Publications by authors named "Chao Zhao"

715 Publications

Integrating transcriptomics and behavior tests reveals how the C. elegans responds to copper induced aging.

Ecotoxicol Environ Saf 2021 Jul 12;222:112494. Epub 2021 Jul 12.

Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China. Electronic address:

Copper (Cu) pollution in water and agricultural soil has always been a worldwide concern. This research aims to investigate the health effects of copper exposure on Caenorhabditis elegans (C. elegans) under the existing environmental quality standards (1 mg/L and 2 mg/L) via lifespan, reproduction, biological markers and transcriptome analysis. The results showed that copper of these two environmental standards shorten the lifespan of nematodes, reduced the brood size, reduced the frequency of pharyngeal pumps and prolonged defecation time as aging-related behaviors, and increased the levels of aging-related markers ROS, MDA and HO. There was a certain effect trend for the two exposure concentrations. Further, the possible molecular mechanism of copper-induced aging and reproductive effects on C. elegans was explored. Differential gene expression analysis was performed, and 2332 genes (567 up- and 1765 down-regulated genes) in the 1 mg/L group, 2449 DEGs (724 up- and 1725 down-regulated genes) in the 2 mg/L group in response to copper treatment. The top 20 regulated genes were vit (vit-1, vit-3, vit-4) genes, col genes (col-35, col-72, col-114, col-123, col-164, col-183, col-185), eea-1, him-18 and grl-20, which suggested that cuticle collagen synthesis and yolk expression were disrupted by copper. Analysis of KEGG pathway showed copper exposure widely affects longevity regulation pathways, thereby promoting aging. In summary, the sequencing results extensively and deeply reveal the health hazards of environmentally relevant doses of copper exposure to C. elegans, and behavioral testing verified that copper promoted aging of C. elegans.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112494DOI Listing
July 2021

Nutritional regulation of oligodendrocyte differentiation regulates perineuronal net remodeling in the median eminence.

Cell Rep 2021 Jul;36(2):109362

MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK. Electronic address:

The mediobasal hypothalamus (MBH; arcuate nucleus of the hypothalamus [ARH] and median eminence [ME]) is a key nutrient sensing site for the production of the complex homeostatic feedback responses required for the maintenance of energy balance. Here, we show that refeeding after an overnight fast rapidly triggers proliferation and differentiation of oligodendrocyte progenitors, leading to the production of new oligodendrocytes in the ME specifically. During this nutritional paradigm, ME perineuronal nets (PNNs), emerging regulators of ARH metabolic functions, are rapidly remodeled, and this process requires myelin regulatory factor (Myrf) in oligodendrocyte progenitors. In genetically obese ob/ob mice, nutritional regulations of ME oligodendrocyte differentiation and PNN remodeling are blunted, and enzymatic digestion of local PNN increases food intake and weight gain. We conclude that MBH PNNs are required for the maintenance of energy balance in lean mice and are remodeled in the adult ME by the nutritional control of oligodendrocyte differentiation.
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http://dx.doi.org/10.1016/j.celrep.2021.109362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293628PMC
July 2021

Trans-generational effects of copper on nerve damage in Caenorhabditis elegans.

Chemosphere 2021 Jul 1;284:131324. Epub 2021 Jul 1.

Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China. Electronic address:

The potential toxicity of copper has received great attention for a long time, however, trans-generational effects of copper have not been extensively investigated. Caenorhabditis elegans (C. elegans) was used to evaluate the trans-generational toxicities of copper several physiological endpoints: growth, head thrashes and body bends and degree of neuronal damage. Copper significantly inhibited growth, body bends, head thrashes and caused degeneration of dopaminergic neurons in a concentration-dependent manner in parental worms. Further we found oxidative damage was to underlying the onset of neuron degeneration. In our study copper promoted ROS accumulation, and led to an increased expression of the oxidative stress response-related genes sod-3 and a decreased expression of metal detoxification genes mtl-1 and mtl-2. Moreover, copper increased the fluorescence intensity of the transgenic strain that encodes the antioxidant enzyme SOD-3. Gradually decline in copper-induced impairments were observed in the filial generations without exposure. No growth impairment was shown in F3, the trend of head thrashes recovery gradually appeared in F2 and no growth impairment was shown in F3, the body bends impairment caused by the parental copper exposure was recovery until F4 and no growth impairment was shown in F5. Besides, dopamine neurons revealed damage related to neurobehavioral endpoints, with hereditary effects in the progeny together. In addition, sequencing results suggested that copper exposure could cause epigenetic changes. QRT-PCR results showed that differentially expressed genes can also be passed on to offspring.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131324DOI Listing
July 2021

Elimination of Cervical Cancer: Challenges Promoting the HPV Vaccine in China.

Indian J Gynecol Oncol 2021 27;19(3):51. Epub 2021 Jun 27.

Deparment of Gynecology and Obstetrics, Peking University People's Hospital, No.11# Xizhimen South St. Xicheng District, Beijing, 100044 China.

Objective: Cervical cancers present major threats to women's health in China. Eliminating cervical cancer in China is a huge challenge, with application of the HPV vaccine, which is an important part.

Methods: There are currently four HPV vaccines available in China: bv-HPV (Wantai, China), bv-HPV, qv-HPV (GSK, UK), and 9v-HPV (MSD, USA). To observe the immunogenicity, efficacy, and safety of these four vaccines in China, we formed the "Chinese Expert Consensus on the Clinical Application of HPV Vaccine."

Results: At 7 months after vaccination, all vaccinated subjects had the same immunogenic response to either HPV16 or HPV18, ranging from 96 to 100%, and antibody production in girls aged 9-14 years was 2-3 times higher than that in adult women. Efficacy of the four vaccines against CIN2 + ranged from 87.3%  to 100%, with prevention of HPV-associated infection reaching 96% ~ 97% at 12 months. Clinical trials showed bv-HPV and qv-HPV vaccine were also safe in women aged 18-45 years. Clinical trials of the 9v-HPV vaccine are underway. HPV vaccination is currently voluntary and self-paid in China. The "Chinese Expert Consensus on the Clinical Application of HPV Vaccine" will work to promote the application of HPV vaccine in China.

Conclusions: In clinical studies, the available HPV vaccines showed excellent efficacy, safety, and immunogenicity in Chinese women. We will continue strengthening screening and encouraging HPV vaccination.
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http://dx.doi.org/10.1007/s40944-021-00536-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236217PMC
June 2021

Cardiac Overexpression of XIN Prevents Dilated Cardiomyopathy Caused by ΔK210 Mutation.

Front Cell Dev Biol 2021 17;9:691749. Epub 2021 Jun 17.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.

mutation is associated with a range of cardiac diseases, including dilated cardiomyopathy (DCM). However, the mechanisms underlying the development of DCM and heart failure remain incompletely understood. In the present study, we found the expression of cardiac XIN protein was reduced in -ΔK210 hESCs-derived cardiomyocytes and mouse heart tissues. We further investigated whether XIN protects against mutation-induced DCM. Overexpression of the repeat-containing isoform XINB decreased the percentage of myofilaments disorganization and increased cell contractility of -ΔK210 cardiomyocytes. Moreover, overexpression of XINB by heart-specific delivery via AAV9 ameliorates DCM remodeling caused by -ΔK210 mutation in mice, revealed by partially reversed cardiac dilation, systolic dysfunction and heart fibrosis. These results suggest that deficiency of XIN may play a critical role in the development of DCM. Consequently, our findings may provide a new mechanistic insight and represent a therapeutic target for the treatment of idiopathic DCM.
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http://dx.doi.org/10.3389/fcell.2021.691749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247596PMC
June 2021

Molar activity of [F]FP-(+)-DTBZ radiopharmaceutical: Determination and its effect on quantitative analysis of VMAT2 autoradiography.

J Pharm Biomed Anal 2021 Sep 16;203:114212. Epub 2021 Jun 16.

NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, 214063, China. Electronic address:

[F]fluoropropyl-(+)-dihydrotetrabenazine ([F]FP-(+)-DTBZ) is a rising positron tracer for imaging vesicular monoamine transporter II (VMAT2) in the central nervous system. The present work was to develop a novel chromatographic method capable of the molar activity (A) determination of [F]FP-(+)-DTBZ. As a complement work of the A measurement, we also investigated the effect of A on the quantitative analysis of VMAT2 autoradiography with [F]FP-(+)-DTBZ. The A determination was performed by high performance liquid chromatography (HPLC) using the non-radioactive standard (FP-(+)-DTBZ) for calibration plot of peak area against concentration. Based on this correlation, the A of [F]FP-(+)-DTBZ was calculated and corrected to the end of synthesis. In the quantitative analysis of in vitro VMAT2 autoradiography, the striatum radioactivity uptake together with the uptake ratio of striatum versus cortex reduced along with the decrease of A and the increase of the FP-(+)-DTBZ content. Therefore, the A and the corresponding FP-(+)-DTBZ content have a significant effect on the quantitative analysis of VMAT2 autoradiography using [F]FP-(+)-DTBZ.
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http://dx.doi.org/10.1016/j.jpba.2021.114212DOI Listing
September 2021

Complete chloroplast genome of medicinal plant Wall. ex Roxb. (Sabiaceae).

Mitochondrial DNA B Resour 2021 Jun 7;6(7):1924-1925. Epub 2021 Jun 7.

College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, PR China.

Wall. ex Roxb., an evergreen climbing woody vine, is a Chinese herbal medicine commonly used by ethnic minorities in some areas of China. In this study, the chloroplast genome of was sequenced for the first time. Its genome is 162,054 bp in length with 38.6% of GC content. The genome consists of a large single copy (LSC) region of 90,001 bp, a small single copy (SSC) region of 18,887 bp, and two inverted repeat (IRa and IRb) regions of 26,583 bp each. A total of 130 genes were annotated, including 85 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. Phylogenetic analysis was conducted by nine species from order Proteales, which demonstrated a close relationship between the family Sabiaceae and Nelumbonaceae.
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http://dx.doi.org/10.1080/23802359.2021.1935350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189099PMC
June 2021

Accuracy of tibial tuberosity-trochlear groove distance and tibial tuberosity-posterior cruciate ligament distance in terms of the severity of trochlear dysplasia.

J Orthop Surg Res 2021 Jun 15;16(1):383. Epub 2021 Jun 15.

Department of Orthopaedic Surgery, Third Hospital of Hebei Medical University, Ziqiang Road 139, Shijiazhuang, 050051, China.

Purpose: Increased tibial tubercle-trochlear groove distance (TT-TG) was proposed as one of the main risk factors for patellofemoral instability (PFI). The increased TT-TG distance indicated externalization of the tibial tubercle with the reference of the trochlear groove. However, in the case of severe trochlear dysplasia, the reference point on the trochlear groove was indistinct, and the accuracy of TT-TG was controversial. The purpose of this study was to evaluate the accuracy of TT-TG and TT-PCL in consideration of the mild and severe trochlear dysplasia.

Methods: From 2015 to 2020, MRI findings of consecutive knee joints with PFI symptoms diagnosed in our hospital were retrospectively analyzed. All knees with trochlear dysplasia were diagnosed by longitudinal MRI scan and lateral radiograph. The knees were classified according to the four-type classification system described by Dejour et al. Twenty cases of type A (mild trochlear dysplasia); 20 cases of type B, C, and D (severe trochlear dysplasia); and 20 cases of normal type were selected and divided into normal group (normal trochlea), mild group (type A), and severe group (type B, type C, type D). Tibial tubercle-trochlear groove distance (TT-TG), tibial tubercle-posterior cruciate ligament distance (TT-PCL), and the Dejour classification of trochlear dysplasia were assessed by 2 experienced orthopedics. The reliability of TT-TG distance and TT-PCL distance was tested by intraclass correlation coefficients (ICCs).

Results: Comparing the differences between TT-TG and TT-PCL in the normal, mild, and severe groups, the TT-TG and TT-PCL in the mild and severe groups show different meanings (normal, 8.83 ± 3.62 mm vs. 8.44 ± 4.57 mm, P > 0.05; mild, 17.30 ± 4.81 mm vs. 20.09 ± 5.05 mm, P < 0.05; severe, 10.79 ± 4.24 mm vs. 12.31 ± 5.43 mm, P > 0.05). The Pearson correlation coefficient of TT-TG and TT-PCL measurements of trochlear dysplasia were r = 0.480 (mild group, P = 0.032) and r = 0.585 (severe group, P < 0.001). The intra-observer ICCs of TT-TG were r = 0.814 (mild group) and r = 0.739 (severe group). The inter-observer ICCs of TT-TG were r = 0.810 (mild group) and r = 0.713 (severe group). In the normal knee, the Pearson correlation coefficient of TT-TG and TT-PCL was r = 0.787(P < 0.001), the intra-observer ICC of TT-TG was r = 0.989, and the inter-observer ICC of TT-TG was r = 0.978.

Conclusion: Compared with the mild trochlear dysplasia, the inter-observer and intra-observer correlations of TT-TG measurements decreased in the group of severe dysplastic trochlea (inter-observer ICC, 0.810 vs. 0.713; intra-observer ICC, 0.814 vs. 0.739). In the present study, the determination of TT-TG and TT-PCL distance are of great significance for patients with low-grade trochlear dysplasia. And TT-PCL, without referring to the abnormal trochlear groove, is an effective indicator to measure the lateralization of tibial tuberosity in patients with severe dysplastic trochlea.
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http://dx.doi.org/10.1186/s13018-021-02527-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204520PMC
June 2021

SyntaLinker: automatic fragment linking with deep conditional transformer neural networks.

Chem Sci 2020 Jul 22;11(31):8312-8322. Epub 2020 Jul 22.

Center of Chemistry and Chemical Biology, Guangzhou Regenerative Medicine and Health Guangdong Laboratory Guangzhou 510530 China

Linking fragments to generate a focused compound library for a specific drug target is one of the challenges in fragment-based drug design (FBDD). Hereby, we propose a new program named SyntaLinker, which is based on a syntactic pattern recognition approach using deep conditional transformer neural networks. This state-of-the-art transformer can link molecular fragments automatically by learning from the knowledge of structures in medicinal chemistry databases ( ChEMBL database). Conventionally, linking molecular fragments was viewed as connecting substructures that were predefined by empirical rules. In SyntaLinker, however, the rules of linking fragments can be learned implicitly from known chemical structures by recognizing syntactic patterns embedded in SMILES notations. With deep conditional transformer neural networks, SyntaLinker can generate molecular structures based on a given pair of fragments and additional restrictions. Case studies have demonstrated the advantages and usefulness of SyntaLinker in FBDD.
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http://dx.doi.org/10.1039/d0sc03126gDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163338PMC
July 2020

Traditional Herbal Medicines, Bioactive Metabolites, and Plant Products Against COVID-19: Update on Clinical Trials and Mechanism of Actions.

Front Pharmacol 2021 28;12:671498. Epub 2021 May 28.

Pharmacology Department, Medical Faculty, Universiti Kebangsaan Malaysia (The National University of Malaysia), Kuala Lumpur, Malaysia.

SARS-CoV-2 is the latest worldwide pandemic declared by the World Health Organization and there is no established anti-COVID-19 drug to combat this notorious situation except some recently approved vaccines. By affecting the global public health sector, this viral infection has created a disastrous situation associated with high morbidity and mortality rates along with remarkable cases of hospitalization because of its tendency to be high infective. These challenges forced researchers and leading pharmaceutical companies to find and develop cures for this novel strain of coronavirus. Besides, plants have a proven history of being notable wellsprings of potential drugs, including antiviral, antibacterial, and anticancer therapies. As a continuation of this approach, plant-based preparations and bioactive metabolites along with a notable number of traditional medicines, bioactive phytochemicals, traditional Chinese medicines, nutraceuticals, Ayurvedic preparations, and other plant-based products are being explored as possible therapeutics against COVID-19. Moreover, the unavailability of effective medicines against COVID-19 has driven researchers and members of the pharmaceutical, herbal, and related industries to conduct extensive investigations of plant-based products, especially those that have already shown antiviral properties. Even the recent invention of several vaccines has not eliminated doubts about safety and efficacy. As a consequence, many limited, unregulated clinical trials involving conventional mono- and poly-herbal therapies are being conducted in various areas of the world. Of the many clinical trials to establish such agents as credentialed sources of anti-COVID-19 medications, only a few have reached the landmark of completion. In this review, we have highlighted and focused on plant-based anti-COVID-19 clinical trials found in several scientific and authenticated databases. The aim is to allow researchers and innovators to identify promising and prospective anti-COVID-19 agents in clinical trials (either completed or recruiting) to establish them as novel therapies to address this unwanted pandemic.
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http://dx.doi.org/10.3389/fphar.2021.671498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194295PMC
May 2021

Identification of a TRIM32 from Penaeus monodon is involved in autophagy and innate immunity during white spot syndrome virus infection.

Dev Comp Immunol 2021 Oct 10;123:104169. Epub 2021 Jun 10.

Key Laboratory of South China Sea Fishery Resources Exploitation and Utilization, Ministry of Agriculture and Rural Affairs, South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, 510300, Guangzhou, Guangdong Province, China; Sanya Tropical Fisheries Research Institute, Sanya, Hainan Province, China; Key Laboratory of Aquatic Genomics, Ministry of Agriculture and Rural Affairs, Chinese Academy of Fishery Science, Guangzhou, Guangdong Province, China. Electronic address:

Many tripartite motif (TRIM) family proteins played an important role in regulating innate immune and autophagy pathway and were important for host defenses against viral pathogens. However, the role of TRIM proteins in autophagy and innate immunity during virus infection was seldom studied in crustaceans. In this study, a novel TRIM32 homolog was identified from Penaeus monodon (named PmTRIM32). PmTRIM32 was significantly upregulated by rapamycin stimulation and WSSV infection. RNA interference experiments showed that PmTRIM32 could restrict WSSV replication and lead P. monodon more resistance to WSSV challenge. Autophagy could be induced by WSSV or rapamycin challenge and has been proved to play a positive role in restricting WSSV replication in P. monodon. The autophagy activity induced by WSSV or rapamycin challenge could be obviously inhibited by silence of PmTRIM32 in P. monodon. Further studies revealed that PmTRIM32 positively regulated the expression of nuclear transcription factor (NF-κB) and it mediated antimicrobial peptides. Moreover, Pull-down and in vitro ubiquitination assay demonstrated that PmTRIM32 could interact with WSSV envelope protein and target it for ubiquitination in vitro. Collectively, this study demonstrated that PmTRIM32 restricted WSSV replication and was involved in positively regulating autophagy and NF-κB pathway during WSSV infection in P. monodon.
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http://dx.doi.org/10.1016/j.dci.2021.104169DOI Listing
October 2021

ICI plus chemotherapy prolonged survival over ICI alone in patients with previously treated advanced NSCLC.

Cancer Immunol Immunother 2021 Jun 7. Epub 2021 Jun 7.

Department of Medical Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer Institute, Tongji University School of Medicine, No. 507, Zheng Min Road, Shanghai, 200433, People's Republic of China.

Objectives: Immune checkpoint inhibitors (ICI) monotherapy was standard of care in second-line treatment of patients with advance non-small cell lung cancer (NSCLC). This study aims to investigate the efficacy of ICI plus chemotherapy in patients with previously treated advanced NSCLC.

Patients And Methods: An investigator-initiated trial (IIT) aiming to evaluate the efficacy and safety of ICI in combination with chemotherapy as second line and beyond for patients with advanced NSCLC was undergone at Shanghai Pulmonary Hospital (ChiCTR1900026203). Patients who received ICI monotherapy as second or later line setting during the same period were also collected as a comparator.

Results: From April 2018 to June 2019, 31 patients were included into this IIT study, simultaneously 51 patients treated with ICI monotherapy were selected as a comparator. ICI plus chemotherapy showed a significantly higher ORR (35.5% vs. 15.7%, p=0.039), prolonged PFS (median: 5.6 vs. 2.5 months, p = 0.013) and OS (median: NE vs. 12.6 months, p = 0.038) compared with ICI alone. In the subgroup of negative PD-L1 expression (9 patients in combination group and 12 patients in monotherapy group), ICI plus chemotherapy also had a favorable ORR (44.4% vs. 8.3%, p = 0.119), longer PFS (median: 6.5 vs 3.0 months, p < 0.05) and OS (median: NE vs. 8.2 months, p = 0.117). Meanwhile, the addition of chemotherapy did not increase immune-related adverse events.

Conclusions: ICI plus chemotherapy showed superior ORR, PFS and OS than ICI alone patients with previous treated advanced NSCLC. These findings warrant further investigation.
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http://dx.doi.org/10.1007/s00262-021-02974-9DOI Listing
June 2021

Zero-Order Controlled Release of Water-Soluble Drugs Using a Marker Pen Platform.

ACS Omega 2021 Jun 19;6(21):13774-13778. Epub 2021 May 19.

Department of Chemical and Biological Engineering, The University of Alabama, Tuscaloosa, Alabama 35487, United States.

Zero-order drug release that releases drugs at a constant rate is beneficial to prolong the therapeutic effect and avoid the side effects of drugs. However, due to the weak interaction between the drug and the carrier, it is particularly challenging to achieve zero-order release of water-soluble drugs. Inspired by the marker pen, which stores the water-based ink in the sponge core and releases a constant amount of ink from the tip for writing, we explore the marker pen as a drug delivery platform to achieve zero-order release of water-soluble drugs. Through the capillary interaction between the material and water, the pen core can absorb the aqueous drug solution to encapsulate and store the water-soluble drug model sodium fluorescein (SF) and can release the encapsulated SF by moving the pen tip across the surface. The results show that the marker pen can release a constant amount of SF at the nanogram level per unit length of the line drawn with the pen, and the cumulative SF release amount has a linear relationship with the length of the line. In addition, the amount of released SF is linear with respect to the SF concentration in the aqueous solution. Moreover, the SF-filled marker pen has excellent long-term stability as evidenced by that the amount of SF released from the pen remains constant within two weeks after filling.
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http://dx.doi.org/10.1021/acsomega.1c01141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173564PMC
June 2021

γ-Glutamyl transpeptidase-activatable near-infrared nanoassembly for tumor fluorescence imaging-guided photothermal therapy.

Theranostics 2021 13;11(14):7045-7056. Epub 2021 May 13.

School of Engineering, China Pharmaceutical University, Nanjing 211198, P. R. China.

Precise treatment of tumors is attracting increasing attention. Molecular probes simultaneously demonstrating the diagnostic signal and pharmacological effect in response to tumor microenvironment are highly desired. γ-glutamyl transpeptidase (GGT) is a biomarker with significantly up-regulated expression in the tumor area. We developed a GGT responsive near-infrared (NIR) nanoassembly for tumor-specific fluorescence imaging-guided photothermal therapy. The GGT responsive NIR probe was constructed by conjugating GGT-specific substrate γ-glutamic acid (γ-Glu) with cyanine fluorophore (NRh-NH) via amide reaction. The resulting NRh-G spontaneously assembled into nanoparticles (NRh-G-NPs) around 50 nm. The NPs were characterized and the properties evaluated in the presence or absence of GGT. Subsequently, we studied fluorescence imaging and photothermal therapy of NRh-G-NPs and . NRh-G-NPs, upon specific reaction with GGT, turned into NRh-NH-NPs, showing a ~180-fold fluorescence enhancement and excellent photothermal effect recovery. NRh-G-NPs could selectively light up U87MG tumor cells while their fluorescence was weak in L02 human normal liver cells. The NPs also showed excellent tumor cell ablation upon laser irradiation. After intravenous injection into tumor-bearing mice, NRh-G-NPs could arrive in the tumor area and specifically light up the tumor. Following laser irradiation, the tumor could be completely erased with no tumor reoccurrence for up to 40 days. NRh-G-NPs were specifically responsive to GGT overexpressed in U87MG tumor cells and selectively lit up the tumor for imaging-guided therapy. Besides, the recovery of photothermal property in the tumor area could improve cancer therapy precision and decreased side effects in normal tissues.
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http://dx.doi.org/10.7150/thno.60586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171106PMC
May 2021

Bufotenine and its derivatives: synthesis, analgesic effects identification and computational target prediction.

Chin J Nat Med 2021 Jun;19(6):454-463

National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address:

Natural product bufotenine (5) which could be isolated from Venenum Bufonis, has been widely used as a tool in central nervous system (CNS) studies. We present here its quaternary ammonium salt (6) which was synthesized with high yields using 5-benzyloxyindole as raw materials, and we firstly discover its analgesic effects in vivo. The analgesic evaluation showed that compounds 5 and 6 had stronger effects on the behavior of formalin induced pain in mice. Moreover, the combination of compound 6 and morphine has a synergistic effect. We intended to explain the molecular mechanism of this effect. Therefore, 36 analgesic-related targets (including 15 G protein-coupled receptors, 6 enzymes, 13 ion channels, and 2 others) were systemically evaluated using reverse docking. The results indicate that bufotenine and its derivatives are closely related to acetyl cholinesterase (AChE) or αβ nicotinic acetylcholine receptor (nAChR). This study provides practitioners a new insight of analgesic effects.
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http://dx.doi.org/10.1016/S1875-5364(21)60044-4DOI Listing
June 2021

Nanoparticle-mediated surfactant therapy in patients with severe COVID-19: a perspective.

J Mater Chem B 2021 Jun 4. Epub 2021 Jun 4.

Department of Chemical and Biological Engineering, The University of Alabama, P. O. Box 870203, Tuscaloosa, AL 35401, USA.

Coronavirus disease 2019 (COVID-19) is an RNA virus-based disease that can be deadly. For critically ill patients, mechanical ventilation is an important life-saving treatment. However, mechanical ventilation shows a trade-off between supporting respiratory function and ventilator-induced lung injury (VILI). Surfactant therapy is a medical administration of exogenous surfactant to supplement or replace deficient or dysfunctional endogenous surfactant. Surfactant therapy can be used to postpone or shorten the use of mechanical ventilation to minimize or avoid VILI, because surfactants can reduce surface tension, improve lung compliance, and enhance oxygenation. In addition, nanotechnology can be applied to improve the therapeutic effect and reduce the adverse effects of surfactants. In this perspective, we discussed how nanoparticles deliver surfactants through intravenous injection and inhalation to the expected lung disease regions where surfactants are mostly needed, and discussed the prospects of nanoparticle-mediated surfactant therapy in the treatment of patients with severe COVID-19.
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http://dx.doi.org/10.1039/d1tb00730kDOI Listing
June 2021

Correlation between neutrophil-to-lymphocyte ratio and clinical manifestations and complications of retinitis pigmentosa.

Acta Ophthalmol 2021 Jun 2. Epub 2021 Jun 2.

Department of Ophthalmology, Xijing Hospital, Eye Institute of Chinese PLA, Fourth Military Medical University, Xi'an, China.

Purpose: The role of inflammation in retinitis pigmentosa (RP) has been receiving additional attention. However, the association between inflammation and the clinical manifestations and complications of RP is still unclear. This study aimed to evaluate the neutrophil-to-lymphocyte ratio (NLR) of RP complicated with cataract and explore the correlations between the NLR and specific clinical features of RP.

Methods: This retrospective study included 79 RP patients complicated with cataract (125 eyes) and 63 age- and sex-matched patients (63 eyes) with age-related cataract (ARC). Patients' ocular examination results were collected and complete blood count results were used to calculate NLRs. The correlations between the NLR of RP patients and the parameters of ocular examinations were analysed.

Results: The NLRs of RP patients with cataracts were significantly higher than those of ARC (1.93 ± 0.83 versus 1.65 ± 0.59, p = 0.029). The NLRs increased with the severity of posterior subcapsular cataract (PSC), zonular deficiency, poor preoperative best-corrected visual acuity (LogMAR>1), and visual field defects. Analysis of receiver operating characteristic curves suggested that NLR > 1.36 could predict higher degrees (PSC area >3%, >P1) of PSC (p = 0.002, 95% CI, 0.672-0.934), and that NLR > 2.12 could predict zonular weakness (p = 0.002, 95% CI, 0.665-0.928) in RP.

Conclusion: The NLRs in RP patients with cataract are not only higher but also associated with several clinical manifestations of RP. The NLR can be a predictive biomarker of higher degrees of PSC (>P1) and zonular weakness in RP before cataract surgery. These results suggest that systemic inflammation may play a role in the pathogenesis of RP.
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http://dx.doi.org/10.1111/aos.14880DOI Listing
June 2021

One-step colorimetric detection of Staphylococcus aureus based on target-induced shielding against the peroxidase mimicking activity of aptamer-functionalized gold-coated iron oxide nanocomposites.

Talanta 2021 Sep 1;232:122448. Epub 2021 May 1.

School of Public Health, Jilin University, Changchun, 130021, China. Electronic address:

Staphylococcus aureus (S. aureus) is one of the most threatened food-borne pathogens. Thus, it is necessary to establish fast, portable and reliable tools to realize the identification of S. aureus. Herein, the authors describe an effective colorimetric-based biosensor for the detection of S. aureus in multiple types of samples. Initially, a nanozyme composed of gold and iron oxide nanoparticles was synthesized and further modified with S. aureus-specific aptamer via Au-S bond. By utilizing the intrinsic peroxidase-like activity of the above magnetic conjugates, 3,3',5,5'-tetramethylbenzidine (TMB) can be transferred to oxTMB by oxidation of hydrogen peroxide (HO), resulting in a visible blue color. However, the introduction of S. aureus can turn off the UV-vis absorbance signals of TMB-HO system, due to the identification property of the nanozyme probe. Consequently, the optical density of the mixed solution measured at 652 nm decreased linearly as the concentration of S. aureus increased from 10 to 10 CFU mL, with the visible limit of detection as low as 10 CFU mL. The as-prepared sensor can detect S. aureus in spiked water, milk and urine samples quantitatively during 12 min without any pre-enrichment, separation or washing steps. In our perception, the one-step colorimetric assay show promise in practical on-site detection of S. aureus.
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http://dx.doi.org/10.1016/j.talanta.2021.122448DOI Listing
September 2021

Peptide nucleic acid-assisted colorimetric detection of single-nucleotide polymorphisms based on the intrinsic peroxidase-like activity of hemin-carbon nanotube nanocomposites.

Talanta 2021 Sep 20;232:122420. Epub 2021 Apr 20.

School of Materials Science and Chemical Engineering, Ningbo University, Ningbo, 315211, PR China. Electronic address:

Here, taking the advantage of single-stranded (ss) DNA specific nuclease (S1) and peptide nucleic acid (PNA), we demonstrated a novel, rapid, and label-free colorimetric nanosensor for the sensitive and accurate detection of SNPs based on the intrinsic peroxidase-like activity of hemin-functionalized single-walled carbon nanotubes (hemin-SWCNTs). PNA, a man-made mimic of DNA with extraordinary stability toward enzymatic degradation, can effectively protect DNA in the fully matched DNA/PNA duplexes from nuclease digestion. While the DNA in DNA/PNA duplexes containing a mismatch can be cleaved into small fragments. This difference can be visually monitored from the specific color change of TMB/HO system by employing the peroxidase activity of hemin-SWCNTs because of its different aggregation states responding to ssPNA or DNA/PNA duplex. Under optimized conditions, the SNPs in the human tumor suppressor gene TP53 have been successfully genotyped in a linear range of 50-1000 nM with a detection limit of 0.11 nM. Moreover, this platform can effectively discriminate a series of single-base mismatches. This assay avoids the assistance of sophisticated instruments and complicated modifications of probes or nanomaterials, and function well for both cell lysate samples and PCR amplicons from standard cell lines, implying its potential practical applications for bioanalysis and biosensors.
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http://dx.doi.org/10.1016/j.talanta.2021.122420DOI Listing
September 2021

Identification of a Shrimp E3 Ubiquitin Ligase TRIM50-Like Involved in Restricting White Spot Syndrome Virus Proliferation by Its Mediated Autophagy and Ubiquitination.

Front Immunol 2021 11;12:682562. Epub 2021 May 11.

Key Laboratory of South China Sea Fishery Resources Exploitation and Utilization, Ministry of Agriculture and Rural Affairs, South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, China.

Most tripartite motif (TRIM) family proteins are critical components of the autophagy machinery and play important roles in host defense against viral pathogens in mammals. However, the roles of TRIM proteins in autophagy and viral infection have not been studied in lower invertebrates, especially crustaceans. In this study, we first identified a gene from (designated ), which, after a white spot syndrome virus (WSSV) challenge, was significantly upregulated at the mRNA and protein levels in the intestine and hemocytes. Knockdown of led to an increase in the WSSV quantity in shrimp, while its overexpression led to a decrease compared with the controls. Autophagy can be induced by WSSV or rapamycin challenge and has been shown to play a positive role in restricting WSSV replication in . The mRNA and protein expression levels of PmTRIM50-like significantly increased with the enhancement of rapamycin-induced autophagy. The autophagy activity induced by WSSV or rapamycin challenge could be inhibited by silencing in shrimp. Further studies showed that rapamycin failed to induce autophagy or inhibit WSSV replication after knockdown of . Moreover, pull-down and ubiquitination assays demonstrated that PmTRIM50-like could interact with WSSV envelope proteins and target them for ubiquitination . Collectively, this study demonstrated that PmTRIM50-like is required for autophagy and is involved in restricting the proliferation of WSSV through its ubiquitination. This is the first study to report the role of a TRIM family protein in virus infection and host autophagy in crustaceans.
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http://dx.doi.org/10.3389/fimmu.2021.682562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144704PMC
May 2021

Adenocarcinoma of High-Grade Patterns Associated with Distinct Outcome of First-Line Chemotherapy or EGFR-TKIs in Patients of Relapsed Lung Cancer.

Cancer Manag Res 2021 17;13:3981-3990. Epub 2021 May 17.

Department of Medical Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, People's Republic of China.

Purpose: High-grade patterns (micropapillary/solid/complex gland) are associated with a higher recurrence rate and shorter disease-free survival. Thus far, it remains unclear whether the efficacy of first-line anticancer therapy is different from that of the other adenocarcinoma subgroups for patients with high-grade patterns. The study aimed to investigate the association between an adenocarcinoma with high-grade patterns with the outcomes of first-line treatment in patients with lung cancer.

Patients And Methods: Patients with a high-grade pattern adenocarcinoma (more than 20% of micropapillary/solid components/complex glandular patterns) were retrospectively analyzed between June 2015 and June 2017. Patients' clinical characteristics and treatment outcomes were compared with those of the remaining control adenocarcinoma subgroups.

Results: In total, 239 patients with adenocarcinoma, including 115 (48.1%) high-grade patterns and 124 (51.9%) control groups, were enrolled. Patients' clinical characteristics such as age, sex, smoking status, and stage were similar between the two groups. Among them, 108 patients received first-line chemotherapy, and 131 received epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). In the chemotherapy group, adenocarcinoma of high-grade patterns had a significantly lower objective response rate (ORR; 15.6% vs 36.4%, P=0.045), shorter progression-free survival (PFS; median 4.1 vs 5.4 months, P=0.007) and overall survival (OS, median 19.6 vs 23.8 months, P=0.048) compared with the control group. As for these treated with EGFR-TKIs, a similar ORR (70.7% vs 72.1%, P=0.703), PFS (median 11.3 vs 13.9 months, P=0.065) and OS (median 34.1 vs 29.6%, p=0.575) were observed between these two groups.

Conclusion: An adenocarcinoma with high-grade patterns is associated with inferior outcomes to first-line chemotherapy in relapsed lung cancer. Patients who received chemotherapy had a significantly shorter PFS and OS and lower ORR than control subjects, while there was no difference in the EGFR-TKI cohort. This study is the first to report the distribution of adenocarcinoma with high-grade patterns.
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http://dx.doi.org/10.2147/CMAR.S302545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139732PMC
May 2021

A System-Wide Spatiotemporal Characterization of ErbB Receptor Complexes by Subcellular Fractionation Integrated Quantitative Mass Spectrometry.

Anal Chem 2021 06 25;93(22):7933-7941. Epub 2021 May 25.

State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China.

Precise spatiotemporal regulation of protein complex assembly is essential for cells to achieve a meaningful rely of information flow via intracellular signaling networks in response to extracellular cues, whose disruption would lead to disease. Although various attempts have been made for spatial and/or temporal analysis of protein complexes, it is still a challenge to track cell-wide dynamics of a particular protein complex under physiological conditions. Here we describe a workflow that combines endogenous expression of tagged proteins, organelle marker distribution-directed subcellular fractionation, scaffold protein-mediated receptor complex purification, and targeted proteomics for spatiotemporal quantification of protein complexes in whole cell scale. We applied our method to investigate the assembly kinetics of EGF-dependent ErbB receptor complexes. After fractionation using the density gradient centrifugation and organelle assignment based on organelle markers, endogenous ErbB complex in different subcellular fractionation was efficiently enriched. By using targeted mass spectrometry, ErbB complex components that expressed medium to low level was precisely quantified with in-depth coverage, simultaneously in time and subcellular spaces. Our results revealed a sophisticated scheme of complex behaviors characterized by multiple subcomplexes with distinct molecular composition formed across subcellular fractions enriched with cytosol, plasma membrane, endosome, or mitochondria, implying organelle-specific ErbB functions. Remarkably, our results demonstrated for the first time that activated ErbB receptors might increase their signaling range through promoting a cytosolic, receptor-free subcomplex, consisting of Shc1, Grb2, Arhgef5, Garem1, and Lrrk1. These findings emphasize the potential of our strategy as a powerful tool to study spatiotemporal dynamics of protein complexes.
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http://dx.doi.org/10.1021/acs.analchem.1c00651DOI Listing
June 2021

Toxic responses of liver in Lateolabrax maculatus during hypoxia and re-oxygenation.

Aquat Toxicol 2021 Jul 21;236:105841. Epub 2021 Apr 21.

Key Laboratory of South China Sea Fishery Resources Exploitation & Utilization, Ministry of Agriculture and Rural Affairs, South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, 510220, PR China; Guangdong Provincial Key Laboratory of Fishery Ecology and Environment, Guangzhou, 510000, P.R. China. Electronic address:

Estuarine environmental have been reported to undergo significant fluctuations in oxygen concentrations with hypoxic conditions and subsequent re-oxygenation events being of significant concern for resident fish populations. In this study we assessed the toxicological effects of hypoxia and re-oxygenation on the liver of hypoxia-sensitive spotted sea bass (Lateolabrax maculatus) that were exposed to hypoxia (1.17 mg/L dissolved oxygen) for 12 h and then re-oxygenated for 12 h. The activities of glutamic-pyruvic transaminase and glutamic-oxalacetic transaminase in serum significantly increased under hypoxia (p < 0.05) and continued to increase during re-oxygenation (p < 0.05), indicating that normal liver function might be disrupted by hypoxia and might become worse during re-oxygenation for 12h. Total protein, albumin, and globulin levels in serum decreased under hypoxia but began to return to normal during re-oxygenation, showing that protein synthesis in the liver decreased during hypoxia but could be restored by re-oxygenation. We also used RNA-Seq technology to identify changes in gene expression in the liver during hypoxia and re-oxygenation. Transcriptome sequencing revealed that the hypoxia-inducible factor (HIF-1) signaling pathway, apoptosis, and purine metabolism transcripts were significantly enriched under hypoxia and re-oxygenation conditions. A total of 15 and 16 apoptosis-related genes were induced by hypoxia and re-oxygenation stress, respectively. The apoptosis index increased from the normal to the hypoxic condition and was highest under re-oxygenation. Additionally, 19 and 29 genes, that are involved in purine metabolism in the liver of L. maculatus during hypoxia and re-oxygenation, respectively, were dysregulated. Unexpectedly, the serum uric acid level significantly increased during hypoxia and significantly decreased under re-oxygenation, indicating the presence of purine metabolic disorder in the liver of L. maculatus. These results illustrate that hypoxia poses a pronounced threat to hepatocyte function in L. maculatus and that liver damage is difficult to reverse with 12 h of re-oxygenation, and it may actually become worse when re-oxygenation is established.
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http://dx.doi.org/10.1016/j.aquatox.2021.105841DOI Listing
July 2021

Dual cascade isothermal amplification reaction based glucometer sensors for point-of-care diagnostics of cancer-related microRNAs.

Analyst 2021 May 9;146(10):3242-3250. Epub 2021 Apr 9.

Cixi Institute of Biomedical Engineering, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201, P. R. China.

The practical use of a point-of-care (POC) device is of particular interest in performing liquid biopsies related to cancer. Herein, taking advantage of the practical convenience of a commercially available personal glucose meter (PGM), we report a convenient, low-cost and sensitive detection strategy for circulating microRNA-155 (miRNA155) in human serum. First, miRNA155 in serum triggers the catalyzed hairpin assembly (CHA) reaction, and then the CHA product is specifically captured by the peptide nucleic acid (PNA) probes attached to the surface of a 96-well plate, which in turn triggers the hybridization chain reaction (HCR), resulting in the local enrichment of invertase. Next, introduction of a substrate (sucrose) for the invertase results in the generation of glucose, which can be detected by a PGM. In this sensor, neutrally charged PNA (12 nt) is more likely to hybridize with the CHA products than with the negatively charged DNA in kinetics, which improves the detection sensitivity and specificity. Due to the synergistic isothermal amplification reaction between CHA and HCR, the sensor is able to achieve a broad dynamic range (from 1 fM to 10 nM) with a detection limit down to 0.36 fM (3 orders of magnitude lower than that without HCR) and is capable of distinguishing single-base mismatched sequences. Thus the convenient, sensitive, robust and low-cost PGM sensor makes on-site nucleic acids detection possible, suggesting its great application prospect as a promising POC device in cancer diagnostics.
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http://dx.doi.org/10.1039/d1an00037cDOI Listing
May 2021

A Network Pharmacology Approach to Predict the Proangiogenesis Mechanism of Huangqi-Honghua Herb Pair after Cerebral Ischemia.

Evid Based Complement Alternat Med 2021 14;2021:9834856. Epub 2021 Apr 14.

Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.

Objective: Huangqi-Honghua herb pair is known for its medicinal value to treat Qi deficiency and blood stasis syndrome with a long history in clinical practice. To understand its possible mechanism in a systematic study, a network pharmacological method was addressed.

Methods: Detailed information on the HH compounds was obtained from two public databases, and oral bioavailability (OB) and drug-like (DL) of the compounds were evaluated. A correlation between HH compounds, its potential targets, and known targets was extrapolated, and the herb-compound-target-disease (H-C-T-D) network was established. Next, the pathway enrichment and essential genes were analyzed. Then, three key genes (VEGFA, VEGFR2, and eNOS), highly associated with angiogenesis, were screened and verified through western blot assay.

Results: Out of 276 compounds, 21 HH compounds and 78 target genes regulating the major pathways associated with CI in the network are analyzed. The bioactive compounds in HH were active in various signal transduction pathways such as the toll-like receptor signaling pathway, VEGF signaling pathway, TNF signaling pathway, and HIF-1 signaling pathway are important pathways that may regulate anti-inflammatory, antiapoptotic, immune correlation, and antioxidative effects. The core genes are PTGS2, TNF, NOS2, IL6, BCL2, IL1B, SOD2, NOS3, SOD1, MMP9, and VEGFA. The in vitro results suggested that HH treatment could significantly elevate the expression of proangiogenic genes such as VEGFA, VEGFR2, and eNOS compared with OGD groups.

Conclusions: Our results predict that HH may regulate the expression of VEGFA, VEGFR2, and eNOS via the VEGF and HIF-1 signaling pathway to promote angiogenesis and alleviate cerebral ischemia injury.
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http://dx.doi.org/10.1155/2021/9834856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064780PMC
April 2021

Case Report: Repeated Low-Dose Rituximab Treatment Is Effective in Relapsing Neuro Behçet's Disease.

Front Neurol 2021 15;12:595984. Epub 2021 Apr 15.

Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.

Neuro Behçet's disease (NBD) is a rare but most aggressive manifestation of Behçet's disease (BD) with a poor prognosis, and some patients even present a relapsing and treatment-resistant progressive course. In some relapsing NBD cases, traditional corticosteroids and immunosuppressive drugs show limited efficacy, while benefits of biological agents, such as anti-B-lymphocyte CD20 biological agent rituximab (RTX), gradually represent potential therapeutic advantages with clinical rapid remission and long-time maintenance. However, up to now, the optimal dosage of RTX in NBD is still elucidated. Here, we report two patients with relapsing NBD, despite continuous high dose steroids and sufficient azathioprine treatment, still presenting severe and relapsing meningoencephalitis or brainstem involvement. Repeated low-dose RTX (100 mg × 3/1 week apart, 100 mg repeated every 6 months) is then attempted with rapid recovery and sustained remission. The approach in our cases may expand therapeutic options and provide helpful references for relapsing NBD treatment.
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http://dx.doi.org/10.3389/fneur.2021.595984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081882PMC
April 2021

Immune Checkpoint Inhibitors in EGFR-Mutated NSCLC: Dusk or Dawn?

J Thorac Oncol 2021 Aug 26;16(8):1267-1288. Epub 2021 Apr 26.

Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China. Electronic address:

Although immune checkpoint inhibitors (ICIs) that target programmed cell death protein-1/programmed cell death ligand-1 axis have significantly shifted the treatment paradigm in advanced NSCLC, clinical benefits of these agents are limited in patients with EGFR-mutated NSCLC. Several predictive biomarkers (e.g., programmed cell death ligand-1 expression, tumor mutation burden), which have been validated in EGFR-wild type NSCLC, however, are not efficacious in EGFR-mutated tumors, suggesting the unique characteristics of tumor microenvironment of EGFR-mutated NSCLC. Here, we first summarized the clinical evidence on the efficacy of ICIs in patients with EGFR-mutated NSCLC. Then, the cancer immunogram features of EGFR-mutated NSCLC was depicted to visualize the state of cancer-immune system interactions, including tumor foreignness, tumor sensitivity to immune effectors, metabolism, general immune status, immune cell infiltration, cytokines, and soluble molecules. We further discussed the potential subpopulations with EGFR mutations that could benefit from ICI treatment. Lastly, we put forward future strategies to adequately maximize the efficacy of ICI treatment in patients with EGFR-mutated NSCLC in the upcoming era of combination immunotherapies.
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http://dx.doi.org/10.1016/j.jtho.2021.04.003DOI Listing
August 2021

Gating control effect facilitates excellent gas selectivity in a novel Na-SSZ-27 zeolite.

Chem Commun (Camb) 2021 Apr;57(34):4170-4173

State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan, 430071, P. R. China.

A novel Na-SSZ-27 zeolite was demonstrated to possess excellent H2/CO2 diffusion selectivity of more than 100. This investigation highlights the crucial effect of the "gating control" of the 8-ring windows on the separation, where sodium cations act as gates to selectively control the diffusion of CO2 and promote the selectivity for H2.
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http://dx.doi.org/10.1039/d1cc00164gDOI Listing
April 2021

High discrepancy in thrombotic events in non-small cell lung cancer patients with different genomic alterations.

Transl Lung Cancer Res 2021 Mar;10(3):1512-1524

Department of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.

Background: Acute complications, such as venous thromboembolism (VTE), are common in patients with advanced severe lung cancers. However, current VTE risk scores cannot adequately identify high-risk patients with non-small cell lung cancer (NSCLC). The study proposed to elucidated the incidence of thromboembolism (TE) in patients with different oncogenic aberrations and the impact of these aberrations on the efficacy of targeted therapy in patients with NSCLC.

Methods: A systemic review was conducted in Web of Science, PubMed, Embase and the Cochrane Library to evaluate the incidence of TE in different molecular subtypes of NSCLC. Data from patients diagnosed of advanced NSCLC who harboring anaplastic lymphoma kinase (ALK) or ROS proto-oncogene 1 receptor tyrosine kinase (ROS1) rearrangements since 2016 to 2019 were also retrospectively collected. A meta-analysis with random-effects model, sensitivity analysis and publication bias were performed. The principal summary measure was incidence of thrombotic events in NSCLC patients. And the efficacy of tyrosine kinase inhibitor (TKI) therapy was compared between the two subgroups.

Results: A total of 5,767 cases from 20 studies were included in the analysis of the incidence of thrombosis in patients with different oncogenic alterations. The pooled analysis showed a higher risk of thrombosis in ROS1-fusion types (41%, 95% CI: 35-47%) and ALK-fusion types (30%, 95% CI: 24-37%) than in EGFR-mutation (12%, 95% CI: 8-17%), KRAS-mutation (25%, 95% CI: 13-50%), and wild-type (14%, 95% CI: 10-20%) cases. A high prevalence of thrombosis (ALK: 24.4%; ROS1: 32.6%) was observed in the Shanghai Pulmonary Hospital (SPH) cohort of 224 patients with ALK or ROS1 fusion. Furthermore, patients with embolism had significantly shorter progression-free survival (PFS) after TKI therapy than those without embolism, both in the ALK+ cohort (5.6 12.9 months, P<0.0001) and in the ROS1+ cohort (9.6 17.6 months, P=0.0481).

Conclusions: NSCLC patients with ALK/ROS1 rearrangements are more likely to develop thrombosis than patients with other oncogenic alterations. Thrombosis may also be associated with an inferior response and PFS after TKI therapy.
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http://dx.doi.org/10.21037/tlcr-20-1290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044490PMC
March 2021

Concurrent use of metformin enhances the efficacy of EGFR-TKIs in patients with advanced EGFR-mutant non-small cell lung cancer-an option for overcoming EGFR-TKI resistance.

Transl Lung Cancer Res 2021 Mar;10(3):1277-1291

Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

Background: Resistance is almost inevitable and is still a major obstacle in epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy. Only limited relevant clinical studies evaluated the therapeutic effects by combing metformin and EGFR-TKIs in non-small cell lung cancer (NSCLC) patients. Therefore, we evaluated the efficacy of concurrent use of metformin with EGFR-TKIs, and assessed whether the addition of metformin may improve clinical outcomes and delay the occurrence of EGFR-TKI resistance.

Methods: We conducted cell proliferation and apoptosis assay for investigation of metformin in combination with EGFR-TKIs to overcome EGFR-TKI resistance . Furthermore, we retrospectively reviewed clinicopathological characteristics and therapeutic outcomes of EGFR-mutant advanced NSCLC diabetic patients who received EGFR-TKIs with or without concurrent use of metformin.

Results: experiment, metformin showed synergistic interaction both with gefitinib in PC9R (CI =0.77) and with osimertinib in PC9R/OR (CI =0.77) in proliferation inhibition assay. Metformin can also augment apoptosis effect of these TKI-resistant cells to EGFR-TKIs. In retrospective cohort, a total of 85 patients were identified (cohort A), in which 28 patients had concurrent use of metformin. The objective response rate in metformin use group was significantly higher (85.7% 47.4%, P=0.001). The median progression-free survival (PFS) and overall survival (OS) in metformin use group were significantly longer (21.6 9.2 months, P=0.000; 48.4 36.6 months, P=0.049). Further analysis revealed that metformin obviously prolonged the median PFS2 of osimertinib treatment among patients who progressed to prior line EGFR-TKIs due to secondary EGFR T790M mutation (cohort B).

Conclusions: Our study suggest that concurrent use of metformin could be beneficial to EGFR-mutant NSCLC patients treated with either first-line EGFR-TKIs or second-line osimertinib.
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http://dx.doi.org/10.21037/tlcr-20-1153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044488PMC
March 2021