Publications by authors named "Chao Hu"

328 Publications

Sedation Effects Produced by a Ciprofol Initial Infusion or Bolus Dose Followed by Continuous Maintenance Infusion in Healthy Subjects: A Phase 1 Trial.

Adv Ther 2021 Sep 24. Epub 2021 Sep 24.

Clinical Trials Center, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Wuhou District, Chengdu, 610041, China.

Introduction: The effects of continuous infusions of ciprofol on its pharmacodynamic and pharmacokinetic properties and safety profiles in healthy Chinese subjects were evaluated.

Methods: In this open-label, randomized, two-way cross-over study, subjects received initial doses of continuous ciprofol/propofol as an infusion for 30 min in part 1 (n = 8) and a bolus dose in part 2 (n = 8) followed by maintenance infusions for a total of 4 h in part 1 and 12 h in part 2. Each subject participated in both parts with a washout time of at least 40 h.

Results: The safety and tolerability parameters of ciprofol were similar to those of propofol, and all treatment-emergent adverse events were mild. The incidences of injection pain and respiratory depression in subjects given ciprofol were lower than those receiving propofol. The pharmacokinetic parameters C, t, t, λz and MRT for ciprofol and propofol were similar, while CL, V and V were statistically significantly different. Pharmacodynamic parameters including the Richmond Agitation Sedation Scale and bispectral index profiles of ciprofol were similar to those of propofol.

Conclusion: Ciprofol has potential for clinical application for continuous intravenous infusion to maintain sedation for 12 h with the same safety, tolerability and efficacy as propofol.
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http://dx.doi.org/10.1007/s12325-021-01914-4DOI Listing
September 2021

Genetic Prion Disease: Insight from the Features and Experience of China National Surveillance for Creutzfeldt-Jakob Disease.

Neurosci Bull 2021 Sep 6. Epub 2021 Sep 6.

State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China.

Human genetic prion diseases (gPrDs) are directly associated with mutations and insertions in the PRNP (Prion Protein) gene. We collected and analyzed the data of 218 Chinese gPrD patients identified between Jan 2006 and June 2020. Nineteen different subtypes were identified and gPrDs accounted for 10.9% of all diagnosed PrDs within the same period. Some subtypes of gPrDs showed a degree of geographic association. The age at onset of Chinese gPrDs peaked in the 50-59 year group. Gerstmann-Sträussler-Scheinker syndrome (GSS) and fatal familial insomnia (FFI) cases usually displayed clinical symptoms earlier than genetic Creutzfeldt-Jakob disease (gCJD) patients with point mutations. A family history was more frequently recalled in P105L GSS and D178N FFI patients than T188K and E200K patients. None of the E196A gCJD patients reported a family history. The gCJD cases with point mutations always developed clinical manifestations typical of sporadic CJD (sCJD). EEG examination was not sensitive for gPrDs. sCJD-associated abnormalities on MRI were found in high proportions of GSS and gCJD patients. CSF 14-3-3 positivity was frequently detected in gCJD patients. Increased CSF tau was found in more than half of FFI and T188K gCJD cases, and an even higher proportion of E196A and E200K gCJD patients. 63.6% of P105L GSS cases showed a positive reaction in cerebrospinal fluid RT-QuIC. GSS and FFI cases had longer durations than most subtypes of gCJD. This is one of the largest studies of gPrDs in East Asians, and the illness profile of Chinese gPrDs is clearly distinct. Extremely high proportions of T188K and E196A occur among Chinese gPrDs; these mutations are rarely reported in Caucasians and Japanese.
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http://dx.doi.org/10.1007/s12264-021-00764-yDOI Listing
September 2021

The Accuracy of Patient Specific Three-Dimensional Digital Ostectomy Template for Mandibular Angle Ostectomy.

Aesthet Surg J 2021 Sep 2. Epub 2021 Sep 2.

Department of Plastic Surgery, The Affiliated Friendship Plastic Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.

Background: Despite the three-dimensional (3D)-printed digital ostectomy template (DOT) helps surgeons perform mandibular angle ostectomy (MAO) more precisely and safely, the clinical application of DOT is problematic.

Objectives: The aim of this study was to evaluate the accuracy of DOT and improve the precision of MAO.

Methods: A total of 20 patients with a prominent mandibular angle (PMA) were allocated into two groups with 10 patients in each group. The conventional digital ostectomy template (CDOT), and the novel digital ostectomy template (NDOT) were applied to guide MAO in group A and B, respectively. The mean time taken for curved osteotomy and the volume of postoperative drainage on one side within 24 hours were recorded. The deviations between the simulated and postoperative lower border of the mandible were measured on both sides.

Results: All the patients were satisfied with the cosmetic outcomes. Statistical results showed that the mean time taken for curved osteotomy in group B was shorter than that of group A, and the volume of postoperative drainage on one side within 24 hours was similar between the two groups. The deviations at the anterior and posterior parts of the inferior border showed the accuracy of osteotomy in group B was higher than that in group A, and there was no significant difference between the two groups in the middle part.

Conclusions: The NDOT is easy to be located and fixed tightly, which reduced the operating time and increased the safety and precision of the procedures.
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http://dx.doi.org/10.1093/asj/sjab330DOI Listing
September 2021

Implementation and Performance Evaluation of a Bivariate Cut-HDMR Metamodel for Semiconductor Packaging Design Problems with a Large Number of Input Variables.

Materials (Basel) 2021 Aug 17;14(16). Epub 2021 Aug 17.

Department of Mechanical Engineering, Iowa State University, Ames, IA 50011, USA.

A metamodeling technique based on Bivariate Cut High Dimensional Model Representation (Bivariate Cut HDMR) is implemented for a semiconductor packaging design problem with 10 design variables. Bivariate Cut-HDMR constructs a metamodel by considering only up to second-order interactions. The implementation uses three uniformly distributed sample points ( = 3) with quadratic spline interpolation to construct the component functions of Bivariate Cut-HDMR, which can be used to make a direct comparison with a metamodel based on Central Composite Design (CCD). The performance of Bivariate Cut-HDMR is evaluated by two well-known error metrics: -squared and Relative Average Absolute Error (). The results are compared with the performance of CCD. Bivariate Cut HDMR does not compromise the accuracy compared to CCD, although the former uses only one-fifth of sample points (201 sample points) required by the latter (1045 sample points). The sampling schemes and the predictions of cut-planes and boundary-planes are discussed to explain possible reasons for the outstanding performance of Bivariate Cut HDMR.
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http://dx.doi.org/10.3390/ma14164619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400015PMC
August 2021

Nano-Zoo Interfacial Interaction as a Design Principle for Hybrid Soil Remediation Technology.

ACS Nano 2021 Aug 23. Epub 2021 Aug 23.

Zhejiang Provincial Key Laboratory of Organic Pollution Process and Control, Department of Environmental Science, Zhejiang University, Hangzhou 310058, China.

Using nanotechnology to remediate contaminated agricultural soil is promising but faces notable technical and economic challenges. Importantly, widely distributed soil invertebrates can potentially act as natural mobile facilitators for nanoscale remediation of contaminated soil. Herein, we have drawn inspiration from nano-bio interaction and established a hybrid remediation framework using nanoscale zerovalent iron (nZVI) and nematodes for organochlorine-contaminated soil. Approximately 80% pentachlorophenol (PCP, initially 50 mg/kg) was synergistically degraded by nZVI and nematodes within 3 days. Mechanistically, exposure to nZVI stimulated the synthesis of reductive biomolecules (including collagen, glutathione, and l-cysteine) which acted as a bioreductive barrier and significantly mitigated the toxicity of PCP. At the microinterface, collagen distributed in the epidermis chelated nZVI; subsequently, l-cysteine and glutathione strongly accelerated nZVI-induced PCP dechlorination by facilitating the reductive dissolution of nZVI oxide shell and electron transfer from Fe core to PCP. On the basis of the interfacial interaction, an optimized soil remediation approach composed of nZVI, nematodes, and l-cysteine was established, demonstrating a 2.1-fold increase in removal efficiency with only 48.5% nZVI consumption compared with the nZVI treatment alone. This work provides a heuristic model for developing cost-efficient remediation technologies with the synergistic force of functional materials and indigenous biota, which may be widely applicable to a range of environmental contamination scenarios.
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http://dx.doi.org/10.1021/acsnano.1c05180DOI Listing
August 2021

Tanshinone IIA Inhibits Osteosarcoma Growth through a Src Kinase-Dependent Mechanism.

Evid Based Complement Alternat Med 2021 30;2021:5563691. Epub 2021 Jun 30.

Department of Spine Surgery and Musculoskeletal Tumor, Zhongnan Hospital of Wuhan University, No. 169th, Donghu Road, Wuchang District, Wuhan 430071, Hubei, China.

Introduction: Osteosarcoma is a malignant tumor associated with high mortality rates due to the toxic side effects of current therapeutic methods. Tanshinone IIA can inhibit cell proliferation and promote apoptosis , but the exact mechanism is still unknown. The aims of this study are to explore the antiosteosarcoma effect of tanshinone IIA via Src kinase and demonstrate the mechanism of this effect.

Materials And Methods: Osteosarcoma MG-63 and U2-OS cell lines were stable transfections with Src-shRNA. Then, the antiosteosarcoma effect of tanshinone IIA was tested The protein expression levels of Src, p-Src, p-ERK1/2, and p-AKt were detected by Western blot and RT-PCR. CCK-8 assay and BrdU immunofluorescence assay were used to detect cell proliferation. Transwell assay, cell scratch assay, and flow cytometry were used to detect cell invasion, migration, and cell cycle. Tumor-bearing nude mice with osteosarcoma were constructed. The effect of tanshinone IIA was detected by tumor HE staining, tumor inhibition rate, incidence of lung metastasis, and X-ray.

Results: The oncogene role of Src kinase in osteosarcoma is reflected in promoting cell proliferation, invasion, and migration and in inhibiting apoptosis. However, Src has different effects on cell proliferation, apoptosis, and cell cycle regulation among cell lines. At a cellular level, the antiosteosarcoma effect of tanshinone IIA is mediated by Src downstream of the MAPK/ERK and PI3K/AKt signaling pathways. At the animal level, tanshinone IIA played a role in resisting osteosarcoma formation by Src downstream of the MAPK/ERK and PI3K/AKt signaling pathways.

Conclusion: Tanshinone IIA plays an antiosteosarcoma role and and inhibits the progression of osteosarcoma mediated by Src downstream of the MAPK/ERK and PI3K/AKt signaling pathways.
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http://dx.doi.org/10.1155/2021/5563691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376467PMC
June 2021

A non-RBM targeted RBD specific antibody neutralizes SARS-CoV-2 inducing S1 shedding.

Biochem Biophys Res Commun 2021 09 20;571:152-158. Epub 2021 Jul 20.

Department of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing, 400010, China; Chongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, Chongqing Medical University, Chongqing, 400010, China. Electronic address:

Potent neutralizing antibodies (Abs) have been proven with therapeutic efficacy for the intervention against SARS-CoV-2. Majority of these Abs function by directly interfering with the virus entry to host cells. Here, we identified a receptor binding domain (RBD) specific monoclonal Ab (mAb) 82A6 with efficient neutralizing potency against authentic SARS-CoV-2 virus. As most Abs targeting the non-receptor binding motif (RBM) region, 82A6 was incapable to block the RBD-ACE2 interaction. In particular, it actively promoted the S1 subunit shedding from the S protein, which may lead to effective reduction of intact SARS-CoV-2 viruses. Importantly, it could block potential syncytia formation associated with post-infectious cell surface expression of S proteins. Our study evidenced a RBD specific Ab with unique beneficial efficacy against SARS-CoV-2 infection, which might bring informative significance to understand the collective effects of neutralizing Abs elicited in COVID-19 patients.
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http://dx.doi.org/10.1016/j.bbrc.2021.07.062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289697PMC
September 2021

Psychological Responses of the Patients in Cabin Hospital to the COVID-19 Outbreak: A Comparative Epidemiologic Analysis.

Front Psychol 2021 12;12:641167. Epub 2021 Jul 12.

Department of Internal Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The building of cabin hospitals in Wuhan has been proven to be clinically successful in curing mild-symptom COVID-19 patients shortly after the outbreak of COVID-19 in late 2019. At the same time, the psychological effect of patients being treated in cabin hospitals and the features of the psychological status of the whole society remained ambiguous. This study adopted a self-administrated questionnaire to investigate the stress, depression, and anxiety status of patients in cabin hospitals ( = 212) and healthy participants outside of Hubei province ( = 221) in a population level from February 29 to March 01, 2020. The research measured participants' stress response, depression level, and anxiety level as well as their social support system and their resilience level. Results indicated that in this sudden outbreak of an unknown pandemic, all people (whether or not infected) showed a generally high level of stress, depression, and anxiety, regardless of age, gender, education level, and employment. It also showed that people with a lower level of psychological resilience and social support reported more severe symptoms of depression, anxiety, and stress. Moreover, the research also found a positive effect of cabin hospitals on the psychological recovery of COVID-19 patients. Stress response of patients increased after entering into cabin hospitals, while after 3-4 weeks' treatment, patients showed a decrease in their depression and anxiety levels. This research advances the understanding of COVID-19 and gives suggestions to optimize the design and the allocation of resources in cabin hospitals and better deal with the unknown pandemics in the future.
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http://dx.doi.org/10.3389/fpsyg.2021.641167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312570PMC
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

A MicroRNA Exerts Antitumor Effects Through Inhibition of Both Cell Migration and Angiogenesis by Targeting PGAM1.

Front Oncol 2021 16;11:652395. Epub 2021 Jun 16.

Institute for Infectious Diseases and Vaccine Development, Tongji University School of Medicine, Shanghai, China.

MicroRNA (miRNA) is an important regulator for gene expression. Recent studies showed that some heterogenous miRNAs derived from both parasite and plant can regulate expression of mammalian gene in a cross-species or even a cross-kingdom manner. Here, we identified a miRNA (designated as sja-miR-61) that is present in the hepatocyte of mice infected with the parasite. The sja-miR-61 mimics significantly inhibited the migration of both mouse and human hepatoma cells . In a xenograft animal model, significant reductions of the tumor volume and weight were observed in mice inoculated with hepatoma cells transfected with sja-miR-61 mimics compared to the controls. We found that the inhibition of tumor growth was through its anti-angiogenesis activity. Mechanically, we identified the phosphoglycerate mutase 1 () gene as a target of sja-miR-61 and found that the sja-miR-61-mediated suppression of cell migration and anti-angiogenesis by cross-species down-regulation of PGAM1 expression. These data indicated that sja-miR-61 is a tumor suppressor miRNA that may have therapeutic potential for human cancers.
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http://dx.doi.org/10.3389/fonc.2021.652395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242254PMC
June 2021

KCNN4-mediated Ca/MET/AKT axis is promising for targeted therapy of pancreatic ductal adenocarcinoma.

Acta Pharmacol Sin 2021 Jun 28. Epub 2021 Jun 28.

Sir Run Run Hospital, Nanjing Medical University, Nanjing, 211166, China.

As a member of the potassium calcium-activated channel subfamily, increasing evidence suggests that KCNN4 was associated with malignancies. However, the roles and regulatory mechanisms of KCNN4 in PDAC have been little explored. In this work, we demonstrated that the level of KCNN4 in PDAC was abnormally elevated, and the overexpression of KCNN4 was induced by transcription factor AP-1. KCNN4 was closely correlated with unfavorable clinicopathologic characteristics and poor survival. Functionally, we found that overexpression of KCNN4 promoted PDAC cell proliferation, migration and invasion. Conversely, the knockdown of KCNN4 attenuated the growth and motility of PDAC cells. In addition to these, knockdown of KCNN4 promoted PDAC cell apoptosis and led to cell cycle arrest in the S phase. In mechanistic investigations, RNA-sequence revealed that the MET-mediated AKT axis was essential for KCNN4, encouraging PDAC cell proliferation and migration. Collectively, these findings reveal a function of KCNN4 in PDAC and suggest it's an attractive therapeutic target and tumor marker. Our studies underscore a better understanding of the biological mechanism of KCNN4 in PDAC and suggest novel strategies for cancer therapy.
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http://dx.doi.org/10.1038/s41401-021-00688-3DOI Listing
June 2021

MAP4K1 functions as a tumor promotor and drug mediator for AML via modulation of DNA damage/repair system and MAPK pathway.

EBioMedicine 2021 Jul 21;69:103441. Epub 2021 Jun 21.

Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Hangzhou, Zhejiang, China; Zhejiang University Cancer Center, Hangzhou, Zhejiang, China. Electronic address:

Background: Acute myeloid leukemia (AML) is a group of heterogeneous hematologic malignancies correlates with poor prognosis. It is important to identify biomarkers for effective treatment of AML. Kinases participate in many regulatory pathways and biological activities in AML. Previous studies demonstrated that MAP4K1, a serine/threonine kinase, was associated with immune regulation and cancer progression. However, its role and mechanism in acute myeloid leukemia (AML) have not been explored.

Methods: RNA-seq profiling was performed for Homoharringtonine (HHT)-resistant and Homoharringtonine (HHT)-sensitive cell lines. Bioinformatic tools were used for differential analysis. Cell culture and transfection, Cell proliferation, apoptosis and Cell cycle assay, Quantitative RT-PCR, and Western blotting analysis were used to explore biological phenotypes in vitro.

Findings: We found that MAP4K1 was highly expressed in HHT-induced resistant AML cell lines. In addition, overexpression of MAP4K1 in AML cells induced resistance of AML cells against HHT. Not only that, the findings of this study showed that overexpression of MAP4K1 was an independent risk factor that predicts poor prognosis of AML. Further, In vitro studies showed that MAP4K1 modulated cell cycle through MAPK and DNA damage/repair pathways. Therefore, MAP4K1 is a potential target for developing therapies for AML.

Interpretation: This study demonstrates that MAP4K1 not only regulates HHT resistance but also independently predicts AML prognosis. In addition, understanding the regulatory mechanism of MAP4K1 reveals novel treatment strategies for resistant and refractory AML. Fundings: This work was supported by the National Natural Science Foundation of China (NSFC) (Grant No.81800199, 81670124, 82070118) and the Natural Science Foundation of Zhejiang Province (LY20H080008).
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http://dx.doi.org/10.1016/j.ebiom.2021.103441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239467PMC
July 2021

p38 inhibition enhances TCR-T cell function and antagonizes the immunosuppressive activity of TGF-β.

Int Immunopharmacol 2021 Sep 11;98:107848. Epub 2021 Jun 11.

Department of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, Chongqing Medical University, Chongqing 400016, China. Electronic address:

The efficacy of adoptive cell therapy (ACT) relies on the abilities of T cells in self-expansion, survival and the secretion of effector molecules. Here, we presented an optimized method to generate T cells with improved functions by supplementing the culture medium with p38 inhibitor and the combination of IL-7 and IL-15 or IL-2 alone. The addition of p38 inhibitor, Doramapimod or SB202190, to IL-7 and IL-15 culture largely increased the capacity of T cells in the proliferation with enrichment of the naïve-like subsets and expression of CD62L. Importantly, we found this regimen has generated complete T cell resistance to TGF-β-induced functional suppression, with sustained levels of the IFN-γ and Granzyme-B productions. Such findings were also validated in the melanoma-associated antigen recognized by T cells (MART-1) specific T cell receptor (TCR) engineered T cells, which were expanded in Doramapimod and IL-7 + IL-15 added media. In conclusion, we have established and optimized a protocol with the combination of p38 inhibitor, IL-7 and IL-15, rather than IL-2, for the generation of functionally enhanced T cells applicable for ACT.
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http://dx.doi.org/10.1016/j.intimp.2021.107848DOI Listing
September 2021

CD36 deficiency ameliorates drug-induced acute liver injury in mice.

Mol Med 2021 06 6;27(1):57. Epub 2021 Jun 6.

Department of Biotherapy, Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, China.

Background: Acetaminophen (APAP) overdose causes hepatotoxicity and even acute liver failure. Recent studies indicate that sterile inflammation and innate immune cells may play important roles in damage-induced hepatocytes regeneration and liver repair. The scavenger receptor CD36 has its crucial functions in sterile inflammation. However, the roles of CD36 in APAP induced acute liver injury remain unclear and warrant further investigation.

Methods: WT C57BL/6 J and CD36 mice were intraperitoneally injected with APAP (300 mg/kg) after fasting for 16 h. Liver injury was evaluated by serum alanine aminotransferase (ALT) level and liver tissue hematoxylin and eosin (H&E) staining. Liver inflammatory factor expression was determined by real-time polymerase chain reaction (PCR). The protein adducts forming from the metabolite of APAP and the metabolism enzyme cytochrome P450 2E1 (CYP2E1) levels were measured by Western blot. Liver infiltrating macrophages and neutrophils were characterized by flow cytometry. RNA sequencing and Western blot were used to evaluate the effect of damage-associated molecular patterns (DAMP) molecule high mobility group B1 (HMGB1) on WT and CD36 macrophages. Moreover, PP2, a Src kinase inhibitor, blocking CD36 signaling, was applied in APAP model.

Results: The expression of CD36 was increased in the liver of mice after APAP treatment. Compared with WT mice, APAP treated CD36 mice show less liver injury. There was no significant difference in APAP protein adducts and CYP2E1 expression between these two strains. However, reduced pro-inflammatory factor mRNA expression and serum IL-1β level were observed in APAP treated CD36 mice as well as infiltrating macrophages and neutrophils. Moreover, CD36 deficiency impaired the activation of c-Jun N-terminal kinase (JNK) caused by APAP. Interestingly, the lack of CD36 reduced the activation of extracellular regulated protein kinases (Erk) and v-akt murine thymoma viral oncogene homolog (Akt) induced by HMGB1. RNA transcription sequencing data indicated that HMGB1 has a different effect on WT and CD36 macrophages. Furthermore, treatment with PP2 attenuated APAP induced mouse liver injury.

Conclusion: Our data demonstrated that CD36 deficiency ameliorated APAP-induced acute liver injury and inflammatory responses by decreasing JNK activation. CD36 might serve as a new target to reduce acute liver injury.
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http://dx.doi.org/10.1186/s10020-021-00325-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182905PMC
June 2021

Au Nanoparticles Supported on Iron-Based Oxides for Soot Oxidation: Physicochemical Properties Before and After the Reaction.

ACS Omega 2021 May 26;6(17):11510-11518. Epub 2021 Apr 26.

Department of Thermal Science and Energy Engineering, University of Science and Technology of China, Jinzhai Road, Hefei 230026, People's Republic of China.

The catalytic performance of Au nanoparticles (NPs) supported on different transition-metal oxides for soot oxidation was studied in this paper. The changes in the morphology, phase structure, and physicochemical properties of Au-supported iron-based oxides before and after the reaction with soot particles were observed by high-resolution transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and temperature-programed reduction. It was found that the catalytic activity of FeO, FeO, CoO, and NiO for soot oxidation was significantly improved after loading Au NPs. Especially, under the action of Au/FeO and Au/FeO, the oxidation of soot was close to 20% below 420 °C, and their values were 73 and 50 °C, respectively. When Au/FeO and Au/FeO reacted with soot, the size of the catalysts increased, and the active oxygen and Fe 2p components decreased. Au promoted the reduction of iron ions to a lower temperature, which was beneficial to improving the oxidation performance of iron-based oxides.
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http://dx.doi.org/10.1021/acsomega.1c00619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154002PMC
May 2021

Cyclic Helix B Peptide Prolongs Skin Allograft Survival Inhibition of B Cell Immune Responses in a Murine Model.

Front Immunol 2021 12;12:682749. Epub 2021 May 12.

Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.

Antibody-mediated rejection (AMR) represents a major cause of allograft dysfunction and results in allograft failure in solid organ transplantation. Cyclic helix B peptide (CHBP) is a novel erythropoietin-derived peptide that ameliorated renal allograft rejection in a renal transplantation model. However, its effect on AMR remains unknown. This study aimed to investigate the effect of CHBP on AMR using a secondary allogeneic skin transplantation model, which was created by transplanting skin from BALB/c mice to C57BL/6 mice with or without CHBP treatment. A secondary syngeneic skin transplantation model, involving transplantation from C57BL/6 mice to C57BL/6 mice, was also created to act as a control. Skin graft rejection, CD19 B cell infiltration in the skin allograft, the percentages of splenic plasma cells, germinal center (GC) B cells, and Tfh cells, the serum levels of donor specific antibodies (DSAs), and NF-B signaling in splenocytes were analyzed. Skin allograft survival was significantly prolonged in the CHBP group compared to the allogeneic group. CHBP treatment also significantly reduced the CD19 B cell infiltration in the skin allograft, decreased the percentages of splenic plasma cells, GC B cells, and Tfh cells, and ameliorated the increase in the serum DSA level. At a molecular level, CHBP downregulated P100, RelB, and P52 in splenocytes. CHBP prolonged skin allograft survival by inhibiting AMR, which may be mediated by inhibition of NF-B signaling to suppress B cell immune responses, thereby decreasing the DSA level.
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http://dx.doi.org/10.3389/fimmu.2021.682749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149941PMC
May 2021

Integrated Analysis of Nine Prognostic RNA-Binding Proteins in Soft Tissue Sarcoma.

Front Oncol 2021 7;11:633024. Epub 2021 May 7.

Department of Spine and Orthopedic Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.

RNA-binding proteins (RBPs) have been shown to be dysregulated in cancer transcription and translation, but few studies have investigated their mechanism of action in soft tissue sarcoma (STS). Here, The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were used to identify differentially expressed RBPs in STS and normal tissues. Through a series of biological information analyses, 329 differentially expressed RBPs were identified. Functional enrichment analysis showed that differentially expressed RBPs were mainly involved in RNA transport, RNA splicing, mRNA monitoring pathways, ribosome biogenesis and translation regulation. Through Cox regression analyses, 9 RBPs (BYSL, IGF2BP3, DNMT3B, TERT, CD3EAP, SRSF12, TLR7, TRIM21 and MEX3A) were all up-regulated in STS as prognosis-related genes, and a prognostic model was established. The model calculated a risk score based on the expression of 9 hub RBPs. The risk score could be used for risk stratification of patients and had a high prognostic value based on the receiver operating characteristic (ROC) curve. We also established a nomogram containing risk scores and 9 key RBPs to predict the 1-year, 3-year, and 5-year survival rates of patients in STS. Afterwards, methylation analysis showed significant changes in the methylation degree of BYSL, CD3EAP and MEX2A. Furthermore, the expression of 9 hub RBPs was closely related to immune infiltration rather than tumor purity. Based on the above studies, these findings may provide new insights into the pathogenesis of STS and will provide candidate biomarkers for the prognosis of STS.
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http://dx.doi.org/10.3389/fonc.2021.633024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138553PMC
May 2021

Bio-Inspired Multi-Mode Pain-Perceptual System (MMPPS) with Noxious Stimuli Warning, Damage Localization, and Enhanced Damage Protection.

Adv Sci (Weinh) 2021 05 8;8(10):2004208. Epub 2021 Mar 8.

CAS Key Laboratory of Magnetic Materials and Devices Ningbo Institute of Materials Technology and Engineering Chinese Academy of Sciences Ningbo 315201 P. R. China.

The multi-mode pain-perceptual system (MMPPS) is essential for the human body to perceive noxious stimuli in all circumstances and make an appropriate reaction. Based on the central sensitization mechanism, the MMPPS can switch between different working modes and thus offers a smarter protection mechanism to human body. Accordingly, before injury MMPPS can offer warning of excessive pressure with normal pressure threshold. After injury, extra care on the periphery of damage will be activated by decreasing the pressure threshold. Furthermore, the MMPPS will gradually recover back to a normal state as damage heals. Although current devices can realize basic functions like damage localization and nociceptor signal imitating, the development of a human-like MMPPS is still a great challenge. Here, a bio-inspired MMPPS is developed for prosthetics protection, in which all working modes is realized and controlled by mimicking the central sensitization mechanism. Accordingly, the system warns one of a potential injury, identifies the damaged area, and subsequently offers extra care. The proposed system can open new avenues for designing next-generation prosthetics, especially make other smart sensing systems operate under complete protection against injuries.
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http://dx.doi.org/10.1002/advs.202004208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132158PMC
May 2021

Fumarylacetoacetate hydrolase is required for fertility in rice.

Planta 2021 May 18;253(6):122. Epub 2021 May 18.

College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, 410128, China.

Main Conclusion: The rice OsFAH gene functions identically to that of Arabidopsis SSCD1 encoding FAH. Loss of OsFAH causes rice sterility. Fumarylacetoacetate hydrolase (FAH) is the last enzyme in the tyrosine (Tyr) degradation pathway that is crucial for animals. By genetic analysis of the mutant of Short-day Sensitive Cell Death 1 gene encoding Arabidopsis FAH, we first found the pathway also plays a critical role in plants (Han et al., Plant Physiol 162:1956-1964, 2013). To further understand the role of the Tyr degradation pathway in plants, we investigated a biological function of the rice FAH. Firstly, the cDNA of rice FAH gene (OsFAH) was cloned and confirmed to be able to rescue the Arabidopsis Short-day Sensitive Cell Death 1 mutant defective in the FAH. Then, we identified the OsFAH T-DNA insertion mutant and generated the OsFAH RNA interference lines, and found that loss of OsFAH results in rice sterility. Furthermore, we analyzed expression of the OsFAH gene in roots, stems, leaves and young panicles at booting stage of rice and found that its transcript level was highest in young panicles and lowest in roots. In addition, the expression analysis of β-glucuronidase driven by OsFAH promoter in transgenic Arabidopsis showed that the OsFAH promoter was highly active in aerial tissues in vegetative stage, and sepals, filaments and stigma in reproductive stage. These results suggested that FAH plays an important role in rice fertility.
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http://dx.doi.org/10.1007/s00425-021-03632-1DOI Listing
May 2021

Psychological responses among nurses caring for patients with COVID-19: a comparative study in China.

Transl Psychiatry 2021 05 6;11(1):273. Epub 2021 May 6.

Department of Psychology, Tsinghua University, Beijing, China.

Frontline healthcare nurses devoted themselves to deal with the outbreak of COVID-19, saving many lives. However, they are under incredible unknown psychological pressures with a considerable risk of infection. In this study, a self-administered questionnaire was used to survey 593 frontline nurses in Wuhan City and non-Hubei provinces for psychological responses from March 1 to March 10, 2020. Compared with nurses outside Hubei Province, those working in Wuhan were more likely to feel physically and mentally exhausted. Their probable depression and anxiety were significantly higher than those of nurses outside Hubei province (31.2%, 18.3% vs. 13.8%, 5.9%). Correspondingly, the depressive symptoms were more often reported in the Wuhan group (70.8% vs. 41.4%). Although Wuhan received wishes, concerns, and abundant psychological and material resources from all of the world, the survey-based study found that frontline nurses in Wuhan still had higher depression and anxiety with less social support compared with nurses from non-Hubei provinces. Unexpectedly, only 4.0% of nurses have sought psychological assistance. These findings suggested that the short-term psychological impact of frontline nurses in Wuhan during the COVID-19 outbreak was extremely high compared with nurses outside Hubei Province. This research enlightened the efficient integration of psychological resources, the optimization of the nurse emergency psychological assistance system, and the mental health care of medical staff during the outbreak of epidemics.
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http://dx.doi.org/10.1038/s41398-020-00993-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101604PMC
May 2021

Impact of COVID-19 Pandemic on Patients With Neurodegenerative Diseases.

Front Aging Neurosci 2021 8;13:664965. Epub 2021 Apr 8.

State Key Laboratory for Infectious Disease Prevention and Control, NHC Key Laboratory of Medical Virology and Viral Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.

COVID-19 pandemic has already produced great impacts on global health security and social-economy. Elderly, particularly those with underlying diseases, are suffering from higher fatality rate. Neurodegenerative diseases are a group of incurable neurological disorders of loss of neuron and/or myelin sheath, which affect hundreds of millions of elderly populations and usually need long-term care. Older population is one of the most vulnerable to COVID-19 pandemic. In this report, we reviewed the current status of COVID-19 on the patients with several neurodegenerative diseases, particularly Alzheimer's disease, Parkinson's disease, prion disease, and amyotrophic lateral sclerosis. Meanwhile, the potential mechanisms of SARS-CoV-2 infection in the pathogenesis of neurodegenerative diseases were also summarized.
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http://dx.doi.org/10.3389/fnagi.2021.664965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060506PMC
April 2021

Oxygen-rich PdSnCu nanocrystals with particle connection features as enhanced catalysts for ethanol oxidation reaction.

Nanotechnology 2021 May 17;32(32). Epub 2021 May 17.

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, People's Republic of China.

Most electrocatalysts show a high mass and special activity during the ethanol oxidation reaction, but those still suffer from limited stability, finite renewable capability and poor anti-poisoning durability. Furthermore, the reliable structure and appropriate composition of catalysts are fairly associated with the electrocatalysis performance. Herein, we report the development of trimetallic PdSnCunanocrystals (NCs) whose rough surfaces are rich in step atoms and coupled with abundant of SnOand CuO, which may effectively boost reaction activity and rapidly remove carbonaceous intermediate, respectively. Under the tuning on the composition, the defect rich PdSnCuNCs exhibit elevated electrocatalysis activity and durability for ethanol oxidation reaction with an optimized mass activity (1.26 AmgPd-1) and specific activity (10.6 mA cm), which is about 2.21 and 2.58 times greater than that of the commercial Pd/C catalyst (0.57 AmgPd-1and 4.1 mA cm).
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http://dx.doi.org/10.1088/1361-6528/abf8dcDOI Listing
May 2021

A Rapid and Efficient Screening System for Neutralizing Antibodies and Its Application for SARS-CoV-2.

Front Immunol 2021 22;12:653189. Epub 2021 Mar 22.

Department of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing, China.

After the pandemic of COVID-19, neutralizing antibodies (NAbs) against SARS-CoV-2 have been developed for the prophylactic and therapeutic purposes. However, few methodologies are described in detail on how to rapidly and efficiently generate effective NAbs to SARS-CoV-2. Here, we integrated and optimized a strategically screening method for NAbs, which has enabled us to obtain SARS-CoV-2 receptor-binding domain (RBD) specific NAbs within 6 days, followed by additional 9 days for antibody production and function analysis. Using this method, we obtained 198 specific Abs against SARS-CoV-2 RBD from the blood samples of COVID-19 convalescent patients, and 96 of them showed neutralizing activity. At least 20% of these NAbs exhibited advanced neutralizing potency and high affinity, with the top two NAbs showing half-maximal inhibitory concentration (IC) to block authentic SARS-CoV-2 at 9.88 and 11.13 ng/ml, respectively. Altogether, our study provides an effective methodology with high applicable value for discovering potential preventative and therapeutic NAbs for the emerging infectious diseases.
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http://dx.doi.org/10.3389/fimmu.2021.653189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019923PMC
April 2021

Multi-Time Resolution Ensemble LSTMs for Enhanced Feature Extraction in High-Rate Time Series.

Sensors (Basel) 2021 Mar 10;21(6). Epub 2021 Mar 10.

Air Force Research Laboratory, Munitions Directorate, Fuzes Branch, Eglin Air Force Base, FL 32542, USA.

Systems experiencing high-rate dynamic events, termed high-rate systems, typically undergo accelerations of amplitudes higher than 100 g-force in less than 10 ms. Examples include adaptive airbag deployment systems, hypersonic vehicles, and active blast mitigation systems. Given their critical functions, accurate and fast modeling tools are necessary for ensuring the target performance. However, the unique characteristics of these systems, which consist of (1) large uncertainties in the external loads, (2) high levels of non-stationarities and heavy disturbances, and (3) unmodeled dynamics generated from changes in system configurations, in combination with the fast-changing environments, limit the applicability of physical modeling tools. In this paper, a deep learning algorithm is used to model high-rate systems and predict their response measurements. It consists of an ensemble of short-sequence long short-term memory (LSTM) cells which are concurrently trained. To empower multi-step ahead predictions, a multi-rate sampler is designed to individually select the input space of each LSTM cell based on local dynamics extracted using the embedding theorem. The proposed algorithm is validated on experimental data obtained from a high-rate system. Results showed that the use of the multi-rate sampler yields better feature extraction from non-stationary time series compared with a more heuristic method, resulting in significant improvement in step ahead prediction accuracy and horizon. The lean and efficient architecture of the algorithm results in an average computing time of 25 μμs, which is below the maximum prediction horizon, therefore demonstrating the algorithm's promise in real-time high-rate applications.
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http://dx.doi.org/10.3390/s21061954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001144PMC
March 2021

Intratumoral Fibrosis in Facilitating Renal Cancer Aggressiveness: Underlying Mechanisms and Promising Targets.

Front Cell Dev Biol 2021 11;9:651620. Epub 2021 Mar 11.

Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.

Intratumoral fibrosis is a histologic manifestation of fibrotic tumor stroma. The interaction between cancer cells and fibrotic stroma is intricate and reciprocal, involving dysregulations from multiple biological processes. Different components of tumor stroma are implicated via distinct manners. In the kidney, intratumoral fibrosis is frequently observed in renal cell carcinoma (RCC). However, the underlying mechanisms remain largely unclear. In this review, we recapitulate evidence demonstrating how fibrotic stroma interacts with cancer cells and mechanisms shared between RCC tumorigenesis and renal fibrogenesis, providing promising targets for future studies.
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http://dx.doi.org/10.3389/fcell.2021.651620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991742PMC
March 2021

Incidence and Associated Risk Factors for Lactic Acidosis Induced by Linezolid Therapy in a Case-Control Study in Patients Older Than 85 Years.

Front Med (Lausanne) 2021 25;8:604680. Epub 2021 Feb 25.

Department of Pulmonary and Critical Care Medicine, The Second Medical Center, National Clinical Research Center for Geriatric Diseases, Chinese People's Liberation Army General Hospital, Beijing, China.

Serum lactic acid is considered a prognostic indicator in critically ill patients. However, studies on linezolid-induced lactic acidosis (LILA) are still limited. Individuals older than 85 years old (very elderly) have limited capacity for organ compensation, and LILA data from these patients are lacking. In this study, we evaluated the risk factors for LILA in patients older than 85 years and established a risk prediction model for geriatric practice. In this retrospective cohort study, blood gas analysis data and arterial lactate levels were monitored in patients older than 85 years during the use of teicoplanin or linezolid. After propensity score matching analyses, we compared the incidence of lactic acidosis between the teicoplanin and linezolid therapy groups and identified the risk factors of LILA. The incidence of lactic acidosis was found to be much lower in the group receiving teicoplanin than those receiving linezolid therapy (0 vs. 35.7%; < 0.0001). A duration of linezolid therapy ≥ 9 days [odds ratio (OR), 3.541; 95% confidence interval (CI), 1.161-10.793; = 0.026], an arterial blood glucose level ≥ 8 mmol/L (OR, 4.548; 95% CI, 1.507-13.725; = 0.007), and a high sequential organ failure assessment score (OR, 1.429; 95% CI, 1.213-1.685; < 0.0001) were risk factors for LILA. The constructed risk model could be used to predict LILA (area under the curve, 0.849; specificity, 65.1%; sensitivity, 91.4%, with a negative predictive value of 93.2% and a positive predictive value of 59.3%). LILA can occur in patients older than 85 years after a relatively shorter duration of linezolid therapy. Therefore, close monitoring of blood gas and arterial lactate levels during linezolid therapy in the very elderly population is necessary.
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http://dx.doi.org/10.3389/fmed.2021.604680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959744PMC
February 2021

ATAD3B is a mitophagy receptor mediating clearance of oxidative stress-induced damaged mitochondrial DNA.

EMBO J 2021 Apr 5;40(8):e106283. Epub 2021 Mar 5.

Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, China.

Mitochondrial DNA (mtDNA) encodes several key components of respiratory chain complexes that produce cellular energy through oxidative phosphorylation. mtDNA is vulnerable to damage under various physiological stresses, especially oxidative stress. mtDNA damage leads to mitochondrial dysfunction, and dysfunctional mitochondria can be removed by mitophagy, an essential process in cellular homeostasis. However, how damaged mtDNA is selectively cleared from the cell, and how damaged mtDNA triggers mitophagy, remain mostly unknown. Here, we identified a novel mitophagy receptor, ATAD3B, which is specifically expressed in primates. ATAD3B contains a LIR motif that binds to LC3 and promotes oxidative stress-induced mitophagy in a PINK1-independent manner, thus promoting the clearance of damaged mtDNA induced by oxidative stress. Under normal conditions, ATAD3B hetero-oligomerizes with ATAD3A, thus promoting the targeting of the C-terminal region of ATAD3B to the mitochondrial intermembrane space. Oxidative stress-induced mtDNA damage or mtDNA depletion reduces ATAD3B-ATAD3A hetero-oligomerization and leads to exposure of the ATAD3B C-terminus at the mitochondrial outer membrane and subsequent recruitment of LC3 for initiating mitophagy. Furthermore, ATAD3B is little expressed in m.3243A > G mutated cells and MELAS patient fibroblasts showing endogenous oxidative stress, and ATAD3B re-expression promotes the clearance of m.3243A > G mutated mtDNA. Our findings uncover a new pathway to selectively remove damaged mtDNA and reveal that increasing ATAD3B activity is a potential therapeutic approach for mitochondrial diseases.
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http://dx.doi.org/10.15252/embj.2020106283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047441PMC
April 2021

Cytokine release syndrome in COVID-19: a major mechanism of morbidity and mortality.

Int Rev Immunol 2021 Feb 22:1-14. Epub 2021 Feb 22.

The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, China.

The coronavirus disease 2019 (COVID-19) triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) erupted in Hubei Province of China in December 2019 and has become a pandemic. Severe COVID-19 patients who suffer from acute respiratory distress syndrome (ARDS) and multi-organ dysfunction have high mortality. Several studies have shown that this is closely related to the cytokine release syndrome (CRS), often loosely referred to as cytokine storm. IL-6 is one of the key factors and its level is positively correlated with the severity of the disease. The molecular mechanisms for CRS in COVID-19 are related to the effects of the S-protein and N-protein of the virus and its ability to trigger NF-κB activation by disabling the inhibitory component IκB. This leads to activation of immune cells and the secretion of proinflammatory cytokines such as IL-6 and TNF-α. Other mechanisms related to IL-6 include its interaction with GM-CSF and interferon responses. The pivotal role of IL-6 makes it a target for therapeutic agents and studies on tocilizumab are already ongoing. Other possible targets of treating CRS in COVID-19 include IL-1β and TNF-α. Recently, reports of a CRS like illness called multisystem inflammatory syndrome in children (MIS-C) in children have surfaced, with a variable presentation which in some cases resembles Kawasaki disease. It is likely that the immunological derangement and cytokine release occurring in COVID-19 cases is variable, or on a spectrum, that can potentially be governed by genetic factors. Currently, there are no approved biological modulators for the treatment of COVID-19, but the urgency of the pandemic has led to numerous clinical trials worldwide. Ultimately, there is great promise that an anti-inflammatory modulator targeting a cytokine storm effect may prove to be very beneficial in reducing morbidity and mortality in COVID-19 patients.
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http://dx.doi.org/10.1080/08830185.2021.1884248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919105PMC
February 2021

Removal effects of Myriophyllum aquaticum on combined pollutants of nutrients and heavy metals in simulated swine wastewater in summer.

Ecotoxicol Environ Saf 2021 Apr 11;213:112032. Epub 2021 Feb 11.

Institute of Botany, Jiangsu Province and Chinese Academy Sciences, Nanjing 210014, China; Jiangsu Engineering Research Center of Aquatic Plant Resources and Water Environment Remediation, Nanjing 210014, China. Electronic address:

Swine wastewater (SW) treatment by Myriophyllum aquaticum is an important biotechnology for its resource utilization. However, some knowledge gaps remain in compound-pollutant removal in SW, especially in practical applications. To clarify the responses of M. aquaticum to the compound pollutants as well as the related operational parameters in SW treatment, three initial doses (0.5, 1.0, and 1.5 kg per pond in 150 L simulated SW) of M. aquaticum and a control (no plant; CK) were allocated to 12 ponds under a plastic roof in Nanjing city of Eastern China during 75 days in the summer of 2019. Results showed that M. aquaticum could be used as a pioneer plant to efficiently remove compounded pollutants of nitrogen (N), phosphorus (P), and especially for heavy metals in simulated SW. Compared with CK, M. aquaticum assisted in improving the total N, NH-N, NO-N, NO-N, and dissolved organic N by 30.1%, 100%, 100%, 97.6%, 20.2%, 39.8% whereas Cu, Zn, and Cd by 50.4%, 36.4% and 47.9% on average during the 75-day experiment in summer, respectively. Moreover, concentrations of Cu and Cd at day 75 were in the ranges of 1.92-2.82 and 0.64-1.47 g kg DW, respectively, exceeding the corresponding limits of the heavy-metal hyperaccumulator. For the operational parameters, the optimized initial dose was 1.0 kg per pond with M. aquaticum harvested after 45 summer days, respectively. Given that M. aquaticum has been widely used as animal feed in recent years and limit values for Cu and Zn in animal feed are not set in China, the toxicities of Cu and Zn should be assessed and the guideline of their limit values needs to be established for safe feed production. Interestingly, NH-N could dominate the removal of heavy metals especially Cd in the simulated SW, however, related mechanisms are needed for further study.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112032DOI Listing
April 2021

International Recommendations on Reirradiation by Intensity Modulated Radiation Therapy for Locally Recurrent Nasopharyngeal Carcinoma.

Int J Radiat Oncol Biol Phys 2021 07 9;110(3):682-695. Epub 2021 Feb 9.

Department of Clinical Oncology, University of Hong Kong Shenzhen Hospital and University of Hong Kong, Hong Kong, China. Electronic address:

Purpose: Reirradiation for locally recurrent nasopharyngeal carcinoma (NPC) is challenging because prior radiation dose delivered in the first course is often close to the tolerance limit of surrounding normal structures. A delicate balance between achieving local salvage and minimizing treatment toxicities is needed. However, high-level evidence is lacking because available reports are mostly retrospective studies on small series of patients. Pragmatic consensus guidelines, based on an extensive literature search and the pooling of opinions by leading specialists, will provide a useful reference to assist decision-making for these difficult decisions.

Methods And Materials: A thorough review of available literature on recurrent NPC was conducted. A set of questions and preliminary draft guideline was circulated to a panel of international specialists with extensive experience in this field for voting on controversial areas and comments. A refined second proposal, based on a summary of the initial voting and different opinions expressed, was recirculated to the whole panel for review and reconsideration. The current guideline was based on majority voting after repeated iteration for final agreement.

Results: The initial round of questions showed variations in clinical practice even among the specialists, reflecting the lack of high-quality supporting data and the difficulties in formulating clinical decisions. Through exchange of comments and iterative revisions, recommendations with high-to-moderate agreement were formulated on general treatment strategies and details of reirradiation (including patient selection, targets contouring, dose prescription, and constraints).

Conclusion: This paper provides useful reference on radical salvage treatment strategies for recurrent NPC and optimization of reirradiation through review of published evidence and consensus building. However, the final decision by the attending clinician must include full consideration of an individual patient's condition, understanding of the delicate balance between risk and benefits, and acceptance of risk of complications.
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http://dx.doi.org/10.1016/j.ijrobp.2021.01.041DOI Listing
July 2021
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