Publications by authors named "Gang Huang"

765 Publications

Toxicity of Lour. and its effects on lipopolysaccharide-induced inflammation and oxidative stress.

Exp Ther Med 2021 Aug 27;22(2):807. Epub 2021 May 27.

Department of Clinical Pharmacology, Lishui People's Hospital, Lishui, Zhejiang 323000, P.R. China.

Lour. (MDL) is component used in traditional Chinese medicine that is widely distributed throughout southern China. MDL has been long utilized in clinical treatment for various conditions, such as inflammation. However, the toxicity and underlying anti-inflammatory mechanism of MDL remain to be elucidated. In the present study, Sprague-Dawley rats received intragastric administration of MDL for 2 months, and the toxicity of MDL was investigated. The rats were treated with lipopolysaccharide (LPS) for 8 h to determine the potential anti-inflammatory mechanism of MDL. The results demonstrated that MDL alone did not affect the expression levels of factors associated with inflammation (IL-1β, IL-6 and TNF-α) and oxidative stress [malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO)] in the rat serum and exerted no effects on rat liver and kidneys. By contrast, MDL attenuated LPS-induced inflammation and oxidative stress by regulating specific cytokines, such as IL-1β, IL-6, TNF-α, MDA, SOD and NO in the rat serum and alleviated LPS-induced liver and kidney damage. Additionally, compared with the LPS group, MDL inhibited CD4 T cell differentiation into Th1 and Th17 cells and enhanced CD4 T cell differentiation into Th2 and Treg cells. MDL also suppressed reactive oxygen species (ROS) production and mitochondrial apoptosis by modulating mitochondrial apoptosis-related proteins in spleen CD4 T cells. In conclusion, the results of the present study demonstrated the non-toxic nature of MDL and revealed that it alleviated LPS-induced inflammation and oxidative stress by regulating differentiation and ROS production in CD4 T cells.
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http://dx.doi.org/10.3892/etm.2021.10239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170668PMC
August 2021

Applications of artificial intelligence in nuclear medicine image generation.

Quant Imaging Med Surg 2021 Jun;11(6):2792-2822

Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai, China.

Recently, the application of artificial intelligence (AI) in medical imaging (including nuclear medicine imaging) has rapidly developed. Most AI applications in nuclear medicine imaging have focused on the diagnosis, treatment monitoring, and correlation analyses with pathology or specific gene mutation. It can also be used for image generation to shorten the time of image acquisition, reduce the dose of injected tracer, and enhance image quality. This work provides an overview of the application of AI in image generation for single-photon emission computed tomography (SPECT) and positron emission tomography (PET) either without or with anatomical information [CT or magnetic resonance imaging (MRI)]. This review focused on four aspects, including imaging physics, image reconstruction, image postprocessing, and internal dosimetry. AI application in generating attenuation map, estimating scatter events, boosting image quality, and predicting internal dose map is summarized and discussed.
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http://dx.doi.org/10.21037/qims-20-1078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107336PMC
June 2021

Nuclear scaffold protein p54/NONO facilitates the hypoxia-enhanced progression of hepatocellular carcinoma.

Oncogene 2021 Jun 2. Epub 2021 Jun 2.

Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.

Hypoxia and related oxidative stress are closely related to the development and treatment of hepatocellular carcinoma (HCC). However, the mechanism mediated by hypoxia in HCC has not yet been elucidated. Here, we found multifunction scaffold protein p54/NONO exerted pleiotropic effects to regulate hypoxia transcription signals, thereby enhancing the progression of liver cancer. Extensive analysis of clinical data demonstrated that NONO was significantly upregulated and represented as a poor prognostic indicator of HCC. The crucial role of NONO in driving angiogenesis and glycolysis, two well-known cancer phenotypes mediated by hypoxia, was examined in vitro an in vivo. Mechanistically, NONO interacted with and stabilized both HIF-1 and HIF-2 complexes thus activating the transcription of hypoxia-induced genes. Besides, NONO bound pre-mRNA and subsequent mRNA of these genes to facilitate them splicing and mRNA stability, respectively. Thus, NONO knockout seriously disrupted the expression of a cluster of HIF-1/2 targets and impeded hypoxia-enhanced progression in HCC. In conclusion, NONO functioned as a multipurpose scaffold that interacted with HIF-1/2 complex and their downstream transcripts to facilitate the expression of hypoxia-induced genes, allowing malignant proliferation, indicating that NONO might be a potential therapeutic target for HCC.
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http://dx.doi.org/10.1038/s41388-021-01848-9DOI Listing
June 2021

Bipolar disorder and the risk for stroke incidence and mortality: a meta-analysis.

Neurol Sci 2021 May 29. Epub 2021 May 29.

Department of Neurology, Jiangxi Provincial People's Hospital Affiliated To Nanchang University, No. 152, Aiguo Road, Nanchang, 330006, Jiangxi, China.

Objective: Bipolar disorder (BD) may be associated with an increased risk of stroke, but to date, the results of the studies are still controversial. This study aimed to assess the association of BD with stroke incidence and mortality by a meta-analysis.

Method: PubMed, EMBASE, the Cochrane library databases, and Web of Science databases were searched from inception to July 2020. We regarded stroke as a composite endpoint. The pooled hazard ratio (HRs) of 95% confidence interval (Cls) was calculated. Subgroup and sensitivity analyses were performed to assess the potential sources of heterogeneity of the pooled estimation.

Results: A total of 7 studies involving a total of 13,305,007 participants were included in this meta-analysis. Pooled analysis showed participants with BD experienced a significantly increased risk of both stroke incidence (combined HR, 1.43; 95% CI, 1.24-1.66; p = 0.000) and stroke mortality (combined HR, 1.54; 95% CI, 1.09-2.18; p = 0.013) compared to participants without BD. In addition, the pooled estimate of multivariate HRs of stroke incidence and mortality were 1.35 (95% CI: 1.26-1.45); 2.30 ( 95% CI: 1.37-3.85) among men and 1.43 (95% CI:1.27-1.60); 2.08 (95% CI:1.60-2.71) among women respectively.

Conclusions: This meta-analysis suggests that BD may modestly increase the risk of both stroke incidence and mortality. Extensive clinical observational studies should be conducted in the future to explore whether BD is a potentially modifiable risk factor for stroke.
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http://dx.doi.org/10.1007/s10072-021-05348-2DOI Listing
May 2021

Fly Ash Carbon Anodes for Alkali Metal-Ion Batteries.

ACS Appl Mater Interfaces 2021 Jun 28;13(22):26421-26430. Epub 2021 May 28.

Materials Science and Engineering, Physical Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.

Graphite has become a critical material because of its essential role in the lithium-ion battery (LIB) industry. However, the synthesis of graphite requires an energy-intensive thermal treatment. Also, when used in sodium-ion and potassium-ion batteries (SIBs and PIBs), the graphite anode shows poor capacities and cycling stability, which hinders the development of next-generation battery technologies. Finding suitable anode materials for commercial alkali metal-ion batteries is not only urgent for the energy storage industry, but is also important for economic and sustainable development. In this work, we use fly ash carbon (FAC), a residue of crude oil combustion, as an anode material for alkali metal-ion batteries. The FAC anodes show relatively high capacities and excellent cycling stability. The charge storage mechanism of FAC anode is shown to be intercalation coupled with redox reactions of oxygen functional groups. This work shows that FAC is a promising scalable anode material for alkali metal-ion batteries.
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http://dx.doi.org/10.1021/acsami.1c06543DOI Listing
June 2021

An AKT/PRMT5/SREBP1 axis in lung adenocarcinoma regulates de novo lipogenesis and tumor growth.

Cancer Sci 2021 May 25. Epub 2021 May 25.

Department of Nuclear Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Protein kinase B (AKT) hyperactivation and de novo lipogenesis are both common in tumor progression. Sterol regulatory element-binding protein 1 (SREBP1) is the master regulator for tumor lipid metabolism, and protein arginine methyltransferase 5 (PRMT5) is an enzyme that can catalyze symmetric dimethyl arginine (SDMA) modification of the mature form of SREBP1 (mSREBP1) to induce its hyperactivation. Here, we report that SDMA-modified mSREBP1 (mSREBP1-SDMA) was overexpressed and correlated with ser473-phosphorylated AKT (AKT-473P) expression and poor patient outcomes in human lung adenocarcinomas. Further, patients with AKT-473P and mSREBP1-SDMA co-expression showed the worst prognosis. Mechanistic investigation revealed that AKT activation upregulated SREBP1 at both the transcriptional and post-translational levels, whereas PRMT5 knockdown reversed AKT signaling-mediated mSREBP1 ubiquitin-proteasome pathway stabilization at the post-translational level. Meanwhile, AKT activation promoted nuclear PRMT5 to the cytoplasm without changing total PRMT5 expression, and the transported cytoplasmic PRMT5 (cPRMT5) induced by AKT activation showed a strong mSREBP1-binding ability. IHC assay demonstrated that AKT-473P and mSREBP1-SDMA were positively correlated with cPRMT5 in lung adenocarcinomas, and high cPRMT5 levels in tumors were associated with poor patient outcomes. Additionally, PRMT5 knockdown reversed AKT activation-induced lipid synthesis and growth advantage of lung adenocarcinoma cells both in vitro and in vivo. Finally, we defined an AKT/PRMT5/SREBP1 axis involved in de novo lipogenesis and the growth of lung cancer. Our data also support that cPRMT5 is a potential therapeutic target for hyperactive AKT-driven lung adenocarcinoma. Supporting Information.
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http://dx.doi.org/10.1111/cas.14988DOI Listing
May 2021

Discovery of first-in-class inhibitors of ASH1L histone methyltransferase with anti-leukemic activity.

Nat Commun 2021 05 14;12(1):2792. Epub 2021 May 14.

Department of Pathology, University of Michigan, Ann Arbor, MI, USA.

ASH1L histone methyltransferase plays a crucial role in the pathogenesis of different diseases, including acute leukemia. While ASH1L represents an attractive drug target, developing ASH1L inhibitors is challenging, as the catalytic SET domain adapts an inactive conformation with autoinhibitory loop blocking the access to the active site. Here, by applying fragment-based screening followed by medicinal chemistry and a structure-based design, we developed first-in-class small molecule inhibitors of the ASH1L SET domain. The crystal structures of ASH1L-inhibitor complexes reveal compound binding to the autoinhibitory loop region in the SET domain. When tested in MLL leukemia models, our lead compound, AS-99, blocks cell proliferation, induces apoptosis and differentiation, downregulates MLL fusion target genes, and reduces the leukemia burden in vivo. This work validates the ASH1L SET domain as a druggable target and provides a chemical probe to further study the biological functions of ASH1L as well as to develop therapeutic agents.
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http://dx.doi.org/10.1038/s41467-021-23152-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121805PMC
May 2021

The value of small airway function parameters and fractional exhaled nitric oxide for predicting positive methacholine challenge test in asthmatics of different ages with FEV  ≥ 80% predicted.

Clin Transl Allergy 2021 Mar;11(1):e12007

Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Small airway function parameters (SAFPs) combined with fractional exhaled nitric oxide (FeNO) can predict a positive methacholine challenge test (MCT) for asthma diagnosis. However, their predictive utility in patients with forced expiratory volume in one second (FEV ) ≥80% predicted within different age ranges remains unclear. This study aimed to assess the utility of SAFPs, alone or combined with FeNO, to predict a positive MCT in patients in two age groups (<55 and ≥55 years) with asthma-suggestive symptoms and FEV  ≥80% predicted.

Methods: We enrolled 846 Chinese patients with suspected asthma and standard spirometry, FeNO, and MCT findings. Using the area under the curves (AUCs), the utility of SAFPs, alone or combined with FeNO, for predicting a positive MCT was analyzed in a discovery (n = 534) and validation cohort (n = 312) in both age groups with FEV ≥80% predicted.

Results: In the discovery cohort, the optimal cut-off values for predicting a positive MCT in patients aged <55 years (74.2% and 74.9% for forced expiratory flow (FEF) and FEF , respectively) were higher than those in patients aged ≥55 years (65.0% and 62.9% for FEF , FEF , respectively). However, the optimal FeNO value in patients aged <55 years (43 ppb) was lower than that in patients aged ≥55 years (48 ppb). FeNO combined with SAFPs (FEF , FEF ) significantly increased the AUCs in both groups (≥55 years [0.851 for FEF and 0.844 for FEF ]; <55 years [0.865 for FEF and 0.883 for FEF ]) compared with a single parameter (p < 0.05). These findings were confirmed in the validation cohort. Compared with patients ≥55 years, those aged <55 years had higher and lower optimal cut-off values for SAFPs and FeNO, respectively. The AUCs of FeNO combined with SAFPs for predicting a positive MCT for asthma diagnosis were significantly higher than those of the individual parameters (p < 0.05) in both age groups.

Conclusions: There were age-group differences in the utility of SAFPs combined with FeNO for predicting a positive MCT. Patients with an asthma-suggestive history and a normal FEV should be stratified by age when using SAFPs combined with FeNO to predict a positive MCT.
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http://dx.doi.org/10.1002/clt2.12007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099229PMC
March 2021

A Cyclodextrin-Hosted Ir(III) Complex for Ratiometric Mapping of Tumor Hypoxia In Vivo.

Adv Sci (Weinh) 2021 04 5;8(8):2004044. Epub 2021 Feb 5.

Key Laboratory of Colloid, Interface and Chemical Thermodynamics Institute of Chemistry Chinese Academy of Sciences Beijing 100190 P. R. China.

Hypoxia is considered as a key microenvironmental feature of solid tumors. Luminescent transition metal complexes particularly those based on iridium and ruthenium have shown remarkable potentials for constructing sensitive oxygen-sensing probes due to their unique oxygen quenching pathway. However, the low aqueous solubility of these complexes largely retards their sensing applications in biological media. Moreover, it remains difficult so far to use the existing complexes typically possessing only one luminescent domain to quantitatively detect the intratumoral hypoxia degree. Herein, an Ir(III) complex showing red emissions is designed and synthesized, and innovatively encapsulated within a hydrophobic pocket of Cyanine7-modified cyclodextrin. The Ir(III) complex enables the oxygen detection, while the cyclodextrin is used not only for improving the water solubility and suppressing the luminescence quenching effect of the surrounding aqueous media, but also for carrying Cyanine7 to establish a ratiometric oxygen fluorescence probe. 2D nuclear magnetic resonance is carried out to confirm the host-guest structure. The oxygen-responsive ability of the resulting ratiometric probe is evaluated through in vitro cell and multicellular experiments. Further animal studies about tumor oxygen level mapping demonstrate that the probe can be successfully used for quantitatively visualizing tumor hypoxia in vivo.
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http://dx.doi.org/10.1002/advs.202004044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061356PMC
April 2021

The added value of F-FDG PET/CT compared to Ga-PSMA PET/CT in patients with castration-resistant prostate cancer.

J Nucl Med 2021 Apr 23. Epub 2021 Apr 23.

Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University,, China.

The Ga-PSMA PET/CT is a commonly used imaging modality in prostate cancers. However, few studies have compared the diagnostic efficiency between Ga-PSMA and F-FDG PET/CT and evaluated whether a heterogeneous metabolic phenotype (especially PSMA-FDG+ lesions) exists in patients with castration-resistant prostate cancer (CRPC). We determined the added value of F-FDG PET/CT compared to Ga-PSMA PET/CT in CRPC patients and identified CRPC patients who may benefit from additional F-FDG PET/CT. Data of 56 patients with CRPC who underwent both Ga-PSMA and F-FDG PET/CT from May 2018 to February 2021 were retrospectively analysed. Patients were classified into two groups with or without PSMA-FDG+ lesions. The differences in patient characteristics between the two groups and predictors of patients who having at least one PSMA-FDG+ lesion were analysed. Although both the detection rate (75.0% vs. 51.8%, = 0.004) and positive lesion number (135 vs. 95) of Ga-PSMA PET/CT were higher than F-FDG PET/CT, there were still 13/56 (23.2%) patients with at least one PSMA-FDG+ lesion. The prostate-specific antigen (PSA) and Gleason score were both higher in the patients with PSMA-FDG+ lesions than in those without PSMA-FDG+ lesions ( = 0.04 and P<0.001, respectively). Multivariate regression analysis showed that the Gleason score (≥8) and PSA (≥7.9 ng/mL) were associated with the detection rate of patients who had PSMA-FDG+ lesions ( = 0.01 and = 0.04, respectively). The incidences of having PSMA-FDG+ lesions in low-probability (Gleason score<8 and PSA<7.9 ng/mL), medium-probability (Gleason score≥8 and PSA<7.9 ng/mL or Gleason score<8 and PSA≥7.9 ng/mL), and high-probability (Gleason score≥8 and PSA≥7.9 ng/mL) groups were 0%, 21.7%, and 61.5%, respectively (P<0.001). Gleason score and PSA are significant predictors for PSMA-FDG+ lesions, and CRPC patients with high Gleason score and PSA may benefit from additional F-FDG PET/CT.
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http://dx.doi.org/10.2967/jnumed.121.262250DOI Listing
April 2021

Germline variants in UNC13D and AP3B1 are enriched in COVID-19 patients experiencing severe cytokine storms.

Eur J Hum Genet 2021 Apr 19. Epub 2021 Apr 19.

CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.

Critically ill coronavirus disease 2019 (COVID-19) is characterized by severe cytokine storms, a hyperinflammatory condition intimately related to the development of fatal outcomes. Why some individuals seem particularly vulnerable to severe cytokine storms is still unknown. Primary immunodeficiency (PID)-related genes are inherited factors that dysregulate host inflammatory responses to infection, especially hemophagocytic lymphohistiocytosis (HLH)-related genes, established as contributors to the development of excessive cytokine storms. We analyzed the association between PID gene variants with severe cytokine storms in COVID-19. We conducted whole-exome sequencing in 233 hospitalized COVID-19 patients and identified four PID gene (UNC13D, AP3B1, RNF168, DHX58) variants were significantly enriched in COVID-19 patients experiencing severe cytokine storms. The total percentage of COVID-19 patients with variants in UNC13D or AP3B1, two typical HLH genes, was dramatically higher in high-level cytokine group than in low-level group (33.3 vs. 5.7%, P < 0.001). Germline variants in UNC13D and AP3B1 were associated with the development of severe cytokine storms, fatal outcomes in COVID-19. These findings advance the understanding of individual susceptibility to severe cytokine storms and help optimize the current management of COVID-19.
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http://dx.doi.org/10.1038/s41431-021-00886-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053565PMC
April 2021

Wobble tRNA modification and hydrophilic amino acid patterns dictate protein fate.

Nat Commun 2021 04 15;12(1):2170. Epub 2021 Apr 15.

Laboratory of Cancer Signaling, University of Liège, Liège, Belgium.

Regulation of mRNA translation elongation impacts nascent protein synthesis and integrity and plays a critical role in disease establishment. Here, we investigate features linking regulation of codon-dependent translation elongation to protein expression and homeostasis. Using knockdown models of enzymes that catalyze the mcms wobble uridine tRNA modification (U-enzymes), we show that gene codon content is necessary but not sufficient to predict protein fate. While translation defects upon perturbation of U-enzymes are strictly dependent on codon content, the consequences on protein output are determined by other features. Specific hydrophilic motifs cause protein aggregation and degradation upon codon-dependent translation elongation defects. Accordingly, the combination of codon content and the presence of hydrophilic motifs define the proteome whose maintenance relies on U-tRNA modification. Together, these results uncover the mechanism linking wobble tRNA modification to mRNA translation and aggregation to maintain proteome homeostasis.
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http://dx.doi.org/10.1038/s41467-021-22254-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050329PMC
April 2021

HBV-pgRNA increases the stemness and promotes the development of HBV-related HCC through reciprocal regulation with IGF2BP3.

Hepatology 2021 Apr 7. Epub 2021 Apr 7.

The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.

HBV-pgRNA has been proposed for predicting the response of NAs treatment, guiding discontinuation of NAs therapy and monitoring the emergence of viral mutations. However, the contributions of HBV-pgRNA to HCC remain largely unknown. Double-center cohorts of serum samples with undetectable serum HBV-DNA (below the lower limit of detection) were obtained from long-term NAs-treated (at least 48 weeks) of HBV-related HCC patients. The correlation between serum pgRNA concentration and the prognosis of HCC were analyzed. The role pgRNA played in HCC development was assessed both in vitro and in vivo. Our findings revealed that for patients underwent long-term NAs therapy with undetectable serum HBV-DNA, patients with high serum pgRNA expression had poorer overall survival rate and higher cumulative recurrence rate after hepatectomy. Experiments demonstrated that pgRNA promotes proliferation, stemness and tumorigenicity of HCC cells. Mechanistically, we found that pgRNA could up-regulate the expression of IGF2BP3, a well-proved oncoprotein, at post-transcriptional level. Furthermore, IFN-α-2a could degrade the stability of pgRNA through increasing its m6A RNA modification. Collectively, our findings uncover that serum pgRNA could serve as a potential biomarker for predicting the prognosis and recurrence of HCC in patients who received long-term NAs therapy with undetectable serum HBV-DNA; And pgRNA-IGF2BP3 axis plays an important role in the development of HBV-related HCC. Moreover, IFN-α-2a could reduce the stability of pgRNA by increasing its m6A RNA modification level, thereby suppressing the development of HBV-related HCC. In conclusion: Our studies reveal a significance and mechanism of HBV-pgRNA in increasing stemness features and offer a potential prognostic marker and a therapeutic target for HBV-related HCC.
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http://dx.doi.org/10.1002/hep.31850DOI Listing
April 2021

COVID-19 infection in patients with connective tissue disease: A multicity study in Hubei province, China.

MedComm (Beijing) 2021 Mar 4;2(1):82-90. Epub 2021 Feb 4.

Department of Rheumatology and Immunology Tongji Hospital Tongji Medical College of Huazhong University of Science and Technology Wuhan Hubei China.

Novel Coronavirus disease 2019 (COVID-19) has spread rapidly around the world. Individuals with immune dysregulation and/or on immunosuppressive therapy, such as rheumatic patients, are considered at greater risk for infections. However, the risks of patients with each subcategory of rheumatic diseases have not been reported. Here, we identified 100 rheumatic patients from 18,786 COVID-19 patients hospitalized in 23 centers affiliated to Hubei COVID-19 Rheumatology Alliance between January 1 and April 1, 2020. Demographic information, medical history, length of hospital stay, classification of disease severity, symptoms and signs, laboratory tests, disease outcome, computed tomography, and treatments information were collected. Compared to gout and ankylosing spondylitis (AS) patients, patients with connective tissue disease (CTD) tend to be more severe after COVID-19 infection (= 0.081). CTD patients also had lower lymphocyte counts, hemoglobin, and platelet counts ( values were 0.033, < 0.001, and 0.071, respectively). Hydroxychloroquine therapy and low- to medium-dose glucocorticoids before COVID-19 diagnosis reduced the progression of COVID-19 to severe/critical conditions (= 0.001 for hydroxychloroquine; = 0.006 for glucocorticoids). Our data suggests that COVID-19 in CTD patients may be more severe compared to patients with AS or gout.
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http://dx.doi.org/10.1002/mco2.56DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013216PMC
March 2021

Protein S-nitrosylation regulates proteostasis and viability of hematopoietic stem cell during regeneration.

Cell Rep 2021 Mar;34(13):108922

Key Laboratory of Regenerative Medicine of Ministry of Education, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Institute of Aging and Regenerative Medicine, Jinan University, Guangzhou, Guangdong 510632, China. Electronic address:

Hematopoietic stem cells (HSCs) regenerate blood cells upon hematopoietic injuries. During homeostasis, HSCs are maintained in a low reactive oxygen species (ROS) state to prevent exhaustion. However, the role of nitric oxide (NO) in controlling HSC regeneration is still unclear. Here, we find increased NO during HSC regeneration with an accumulation of protein aggregation. S-nitrosoglutathione reductase (GSNOR)-deleted HSCs exhibit a reduced reconstitution capacity and loss of self-renewal after chemotherapeutic injury, which is resolved by inhibition of NO synthesis. Deletion of GSNOR enhances protein S-nitrosylation, resulting in an accumulation of protein aggregation and activation of unfolded protein response (UPR). Treatment of taurocholic acid (TCA), a chemical chaperone, rescues the regeneration defect of Gsnor HSCs after 5-fluorouracil (5-FU) treatment. Deletion of C/EBP homologous protein (Chop) restores the reconstitution capacity of Gsnor HSCs. These findings establish a link between S-nitrosylation and protein aggregation in HSC in the context of blood regeneration.
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http://dx.doi.org/10.1016/j.celrep.2021.108922DOI Listing
March 2021

Fire needle therapy for blood stasis syndrome of plaque psoriasis: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Apr;100(13):e25312

Affifiliated Hospital of Jiangxi University of Traditional Chinese Medicine.

Background: Plaque psoriasis (PSO) is a common clinical chronic inflammatory skin disease. The incidence rate is increasing year by year due to the fast pace of work and unhealthy diet. Fire needle has been widely used in the treatment of PSO. However, the efficacy of fire needle for PSO is uncertain. Thus, the purpose of this systematic review is to evaluate the effectiveness and safety of fire needle for PSO (blood stasis syndrome).

Methods: The following electronic databases will be searched from inception to October 2020:PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, WangFang Database, Chinese Science Journal Database, Chinese Biomedical Literature Database. In addition, other documents that meet the requirements will be manually searched, including conference papers, dissertations, etc. All randomized controlled trials using fire needle to treat PSO (blood stasis syndrome) that meet the criteria for inclusion will be included. The primary outcomes are clinical efficacy, Psoriasis area and severity index. Secondary outcomes include Itchy, TCM evaluation standard syndrome score, Dermatological quality of life index, and adverse events. To complete data synthesis and assess the risk of bias, we will use the RevMan V.5.3 software.

Results: The review results will be published in a peer-reviewed journal.

Conclusion: This study will provide high-quality evidence based medicine to evaluate the effectiveness and safety of fire needle for PSO (blood stasis syndrome), and further seek its scientific and effective chinese medicine treatment methods.

Inplasy Registration Number: INPLASY202120007.
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http://dx.doi.org/10.1097/MD.0000000000025312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021280PMC
April 2021

Moxibustion therapy for treating psoriasis vulgaris: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Mar;100(12):e25250

Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, China.

Background: Psoriasis vulgaris (PV) is an immune-mediated skin disease, which has seriously affected the quality of life of patients. At present, moxibustion therapy has been widely used in the treatment of PV. The purpose of this study is to provide high-quality evidence-based medicine to evaluate the effectiveness and safety of moxibustion for PV.

Methods: We will search the following Electronic databases from their inceptions to February 2021 without any language limitation: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, WangFang Database, Chinese Science Journal Database, Chinese Biomedical Literature Database. What's more, the grey literature and the references of all included literature will also be retrieved manually. Any clinical randomized controlled trials (RCTs) related to moxibustion therapy for PV will be taken into. In order to complete data synthesis and assess the risk of bias, we will use the RevMan V.5.3 software.

Results: This systematic review will provide an assessment of the current state of moxibustion for PV, aiming to assess the efficacy and safety of moxibustion for patients with PV.

Conclusion: This systematic review will establish convincing evidence to prove the effectiveness and safety of moxibustion for PV.

Inplasy Registration Number: INPLASY202120008.
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http://dx.doi.org/10.1097/MD.0000000000025250DOI Listing
March 2021

VEXAS syndrome in myelodysplastic syndrome with autoimmune disorder.

Exp Hematol Oncol 2021 Mar 19;10(1):23. Epub 2021 Mar 19.

State Key Laboratory of Experimental Haematology, Institute of Haematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly-described adult-onset inflammatory syndrome characterized by vacuoles in myeloid and erythroid precursor cells and somatic mutations affecting methionine-41 (p.Met41) in UBA1. The VEXAS syndrome often overlaps with myelodysplastic syndromes (MDS) with autoimmune disorders (AD). By screening the UBA1 gene sequences derived from MDS patients with AD from our center, we identified one patient with a p.Met41Leu missense mutation in UBA1, who should have been diagnosed as MDS comorbid with VEXAS syndrome. This patient respond poorly to immune suppressive drugs. Patients with MDS and AD who have characteristic vacuoles in myeloid and erythroid precursor cells should be screened for UBA1 mutation, these patients are likely to have VEXAS syndrome and unlikely to improve with immunosuppressive drugs and should be considered for other alternative therapies.
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http://dx.doi.org/10.1186/s40164-021-00217-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976711PMC
March 2021

Long-term temperature variability and the incidence of cardiovascular diseases: A large, representative cohort study in China.

Environ Pollut 2021 Jun 1;278:116831. Epub 2021 Mar 1.

Department of Cardiology, Fuwai Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, 100037, China.

In the context of global climate change, far less is known about the impact of long-term temperature variability (TV), especially in developing countries. The current study aimed to estimate the effect of long-term TV on the incidence of cardiovascular disease (CVD) in China. A total of 23,721 individuals with a mean age of 56.15 years were enrolled at baseline from 2012 to 2016 and followed up during 2017-2019. TV was defined as the standard deviation of daily temperatures during survey years and was categorized into tertiles (lowest≤ 8.78 °C, middle = 8.78-10.07 °C, highest ≥ 10.07 °C). The Cox proportional hazards regression was used to estimate the multivariable-adjusted hazard ratio (HR) between TV and CVD. During the median follow-up of 4.65 years, we ascertained 836 cases of incident CVD. For per 1 °C increase in TV, there was a 6% increase of CVD (HR = 1.06 [95% confidence interval (CI): 1.01-1.11]). A significant positive trend was observed between CVD risk and increasing levels of TV compared to the lowest tertile [HR = 1.34 (95% CI: 1.13-1.59) for the medium tertile, HR = 1.72 (95% CI: 1.35-2.19) for the highest tertile, P < 0.001]. Exposure to high TV would lose 2.11 disease-free years for the population aged 35-65 years and 66 CVD cases (or 7.95% cases) could been attributable to TV higher than 8.11 °C in the current study. The current findings suggested that long-term TV was associated with a higher risk of CVD incidence, it is needed to reduce the TV-related adverse health effect.
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http://dx.doi.org/10.1016/j.envpol.2021.116831DOI Listing
June 2021

Integrated molecular modeling techniques to reveal selective mechanisms of inhibitors to PI3Kδ with marketed Idelalisib.

Chem Biol Drug Des 2021 Jun 13;97(6):1158-1169. Epub 2021 Mar 13.

School of Pharmaceutical Sciences, Jiangnan University, Wuxi, China.

Phosphatidylinositol-3-kinase (PI3K) is important for cell proliferation, differentiation, and apoptosis, and the diverse physiological roles of different PI3K isoforms have highlighted the significance of the development of PI3Kδ inhibitors. A large number of PI3Kδ inhibitors have been reported after the FDA approval of Idelalisib, but the clinical use of Idelalisib was limited because of its serious side effects. Therefore, great efforts have been made on the development of PI3Kδ inhibitors with higher selectivity and lower toxicity, but there is no new PI3Kδ inhibitor coming into the market so far. Even so, as the first listed PI3K inhibitor, Idelalisib could be used as an effective tool to investigate the selective inhibition mechanism of PI3Kδ. Thus, in this study, a modeling strategy integrated 3D-QSAR, pharmacophore model, and molecular dynamics simulation was employed to reveal the key chemical characteristics of Idelalisib analogs and the binding pattern between the inhibitors and PI3Kδ. First, the CoMFA model with high statistical significance was built to reveal the general structure-activity relationships. And then, a reliable pharmacophore model with a robust discrimination capability was constructed to expound the main chemical characteristics of the PI3Kδ inhibitors. Finally, molecular dynamics simulation was conducted to explore the binding modes and some key residues refer to δ-selective binding were highlighted with binding-free energy calculation. In summary, these models and results would provide some effective help for the discovery or the rational design of novel PI3Kδ inhibitors.
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http://dx.doi.org/10.1111/cbdd.13838DOI Listing
June 2021

NIR-laser-triggered gadolinium-doped carbon dots for magnetic resonance imaging, drug delivery and combined photothermal chemotherapy for triple negative breast cancer.

J Nanobiotechnology 2021 Mar 2;19(1):64. Epub 2021 Mar 2.

State Key Laboratory of Non-Food Biomass and Enzyme Technology, Guangxi Academy of Sciences, Nanning, 530007, China.

Background: Owing to high genetic diversities of tumor cells and low response rate of standard chemotherapy, patients with triple negative breast cancer (TNBC) have short progression-free survivals and poor outcomes, which need to explore an effective approach to improve therapeutic efficacy.

Methods: Novel gadolinium doped carbon dots ([email protected]) have been designed and prepared through hydrothermal method with 3,4-dihydroxyhydrocinnamic acid, 2,2'-(ethylenedioxy)bis(ethylamine) and gadolinium chloride. The synthesized nanostructures were characterized. Taking advantage of good biocompatibility of [email protected], a nanoplatform based on [email protected] has been developed to co-deliver chemotherapy drug doxorubicin hydrochloride (Dox) and a near-infrared (NIR) photothermal agent, IR825 for magnetic resonance imaging (MRI) guided photothermal chemotherapy for TNBC.

Results: The as-synthesized [email protected]@[email protected] displayed favorable MRI ability in vivo. Upon NIR laser irradiation, [email protected]@[email protected] could convert the NIR light to heat and efficiently inhibit tumor growth through photothermal chemotherapy in vitro and in vivo. Additionally, the impact of photothermal chemotherapy on the murine motor coordination was assessed by rotarod test. [email protected]@[email protected] presented low toxicity and high photothermal chemotherapy efficiency.

Conclusion: A noble theranostic nanoplatform ([email protected]@[email protected]) was developed that could be tailored to achieve loading of Dox and IR825, intracellular delivery, favorable MRI, excellent combination therapy with photothermal therapy and chemotherapy to enhance therapeutic effect against TNBC cells. This study will provide a promising strategy for the development of Gd-based nanomaterials for MRI and combinational therapy for TNBC.
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http://dx.doi.org/10.1186/s12951-021-00811-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923633PMC
March 2021

Arsenic Dispensing Powder Promotes Erythropoiesis in Myelodysplastic Syndromes via Downregulation of HIF1A and Upregulation of GATA Factors.

Am J Chin Med 2021 25;49(2):461-485. Epub 2021 Feb 25.

Divisions of Pathology and Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, OH, USA.

Traditional Chinese Medicine (TCM) is a practical medicine based on thousands of years of medical practice in China. Arsenic dispensing powder (ADP) has been used as a treatment for MDS patients with a superior efficacy on anemia at Xiyuan Hospital of China Academy of Chinese Medical Sciences. In this study, we retrospectively analyzed MDS patients that received ADP treatment in the past 9 years and confirmed that ADP improves patients' anemia and prolongs overall survival in intermediate-risk MDS patients. Then, we used the MDS transgenic mice model and cell line to explore the drug mechanism. In normal and MDS cells, ADP does not show cellular toxicity but promotes differentiation. In mouse MDS models, we observed that ADP showed significant efficacy on promoting erythropoiesis. In the BFU-E and CFU-E assays, ADP could promote erythropoiesis not only in normal clones but also in MDS clones. Mechanistically, we found that ADP could downregulate HIF1A in MDS clones through upregulation of VHL, P53 and MDM2, which is involved in two parallel pathways to downregulate HIF1A. We also confirmed that ADP upregulates GATA factors in normal clones. Thus, our clinical and experimental studies indicate that ADP is a promising drug to promote erythropoiesis in both MDS and normal clones with a superior outcome than current regular therapies. ADP promotes erythropoiesis in myelodysplastic syndromes via downregulation of HIF1A and upregulation of GATA factors.
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http://dx.doi.org/10.1142/S0192415X2150021XDOI Listing
February 2021

Preparation and validation of cyclodextrin-based excipients for radioiodinated hypericin applied in a targeted cancer radiotherapy.

Int J Pharm 2021 Apr 25;599:120393. Epub 2021 Feb 25.

Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China. Electronic address:

Background: Iodine-131 labeled hypericin (I-Hyp) has been utilized as a necrosis-avid theragnostic tracer in a dual targeting pan-anticancer strategy called OncoCiDia. Widespread use of previously-tested solvent dimethyl sulfoxide (DMSO) is limited by safety concerns. To tackle this, the present study was designed to explore a clinically feasible excipient for the formulation of the hydrophobic I-Hyp for intravenous administration.

Method: Solubility of Hyp in serial solutions of already-approved hydroxypropyl-β-cyclodextrin (HP-β-CD) was evaluated by UVspectrophotometry and 50% HP-β-CD was chosen for further experiments. Two novel HP-β-CD-based formulations of I-Hyp were compared with previous DMSO-based formulation, with regards to necrosis-targetability and biodistribution, by magnetic resonance imaging, single-photon emission computed tomography (SPECT), gamma counting, autoradiography, fluorescence microscopy and histopathology.

Results: Hyp solubility was enhanced with increasing HP-β-CD concentrations. The radiochemical purity of I-Hyp was higher than 90% in all formulations. The necrosis-targetability of I-Hyp in the novel formulations was confirmed in vivo by SPECT and in vitro by autoradiography, fluorescence microscopy and histopathology. The plasma clearance of radioactivity was faster in the novel formulations.

Conclusion: The novel I-Hyp formulations with HP-β-CD could be a suitable pharmaceutical excipient for I-Hyp for intravenous administration.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120393DOI Listing
April 2021

Population Dynamics and Life History Response to Precipitation Changes for a Desert Ephemeral Plant With Biseasonal Germination.

Front Plant Sci 2021 3;12:625475. Epub 2021 Feb 3.

State Key Laboratory of Desert and Oasis Ecology/Fukang Station of Desert Ecology, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi, China.

The changing availability of water resources and frequent extreme drought events in the context of global change will have a profound impact on desert vegetation, especially on herbaceous populations such as ephemerals. is the dominant species in the Gurbantunggut Desert. It can germinate both in spring and autumn, which is important for herbaceous layer coverage and productivity. Therefore, we tracked and recorded the survival and reproduction of the population under different precipitation treatments and established a population matrix model, monitored the allometry and leaf traits of the plants, and compared the performance of spring-germinating and autumn-germinating plants. Our results showed that: (1) The population dynamics were significantly affected by precipitation changes; (2) drought reduced the survival rate of the plants and accelerated the completion of their life history; (3) precipitation had a significant effect on seed production and growth rate, but not on plant height and allometry; (4) biomass, leaf area, specific leaf area, and 100-grain weight of also responded to changes in precipitation; and (5) autumn-germinated plants had higher productivity, whereas spring-germinated plants exhibited higher reproductive efficiency, indicating that they had difference life history strategies. In conclusion, our results suggested that, although frequent or prolonged drought can significantly inhibit population growth, species with biseasonal germination are likely to be less affected.
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http://dx.doi.org/10.3389/fpls.2021.625475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901992PMC
February 2021

Autophagy Gene Panel-Based Prognostic Model in Myelodysplastic Syndrome.

Front Oncol 2020 5;10:606928. Epub 2021 Feb 5.

Department of Hematology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Abnormal autophagy is related to the pathogenesis and clinical symptoms of myelodysplastic syndrome (MDS). However, the effect of autophagy-related genes (ARGs) on the prognosis of MDS remains unclear. Here, we examined the expression profile of 108 patients with MDS from the GSE58831 dataset, and identified 22 genes that were significantly associated with overall survival. Among them, seven ARGs were screened and APIs were calculated for all samples based on the expression of the seven ARGs, and then, MDS patients were categorized into high- and low-risk groups based on the median APIs. The overall survival of patients with high-risk scores based on these seven ARGs was shorter than patients with low-risk scores in both the training cohort (P = 2.851e-06) and the validation cohort (P = 9.265e-03). Additionally, API showed an independent prognostic indicator for survival in the training samples [hazard ratio (HR) = 1.322, 95% confidence interval (CI): 1.158-1.51; P < 0.001] and the validation cohort (HR = 1.05, 95% CI: 1-1.1; P < 0.01). The area under the receiver operating characteristic curve (AUROC) of API and IPSS were 43.0137 and 66.0274 in the training cohorts and the AUC of the validation cohorts were 41.5361 and 72.0219. Our data indicate these seven ARGs can predict prognosis in patients with MDS and could guide individualized treatment.
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http://dx.doi.org/10.3389/fonc.2020.606928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894207PMC
February 2021

CRISPR/Cas9-mediated knockout of the NlCSAD gene results in darker cuticle pigmentation and a reduction in female fecundity in Nilaparvata lugens (Hemiptera: Delphacidae).

Comp Biochem Physiol A Mol Integr Physiol 2021 Jun 19;256:110921. Epub 2021 Feb 19.

State Key Laboratory of Biocontrol and School of Life Sciences, Sun Yat-sen University, Guangzhou, China. Electronic address:

In insects, cuticular pigmentation genes have been exploited as potential visible markers for constructing genetic manipulation systems. Here, we cloned cysteine sulfinic acid decarboxylase (CSAD), an orthologue of melanin metabolism pathway genes, and performed RNAi experiments in the brown planthopper Nilaparvata lugens (Hemiptera: Delphacidae). The results showed that a decrease in the level of transcription of NlCSAD increased melanin deposition in the body compared to the control group, resulting in darker cuticle pigmentation. Female adults treated with dsNlCSAD and mated with wild-type males laid significantly fewer eggs than the dsGFP-treated group, and lower hatchability of the eggs was also observed. In addition, two melanic mutant N. lugens strains (NlCSAD and NlCSAD) constructed by the CRISPR/Cas9 genome editing system showed darker cuticular melanisation and a reduced oviposition and hatching rate, but the homozygotes had a darker body colour, fewer eggs and lower hatchability than heterozygotes or individuals after RNAi. Thus, we have provided the first evidence that NlCSAD is required for normal body pigmentation in adults and has a role in the fecundity of females and hatchability of eggs in N. lugens via a combination of RNAi and knockout of target genes based on the CRISPR/Cas9 genome editing system. Our results suggest that NlCSAD is a candidate visual reference gene for genetic manipulation of this important crop pest.
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http://dx.doi.org/10.1016/j.cbpa.2021.110921DOI Listing
June 2021

The effect of moving cupping on psoriasis vulgaris and its influence on PASI score: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Feb;100(6):e24217

Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine.

Background: We aim to study the treatment of psoriasis vulgaris with moving cupping.

Methods: We will search PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure, Chinese Science and Technology Periodical Database, Wanfang Database, and Chinese Biomedical Literature Database of randomized controlled trials beginning from their inception to August 2020. The primary outcomes are that PASI score and clinical effective rate will be the main outcome indicators. Additional outcome is The Quality of life index score and safety assessment will be considered a secondary outcome. Two independent authors will based on the Cochrane system evaluation manual 5.1.0 version of RCT bias risk assessment tool to evaluate the risk of bias among the final included studies. And we will use the RevMan 5.3 software to analysis data.

Results: This study will provide an assessment of the current state of moving cupping for the psoriasis vulgaris, aiming to show the efficacy and safety of this treatment.

Conclusion: This study will provide evidence to judge whether moving cupping is an effective therapy for psoriasis vulgaris.

Inplasy Registration Number: INPLASY2020120061.
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http://dx.doi.org/10.1097/MD.0000000000024217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982156PMC
February 2021

An SiO anode strengthened by the self-catalytic growth of carbon nanotubes.

Nanoscale 2021 Feb 10;13(6):3808-3816. Epub 2021 Feb 10.

State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry Chinese Academy of Sciences, Changchun, 130022, China.

Modification using carbon nanotubes (CNTs) is one of the most important strategies to boost the performance of materials in various applications, among which the CNT-modified silicon-based anodes have gained considerable attention in lithium-ion batteries (LIBs) due to their improved conductivity and cycle stability. However, the realization of a close-knit CNT coating on silicon (Si) through an efficient and cost-effective approach remains challenging. Herein, a new in situ self-catalytic method by acetylene treatment is presented, in which, CNTs can be directly grown and knitted on the SiO particles to construct a conductive additive-free [email protected] anode. The in situ grown CNTs can not only enhance electric conductivity and alleviate the volume effect of SiO effectively, but also mitigate the electrolyte decomposition with improved coulombic efficiency. As a result, an extremely high capacity of 1012 mA h g, long lifespan over 500 cycles at a current density of 2 A g as well as a good performance in full LIBs with a working potential of about 3.4 V (vs. nickel-rich cathode) were obtained. The rationally constructed [email protected] with easy synthesis and high throughput will hopefully promote LIBs with energy density above 300 W h kg. This study opens a new avenue to prepare CNT-decorated functional materials and brings the SiO-based anode one step closer to practical applications.
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http://dx.doi.org/10.1039/d0nr08297jDOI Listing
February 2021

ImmunoPET imaging of human CD8 T cells with novel Ga-labeled nanobody companion diagnostic agents.

J Nanobiotechnology 2021 Feb 9;19(1):42. Epub 2021 Feb 9.

Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Rd, Shanghai, 200127, China.

Background: Although immunotherapy has revolutionized treatment strategies for some types of cancers, most patients failed to respond or obtain long-term benefit. Tumor-infiltrating CD8 T lymphocytes are closely related to the treatment outcome and prognosis of patients. Therefore, noninvasive elucidation of both systemic and tumor-infiltrating CD8 T lymphocytes is of extraordinary significance for patients during cancer immunotherapy. Herein, a panel of Ga-labeled Nanobodies were designed and investigated to track human CD8 T cells in vivo through immuno-positron emission tomography (immunoPET).

Results: Among the screened Nanobodies, SNA006a showed the highest binding affinity and specificity to both human CD8 protein and CD8 cells in vitro, with the equilibrium dissociation constant (K) of 6.4 × 10 M and 4.6 × 10 M, respectively. Ga-NOTA-SNA006 was obtained with high radiochemical yield and purity, and stayed stable for at least 1 h both in vitro and in vivo. Biodistribution and Micro-PET/CT imaging studies revealed that all tracers specifically concentrated in the CD8 tumors with low accumulation in CD8 tumors and normal organs except the kidneys, where the tracer was excreted and reabsorbed. Notably, the high uptake of Ga-NOTA-SNA006a in CD8 tumors was rapid and persistent, which reached 24.41 ± 1.00% ID/g at 1.5 h after intravenous injection, resulting in excellent target-to-background ratios (TBRs). More specifically, the tumor-to-muscle, tumor-to-liver, and CD8 to CD8 tumor was 28.10 ± 3.68, 5.26 ± 0.86, and 19.58 ± 2.70 at 1.5 h, respectively. Furthermore, in the humanized PBMC-NSG and HSC-NPG mouse models, Ga-NOTA-SNA006a accumulated in both CD8 tumors and specific tissues such as liver, spleen and lung where human CD8 antigen was overexpressed or CD8 T cells located during immunoPET imaging.

Conclusions: Ga-NOTA-SNA006a, a novel Nanobody tracer targeting human CD8 antigen, was developed with high radiochemical purity and high affinity. Compared with other candidates, the long retention time, low background, excellent TBRs of Ga-NOTA-SNA006a make it precisely track the human CD8 T cells in mice models, showing great potential for immunotherapy monitoring and efficacy evaluation.
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http://dx.doi.org/10.1186/s12951-021-00785-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871532PMC
February 2021

A Novel Method to Treat Progressive Desmoid Tumors Involving Neurovascular Bundles: A Retrospective Cohort Study.

Neurosurgery 2021 May;88(6):1095-1102

Department of Orthopedic Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

Background: More effective therapies are needed to treat progressive desmoid tumors when active surveillance and systemic therapy fail.

Objective: To assess the efficacy and safety of sandwich isolation surgery on the local control of progressive desmoid tumors involving neurovascular bundles.

Methods: A total of 27 patients with progressive desmoid tumors at extremities involving neurovascular bundles who received surgery at our hospital between August 2014 and August 2018 were identified. A total of 13 patients received sandwich isolation surgery, in which R2 resection was performed in neurovasculature-involving regions, and a biomaterial patch was used to envelop involved neurovascular structures and isolate residual tumors. In non-neurovasculature-involving regions, wide resection was performed without isolation. A total of 14 patients received traditional surgery, which included tumor resection without isolation procedure.

Results: In sandwich isolation group, tumor progressions and local recurrences occurred in 3 patients outside the isolated neurovasculature-involving regions. However, no progressions or recurrences occurred in any patients in the isolated neurovasculature-involving regions where R2 resection was performed. Sandwich isolation surgery group and traditional surgery group shared similar baseline clinical characteristics. The estimated 3-yr event-free survival rate was 76.9% after sandwich isolation surgery, and 32.7% after traditional surgery (P = .025). Patients who received sandwich isolation surgery were less likely to have local recurrence (hazard ratio: 0.257, P = .040). No complications were noted except intermittent mild pain in operative regions (2 cases).

Conclusion: Sandwich isolation surgery is effective and safe for local control of desmoid tumors involving neurovascular bundles.
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http://dx.doi.org/10.1093/neuros/nyaa589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117464PMC
May 2021