receptor potential vanilloid 1 (TRPV1) channels in hippocampus adversely affects neurodevelopment. The current study explored the underlying mechanism of TRPV1 channels on long-lasting cognitive dysfunction induced by anesthetic exposure to the developing brain. we demonstrated that TRPV1 expression was increased after sevoflurane exposure both and . Sevoflurane exposure to hippocampal neurons decreased the synaptic density and the surface GluA1 expression, as well as increased co-localization of internalized AMPAR in early and recycling endosomes. Sevoflurane exposure to newborn mice impaired learning and memory in adulthood, and reduced AMPAR subunit GluA1, 2 and 3 expressions in the crude synaptosomal fractions from mouse hippocampus. The inhibition of TRPV1 reversed the phenotypic changes induced by sevoflurane. Moreover, sevoflurane exposure increased Src phosphorylation at tyrosine 416 site thereby reducing cofilin phosphorylation. TRPV1 blockade reversed these suppressive effects of sevoflurane. Our data suggested that TRPV1 antagonist may protect against synaptic damage and cognitive dysfunction induced by sevoflurane exposure during the brain developing stage.
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http://dx.doi.org/10.3389/fcell.2021.684516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293754PMC
July 2021

Response of microbial nitrogen transformation processes to antibiotic stress in a drinking water reservoir.

Sci Total Environ 2021 Jul 18;797:149119. Epub 2021 Jul 18.

Key Laboratory of Water and Sediment Sciences, Ministry of Education, College of Environmental Sciences and Engineering, Peking University, Beijing 100871, China; State Environmental Protection Key Laboratory of All Materials Flux in River Ecosystems, Beijing 100871, China.

Effects of antibiotics on microbial nitrogen transformation processes in natural aquatic ecosystems are largely unknown. In this study, we utilized the N stable isotope tracers and metagenomic sequencing to identify how antibiotics drive nitrogen transformation processes in Danjiangkou Reservoir, which is the largest artificial drinking water reservoir in China. We retrieved 51 nitrogen functional genes, and found that the highest abundances of nitrate reduction and denitrification-related genes occurred in dissimilatory nitrogen transformation pathways. N-labelling analysis substantiated that denitrification was the main pathway for nitrogen removal, accounting for 57.1% of nitrogen loss. Nitrogen functional genes and antibiotic resistance genes co-occurred in Danjiangkou Reservoir, and they were mainly carried by the denitrifying bacteria such as Rhodoferax, Polaromonas, Limnohabitans, Pararheinheimera, Desulfobulbus, and Pseudopelobacter. Genome annotation revealed that antibiotic deactivation, Resistance-Nodulation-Division and facilitator superfamily efflux pumps were responsible for the multiple-resistance to antibiotics in these bacteria. Moreover, antibiotics showed non-significant effects on nitrogen transformation processes. It is speculated that denitrifying bacteria harboring ARGs played crucial roles in protecting nitrogen transformation from low-level antibiotics stress in the reservoir. Our results highlight that denitrifying bacteria are important hosts of ARGs, which provides a novel perspective for evaluating the effects of antibiotics on nitrogen cycle in natural aquatic ecosystems.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149119DOI Listing
July 2021

Inhalable nanocatchers for SARS-CoV-2 inhibition.

Proc Natl Acad Sci U S A 2021 07 2;118(29). Epub 2021 Jul 2.

Institute of Functional Nano and Soft Materials, Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou 215123, China;

The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2), presents an urgent health crisis. More recently, an increasing number of mutated strains of SARS-CoV-2 have been identified globally. Such mutations, especially those on the spike glycoprotein to render its higher binding affinity to human angiotensin-converting enzyme II (hACE2) receptors, not only resulted in higher transmission of SARS-CoV-2 but also raised serious concerns regarding the efficacies of vaccines against mutated viruses. Since ACE2 is the virus-binding protein on human cells regardless of viral mutations, we design hACE2-containing nanocatchers (NCs) as the competitor with host cells for virus binding to protect cells from SARS-CoV-2 infection. The hACE2-containing NCs, derived from the cellular membrane of genetically engineered cells stably expressing hACE2, exhibited excellent neutralization ability against pseudoviruses of both wild-type SARS-CoV-2 and the D614G variant. To prevent SARS-CoV-2 infections in the lung, the most vulnerable organ for COVID-19, we develop an inhalable formulation by mixing hACE2-containing NCs with mucoadhesive excipient hyaluronic acid, the latter of which could significantly prolong the retention of NCs in the lung after inhalation. Excitingly, inhalation of our formulation could lead to potent pseudovirus inhibition ability in hACE2-expressing mouse model, without imposing any appreciable side effects. Importantly, our inhalable hACE2-containing NCs in the lyophilized formulation would allow long-term storage, facilitating their future clinical use. Thus, this work may provide an alternative tactic to inhibit SARS-CoV-2 infections even with different mutations, exhibiting great potential for treatment of the ongoing COVID-19 epidemic.
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http://dx.doi.org/10.1073/pnas.2102957118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307760PMC
July 2021

A Bioequivalence Study of Avanafil in Healthy Chinese Male Subjects Under Fasting and Fed Conditions: Results of a Randomized, Open-Label, Single-Dose, 2-Sequence, 2-Period Crossover Study.

Clin Pharmacol Drug Dev 2021 Jul 19. Epub 2021 Jul 19.

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

This bioequivalence study was conducted to determine the pharmacokinetics and safety profiles of an originator and a generic avanafil formulation in Chinese male subjects under fed and fasting conditions. Each eligible subject was initially randomly given avanafil (200 mg) in a test-reference or reference-test order, before being switched to another study drug sequence after 7 drug-free days. The bioequivalence of test and reference avanafil were determined if the 90%CIs of the geometric mean ratio (GMR) for the area under plasma concentration-time curve (AUC) from time 0 to infinity (AUC ), AUC from time 0 to the last detectable concentration (AUC ), and the maximum plasma concentration (C ) fell within the range 80%-125%. Under fasting/fed conditions, the 90%CIs of GMR for AUC , AUC , and C were 98.9% to 109.5%/96.0% to 101.2%, 99.6% to 110.3%/96.6% to 102.4%, and 99.3% to 116.8%/94.3% to 106.7%, respectively, which were all within the 80%-125% range. Adverse events (AEs) occurred in 20.8% of subjects under fasting conditions and 20.7% of subjects under fed conditions, with a severity of grade 1. No significant difference was found in the rate of occurrence of AEs and drug-related AEs in the test and reference-avanafil groups (all P > .05). We concluded that the test and reference avanafil were bioequivalent in healthy Chinese male subjects under fasting and fed conditions.
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http://dx.doi.org/10.1002/cpdd.998DOI Listing
July 2021

Evaluation of flavor characteristics of bacon smoked with different woodchips by HS-SPME-GC-MS combined with an electronic tongue and electronic nose.

Meat Sci 2021 Jul 14;182:108626. Epub 2021 Jul 14.

College of Food Science, Northeast Agricultural University, Harbin, Heilongjiang 150030, China. Electronic address:

This study investigated the effects of different woodchip types (beech, oak, pear, and apple) on the volatile compounds and sensory characteristics of smoked bacon. The volatile compounds were influenced by woodchip types and the total content of ketones and phenols in pear-smoked bacon were higher than in bacon smoked with other woodchips (P < 0.05). The E-tongue combined with E-nose can effectively distinguish the difference in the flavor of bacon smoked with different woodchip types by the signal intensities. Sensory analysis showed that smoking increased bacon's redness, saltiness, and smoky flavor compared with the control (unsmoked bacon) (P < 0.05) and it had little impact on off-odor (P > 0.05). Correlation analysis showed that the E-nose and E-tongue data were highly correlated with contents of alcohols, aldehydes, and ketones. This study revealed that the different smoked materials greatly influenced the flavor and sensory properties of bacon.
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http://dx.doi.org/10.1016/j.meatsci.2021.108626DOI Listing
July 2021

Report of the Largest Chinese Cohort With Gene Defect and Literature Review.

Front Genet 2021 1;12:683255. Epub 2021 Jul 1.

Department of Neurology, National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, China.

Thiamine metabolism dysfunction syndrome 2 (THMD2) is a rare metabolic disorder caused by mutations, inherited in autosomal recessive pattern. As a treatable disease, early diagnosis and therapy with vitamin supplementation is important to improve the prognosis. So far, the reported cases were mainly from Saudi Arab regions, and presented with relatively simple clinical course because of the hot spot mutation (T422A). Rare Chinese cases were described until now. In this study, we investigated 18 Chinese THMD2 patients with variable phenotypes, and identified 23 novel mutations, which expanded the genetic and clinical spectrum of the disorder. Meanwhile, we reviewed all 146 reported patients from different countries. Approximately 2/3 of patients presented with classical BTBGD, while 1/3 of patients manifested as much earlier onset and poor prognosis, including infantile Leigh-like syndrome, infantile spasms, neonatal lactic acidosis and infantile BTBGD. Literature review showed that elevated lactate in blood and CSF, as well as abnormal OXPHOS activities of muscle or skin usually correlated with infantile phenotypes, which indicated poor outcome. Brainstem involvement on MRI was more common in deceased cases. Thiamine supplementation is indispensable in the treatment of THMD2, whereas combination of biotin and thiamine is not superior to thiamine alone. But biotin supplementation does work in some patients. Genotypic-phenotypic correlation remains unclear which needs further investigation, and biallelic truncated mutations usually led to more severe phenotype.
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http://dx.doi.org/10.3389/fgene.2021.683255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281341PMC
July 2021

A New Fitness Test of Estimating VO in Well-Trained Rowing Athletes.

Front Physiol 2021 2;12:701541. Epub 2021 Jul 2.

School of Sports Science, Wenzhou Medical University, Wenzhou, China.

Background: This study was designed to investigate the validity of maximal oxygen consumption (VO) estimation through the Firstbeat fitness test (FFT) method when using submaximal rowing and running programs for well-trained athletes.

Methods: Well-trained flatwater rowers ( = 45, 19.8 ± 3.0 years, 184 ± 8.7 cm, 76 ± 12.9 kg, and 58.7 ± 6.0 mL⋅kg⋅min) and paddlers ( = 45, 19.0 ± 2.5 years, 180 ± 7.7 cm, 74 ± 9.4 kg, and 59.9 ± 4.8 mL⋅kg⋅min) completed the FFT and maximal graded exercise test (GXT) programs of rowing and running, respectively. The estimated VO was calculated using the FFT system, and the measured VO was obtained from the GXT programs. Differences between the estimated and measured VO values were analyzed to assess the accuracy and agreement of the predictions. Equations from the previous study were also used to predict the VO in the submaximal programs to compare the accuracy of prediction with the FFT method.

Results: The FFT method was in good agreement with the measured VO in both groups based on the intraclass correlation coefficients (>0.8). Additionally, the FFT method had considerable accuracy in VO estimation as the mean absolute percentage error (≤5.0%) and mean absolute error (<3.0 mL⋅kg⋅min) were fairly low. Furthermore, the FFT method seemed more accurate in the estimation of VO than previously reported equations, especially in the rowing test program.

Conclusion: This study revealed that the FFT method provides a considerably accurate estimation of VO in well-trained athletes.
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http://dx.doi.org/10.3389/fphys.2021.701541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283806PMC
July 2021

Epigenetic Regulation of Hepatic Stellate Cell Activation and Macrophage in Chronic Liver Inflammation.

Front Physiol 2021 1;12:683526. Epub 2021 Jul 1.

Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, China.

Chronic liver inflammation is a complex pathological process under different stress conditions, and the roles of stellate cells and macrophages in chronic liver inflammation have been widely reported. Moderate liver inflammation can protect the liver from damage and facilitate the recovery of liver injury. However, an inflammatory response that is too intense can result in massive death of hepatocytes, which leads to irreversible damage to the liver parenchyma. Epigenetic regulation plays a key part in liver inflammation. This study reviews the regulation of epigenetics on stellate cells and macrophages to explore the new mechanisms of epigenetics on liver inflammation and provide new ideas for the treatment of liver disease.
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http://dx.doi.org/10.3389/fphys.2021.683526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281248PMC
July 2021

Clinical characteristics of optic neuritis phenotypes in a 3-year follow-up Chinese cohort.

Sci Rep 2021 Jul 16;11(1):14603. Epub 2021 Jul 16.

Department of Ophthalmology, Eye Ear Nose and Throat Hospital of Fudan University, 83 Fenyang Road, Shanghai, 200031, China.

To evaluate the clinical characteristics of optic neuritis (ON) with different phenotypes. This prospective study recruited patients with new-onset ON between January 2015 and March 2017 who were followed-up for 3 years. They were divided into the myelin oligodendrocyte glycoprotein-seropositive (MOG-ON), aquaporin-4-seropositive (AQP4-ON), and double-seronegative (seronegative-ON) groups, and their clinical characteristics and imaging findings were evaluated and compared. Two-hundred-eighty patients (405 eyes) were included (MOG-ON: n = 57, 20.4%; AQP4-ON: n = 98, 35.0%; seronegative-ON: n = 125, 44.6%). The proportion of eyes with best-corrected visual acuity > 20/25 at the 3-year follow-up was similar between the MOG-ON and seronegative-ON groups; the proportion in both groups was higher than that in the AQP4-ON group (p < 0.001). Relapse rates were higher in the MOG-ON and AQP4-ON groups than in the seronegative-ON group (p < 0.001). Average retinal nerve fiber layer (RNFL) thickness at 3 years was similar between the MOG-ON and AQP4-ON groups (63.41 ± 13.39 and 59.40 ± 11.46 μm, p = 0.476) but both were thinner than the seronegative-ON group (74.06 ± 11.14 μm, p < 0.001). Macular ganglion cell-inner plexiform layer (GCIPL) revealed the same pattern. Despite RNFL and GCIPL thinning, the MOG-ON group's outcome was as favorable as that of the seronegative-ON group, whereas the AQP4-ON group showed unsatisfactory results.
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http://dx.doi.org/10.1038/s41598-021-93976-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285465PMC
July 2021

USP29-mediated HIF1α stabilization is associated with Sorafenib resistance of hepatocellular carcinoma cells by upregulating glycolysis.

Oncogenesis 2021 Jul 16;10(7):52. Epub 2021 Jul 16.

Department of Biomedicine, University of Basel, Basel, Switzerland.

Understanding the mechanisms underlying evasive resistance in cancer is an unmet medical need to improve the efficacy of current therapies. In hepatocellular carcinoma (HCC), aberrant expression of hypoxia-inducible factor 1 α (HIF1α) and increased aerobic glycolysis metabolism are drivers of resistance to therapy with the multi-kinase inhibitor Sorafenib. However, it has remained unknown how HIF1α is activated and how its activity and the subsequent induction of aerobic glycolysis promote Sorafenib resistance in HCC. Here, we report the ubiquitin-specific peptidase USP29 as a new regulator of HIF1α and of aerobic glycolysis during the development of Sorafenib resistance in HCC. In particular, we identified USP29 as a critical deubiquitylase (DUB) of HIF1α, which directly deubiquitylates and stabilizes HIF1α and, thus, promotes its transcriptional activity. Among the transcriptional targets of HIF1α is the gene encoding hexokinase 2 (HK2), a key enzyme of the glycolytic pathway. The absence of USP29, and thus of HIF1α transcriptional activity, reduces the levels of aerobic glycolysis and restores sensitivity to Sorafenib in Sorafenib-resistant HCC cells in vitro and in xenograft transplantation mouse models in vivo. Notably, the absence of USP29 and high HK2 expression levels correlate with the response of HCC patients to Sorafenib therapy. Together, the data demonstrate that, as a DUB of HIF1α, USP29 promotes Sorafenib resistance in HCC cells, in parts by upregulating glycolysis, thereby opening new avenues for therapeutically targeting Sorafenib-resistant HCC in patients.
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http://dx.doi.org/10.1038/s41389-021-00338-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285469PMC
July 2021

Spatially Controlled Preparation of Layered Metallic-Semiconducting Metal Chalcogenide Heterostructures.

ACS Nano 2021 Jul 16. Epub 2021 Jul 16.

Frontiers Science Center for Flexible Electronics, Xi'an Institute of Flexible Electronics (IFE) and Xi'an Institute of Biomedical Materials & Engineering, Northwestern Polytechnical University, 127 West Youyi Road, Xi'an 710072, China.

Spatially controlled preparation of heterostructures composed of layered materials is important in achieving interesting properties. Although vapor-phased deposition methods can prepare vertical and lateral heterostructures, liquid-phased methods, which can enable scalable production and further solution processes, have shown limited controllability. Herein, we demonstrate by using wet chemical methods that metallic SnMoS nanosheets can be deposited epitaxially on the edges of semiconducting SnS nanoplates to form SnS/SnMoS lateral heterostructures or coated on both the edges and basal surfaces of SnS to give [email protected] [email protected] heterostructures. They also showed good light-to-heat conversion ability due to the metallic property of SnMoS. In particular, the [email protected] heterostructure showed a higher photothermal conversion efficiency than the lateral counterpart, largely due to its randomly oriented and polycrystalline SnMoS layers with larger interfacing area for multiple internal light scattering.
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http://dx.doi.org/10.1021/acsnano.1c03688DOI Listing
July 2021

A Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TPN171H, a Novel Phosphodiesterase Type 5 Inhibitor, in Healthy Subjects.

Drug Des Devel Ther 2021 6;15:2947-2959. Epub 2021 Jul 6.

Central Laboratory, Shanghai Xuhui Central Hospital, Shanghai, 200031, People's Republic of China.

Purpose: TPN171H is a novel, potent and selective phosphodiesterase type 5 (PDE5) inhibitor for the treatment of pulmonary arterial hypertension (PAH). The objective of this study was to evaluate the safety, tolerability, and pharmacokinetics of TPN171H in healthy subjects after single and multiple dosing, in addition, to investigate the food effect on pharmacokinetics and safety of TPN171H.

Methods: The entire study was comprised of three parts: Part I (single ascending-dose study), Part II (food effect study), and Part III (multiple ascending-dose study). A total of 63 healthy subjects were enrolled in the study. TPN171H tablet or placebo was administered per protocol requirements. Blood samples were collected at the designated time points for pharmacokinetic analysis. Safety was assessed by clinical examinations and adverse events.

Results: In Part I, AUC and C were proved to be linear within the 5-30 mg dose range. T of TPN171H was 8.02-10.88 h. In Part II, we figured out that TPN171H administration under fed condition could decrease C, prolong T, but had no effect on AUC. In Part III, the accumulation ratio at steady-state for AUC and C indicated that TPN171H has a slight accumulation upon repeated dosing. Subjects were generally tolerable after TPN171H administration. Compared with other PDE5 inhibitors, TPN171H was found to have no impact on blood pressure and color discrimination.

Conclusion: TPN171H was safe and generally tolerated in healthy subjects. Based on the half-life, food effect, and safety profile of TPN171H, we recommend a once-daily, post-meal administration of TPN171H in subsequent clinical studies in healthy subjects and patients with PAH.
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http://dx.doi.org/10.2147/DDDT.S308610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273902PMC
July 2021

Interaction between antibiotic use and MS4A2 gene polymorphism on childhood eczema: a prospective birth cohort study.

BMC Pediatr 2021 Jul 14;21(1):314. Epub 2021 Jul 14.

Department of Pediatric Pulmonology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China.

Background: Eczema is usually the first allergic manifestation to appear in life attributed to gene-environment interactions. IL13, IL4, MS4A2 and ILR4A are four key inflammatory genes associated with atopy. This study aimed to explore gene-environment interactions on eczema in early life among the above four genes and environmental factors in Chinese Han children.

Methods: Five hundred ninety-seven children from a birth cohort who completed two-year follow-up were enrolled and their cord blood was collected. Subjects were genotyped for six polymorphisms in the aforementioned four genes. The children were followed at 6, 12 and 24 months, with epidemiologic information and medical history of eczema collected by questionnaire and eczema assessed by dermatologists.

Results: Among the 597 children, 168 were diagnosed with eczema and the others were not after 2 years of follow-up. MS4A2 rs569108 GG genotype (P = 1.68E-02, odds ratio (OR) = 4.66) and antibiotic use (P = 3.75E-4, OR = 2.02) were found independently associated with development of childhood eczema. Children with both antibiotic use and MS4A2 rs569108 GG genotype were more likely to develop eczema than those with only antibiotic use or GG homozygote (OR = 6.24 VS. 2.04 or 4.68).

Conclusions: MS4A2 rs569108 polymorphism and antibiotic use were solely associated with eczema, and they interacted with each other to increase the risk of developing the disease in Chinese Han toddlers. Long-term follow-up along with functional and replication studies are still needed.
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http://dx.doi.org/10.1186/s12887-021-02786-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278718PMC
July 2021

Gene-gene and gene-environment interactions on cord blood total IgE in Chinese Han children.

Allergy Asthma Clin Immunol 2021 Jul 9;17(1):69. Epub 2021 Jul 9.

Department of Pediatric Pulmonology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China.

Background: IL13, IL4, IL4RA, FCER1B and ADRB2 are susceptible genes of asthma and atopy. Our previous study has found gene-gene interactions on asthma between these genes in Chinese Han children. Whether the interactions begin in fetal stage, and whether these genes interact with prenatal environment to enhance cord blood IgE (CBIgE) levels and then cause subsequent allergic diseases have yet to be determined. This study aimed to determine whether there are gene-gene and gene-environment interactions on CBIgE elevation among the aforementioned five genes and prenatal environmental factors in Chinese Han population.

Methods: 989 cord blood samples from a Chinese birth cohort were genotyped for nine single-nucleotide polymorphisms (SNPs) in the five genes, and measured for CBIgE levels. Prenatal environmental factors were collected using a questionnaire. Gene-gene and gene-environment interactions were analyzed with generalized multifactor dimensionality methods.

Results: A four-way gene-gene interaction model (IL13 rs20541, IL13 rs1800925, IL4 rs2243250 and ADRB2 rs1042713) was regarded as the optimal one for CBIgE elevation (testing balanced accuracy = 0.5805, P = 9.03 × 10). Among the four SNPs, only IL13 rs20541 was identified to have an independent effect on elevated CBIgE (odds ratio (OR) = 1.36, P = 3.57 × 10), while the other three had small but synergistic effects. Carriers of IL13 rs20541 TT, IL13 rs1800925 CT/TT, IL4 rs2243250 TT and ADRB2 rs1042713 AA were estimated to be at more than fourfold higher risk for CBIgE elevation (OR = 4.14, P = 2.69 × 10). Gene-environment interaction on elevated CBIgE was found between IL4 rs2243250 and maternal atopy (OR = 1.41, P = 2.65 × 10).

Conclusions: Gene-gene interaction between IL13 rs20541, IL13 rs1800925, IL4 rs2243250 and ADRB2 rs1042713, and gene-environment interaction between IL4 rs2243250 and maternal atopy begin in prenatal stage to augment IgE production in Chinese Han children.
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http://dx.doi.org/10.1186/s13223-021-00571-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268446PMC
July 2021

AOPPs induce HTR-8/SVneo cell apoptosis by downregulating the Nrf-2/ARE/HO-1 anti-oxidative pathway: Potential implications for preeclampsia.

Placenta 2021 Jun 17;112:1-8. Epub 2021 Jun 17.

Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address:

Introduction: Advanced oxidation protein products (AOPPs), which are novel markers of oxidant-mediated protein damage, are prevalent in numerous diseases. We previously demonstrated that AOPPs act as a new class of pathogenic mediators in preeclampsia by causing trophoblast damage and dysfunction. Herein, we explored whether AOPPs could regulate the Nrf-2/ARE/HO-1 anti-oxidative pathway to facilitate the progression of preeclampsia.

Methods: To investigate the pathophysiology of preeclampsia, we evaluated the effects of AOPPs on trophoblast damage, apoptotic proteins, and Nrf-2/ARE/HO-1 anti-oxidative pathway expression, as well as their underlying mechanisms.

Results: AOPPs directly increased the expression of apoptotic proteins and significantly inhibited the expression of Nrf-2/ARE/HO-1 pathway in trophoblasts. Nrf-2 silencing aggravated the AOPPs-induced cell apoptosis in vitro by activating p53 and caspase cascade, whereas Nrf-2 overexpression had the opposite effect. Moreover, Nrf-2 exerted cytoprotective effects by increasing HO-1.

Discussion: These findings suggest that AOPPs induce trophoblast apoptosis by triggering p53 and caspase activation via inhibition of the Nrf-2/ARE/HO-1 anti-oxidative pathway. Hence, Nrf-2/ARE/HO-1 pathway activation plays a protective role in AOPPs-induced cell apoptosis; thus, holding potential as a therapeutic target against preeclampsia.
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http://dx.doi.org/10.1016/j.placenta.2021.06.008DOI Listing
June 2021

Cyclic Amplification of the Afterglow Luminescent Nanoreporter Enables to Predict Anti-cancer Efficiency.

Angew Chem Int Ed Engl 2021 Jul 7. Epub 2021 Jul 7.

Hunan University, College of Chemistry and Chemical Engineering, Hunan University, 410082, Changsha, CHINA.

Immunogenic cell death (ICD)-associated immunogenicity evoked through reactive oxygen species (ROS) is an efficient way to fight against the immune-dysfunctional microenvironment, so as to provoke potent anti-tumor immunity. However, the unknown ROS dose during cancer therapies may induce adverse immune responses (e.g., insufficient ICD, toxicity toward normal tissues or immune system). Herein, we developed a novel cyclic amplification method for an organic afterglow nanoreporter for the real-time visualization of self-generated ROS. First, we promoted semiconducting polymer nanoparticles (PFODBT) as a novel candidate for emitting near-infrared afterglow luminescence. Second, the introduction of a chemiluminescent substrate (CPPO) into PFODBT ([email protected]) resulted in a significant enhancement of afterglow intensity through the dual cyclic amplification pathway involving singlet oxygen ( 1 O 2 ). Third, 1 O 2 produced by [email protected] induced cancer cell necrosis and promoted the release of damage-related molecular patterns, thereby evoking ICD-associated immune responses through ROS-based oxidative stress. Notably, the afterglow luminescent signals of the nanoreporter were well correlated with light-driven 1 O 2 generation and anti-cancer efficiency, respectively. Overall, our imaging strategy provided a non-invasive tool for predicting the degree of ICD that occurs during ROS-mediated cancer therapy, which may contribute to precise immunotherapy.
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http://dx.doi.org/10.1002/anie.202104127DOI Listing
July 2021

Pretreatment intranetwork connectivity can predict the outcomes in idiopathic tinnitus patients treated with sound therapy.

Hum Brain Mapp 2021 Jul 7. Epub 2021 Jul 7.

Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

Previous studies demonstrated that brain morphological differences and distinct patterns of neural activation exist in tinnitus patients with different prognoses after sound therapy. This study aimed to explore possible differences in intrinsic network-level functional connectivity (FC) in patients with different outcomes after sound therapy (narrow band noise). We examined intrinsic FC using resting-state functional magnetic resonance imaging in 78 idiopathic tinnitus patients (including 35 effectively treated and 43 ineffectively treated) and 52 healthy controls (HCs) via independent component analysis. We also investigated the associations between the differences in FC and clinical variables. Analyses revealed significantly altered intranetwork connectivity in the auditory network (AUN) and some nonauditory-related networks in the EG/IG patients compared to HCs; compared with EG patients, IG patients showed decreased intranetwork connectivity in the anterior default mode network (aDMN) and AUN. Meanwhile, robust differences were also evident in internetwork connectivity between some nonauditory-related networks (salience network and executive control network; posterior default mode network and dorsal attention network) in the EG relative to IG patients. We combined intranetwork connectivity in the aDMN and AUN as an imaging indicator to evaluate patient outcomes and screen patients before treatment; this approach reached a sensitivity of 94.3% and a specificity of 76.7%. Our study suggests that tinnitus patients with different outcomes show distinct network-level functional reorganization patterns. Intranetwork connectivity in the aDMN and AUN may be indicators that can be used to predict prognoses in patients with idiopathic tinnitus and screen patients before sound therapy.
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http://dx.doi.org/10.1002/hbm.25584DOI Listing
July 2021

High hydrostatic pressure combined with moisture regulators improves the tenderness and quality of beef jerky.

Meat Sci 2021 Nov 30;181:108617. Epub 2021 Jun 30.

College of Food Science, Northeast Agricultural University, Harbin, Heilongjiang 150030, China. Electronic address:

The influence of high hydrostatic pressure (HHP) at different pressure levels (0.1, 100, 200, and 300 MPa) combined with moisture regulators (MR) on the tenderness, water content, and quality of beef jerky was investigated. HHP treatment reduced the shear force (SF) of beef jerky (P < 0.05). The beef jerky treated with MR+HHP exhibited higher tenderness than the beef jerky treated only with HHP (P < 0.05). The MR+HHP samples had significantly higher moisture content than the HHP samples (P > 0.05) when the water activity was maintained at approximately 0.7. MR+HHP contributed to a shorter T value and a higher P value, which indicated an improvement in the water-binding ability of the beef muscle. Analysis of the microstructure showed that MR+HHP led to the fracture of the Z-line and destruction of the sarcomere structure. Sensory analysis showed that MR+HHP-200 samples had significantly higher tenderness and overall acceptable scores than other samples (P < 0.05).
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http://dx.doi.org/10.1016/j.meatsci.2021.108617DOI Listing
November 2021

Ni(OH) Templated Synthesis of Ultrathin Ni S Nanosheets as Bifunctional Electrocatalyst for Overall Water Splitting.

Small 2021 Jul 6:e2102097. Epub 2021 Jul 6.

School of Materials Science and Engineering, Beihang University, Beijing, 100191, P. R. China.

Ultrathin nickel (Ni)-based sulfide nanosheets have been reported as excellent electrocatalysts for overall water splitting; however, the uncontrollability over thickness due to the nonlayered structure still hampers its practical application. Herein, a simple topochemical conversion strategy is employed to synthesize cobalt-doped Ni S (Co-Ni S ) ultrathin nanosheets on Ni foam. The Co-Ni S nanosheets are controlled synthesized by using Co-Ni(OH) ultrathin nanosheets as templates with anneal and sulfurization treatment, showing exceptional electrocatalytic activity. This template-assisted method can also be applied to obtain Ni, NiO, and NiP nanosheets, providing a universal strategy to synthesize ultrathin nanosheets of nonlayered materials. The overall water splitting of this Co-Ni S ultrathin nanosheets achieves a low voltage of 1.54 V at a current density of 10 mA cm and high durability in 1 m KOH, comparable to the best performance of electrochemical water splitting ever reported. The detailed structural transformation of Ni-based sulfides in the catalytic process and its mechanism are further explored both experimentally and theoretically.
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http://dx.doi.org/10.1002/smll.202102097DOI Listing
July 2021

The hemodynamic effect through a novel endoscopic intervention in management of varices and hypersplenism (with video).

Gastrointest Endosc 2021 Jul 2. Epub 2021 Jul 2.

The Division of Gastroenterology, Department of Internal Medicine at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST, Wuhan, 430030, China; Hubei key Laboratory of Hepato-Pancreato-Biliary Disease, Wuhan, 430030, China. Electronic address:

Background And Aims: We previously reported a new and combined EUS-guided intervention in a patient with portal hypertension, consisting of obliteration of varices and partial splenic embolization (PSE). Performing PSE is known to diminish the increase in portal venous pressure after endoscopic intervention for varices. The aim of this study was to use multidetector computer tomography portal venography (MDCTPV) to evaluate the anatomy of esophagogastric varices (EGV) and the impact on hemodynamics of portosystemic collaterals shortly after the concomitant procedures.

Methods: From October 2019 to December 2020, 5 patients with cirrhosis and with clinically significant portal hypertension who had variceal bleeding history and hypersplenism were treated with combined endoscopic obliteration for varices and EUS-guided PSE. MDCTPV was applied to assess the anatomical drainage patterns of the esophagogastric varices, the diameters of feeders and drainage vessels, and splenic embolization rate, respectively.

Results: Within 5 days after concomitant endoscopic interventions, we observed the decrease of mean diameters for left gastric vein (LGV), short gastric vein (SGV), and azygos vein (AZV) as 0.3 mm, 1.0 mm, and 5.2 mm compared with 3.11 mm, 7.1 mm, and 5.4 mm before the procedures. Patients showed increase for both white blood cells (mean count, 2.7X10/L before vs 5.8X10/L after), and platelet counts (mean count, 52.8X10/L before vs 95.8X10/L after). The mean splenic embolization rate was 64.5% (range 28.8% to 84.6%).

Conclusions: Our experience may illustrate an alternative technique of combining EUS-guided PSE with endoscopic therapy of varices to treat patients with portal hypertension.
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http://dx.doi.org/10.1016/j.gie.2021.06.029DOI Listing
July 2021

Identification of Cross-Reactive CD8 T Cell Receptors with High Functional Avidity to a SARS-CoV-2 Immunodominant Epitope and Its Natural Mutant Variants.

Genes Dis 2021 Jun 29. Epub 2021 Jun 29.

Department of Immunology, College of Basic Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, PR China.

Despite the growing knowledge of T cell responses in COVID-19 patients, there is a lack of detailed characterizations for T cell-antigen interactions and T cell functions. Here, with a predicted peptide library from SARS-CoV-2 S and N proteins, restricted to three of the most prominent HLA-A alleles in the Asian population, we found that specific CD8 T cell responses were identified in over 75% of COVID-19 convalescent patients (15/20). A total of 15 SARS-CoV-2 epitopes from the S and N proteins were identified, and among them, 3 dominant epitopes were further characterized. We found that an epitope from the N protein, N (KTFPPTEPK), was the most dominant epitope from our selected peptide library. Importantly, we discovered 2 N-specific T cell receptors (TCRs) with high functional avidity that were independent of the CD8 co-receptor. These TCRs exhibited complementary cross-reactivity to several presently reported N mutant variants, as to the wild-type epitope. Further, the natural functions of these TCRs in the cytotoxic immunity against SARS-CoV-2 were determined with dendritic cells (DCs) and the lung organoid model. We found that the N epitope could be normally processed and endogenously presented by these different types of antigen presenting cells, to elicit successful activation and effective cytotoxicity of CD8 T cells . Our study evidenced potential mechanisms of cellular immunity to SARS-CoV-2, and illuminated potential ways of viral clearance in COVID-19 patients. These results indicate that utilizing CD8-independent TCRs against SARS-CoV-2-associated antigens may provide functional superiority that is beneficial for the adoptive cell immunotherapies based on natural or genetically engineered T cells. Additionally, this information is highly relevant for the development of the next-generation vaccines with protections against continuously emerged SARS-CoV-2 mutant strains.
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http://dx.doi.org/10.1016/j.gendis.2021.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240504PMC
June 2021

bacteremia in a centenarian and pathogen traceability: A case report.

World J Clin Cases 2021 Jun;9(18):4873-4880

Department of Geriatric Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.

Background: Early diagnosis and appropriate antibiotic treatment are important to survival of () bacteremia. Penicillin tends to be the most commonly used antibiotic. However, there are limited data on antibiotic use in elderly patients with serious complications. We describe the clinical presentation, antibiotic therapy, and traceability of in a centenarian with a history of eating frozen food.

Case Summary: A 102-year-old man suffered from high fever with chill after hematochezia. Tentative diagnoses were lower gastrointestinal hemorrhage and localized peritonitis. Meropenem and ornidazole were the empirical therapy. The patient did not respond and developed multiple system dysfunction even after teicoplanin was added to the therapy. was identified from blood cultures on day 5 of admission. The patient had a history of consuming frozen dumplings. Meropenem/ornidazole/teicoplanin were replaced with meropenem/linezolid. The patient gradually became afebrile. He received meropenem/linezolid for 10 d, and piperacillin/tazobactam was applied as step-down treatment for 2 wk with good clinical results. There was no sign of relapse during follow-up after discharge. isolates from the patient and frozen dumplings belonged to different serotypes and sequence types (STs): 1/2b and ST5 from the patient and 1/2c and ST9 from the dumplings.

Conclusion: More awareness of listeriosis should be raised. Linezolid might be an option for listeriosis in elderly people with serious complications.
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http://dx.doi.org/10.12998/wjcc.v9.i18.4873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223858PMC
June 2021

Understanding the Pathophysiology of Exosomes in Schistosomiasis: A New Direction for Disease Control and Prevention.

Front Immunol 2021 16;12:634138. Epub 2021 Jun 16.

Division of Gastroenterology, Department of Internal Medicine at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China.

Schistosomiasis is a parasitic disease endemic to freshwater areas of Southeast Asia, Africa, and South America that is capable of causing serious damage to the internal organs. Recent studies have linked exosomes to the progression of schistosomiasis. These structures are important mediators for intercellular communication, assist cells to exchange proteins, lipids, and genetic material and have been shown to play critical roles during host-parasite interactions. This review aims to discuss the pathophysiology of exosomes in schistosomiasis and their roles in regulating the host immune response. Understanding how exosomes are involved in the pathogenesis of schistosomiasis may provide new perspectives in diagnosing and treating this neglected disease.
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http://dx.doi.org/10.3389/fimmu.2021.634138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242937PMC
June 2021
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