Publications by authors named "Hang Su"

362 Publications

Nature of glutamate alterations in substance dependence: A systematic review and meta-analysis of proton magnetic resonance spectroscopy studies.

Psychiatry Res Neuroimaging 2021 Jul 7;315:111329. Epub 2021 Jul 7.

Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China; Shanghai Key Laboratory of Psychotic Disorders, Shanghai, PR China; Institute of Psychological and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China; CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Chinese Academy of Sciences, Shanghai, China. Electronic address:

Animal studies have reported the brain glutamatergic dysfunction in substance dependence. However, proton magnetic resonance spectroscopy (H-MRS) studies of glutamate in substance-dependent patients published contradicting results. In order to investigate the characteristics of brain glutamatergic alterations in substance-dependent patients, we conducted systematic reviews and meta-analyses of H-MRS studies that have investigated the glutamate, glutamine, and Glx (glutamate + glutamine) concentration in substance-dependent patients. Multiple databases were searched until Sep 10, 2020. Twenty-nine studies comprising 982 patients and 787 controls were included. There was significantly decreased glutamate level in dorsolateral prefrontal cortex in patients compared with controls. Higher glutamate levels in medial prefrontal cortex and basal ganglia region were also demonstrated in patients compared with controls. Subgroup analyses based on the substance type and abstinence period (short vs medium-term abstinence period) were performed. The results revealed Glx and glutamate concentrations in all investigated brain regions were not different in patients with any types of substance dependence compared with controls. The abstinence period had no effect on the glutamate levels. In summary, substance dependence is associated with glutamatergic dysfunction of prefrontal cortex and basal ganglia. Present findings partially support the hypothesis that addiction is associated with abnormal brain glutamatergic neurotransmission.
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http://dx.doi.org/10.1016/j.pscychresns.2021.111329DOI Listing
July 2021

Male heterogametic sex determination in Rana dybowskii based on sex-linked molecular markers.

Integr Zool 2021 Jul 12. Epub 2021 Jul 12.

College of Animal Science and Technology, Northeast Agricultural University, Harbin, China.

Identifying the mechanism for sex determination in amphibians is challenging. Very little is known about sex determination mechanisms of Rana dybowskii, a species of importance to evolutionary and conservation biology. We screened for sex-linked molecular markers in R. dybowskii in China using target region amplification polymorphism (TRAP) with two fixed primers against the sequences of Dmrt1. We found two male-linked molecular markers in R. dybowskii, which were 222 bp and 261 bp long. The detection rates of 222bp marker in males form Xinglong, Huadian, and Dandong were 93.79%, 69.64% and 13.64%, respectively, while the rate in females from Huadian was 27.50%. Besides, the detection rates of 261bp marker in the above three regions were only observed in males at the rate of 93.79%, 87.50%, and 32.73%, respectively. The inheritance patterns of sex-linked molecular markers showed that the two sex-linked molecular markers were heterozygous. Compared to the XY-male parent, progeny from XX-pseudo-male parent possessed lower sex reversal ratio at the same rearing temperature, and the proportion of female froglets from an XX-pseudo-male parent was more than 95% at low rearing temperature (15°C). Our findings suggest that R. dybowskii displays male heterogamety, and the two sex-linked molecular markers may have a guiding significance for the protection and utilization of R. dybowskii. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/1749-4877.12577DOI Listing
July 2021

Comparative observation of atmospheric nitrous acid (HONO) in Xi'an and Xianyang located in the GuanZhong basin of western China.

Environ Pollut 2021 Jul 5;289:117679. Epub 2021 Jul 5.

State Key Laboratory for Structural Chemistry of Unstable and Stable Species Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China; Center for Excellence in Regional Atmospheric Environment, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, PR China; University of Chinese Academy of Sciences, Beijing, China.

HONO is an important component of reactive nitrogen (N) and precursors of OH radical. However, the source and removal of HONO are not clear. Here, measurements of HONO (May 18-31, 2018) were conducted in Xi'an and Xianyang simultaneously for the first time. The relationship between HONO and other N (such as NO and NO) in two cities was analyzed. The mixing ratio of HONO in Xi'an was 1.2 ± 0.8 ppbv, and that in Xianyang was 1.2 ± 1.1 ppbv. The nighttime HONO mixing ratio was higher in Xianyang, while the daytime HONO was higher in Xi'an. Compared with the contribution from heterogeneous process of NO, direct emissions and homogeneous processes (NO + OH) were less important for nocturnal HONO formation in these two cities. The relative contribution of heterogeneous process in Xianyang was more important than that in Xi'an. The reaction of NO upon aerosols surface was identified as an important source of HONO for two sites. The conversion of NO on the other surfaces might attend the heterogeneous formation of HONO in Xianyang site. Daytime HONO budget analysis indicated that there was an additional unknown formation process of HONO at two sites. The net OH production rate from HONO (from 08:00 to 17:00) was 1.6 × 10 and 1.3 × 10 molecule/(cm s) for Xian and Xianyang, 5.2 and 3.5 times higher than from O photolysis. Besides, a dust storm appeared during this observation period, and the impact of local emission and transport processes was separately analyzed. The sources, characteristics, and effects of HONO identified in this study laid a foundation for further research on HONO and air pollution in the Guanzhong area.
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http://dx.doi.org/10.1016/j.envpol.2021.117679DOI Listing
July 2021

Evaluation of short-term (16-week) effectiveness and safety of guselkumab in patients with psoriasis: A prospective real-life study on the Chinese population.

Dermatol Ther 2021 Jul 6:e15054. Epub 2021 Jul 6.

Dermatology Hospital of Southern Medical University, Guangzhou, Guangdong Province, China.

Real-life data on guselkumab in psoriasis are limited and not available in China hitherto. This study aimed to evaluate the short-term effectiveness and safety of guselkumab in patients with psoriasis under Chinese real-life conditions and to explore the effect of guselkumab on CD4 CD25 Foxp3 regulatory T cells (Tregs). A Chinese prospective and real-life study involving patients with psoriasis in Dermatology Hospital of Southern Medical University, Guangzhou, China from April to September 2020 was conducted. A total of 45 patients with psoriasis were finally enrolled in the study. Psoriasis Area Severity Index (PASI) 90 and 100 responses at week 16 were achieved by 88.6% and 45.5% of patients, respectively. The analysis of PASI response in different subgroups showed no statistically significant difference. Univariate logistic regression analysis revealed that at week 16, none of the variables were associated with decreasing PASI 90 response, whereas age at onset of disease was a predictor of PASI 100 response. Dynamic detection of CD4 CD25 Foxp3 Tregs frequency from peripheral blood suggested a stable maintained trend in terms of guselkumab treatment duration. No severe adverse events occurred during the follow-up period. This study confirmed the short-term effectiveness and safety of guselkumab, as well as its good tolerance against psoriasis, in the Chinese population. Guselkumab treatment maintains levels of Tregs in patients with psoriasis.
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http://dx.doi.org/10.1111/dth.15054DOI Listing
July 2021

Teleost-Specific MxG, a Traitor in the Mx Family, Negatively Regulates Antiviral Responses by Targeting IPS-1 for Proteasomal Degradation and STING for Lysosomal Degradation.

J Immunol 2021 Jun 16. Epub 2021 Jun 16.

Department of Aquatic Animal Medicine, College of Fisheries, Huazhong Agricultural University, Wuhan, China;

IFN-β promoter stimulator-1 (IPS-1)- and stimulator of IFN genes (STING)-mediated type I IFNs play a critical role in antiviral responses. Myxovirus resistance (Mx) proteins are pivotal components of the antiviral effectors induced by IFNs in many species. An unprecedented expansion of Mx genes has occurred in fish. However, the functions and mechanisms of Mx family members remain largely unknown in fish. In this study, we found that grass carp () MxG, a teleost-specific Mx protein, is induced by IFNs and viruses, and it negatively regulates both IPS-1- and STING-mediated antiviral responses to facilitate grass carp reovirus, spring viremia of carp virus, and cyprinid herpesvirus-2 replication. MxG binds and degrades IPS-1 via the proteasomal pathway and STING through the lysosomal pathway, thereby negatively regulating IFN1 antiviral responses and NF-κB proinflammatory cytokines. MxG also suppresses the phosphorylation of STING IFN regulatory factor 3/7, and it subsequently downregulates IFN1 and NF-κB1 at the promoter, transcription, and protein levels. GTPase and GTPase effector domains of MxG contribute to the negative regulatory function. On the contrary, MxG knockdown weakens virus replication and cytopathic effect. Therefore, MxG can be an ISG molecule induced by IFNs and viruses, and degrade IPS-1 and STING proteins in a negative feedback manner to maintain homeostasis and avoid excessive immune responses after virus infection. To our knowledge, this is the first identification of a negative regulator in the Mx family, and our findings clarify a novel mechanism by which the IFN response is regulated.
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http://dx.doi.org/10.4049/jimmunol.2000555DOI Listing
June 2021

Quantifying the role of PM dropping in variations of ground-level ozone: Inter-comparison between Beijing and Los Angeles.

Sci Total Environ 2021 Sep 18;788:147712. Epub 2021 May 18.

College of Environmental Sciences and Engineering, Peking University, Beijing, China.

In recent decade the ambient fine particle (PM) levels have shown a trend of distinct dropping in China, while ground-level ozone concentrations have been increasing in Beijing and many other Chinese mega-cities. The variation pattern in Los Angeles was markedly different, with PM and ozone decreasing together over past decades. In this study, we utilize observation-based methods to establish the parametric relationship between PM concentration and key aerosol physical properties (including aerosol optical depth and aerosol surface concentration), and an observation-based 1-D photochemical model to quantify the response of PM decline in enhancing ground-level ozone pollution over a large PM concentration range (10-120 μg m). We find that the significance of ozone enhancement due to PM dropping depends on both the PM levels and optical properties of particles. Ozone formation increased by 37% in 2006-2016 due to PM dropping in Beijing, while it becomes less important (7%) as PM reaches below 40 μg/m, similar to Los Angeles since 1980s. Therefore, the two cities show the convergence of air pollutant characteristics. Hence a control strategy prioritizing reactive volatile organic compound abatement is projected to yield simultaneous ozone and PM reductions in Beijing, as experienced in Los Angeles.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147712DOI Listing
September 2021

Nasal delivery of an IgM offers broad protection from SARS-CoV-2 variants.

Nature 2021 Jun 3. Epub 2021 Jun 3.

Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA.

Resistance represents a major challenge for antibody-based therapy for COVID-19. Here we engineered an immunoglobulin M (IgM) neutralizing antibody (IgM-14) to overcome the resistance encountered by immunoglobulin G (IgG)-based therapeutics. IgM-14 is over 230-fold more potent than its parental IgG-14 in neutralizing SARS-CoV-2. IgM-14 potently neutralizes the resistant virus raised by its corresponding IgG-14, three variants of concern-B.1.1.7 (Alpha, which first emerged in the UK), P.1 (Gamma, which first emerged in Brazil) and B.1.351 (Beta, which first emerged in South Africa)-and 21 other receptor-binding domain mutants, many of which are resistant to the IgG antibodies that have been authorized for emergency use. Although engineering IgG into IgM enhances antibody potency in general, selection of an optimal epitope is critical for identifying the most effective IgM that can overcome resistance. In mice, a single intranasal dose of IgM-14 at 0.044 mg per kg body weight confers prophylactic efficacy and a single dose at 0.4 mg per kg confers therapeutic efficacy against SARS-CoV-2. IgM-14, but not IgG-14, also confers potent therapeutic protection against the P.1 and B.1.351 variants. IgM-14 exhibits desirable pharmacokinetics and safety profiles when administered intranasally in rodents. Our results show that intranasal administration of an engineered IgM can improve efficacy, reduce resistance and simplify the prophylactic and therapeutic treatment of COVID-19.
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http://dx.doi.org/10.1038/s41586-021-03673-2DOI Listing
June 2021

Face masks effectively limit the probability of SARS-CoV-2 transmission.

Science 2021 May 20. Epub 2021 May 20.

State Environmental Protection Key Laboratory of Formation and Prevention of Urban Air Pollution Complex, Shanghai Academy of Environmental Sciences, Shanghai 200233, China.

Airborne transmission by droplets and aerosols is important for the spread of viruses. Face masks are a well-established preventive measure, but their effectiveness for mitigating SARS-CoV-2 transmission is still under debate. We show that variations in mask efficacy can be explained by different regimes of virus abundance and related to population-average infection probability and reproduction number. For SARS-CoV-2, the viral load of infectious individuals can vary by orders of magnitude. We find that most environments and contacts are under conditions of low virus abundance (virus-limited) where surgical masks are effective at preventing virus spread. More advanced masks and other protective equipment are required in potentially virus-rich indoor environments including medical centers and hospitals. Masks are particularly effective in combination with other preventive measures like ventilation and distancing.
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http://dx.doi.org/10.1126/science.abg6296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168616PMC
May 2021

Thiol functionalized covalent organic framework for highly selective enrichment and detection of mercury by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Analyst 2021 May;146(9):2991-2997

Partner State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, 224 Waterloo Road, Kowloon Tong, Hong Kong, SAR, P. R. China.

A spherical thiol-functionalized covalent organic framework (COF-SH) was designed via a facile thiol-yne click reaction of a alkynyl-terminated COF and pentaerythritol tetra(3-mercaptopropionate). The COF-SH was explored as a new adsorbent for the selective enrichment of Hg2+. The as-prepared COF-SH exhibited a uniform mesoporous structure, a high abundance of binding sites, and good chemical stability, which endow it with great performance for the adsorption of Hg2+ and its corresponding maximum adsorption capacity was up to 617.3 mg g-1. Furthermore, the adsorption behavior of Hg2+ on the COF-SH wasin good agreement with the Langmuir and pseudo-second-order models. The influences of adsorbent dosage, pH, selectivity, and reusability of the COF-SH on Hg2+ adsorption were also investigated. Besides this, the COF-SH showed high selectivity towards Hg2+ even in the presence of a high concentration of K+, Na+, Ca2+, Mg2+ and Zn2+ metal ions. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), the corresponding limit of detection (LOD) of Hg2+ was determined at very low concentrations of 80 pg mL-1 (equal to 396 amoL μL-1). In addition, the COF-SH was successfully applied to rapidly enrich and sensitively detect Hg2+ in industrial sewage, with recoveries in the range of 101.8-103.4%, demonstrating the promising potential of COF-SH as an effective adsorbent for use in environmental sample pretreatment.
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http://dx.doi.org/10.1039/d1an00282aDOI Listing
May 2021

Broadband Absorption Based on Thin Refractory Titanium Nitride Patterned Film Metasurface.

Nanomaterials (Basel) 2021 Apr 23;11(5). Epub 2021 Apr 23.

Institute of Modern Optics, Department of Physics, Harbin Institute of Technology, Harbin 150001, China.

In this paper, a thin metasurface perfect absorber based on refractory titanium nitride (TiN) is proposed. The size parameter of the metasurface is investigated based on the finite difference time domain method and transfer matrix method. With only a 15-nm-thick TiN layer inside the silica/TiN/silica stacks standing on the TiN substrate, the near-perfect absorption throughout the visible regime is realized. The cross-talk between the upper and lower dielectric layers enables the broadening of the absorption peak. After patterning the thin film into a nanodisk array, the resonances from the nanodisk array emerge to broaden the high absorption bandwidth. As a result, the proposed metasurface achieves perfect absorption in the waveband from 400 to 2000 nm with an average absorption of 95% and polarization-insensitivity under the normal incidence. The proposed metasurface maintains average absorbance of 90% up to 50-degree oblique incidence for unpolarized light. Our work shows promising potential in the application of solar energy harvesting and other applications requiring refractory metasurfaces.
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http://dx.doi.org/10.3390/nano11051092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145760PMC
April 2021

Exosomes from adipose derived mesenchymal stem cells alleviate diabetic osteoporosis in rats through suppressing NLRP3 inflammasome activation in osteoclasts.

J Biosci Bioeng 2021 Jun 10;131(6):671-678. Epub 2021 Apr 10.

Cangzhou Central Hospital, No. 16 Xinhuaxi Road, Cangzhou 061000, Hebei, China.

Inflammation is one of major contributors of diabetic osteoporosis. Adipose derived mesenchymal stem cells (AD-MSCs) show great potential to inhibit inflammation. We investigated the anti-osteoporosis role of AD-MSCs-derived exosomes in diabetic osteoporosis and the underlying molecular mechanism. Cellular and animal diabetic osteoporosis models were created through high glucose exposure and streptozotocin injection. AD-MSCs-derived exosomes were isolated and characterized. Pro-inflammatory cytokines and osteoclast markers were determined by ELISA. Bone mineral content and density were detected to evaluate bone loss. qRT-PCR and Western blots were performed to detect the expression of target genes. AD-MSCs-derived exosomes inhibited the secretion of IL-1β and IL-18 in HG treated osteoclasts and restored the bone loss in streptozotocin-induced diabetic osteoporosis rats. Mechanistically, AD-MSCs-derived exosomes suppress NLRP3 inflammasome activation in osteoclasts, and then reduce bone resorption and recover bone loss. AD-MSCs-derived exosomes alleviate diabetic osteoporosis through suppressing NLRP3 inflammasome activation in osteoclasts, which might be a potential cell-free therapeutic approach for diabetes-induced bone loss treatment.
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http://dx.doi.org/10.1016/j.jbiosc.2021.02.007DOI Listing
June 2021

The Potential Regulatory Network of Glutamate Metabolic Pathway Disturbance in Chinese Han Withdrawal Methamphetamine Abusers.

Front Genet 2021 23;12:653443. Epub 2021 Mar 23.

Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Objects: To explore the long-term influence of methamphetamine abuse on metabolomics character, with gas chromatography-mass spectrometry (GS-MS) technology, and the potential regulatory network using the bioinformatics method.

Methods: Forty withdrawal methamphetamine abusers (WMA) were recruited from Shanghai Gaojing Forced Isolation Detoxification Institute. Forty healthy controls (HC) were recruited from society. GS-MS technology was used to detect metabolic products in serum. A bioinformatics method was used to build a regulatory network. Q-PCR was used to detect the candidate gene expressions, and ELISA was used to detect the regulatory enzyme expressions.

Results: Four pathways were significantly changed in the MA compared to the HC: (1) the arginine synthesis pathway, (2) alanine, aspartic acid and glutamate metabolic pathway, (3) cysteine and methionine metabolic pathway, and (4) the ascorbate and aldarate pathway (enrichment analysis < 0.05, Impactor factor > 0.2). When focusing on the 'Alanine, aspartate, and glutamate metabolism' pathway, a regulatory network was established, and the expression of candidate regulatory genes and enzymes was verified. It was found that the expression of (Discs large MAGUK scaffold protein 2), (Phospholipase A2 group IVE), (Phosphodiesterase 4D), (Phosphodiesterase 4B), and (Ephrin type-B receptor 2) were significantly different between the two groups ( < 0.05), However, after adjusting for age and BMI, only , and 2 remained significant ( < 0.05). The expression of enzymes was not significantly different ( > 0.05).

Conclusion: Methamphetamine abuse influences the metabolic process in the long term, and , and may regulate the glutamate metabolism pathway.
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http://dx.doi.org/10.3389/fgene.2021.653443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021790PMC
March 2021

Puerarin facilitates osteogenesis in steroid-induced necrosis of rabbit femoral head and osteogenesis of steroid-induced osteocytes via miR-34a upregulation.

Cytokine 2021 Jul 3;143:155512. Epub 2021 Apr 3.

Department of No. 5 Orthopedic Surgery, The Third Affiliated Hospital of Qiqihar Medical University, China. Electronic address:

The present study investigated the effect of puerarin on promoting the osteogenesis in steroid-induced necrosis of the femoral head (SONFH). New Zealand rabbits were administrated with horse serum and methylprednisolone (MPS) for establishing SONFH in vivo model, which was then treated with puerarin treatment. Histo-morphological changes in the femoral head were examined by hematoxylin-eosin staining. Osteoblasts were isolated from healthy rabbits and treated by individual or combined administration of dexamethasone and puerarin. Osteoblast viability was measured by CCK-8 assay. Mineralized nodule formation was evaluated by alizarin red assay. Expressions of RUNX family transcription factor 2 (RUNX2), Type-I collagen α 1 (COL1A1), ALP and miR-34a in the femoral head were determined by qRT-PCR and Western blot. Puerarin attenuated the effect of SONFH on promoting histopathological abnormalities and counteracted SONFH inhibition on the expressions of ALP, RUNX2, COL1A1 and miR-34a in the rabbits. Rabbit osteoblasts were successfully isolated, as they showed red mineralized nodules. Dexamethasone exposure decreased osteoblast viability, which was increased by puerarin treatment. Furthermore, puerarin treatment attenuated dexamethasone-induced inhibition on the viability, osteoblastic differentiation, and the expressions of ALP, RUNX2, COL1A1 and miR-34a in the osteoblasts. Puerarin facilitated osteogenesis of steroid-induced necrosis of rabbit femoral head and osteogenesis of steroid-induced osteocytes via miR-34a upregulation.
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http://dx.doi.org/10.1016/j.cyto.2021.155512DOI Listing
July 2021

The combination of chidamide with the CHOEP regimen in previously untreated patients with peripheral T-cell lymphoma: a prospective, multicenter, single arm, phase 1b/2 study.

Cancer Biol Med 2021 Mar 23. Epub 2021 Mar 23.

Department of Hematology, Peking Union Medical College Hospital, Beijing 100730, China.

Objective: To assess the efficacy and safety of the novel histone deacetylase inhibitor, chidamide, in combination with cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (Chi-CHOEP) for untreated peripheral T-cell lymphoma (PTCL).

Methods: A prospective, multicenter, single arm, phase 1b/2 study was conducted. A total of 128 patients with untreated PTCL (18-70 years of age) were enrolled between March 2016 and November 2019, and treated with up to 6 cycles with the Chi-CHOEP regimen. In the phase 1b study, 3 dose levels of chidamide were evaluated and the primary endpoint was determination of the maximum-tolerated dose and recommended phase 2 dose (RP2D). The primary endpoint of the phase 2 study was 2-year progression-free survival (PFS).

Results: Fifteen patients were enrolled in the phase 1b study and the RP2D for chidamide was determined to be 20 mg, twice a week. A total of 113 patients were treated at the RP2D in the phase 2 study, and the overall response rate was 60.2%, with a complete response rate of 40.7%. At a median follow-up of 36 months, the median PFS was 10.7 months, with 1-, 2-, and 3-year PFS rates of 49.9%, 38.0%, and 32.8%, respectively. The Chi-CHOEP regimen was well-tolerated, with grade 3/4 neutropenia occurring in approximately two-thirds of the patients. No unexpected adverse events (AEs) were reported and the observed AEs were manageable.

Conclusions: This large cohort phase 1b/2 study showed that Chi-CHOEP was well-tolerated with modest efficacy in previously untreated PTCL patients.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0413DOI Listing
March 2021

Morphological Subtypes of Tumor Spread Through Air Spaces in Non-Small Cell Lung Cancer: Prognostic Heterogeneity and Its Underlying Mechanism.

Front Oncol 2021 4;11:608353. Epub 2021 Mar 4.

Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

Background: Tumor spread through air spaces (STAS) has three morphologic subtypes: single cells, micropapillary clusters, and solid nests. However, whether their respective clinical significance is similar remains unclear.

Methods: We retrospectively reviewed 803 patients with resected non-small cell lung cancer (NSCLC) from January to December 2009. Recurrence-free survival (RFS) and overall survival (OS) were compared among patients stratified by STAS subtypes. We also performed a prospective study of NSCLC resection specimens to evaluate the influence of a prosecting knife on the presence of STAS subtypes during specimen handling (83 cases).

Results: STAS was found in 370 NSCLCs (46%), including 47 single cell STAS (13%), 187 micropapillary cluster STAS (50%), and 136 solid nest STAS (37%). STAS-negative patients had significantly better survival than patients with micropapillary cluster STAS (RFS: < 0.001; OS: < 0.001) and solid nest STAS (RFS: < 0.001; OS: < 0.001), but similar survival compared with those with single cell STAS (RFS: = 0.995; OS: = 0.71). Multivariate analysis revealed micropapillary cluster (RFS: < 0.001; OS: < 0.001) and solid nest STAS (RFS: = 0.001; OS: = 0.003) to be an independent prognostic indicator, but not for single cell STAS (RFS: = 0.989; OS: = 0.68). Similar results were obtained in subgroup analysis of patients with adenocarcinoma. The prospective study of NSCLC specimens suggested that 18 cases were considered as STAS false-positive, and most were singe cell pattern (13/18, 72%).

Conclusions: Single cell STAS was the common morphologic type of artifacts produced by a prosecting knife. A precise protocol of surgical specimen handling is required to minimize artifacts as much as possible.
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http://dx.doi.org/10.3389/fonc.2021.608353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970243PMC
March 2021

Light absorption of black carbon and brown carbon in winter in North China Plain: comparisons between urban and rural sites.

Sci Total Environ 2021 May 27;770:144821. Epub 2021 Jan 27.

State Key Laboratory of Atmospheric Boundary Layer Physics and Atmospheric Chemistry, Institute of Atmospheric Physics, Chinese Academy of Sciences, Beijing 100029, China; College of Earth and Planetary Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; Center for Excellence in Regional Atmospheric Environment, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China. Electronic address:

The light absorption black carbon (BC) and brown carbon (BrC) are two important sources of uncertainties in radiative forcing estimate. Here we investigated the light absorption enhancement (E) of BC due to coated materials at an urban (Beijing) and a rural site (Gucheng) in North China Plain (NCP) in winter 2019 by using a photoacoustic extinctiometer coupled with a thermodenuder. Our results showed that the average (±1σ) E was 1.32 (±0.15) at the rural site, which was slightly higher than that at the urban site (1.24 ± 0.15). The dependence of E on coating materials was found to be relatively limited at both sites. However, E presented considerable increases as a function of relative humidity below 70%. Further analysis showed that E during non-heating period in Beijing was mainly caused by secondary components, while it was dominantly contributed by enhanced primary emissions in heating season at both sites. In particular, aerosol particles mixed with coal combustion emissions had a large impact on E (>1.40), while the fresh traffic emissions and freshly oxidized secondary OA (SOA) had limited E (1.00-1.23). Although highly aged or aqueous-phase processed SOA coated on BC showed the largest E, their contributions to the bulk absorption enhancement were generally small. We also quantified the absorption of BrC and source contributions. The results showed the BrC absorption at the rural site was nearly twice that of urban site, yet absorption Ångström exponents were similar. Multiple linear regression analysis highlighted the major sources of BrC being coal combustion emissions and photochemical SOA at both sites with additional biomass burning at the rural site. Overall, our results demonstrated the relatively limited winter light absorption enhancement of BC in different chemical environments in NCP, which needs be considered in regional climate models to improve BC radiative forcing estimates.
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http://dx.doi.org/10.1016/j.scitotenv.2020.144821DOI Listing
May 2021

Treatment, Survival, and Prognosis of Advanced-Stage Natural Killer/T-Cell Lymphoma: An Analysis From the China Lymphoma Collaborative Group.

Front Oncol 2020 19;10:583050. Epub 2021 Feb 19.

Department of Radiation Oncology Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China.

Patients with advanced-stage natural killer/T-cell lymphoma (NKTCL) usually have a poor prognosis. However, there is limited data of comprehensive analysis on this particular patient population due to the rarity of the disease. The present study aimed to investigate the treatment models, survival outcomes, and prognosis of advanced-stage NKTCL. Data from 336 patients with advanced-stage NKTCL diagnosed between 2006 and 2015 in the China Lymphoma Collaborative Group database were retrospectively analyzed. The median age was 42 years and the male/female ratio was 2.4:1. About 97% of patients had stage IV disease and 77% had >1 extranodal involvement site. All patients received chemotherapy, with the most common option being asparaginase (Asp)-containing regimens (n=146; 43.5%). Among 286 patients with available response data, the overall response rate (ORR) was 57.3% with a complete remission (CR) rate of 35.7%. Asp-containing regimens led to better ORRs (86/132, 65.2% vs. 54/113, 47.8%, = 0.006) and CR rates (60/132, 45.5% vs. 27/113, 23.9%, < 0.001) than non-Asp-containing regimens. The expected 5-year progression-free survival (PFS) and overall survival (OS) rates were 22.6 and 32.0%, respectively, for the whole cohort. Compared to non-Asp-containing chemotherapy, Asp-containing chemotherapy improved 5-year PFS (34.2 vs. 17.1%, < 0.001) and OS (45.3 vs. 27.8%, < 0.001). A trend toward improvement in OS was observed when gemcitabine was added to Asp-containing chemotherapies. Moreover, those undergoing autologous hematopoietic stem cell transplantation had prolonged survival time. In conclusion, Asp-containing chemotherapy could improve the prognosis of advanced-stage NKTCL, and refinement of treatment models is warranted in the future.
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http://dx.doi.org/10.3389/fonc.2020.583050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7945040PMC
February 2021

Dose escalation and expansion (phase Ia/Ib) study of GLS-010, a recombinant fully human antiprogrammed death-1 monoclonal antibody for advanced solid tumors or lymphoma.

Eur J Cancer 2021 May 7;148:1-13. Epub 2021 Mar 7.

The First Affiliated Hospital of Bengbu Medical School, No 287 Changhuai Road, Longzihu District, Bengbu, 233000, China.

Background: GLS-010, a novel engineered fully human immunoglobin G4 monoclonal antibody, can specially block the PD-1/PD-L1/2 axis and reactivate the antitumor immunity.

Aim: This phase Ia/Ib study was carried out to evaluate the safety, recommended phase II dose (R2PD), and primary antitumor effects of GLS-010 in patients with advanced, refractory lymphoma and solid tumors.

Methods: In phase Ia study, patients with refractory solid tumors and lymphoma enrolled and received GLS-010 at a dose of 1, 4, or 10 mg/kg Q2W; 240 mg Q3W or Q2W. The primary objective was to assess the dose-limiting toxicity (DLT). In phase Ib study, doses were expanded in 9 specific tumors to ensure the R2PD and explore the efficacy. Tumor mutation burden level and PD-L1 expression were also assessed with whole-exome sequencing and immunohistochemistry (SP263), respectively.

Results: Up to April 18, 2020, a total of 289 patients (n = 24, phase Ia; n = 265, phase Ib) were enrolled. DLT was not observed in phase Ia part. The T, CL, and V were similar among all dose groups and different tumors. The most common treatment-emergent adverse events (TEAEs) were anemia, leukopenia, elevated alanine aminotransaminase/asparate aminotransferase (ALT/AST), and elevated bilirubin. And hypothyroidism was the most common immune-related adverse event (irAE). The incidence of grade ≥3 TEAE was 39.8%, while grade ≥3 irAE was only 4.5%. Based on safety studies, pharmacokinetics/pharmacodynamics, and preclinical data, 240-mg Q2W was recommended as the expansion dose. The overall objective response rate was 23.6%, with 10 patients achieving complete response. Patients with a high PD-L1 expression level (31.3% Versus. 13.7%, p = 0.012) or t-issue tumor mutation burden level (31.3% Versus. 5.6%, p = 0.009) showed a significantly better response.

Conclusion: GLS-010 showed acceptable safety profile and favorable clinical response. The dose of 240 mg Q2W was an optimal recommended dose as monotherapy.
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http://dx.doi.org/10.1016/j.ejca.2021.01.020DOI Listing
May 2021

Induction of ferroptosis in human nasopharyngeal cancer cells by cucurbitacin B: molecular mechanism and therapeutic potential.

Cell Death Dis 2021 03 4;12(3):237. Epub 2021 Mar 4.

Department of Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China.

Cucurbitacin B (CuB) is a widely available triterpenoid molecule that exhibits various biological activities. Previous studies on the anti-tumour mechanism of CuB have mostly focused on cell apoptosis, and research on the ferroptosis-inducing effect has rarely been reported. Herein, we first discovered the excellent cytotoxicity of CuB towards human nasopharyngeal carcinoma cells and elucidated its potential ferroptosis-inducing mechanisms. Morphology alterations of mitochondrial ultrastructure, as observed via transmission electron microscopy, showed that CuB-treated cells undergo ferroptosis. CuB caused intracellular accumulation of iron ions and depletion of glutathione. Detailed molecular mechanism investigation confirmed that CuB both induced widespread lipid peroxidation and downregulated the expression of GPX4, ultimately initiating a multipronged mechanism of ferroptosis. Furthermore, CuB exhibited anti-tumour effects in vitro by inhibiting cellular microtubule polymerization, arresting cell cycle and suppressing migration and invasion. Finally, CuB significantly inhibited tumour progression without causing obvious side effects in vivo. Altogether, our study highlighted the therapeutic potential of CuB as a ferroptosis-inducing agent for nasopharyngeal cancer, and it provided valuable insights for developing effective anti-tumour agents with novel molecular mechanisms derived from natural products.
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http://dx.doi.org/10.1038/s41419-021-03516-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933245PMC
March 2021

YF-H-2015005, a CXCR4 Antagonist, for the Mobilization of Hematopoietic Stem Cells in Non-Hodgkin Lymphoma Patients: A Randomized, Controlled, Phase 3 Clinical Trial.

Front Med (Lausanne) 2021 2;8:609116. Epub 2021 Feb 2.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China.

YF-H-2015005, a novel CXCR4 antagonist, has been proven to increase the quantities of circulating hematopoietic stem cells (HSCs), which results in an adequate collection of HSCs in non-Hodgkin lymphoma (NHL) patients. This was a multicenter, double-blind, randomized (1:1), placebo-controlled phase III clinical trial. All patients received granulocyte colony-stimulating factor (G-CSF) for up to 8 consecutive days. YF-H-2015005 or placebo was administrated on the evening of day 4 and continued daily for up to 4 days. Apheresis was conducted 9-10 h after each dose of YF-H-2015005 or placebo. The primary endpoint was the proportion of NHL patients procuring ≥5 × 10/kg CD34 HSCs within ≤4 apheresis sessions. In total, 101 patients with NHL were enrolled. The proportions of patients achieving primary endpoint were 57 and 12% in YF-H-2015005 and placebo groups, respectively ( < 0.001). Moreover, a higher proportion of YF-H-2015005-treated patients reached a minimum target collection of ≥2 × 10/kg CD34 HSCs in ≤4 apheresis days compared to placebo-treated patients (86 vs. 38%, < 0.001). Furthermore, the median time to collect ≥2 or 5 × 10/kg CD34+ HSCs were 1 and 3 days in YF-H-2015005-treated patients, but 4 days and not reached in placebo-treated patients, respectively. No severe treatment emergent adverse events were observed in both YF-H-2015005 treatment and placebo groups. YF-H-2015005 plus G-CSF regimen was a tolerable combination with high efficacy, which might be used to rapidly mobilize and collect HSCs in NHL patients.
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http://dx.doi.org/10.3389/fmed.2021.609116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884449PMC
February 2021

Tectorigenin attenuates the OGD/R-induced HT-22 cell damage through regulation of the PI3K/AKT and the PPARγ/NF-κB pathways.

Hum Exp Toxicol 2021 Aug 16;40(8):1320-1331. Epub 2021 Feb 16.

Department of Anesthesiology, Affiliated Hospital of 107652Shaanxi University of Traditional Chinese Medicine, Xianyang, China.

Tectorigenin (TEC) is an effective compound that derived from many plants, such as . Evidence suggested that TEC has anti-tumor, anti-oxidant activity, anti-bacterial and anti-inflammatory effects. In addition, there has some evidence indicated that TEC is a potential anti-stroke compound; however, its specific roles and associated mechanism have not yet been elucidated. In the present study, we aimed to investigate the anti-inflammatory, anti-oxidant activity and anti-apoptosis effects of TEC on oxygen-glucose deprivation/reperfusion (OGD/R)-induced HT-22 cells, and clarified the relevant mechanisms. Here, we observed that TEC significantly promoted cell survival, impeded cell apoptosis, inhibited ROS and inflammatory cytokines IL-1β, IL-6, TNF-α production in OGD/R-induced HT-22 cells. Moreover, TEC activated PI3K/AKT signal pathway, increased PPARγ expression and inhibited NF-κB pathway activation in OGD/R-induced HT-22 cells. Further studies indicated that PPARγ inhibitor GW9662 activated NF-κB pathway after TEC treatment in OGD/R-induced HT-22 cells. Also, PI3K/AKT inhibitor LY294002, PPARγ inhibitor GW9662 and NF-κB activator LPS both reversed the effects of TEC on OGD/R-induced HT-22 cell biology. Taken together, this research confirmed that TEC benefit to HT-22 cell survival and against OGD/R damage through the PI3K/AKT and PPARγ/NF-κB pathways. These results indicated that TEC might be an effective compound in the treatment for ischemic brain injury.
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http://dx.doi.org/10.1177/0960327121993213DOI Listing
August 2021

Donepezil Combined with DL-3-n-Butylphthalide Delays Cognitive Decline in Patients with Mild to Moderate Alzheimer's Disease: A Multicenter, Prospective Cohort Study.

J Alzheimers Dis 2021 ;80(2):673-681

Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Background: Vascular factors and mitochondria dysfunction contribute to the pathogenesis of Alzheimer's disease (AD). DL-3-n-butylphthalide (NBP) has an effect in protecting mitochondria and improving microcirculation.

Objective: The aim was to investigate the effect of donepezil combined NBP therapy in patients with mild-moderate AD.

Methods: It was a prospective cohort study. 92 mild-moderate AD patients were classified into the donepezil alone group (n = 43) or the donepezil combined NBP group (n = 49) for 48 weeks. All patients were evaluated with Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-cog), Clinician's Interview-Based Impression of Change plus caregiver input (CIBIC-plus), Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), and Neuropsychiatric Inventory (NPI) every 12 weeks. All patients were monitored for adverse events (AEs). The efficacy was analyzed using multivariate logistic regression analysis.

Results: The multivariate logistic regression analysis showed that the changes of ADAS-cog score (OR = 2.778, 95% CI: [1.087, 7. 100], p = 0.033) and ADCS-ADL score (OR = 2.733, 95% CI: [1.002, 7.459], p = 0.049) had significant difference between donepezil alone group and donepezil combined NBP group, while the changes of NPI (OR = 1.145, 95% CI: [0.463, 2.829], p = 0.769), MMSE (OR = 1.563, 95% CI: [0.615, 3.971], p = 0.348) and CIBIC-plus (OR = 2.593, 95% CI: [0.696, 9.685], p = 0.156) had no significant difference. The occurrence of AEs was similar in the two groups.

Conclusion: Over the 48-week treatment period, donepezil combined NBP group had slower cognitive decline and better activities of daily living in patients with mild to moderate AD. These indicated that the multi-target therapeutic effect of NBP may be a new choice for AD treatment.
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http://dx.doi.org/10.3233/JAD-201381DOI Listing
January 2021

Predictors of upstage and treatment strategies for stage IA lung cancers after sublobar resection for adenocarcinoma in situ and minimally invasive adenocarcinoma.

Transl Lung Cancer Res 2021 Jan;10(1):32-44

Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

Background: Invasive adenocarcinoma intraoperatively underestimated as adenocarcinoma in situ (AIS) or minimally invasive adenocarcinoma (MIA) based on frozen section (FS) is more likely to undergo insufficient resection. We aimed to investigate the predictors of upstage and treatment strategies for stage IA invasive adenocarcinoma after sublobar resection for AIS and MIA.

Methods: We identified 2,006 patients from January 2012 to December 2016 with early-stage lung adenocarcinoma who underwent sublobar resection based on FS diagnosis to guide surgical decision-making. All FS were categorized into three groups in real-time: (I) atypical adenomatous hyperplasia (AAH), (II) AIS, and (III) MIA.

Results: A total of 272 (13.5%, 272/2,006) cases were upstaged in the final pathology (FP) diagnosis (82 AAH to AIS, 127 AIS to MIA, and nine AIS and 54 MIA to invasive adenocarcinoma), and most upstage cases (64.3%, 175/272) were attributed to sampling error. Multivariate logistic regression showed that tumor size ≥1 cm was the only independent predictor of upstage. The upstage of 209 cases to AIS or MIA had no influence on the therapy because the extent of their resection was enough. Of the 63 cases upstaged to invasive adenocarcinoma, only 13 cases agreed to receive complementary treatment: five patients underwent complementary lobectomy, and seven patients received chemotherapy. Two invasive adenocarcinoma cases without complementary treatment experienced a local recurrence after surgery. No recurrence was observed in AAH, AIS and MIA. No patient died until December 01, 2019.

Conclusions: Timely complementary treatment is encouraged in AIS/MIA upstaged to invasive adenocarcinoma based on the FP after sublobar resection to avoid local recurrence. Pathologists should be more cautious about AIS and MIA with tumor size ≥1 cm to avoid underestimation and potentially insufficient resection.
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http://dx.doi.org/10.21037/tlcr-20-828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867766PMC
January 2021

The Role of α-Synuclein in Methamphetamine-Induced Neurotoxicity.

Neurotox Res 2021 Jun 8;39(3):1007-1021. Epub 2021 Feb 8.

Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Methamphetamine (METH), a highly addictive psychostimulant, is the second most widely used illicit drug. METH produces damage dopamine neurons and apoptosis via multiple inter-regulating mechanisms, including dopamine overload, hyperthermia, oxidative stress, mitochondria dysfunction, endoplasmic reticulum stress, protein degradation system dysfunction, and neuroinflammation. Increasing evidence suggests that chronic METH abuse is associated with neurodegenerative changes in the human brain and an increased risk of Parkinson's disease (PD). METH use and PD may share some common steps in causing neurotoxicity. Accumulation of α-synuclein, a presynaptic protein, is the pathological hallmark of PD. Intriguingly, α-synuclein upregulation and aggregation are also found in dopaminergic neurons in the substantia nigra in chronic METH users. This suggests α-synuclein may play a role in METH-induced neurotoxicity. The mechanism of α-synuclein cytotoxicity in PD has attracted considerable attention; however, how α-synuclein affects METH-induced neurotoxicity has not been reviewed. In this review, we summarize the relationship between METH use and PD, interdependent mechanisms that are involved in METH-induced neurotoxicity and the significance of α-synuclein upregulation in response to METH use. The identification of α-synuclein overexpression and aggregation as a contributor to METH-induced neurotoxicity may provide a novel therapeutic target for the treatment of the deleterious effect of this drug and drug addiction.
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http://dx.doi.org/10.1007/s12640-021-00332-2DOI Listing
June 2021

Molecular Mechanism of Lipid Accumulation and Metabolism of Oleaginous GD from Soil under Salt Stress.

Int J Mol Sci 2021 Jan 28;22(3). Epub 2021 Jan 28.

School of Life Science, Shanxi University, Taiyuan 030006, China.

The oleaginous microalgae species GD is a promising feedstock for biodiesel production from soil. However, its metabolic mechanism of lipid production remains unclear. In this study, the lipid accumulation and metabolism mechanisms of GD were analyzed under salt stress based on transcriptome sequencing. The biomass and lipid content of the alga strain were determined under different NaCl concentrations, and total RNA from fresh cells were isolated and sequenced by HiSeq 2000 high throughput sequencing technology. As the salt concentration increased in culture medium, the algal lipid content increased but the biomass decreased. Following transcriptome sequencing by assembly and splicing, 24,128 unigenes were annotated, with read lengths mostly distributed in the 200-300 bp interval. Statistically significant differentially expressed unigenes were observed in different experimental groups, with 2051 up-regulated genes and 1835 down-regulated genes. The lipid metabolism pathway analysis showed that, under salt stress, gene-related fatty acid biosynthesis (ACCase, KASII, KAR, HAD, FATA) was significantly up-regulated, but some gene-related fatty acid degradation was significantly down-regulated. The comprehensive results showed that salt concentration can affect the lipid accumulation and metabolism of GD, and the lipid accumulation is closely related to the fatty acid synthesis pathway.
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http://dx.doi.org/10.3390/ijms22031304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865546PMC
January 2021