Publications by authors named "Jie Gao"

1,592 Publications

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Tandem molecular self-assembly for selective lung cancer therapy with an increase in efficiency by two orders of magnitude.

Nanoscale 2021 Jun 14. Epub 2021 Jun 14.

State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Collaborative Innovation Center of Chemical Science and Engineering, and National Institute of Functional Materials, Nankai University, Tianjin 300071, P. R. China.

In situ self-assembly of prodrug molecules into nanomedicine can elevate the therapeutic efficacy of anticancer medications by enhancing the targeting and enrichment of anticancer drugs at tumor sites. However, the disassembly and biodegradation of nanomedicine after enrichment prevents the further improvement of the efficiency, and avoiding such disassembly and biodegradation remains a challenge. Herein, we rationally designed a tandem molecular self-assembling prodrug that could selectively improve the therapeutic efficacy of HCPT against lung cancer by two orders of magnitude. The tandem molecular self-assembly utilized an elevated level of alkaline phosphatase and reductase in lung cancer cells. The prodrug first self-assembled into nanofibers by alkaline phosphatase catalysis and was internalized more efficiently by lung cancer cells than free HCPT. The resulting nanofiber was next catalyzed by intracellular reductase to form a more hydrophobic nanofiber that prevented the disassembly and biodegradation, which further significantly improved the efficacy of HCPT against lung cancer both in vitro and in vivo.
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http://dx.doi.org/10.1039/d1nr01174jDOI Listing
June 2021

Right Frontoinsular Cortex: A Potential Imaging Biomarker to Evaluate T2DM-Induced Cognitive Impairment.

Front Aging Neurosci 2021 28;13:674288. Epub 2021 May 28.

Department of MRI, Shaanxi Provincial People's Hospital, Xi'an, China.

Cognitive impairment in type 2 diabetes mellitus (T2DM) is associated with functional and structural abnormalities in the intrinsic brain network. The salience network (SN) is a neurocognitive network that maintains normal cognitive function, but it has received little attention in T2DM. We explored SN changes in patients with T2DM with normal cognitive function (DMCN) and in patients with T2DM with mild cognitive impairment (DMCI). Sixty-five T2DM patients and 31 healthy controls (HCs) underwent a neuropsychological assessment, independent component analysis (ICA), and voxel-based morphometry (VBM) analysis. The ICA extracted the SN for VBM to compare SN functional connectivity (FC) and gray matter (GM) volume (GMV) between groups. A correlation analysis examined the relationship between abnormal FC and GMV and clinical/cognitive variables. Compared with HCs, DMCN patients demonstrated increased FC in the left frontoinsular cortex (FIC), right anterior insula, and putamen, while DMCI patients demonstrated decreased right middle/inferior frontal gyrus FC. Compared with DMCN patients, DMCI patients showed decreased right FIC FC. There was no significant difference in SN GMV in DMCN and DMCI patients compared with HCs. FIC GMV was decreased in the DMCI patients compared with DMCN patients. In addition, right FIC FC and SN GMV positively correlated with Montreal Cognitive Assessment and Mini-Mental State Examination (MMSE) scores. These findings indicate that changes in SN FC, and GMV are complex non-linear processes accompanied by increased cognitive dysfunction in patients with T2DM. The right FIC may be a useful imaging biomarker for supplementary assessment of early cognitive dysfunction in patients with T2DM.
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http://dx.doi.org/10.3389/fnagi.2021.674288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193040PMC
May 2021

Crystal structure of TbAlba1 from Trypanosoma brucei.

J Struct Biol 2021 Jun 6;213(3):107751. Epub 2021 Jun 6.

Hefei National Laboratory for Physical Sciences at Microscale, and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, PR China. Electronic address:

Alba (Acetylation lowers binding affinity) domain is a small, dimeric nucleic acid-binding domain, which is widely distributed in archaea and numbers of eukaryotes. Alba domain containing proteins have been reported to be involved in many cellular processes, such as regulation of translation, maintaining genome stability, regulation of RNA processing and so on. In Trypanosoma brucei (T. brucei), there are four Alba proteins identified, which are named TbAlba1 to TbAlba4. However, the structure and function of TbAlba proteins are still unknown. Here, we solved the crystal structure of TbAlba1 to a resolution of 2.46 Å. TbAlba1 adopts a similar Alba-fold, which comprises of four β-strands (β1-β4) and three long α-helices (α1-α3). Furthermore, TbAlba1 displays some structural features quite different from other Alba proteins. These differences may imply the diverse biological roles of Alba family members.
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http://dx.doi.org/10.1016/j.jsb.2021.107751DOI Listing
June 2021

Differences in clinical characteristics and liver injury between suspected and confirmed COVID-19 patients in Jingzhou, Hubei Province of China.

Medicine (Baltimore) 2021 May;100(19):e25913

Department of Gastroenterology, First Hospital of Yangtze University.

Abstract: To evaluate the clinical characteristics and liver injury in coronavirus disease 2019 (COVID-19) patients, and analyze the differences between suspected and confirmed COVID-19 patients, this retrospective study was performed on 157 COVID-19 patients and 93 suspected patients who were ultimately excluded from COVID-19 (control patients). Differences in clinical characteristics and liver injury between suspected and confirmed COVID-19 patients were analyzed. Age, male sex, fever, chest tightness and dyspnea were related to the severity of COVID-19. C-reactive protein (CRP) and D-dimer may be predictors of the severity of COVID-19. Computed tomography (CT) played an important role in the screening of COVID-19 and the evaluation of disease severity. Multiple factors may cause liver injury in COVID-19 patients. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be more likely to cause liver injury than common respiratory infectious diseases. Age, temperature (T), white blood cell (WBC), lymphocytes (LY), hematocrit (HCT), CRP, and finger pulse oxygen saturation (SpO2) may correlate with liver function impairment and may predict the occurrence and severity of liver function impairment. Some therapeutic drugs (like glucocorticoid) may be involved in the liver function impairment of COVID-19 patients. Most liver function indices improved significantly after active treatment. Although COVID-19 and other common respiratory infectious diseases share some clinical characteristics, COVID-19 has its own characteristics.
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http://dx.doi.org/10.1097/MD.0000000000025913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133163PMC
May 2021

Tibet Kefir Milk Regulated Metabolic Changes Induced by High-Fat Diet via Amino Acids, Bile Acids, and Equol Metabolism in Human-Microbiota-Associated Rats.

J Agric Food Chem 2021 Jun 3;69(23):6720-6732. Epub 2021 Jun 3.

Department of Food Science and Technology, Hebei Agricultural University, No. 2596, Lekai South Street, Baoding, Hebei CN 071000, China.

This study aimed to confirm the effects of Tibet kefir milk (TKM) on gut microbiota and metabolism. An obesity model was established by feeding a high-fat diet (HFD) to human-microbiota-associated rats. Next-generation sequencing and ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry were applied for gut microbiota and untargeted metabolomics, respectively. After 8 weeks of feeding, the enterotype in the HFD group was switched from ET1 (/-dominant) to ET2 (/-dominant). Branched-chain amino-acids- and aromatic amino-acids-metabolism increased, and taurine-conjugated bile acids decreased in the HFD group. Compared with the HFD group, taurocholic acid increased in the TKM1 group, while l-threonine decreased, and equol, taurochenodeoxycholate, and taurodeoxycholic acid increased in the TKM2 group. The metabolite alteration suggested restorative bile acid metabolism, modified metabolic pattern of amino acids, and elevation of anti-obesity factors in the TKM-intervened animals. It can be deduced that changes by TKM intervention in the host gut metabolites are the major contributors to reducing fat deposition.
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http://dx.doi.org/10.1021/acs.jafc.1c02430DOI Listing
June 2021

polysaccharides alleviate cognitive decline in aging model mice by restoring the gut microbiota-brain axis.

Aging (Albany NY) 2021 Jun 3;13(11):15320-15335. Epub 2021 Jun 3.

Inner Mongolia Medical University, Hohhot 010110, China.

Recent evidence suggests alterations in the gut microbiota-brain axis may drive cognitive impairment with aging. In the present study, we observed that prolonged administration of D-galactose to mice induced cognitive decline, gut microbial dysbiosis, peripheral inflammation, and oxidative stress. In this model of age-related cognitive decline, polysaccharides (CDPS) improved cognitive function in D-galactose-treated mice by restoring gut microbial homeostasis, thereby reducing oxidative stress and peripheral inflammation. The beneficial effects of CDPS in these aging model mice were abolished through ablation of gut microbiota with antibiotics or immunosuppression with cyclophosphamide. Serum metabolomic profiling showed that levels of creatinine, valine, L-methionine, o-Toluidine, N-ethylaniline, uric acid and proline were all altered in the aging model mice, but were restored by CDPS. These findings demonstrated that CDPS improves cognitive function in a D-galactose-induced aging model in mice by restoring homeostasis of the gut microbiota-brain axis, which alleviated an amino acid imbalance, peripheral inflammation, and oxidative stress. CDPS thus shows therapeutic potential for patients with memory and learning disorders, especially those related to gut microbial dysbiosis.
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http://dx.doi.org/10.18632/aging.203090DOI Listing
June 2021

Ambient hydrogenation and deuteration of alkenes using a nano-structured Ni-core-shell catalyst.

Angew Chem Int Ed Engl 2021 Jun 2. Epub 2021 Jun 2.

Leibniz-Institut für Katalyse, Homogeneous Catalysis, Albert-Einstein-Straße 29a, 18059, Rostock, GERMANY.

A general protocol for the selective hydrogenation and deuteration of a variety of alkenes is presented. Key to success for these reactions is the use of a specific nickel-graphitic shell-based core-shell structured catalyst, which is conveniently prepared by impregnation and subsequent calcination of nickel nitrate on carbon at 450 oC under argon. Applying this nano-structured catalyst, both terminal and internal alkenes, which are of industrial and commercial importance, were selectively hydrogenated and deuterated at ambient conditions (room temperature using 1 bar hydrogen or 1 bar deuterium), giving access to the corresponding alkanes and deuterium-labelled alkanes in good to excellent yields. The synthetic utility and practicability of this Ni-based hydrogenation protocol is demonstrated by gram-scale reactions as well as efficient catalyst recycling experiments.
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http://dx.doi.org/10.1002/anie.202105492DOI Listing
June 2021

Transcriptional Cascade in the Regulation of Flowering in the Bamboo Orchid .

Biomolecules 2021 May 21;11(6). Epub 2021 May 21.

Guangdong Key Laboratory of Ornamental Plant Germplasm Innovation and Utilization, Environmental Horticulture Research Institute, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China.

Flowering in orchids is the most important horticultural trait regulated by multiple mechanisms. flowers throughout the year unlike other orchids with a narrow flowering span. However, little is known of the genetic regulation of this peculiar flowering pattern. This study identifies a number of transcription factor (TF) families in five stages of flower development and four tissue types through RNA-seq transcriptome. About 700 DEGs were annotated to the transcription factor category and classified into 35 TF families, which were involved in multiple signaling pathways. The most abundant TF family was bHLH, followed by MYB and WRKY. Some important members of the bHLH, WRKY, MYB, TCP, and MADS-box families were found to regulate the flowering genes at transcriptional levels. Particularly, the TFs WRKY34 and ERF12 possibly respond to vernalization and photoperiod signaling, MYB108, RR9, VP1, and bHLH49 regulate hormonal balance, and CCA1 may control the circadian pathway. MADS-box TFs including MADS6, 14, 16, AGL5, and SEP may be important regulators of flowering in . Therefore, this study provides a theoretical basis for understanding the molecular mechanism of flowering in .
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http://dx.doi.org/10.3390/biom11060771DOI Listing
May 2021

Photocatalytic Cyclization/Defluorination Domino Sequence to Access 3-Fluoro-1,5-dihydro-2-pyrrol-2-one Scaffold.

Org Lett 2021 Jun 1;23(12):4754-4758. Epub 2021 Jun 1.

College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, P. R. China.

We herein report an unprecedented photoinduced cyclization/defluorination domino process of -allylbromodifluoroacetamide with cyclic secondary amines. Consequently, a wide array of valuable 3-fluoro-1,5-dihydro-2-pyrrol-2-ones were facilely prepared from readily available starting materials under mild conditions. Preliminary mechanistic investigations suggest that a radical chain propagation and amine-promoted defluorination pathway are presumably involved in this transformation.
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http://dx.doi.org/10.1021/acs.orglett.1c01477DOI Listing
June 2021

GE11 Modified PLGA/TPGS Nanoparticles Targeting Delivery of Salinomycin to Breast Cancer Cells.

Technol Cancer Res Treat 2021 Jan-Dec;20:15330338211004954

Institute of Translational Medicine, Shanghai University, Shanghai, China.

Salinomycin (Sal) is a potent inhibitor with effective anti-breast cancer properties in clinical therapy. The occurrence of various side effect of Sal greatly limits its application. The epidermal growth factor receptor (EGFR) family is a family of receptors highly expressed in most breast cancer cells. GE11 is a dodecapeptide which shows excellent EGFR affinity. A series of nanoparticles derivatives with GE11 peptide conjugated PLGA/TPGS were synthesized. Nanoprecipitation method was used to prepare the Sal loaded nanoparticles at the optimized concentration. The characterization, targeting efficacy, and antitumor activity were detected both and . Encapsulation of Sal in GE11 modified PLGA/TPGS nanoparticles shows an improved therapy efficacy and lower systemic side effect. This represents the delivery system a promising strategy to enhance the therapeutic effect against EGFR highly expressed breast cancer.
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http://dx.doi.org/10.1177/15330338211004954DOI Listing
May 2021

Tibetan Medicines and Tibetan Prescriptions for the Treatment of Diabetes Mellitus.

Evid Based Complement Alternat Med 2021 17;2021:5532159. Epub 2021 May 17.

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.

Diabetes mellitus (DM) is one of the most serious diseases threatening human health and because of that, it is imperative to look for drugs to tackle it. The Tibetan medicine, a traditional medical system used in China, is currently being the focus of research towards the discovery of new effective drugs against several diseases. Based on the literature survey of Tibetan medicine monographs and drug standards, the Tibetan medicine, and Tibetan prescription used in the traditional Tibetan medical system, here, we summarise the methods indicated for DM treatment. In the Tibetan medical system, 56 types of Tibetan medicine and 25 Tibetan prescriptions were found for the treatment of DM. The most commonly used are Curcuma, Berberidis Cortex, and Carthami Flos. Their names, families, medicinal parts, phytochemical components, and pharmacological activities were described in detail in our research. These Tibetan medicines and prescriptions are valuable gifts from the Tibetan medicine to the world and may be the source of potential drugs for the treatment of DM. With the help of modern phytochemistry, pharmacology, metabonomics, and/or clinical trial methods, further research is needed to prove its medicinal value, identify bioactive components, elucidate potential mechanisms of action, and assess potential side effects or toxicity. This study provides the first available data compilation for the ethnic medical knowledge of Tibetan medicine for the treatment of DM, providing new ideas and sources for drugs against DM.
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http://dx.doi.org/10.1155/2021/5532159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149248PMC
May 2021

Differential roles of prelimbic and anterior cingulate cortical region in the modulation of histaminergic and non-histaminergic itch.

Behav Brain Res 2021 May 27;411:113388. Epub 2021 May 27.

Experimental Center of Basic Medicine, College of Basic Medical Sciences, Army Medical University, Chongqing, 400038, China. Electronic address:

Itch is an unpleasant sensation that evokes a desire to scratch. Itch processing in the peripheral and spinal cord has been studied extensively, but the mechanism of itch in the central nervous system is still unclear. Anterior cingulate cortex (ACC) and prelimbic cortex (Prl), two subregions of the prefrontal cortex closely related to emotion and motivation, have been reported to be activated during itching in a series of functional imaging studies. However, the exact role of Prl and the differences between ACC and Prl in itch modulation remains unknown. To directly test the differential roles of ACC and Prl in itch processing, we chemogeneticlly inhibited the caudal ACC and Prl, respectively. We found that inhibition of caudal ACC reduced histaminergic but not non-histaminergic itch-induced scratching behaviors. In contrast, inhibition of Prl reduced both histaminergic and non-histaminergic itch-induced scratching behaviors. Our study provided direct evidence of Prl involvement in itch modulation and revealed the differential roles of caudal ACC and Prl in regulating histaminergic and non-histaminergic itch.
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http://dx.doi.org/10.1016/j.bbr.2021.113388DOI Listing
May 2021

Radiographic features and prognosis of early- and late-onset non-small cell lung cancer immune checkpoint inhibitor-related pneumonitis.

BMC Cancer 2021 May 29;21(1):634. Epub 2021 May 29.

Department of Respiratory and Critical Care, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.

Background: Immunotherapy is becoming a standard of care for non-small cell lung cancer (NSCLC). Checkpoint inhibitor-associated pneumonia (CIP) is a rare and potentially life-threatening event that can occur at any time during tumor immunotherapy. However, there may be differences in the radiological patterns and prognosis of CIP during different periods. This study aimed to investigate the radiographic features and prognosis of early- and late-onset immune-related pneumonitis.

Methods: We retrospectively analyzed the clinical data of 677 NSCLC patients receiving immunotherapy to identify 32 patients with CIP, analyzed the clinical and radiographic data, and summarized the radiological features and prognosis of early- and late-onset CIP.

Results: CIP had an incidence of 4.7%, a median onset time of 10 weeks, and a mortality of 28.1%. Among these, CIP included 14 early-onset cases, where grade ≥ 3 CIP accounted for 92.9%, main radiographic pattern was organizing pneumonia (OP)-like pattern, and mortality was 50.0%. We also identified 18 late-onset CIPs, where grade ≥ 3 CIP accounted for 50.0%, main radiographic pattern was nonspecific interstitial pneumonia (NSIP)-like pattern, and mortality was 11.1%. The overall survival rate of the early-onset group was significantly lower than that of the late-onset group (P < 0.05).

Conclusion: Early-onset CIP cases were higher in the Common Terminology Criteria for Adverse Events (CTCAE v5.0) grade and mainly presented with an OP-like radiographic pattern; whereas, late-onset CIP cases were lower in CTCAE grade and mainly presented with an NSIP-like radiographic pattern. Finally, the prognosis of the early-onset CIP group was poorer than that of the late-onset CIP group. We believe that this study will be helpful for clinicians for making early diagnosis and deciding treatment modalities for patients with CIP.
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http://dx.doi.org/10.1186/s12885-021-08353-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164260PMC
May 2021

Sex differences in the factors associated with sleep duration in university students: A cross-sectional study.

J Affect Disord 2021 Jul 21;290:345-352. Epub 2021 Apr 21.

Department of Public Health, Medical College, Qinghai University, Xining, Qinghai, China.. Electronic address:

Background: Insufficient sleep duration among university students was commonly associated with many detrimental effects. University students experience substantial environmental and psychological changes. Female and male university students may differ in many spheres. However, most research on sleep duration of university students is based on an aggregate sample rather than digging the sex-specific profiles. The objective of this study is to examine potential sex differences in the correlates of sleep duration and explore the underlying mechanism of correlations.

Methods: This is a large-scale university-based mental health survey, which was conducted in university students in Qinghai Province in Northwest China in December 2019. A multi-stage logistic regression was separately fitted by sex to examine the factors associated with short sleep duration in university students.

Results: A total of 5,552 university students with an average sleep duration of 6.88 h (SD = 1.04) were included, among which 35.0% of the participants may currently be sleeping less than the optimal duration. Female students (6.84 h, SD = 1.00) slept shorter than males (6.94 h, SD = 1.09). The only parallel between sexes was that both female and male students with 3-5 times weekly breakfast were less likely to have short sleep duration. Adjusting for depressive symptoms in the following step eliminated the association between anxiety symptoms and short sleep duration in the model for female students. Female-specific associated factors with short sleep duration were age, grade, academic pressure, weekly physical exercise, depressive symptoms. Male-specific characteristics were current smoking tobacco cigarette, self-perceived health, duration of daily Internet use.

Conclusion: Characteristic profiles of sleep duration differed between female and male university students; only a few male-specific factors were identified. Psychological guidance and education courses as well as other interventions to improve university students' sleep and related health should be designed and implemented based on sex differences.
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http://dx.doi.org/10.1016/j.jad.2021.04.025DOI Listing
July 2021

A potential probiotic bacterium for antipsychotic-induced metabolic syndrome: mechanisms underpinning how Akkermansia muciniphila subtype improves olanzapine-induced glucose homeostasis in mice.

Psychopharmacology (Berl) 2021 May 27. Epub 2021 May 27.

Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, Guangdong, China.

Background: Olanzapine (OLZ) is one of the most effective atypical antipsychotics but is associated with severe metabolic side effects, in which the gut microbiota plays an important role. Akkermansia muciniphila (A. muciniphila; Akk), a Gram-negative anaerobic bacterium in the intestine, can potentially improve metabolic syndrome.

Objective: This study investigated the effect and underlying mechanisms of an A. muciniphila subtype (A. muciniphila; Akk) on OLZ-induced metabolic dysfunction in lean and obese mice.

Methods: C57BL/6 female mice were fed a high-fat diet to induce obesity or normal chow for 8 weeks before OLZ treatment for 16 weeks. During the treatment period, mice in each group were orally administrated A. muciniphila. Weight gain, glucose and lipid metabolism, and inflammation were evaluated.

Results: A. muciniphila decreased OLZ-related weight gain only at week 16 in lean mice and significantly alleviated OLZ-induced hyperglycemia irrespective of diet. This was accompanied by reduced levels of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK)-key enzymes in hepatic gluconeogenesis-and OLZ-associated insulin resistance. Moreover, OLZ-induced increases in serum interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels were improved by A. muciniphila in both obese and lean mice. OLZ did not increase serum lipid levels or hepatic fat accumulation.

Conclusions: A. muciniphila improves OLZ-related hyperglycemia via regulation of G6Pase and PEPCK levels and insulin resistance. Moreover, A. muciniphila alleviates systemic inflammation caused by OLZ. A. muciniphila is a promising probiotic treatment for OLZ-induced metabolic dysfunction.
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http://dx.doi.org/10.1007/s00213-021-05878-9DOI Listing
May 2021

The intervention of intestinal Wnt/β-catenin pathway alters inflammation and disease severity of CIA.

Immunol Res 2021 May 26. Epub 2021 May 26.

Department of Rheumatology and Immunology, Changhai Hospital, The Second Military Medical University, Shanghai, China.

Autoreactive T cell is one of the leading causes of immunological tolerance defects in the chronic inflammatory lesions of rheumatoid arthritis (RA). There have been several extracellular signals and intracellular pathways reported in regulating this process but largely remain unknown yet. In this study, we explored the roles of intestinal Wnt/β-catenin on disease severity during collagen-induced arthritis model (CIA), an animal model of RA. We first testified the activity pattern Wnt/β-catenin shifted by intragastric administration of LiCl and DKK-1 in the intestine by real-time PCR and WB analysis. The arthritis scores showing the disease severity in the DKK-1 group was significantly ameliorated compared with the control group at the late stage of the disease, while in the LiCl group, the scores were significantly elevated which was consistent with pathology score analysis of H&E staining. Next, ELISA was performed and showed that TNF-α and IL-17 in the LiCl group were significantly higher than that of the control group. IL-10 in the DKK-1 group was significantly higher than that in the LiCl-1 group and control group, P < 0.05. Flow cytometry of spleen T cells differentiation ratio showed that: Th1 from the DKK-1 and LiCl groups and Th17 from the LiCl group was significantly different from that of the blank model group, P < 0.05. Finally, we explored the effects of intestinal Wnt/β-catenin on T cell differentiation regulator ROR-γt and TCF1 and found that both transcription factors were up-regulated in the LiCl group. Together, these data suggested the pro-information role of Wnt/β-catenin pathway from the intestine in the CIA mouse, implying its use as a potential therapeutic target for the treatment of inflammatory diseases such as RA.
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http://dx.doi.org/10.1007/s12026-021-09190-8DOI Listing
May 2021

Identification of a bacterial-type ATP-binding cassette transporter implicated in aluminum tolerance in sweet sorghum ( L.).

Plant Signal Behav 2021 Jul 26;16(7):1916211. Epub 2021 May 26.

Jilin Province Engineering Laboratory of Plant Genetic Improvement, College of Plant Science, Jilin University, Changchun, China.

Aluminum (Al) toxicity in acidic soils severely reduces crop production worldwide. Sorghum ( L.) is an important agricultural crop widely grown in tropical and subtropical regions, where Al toxicity is prevalent. ATP-binding cassette (ABC) transporters play key roles in the development of plants and include the member sensitive to aluminum rhizotoxicity 1 (STAR1), which is reported to be associated with Al tolerance in a few plant species. However, a STAR1 homolog has not been characterized in sorghum with respect to Al tolerance. Here, we identified and characterized a gene in sweet sorghum encoding the nucleotide-binding domain of a bacterial-type ABC transporter. The transcriptional expression of is induced by Al in a time- and dosage-dependent manner in root, especially in root tip, which is the key site of Al toxicity in plants. The typical Al-associated transcription factor SbSTOP1 showed transcriptional regulation of . SbSTAR1 was present at both the cytoplasm and nuclei. Overexpression of significantly enhanced the Al tolerance of transgenic plants, which possibly via regulating the hemicellulose content in root cell wall. This study provides the first ABC protein in sorghum implicated in Al tolerance, suggesting the existence of a SbSTAR1-mediated Al tolerance mechanism in sorghum.
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http://dx.doi.org/10.1080/15592324.2021.1916211DOI Listing
July 2021

Tislelizumab Plus Chemotherapy as First-line Treatment for Locally Advanced or Metastatic Nonsquamous Non-Small Cell Lung Cancer (RATIONALE 304): A Randomized Phase 3 Trial.

J Thorac Oncol 2021 May 22. Epub 2021 May 22.

Peking Union Medical College Hospital, 41 Damucang Hutong, Xicheng District, Beijing, China 100000.

Hypothesis: Tislelizumab, an anti-PD-1 antibody, was specifically engineered to minimize FcɣR macrophages binding to abrogate antibody-dependent phagocytosis. Compared with chemotherapy alone, tislelizumab plus chemotherapy may improve clinical outcomes in patients with advanced nonsquamous non-small cell lung cancer (nsq-NSCLC).

Methods: In this open-label phase 3 trial (RATIONALE 304; NCT03663205), patients with histologically confirmed stage IIIB/IV nsq-NSCLC were randomized (2:1) to receive either Arm A: tislelizumab plus platinum (carboplatin or cisplatin) and pemetrexed every 3 weeks (Q3W) or Arm B: platinum and pemetrexed alone Q3W during induction treatment, followed by intravenous maintenance pemetrexed Q3W. The primary endpoint was progression-free response (PFS) assessed by an independent review committee; clinical response and safety/tolerability were secondary endpoints.

Results: Overall, 332 patients (n=222 [A]; n=110 [B]) received treatment. With a median study follow-up of 9.8 months, PFS was significantly longer with tislelizumab plus chemotherapy compared with chemotherapy alone (median PFS: 9.7 versus 7.6 months; HR=0.645 [95% CI: 0.462, 0.902]; P=0.0044). Additionally, response rates were higher and response duration was longer with combination therapy versus chemotherapy alone. Hematologic adverse events (AEs) were common in both treatment arms; the majority of reported AEs were grade 1-2 in severity. The most common grade ≥3 AEs were associated with chemotherapy and included neutropenia (44.6% [A]; 35.5% [B]) and leukopenia (21.6% [A]; 14.5% [B]).

Conclusions: Addition of tislelizumab to chemotherapy resulted in significantly prolonged PFS, higher response rates, and longer response duration compared with chemotherapy alone, identifying a new potential option for first-line treatment of advanced nsq-NSCLC irrespective of disease stage.
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http://dx.doi.org/10.1016/j.jtho.2021.05.005DOI Listing
May 2021

CUL4B Promotes Breast Carcinogenesis by Coordinating with Transcriptional Repressor Complexes in Response to Hypoxia Signaling Pathway.

Adv Sci (Weinh) 2021 05 16;8(10):2001515. Epub 2021 Mar 16.

Beijing Key Laboratory of Cancer Invasion and Metastasis Research Advanced Innovation Center for Human Brain Protection Department of Biochemistry and Molecular Biology School of Basic Medical Sciences Capital Medical University Beijing 100069 China.

Cullin4B (CUL4B) is a scaffold protein of the CUL4B-Ring E3 ligase (CRL4B) complex. However, the role of CUL4B in the development of breast cancer remains poorly understood. Here it is shown that CRL4B interacts with multiple histone deacetylase (HDAC)-containing corepressor complexes, including MTA1/NuRD, SIN3A, CoREST, and NcoR/SMRT complexes. It is demonstrated that CRL4B/NuRD(MTA1) complexes cooccupy the E-cadherin and AXIN2 promoters, and could be recruited by transcription factors including Snail and ZEB2 to promote cell invasion and tumorigenesis both in vitro and in vivo. Remarkably, CUL4B responded to transformation and migration/invasion stimuli and is essential for multiple epithelial-mesenchymal transition (EMT) signaling pathways such as hypoxia. Furthermore, the transcription of CUL4B is directedly activated by hypoxia-inducible factor 1 (HIF1) and repressed by the ER-GATA3 axis. Overexpressing of CUL4B successfully induced CSC-like properties. Strikingly, CUL4B expression is markedly upregulated during breast cancer progression and correlated with poor prognosis. The results suggest that CUL4B lies at a critical crossroads between EMT and stem cell properties, supporting CUL4B as a potential novel target for the development of anti-breast cancer therapy.
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http://dx.doi.org/10.1002/advs.202001515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132058PMC
May 2021

Preliminary investigation on iodine nutrition in captive giant pandas.

J Trace Elem Med Biol 2021 Sep 18;67:126780. Epub 2021 May 18.

Chengdu Research Base of Giant Panda Breeding, 610081, Chengdu, China; Sichuan Key Laboratory of Conservation Biology for Endangered Wildlife, 610081, Chengdu, China; Sichuan Academy of Giant Panda, 610081, Chengdu, China. Electronic address:

Background/objective: The giant panda belongs to the family Ursidae and, as a species of bear, still retains the simple digestive system of a Carnivoran. However, under the pressure of a specific habitat they had to adapt to a plant mono-diet consisting of bamboo with different species and growth stages around the year. A plant-based diet has relatively low iodine content with risk of iodine deficiency. Furthermore, bamboo contains cyanogenic glycosides releasing cyanide whose detoxification metabolite the thiocyanate acts as antagonist against iodine uptake and storage in the thyroid. To date very little is known about the iodine nutritional status of the giant panda, thus this study was conducted to receive the first information about the iodine nutrition of captive giant panda.

Subjects/methods: Here we investigated the iodine content of bamboo with different plant parts/vegetation stage and species and further compounds of the captive giant panda diet. Next, the urinary iodine (UI) and urinary thiocyanate (UT) levels of infant, sub-adult, adult and geriatric captive giant pandas was measured during the periods when the pandas consume both bamboo leaves- and culm (bamboo leaf-culm stage). Afterwards, the UI of 19 adult giant pandas was measured again for the different iodine intake during bamboo shoot stage. Finally, in this study part also the fecal iodine concentration was analyzed for calculation of total iodine excretion in relation to the iodine intake.

Results: Bamboo leaves had the highest iodine content (453 μg/kg dry matter (DM)), followed by the shoots (84 μg/kg DM, p <  0.05), while bamboo culm had the lowest value (12 μg/kg DM, p <  0.05). During bamboo leaf-culm stage, giant pandas of different age groups had different UI and UT levels (p <  0.05). Furthermore, UI and UT were positively correlated among sub-adult, adult and geriatric giant pandas (p <  0.05). In adult giant pandas during bamboo shoot stage, the iodine excretion in feces was not different from that in urine while their total iodine excretion was less than their iodine intake (p <  0.05). Moreover, during bamboo shoot stage, the UI level of adult giant pandas was much lower than noted during bamboo leaf-culm stage (p <  0.05).

Conclusions: Our results indicate that UI of captive giant pandas was related to their age as well as to the vegetation stage/part of bamboo they consumed reflecting a different periodic iodine supply. Thiocyanate and fecal excretion should be emphasized when considering the iodine nutrition of giant pandas.
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http://dx.doi.org/10.1016/j.jtemb.2021.126780DOI Listing
September 2021

miR-375 acts as a novel factor modulating pituitary prolactin synthesis through Rasd1 and Esr1.

J Endocrinol 2021 May 1. Epub 2021 May 1.

S Cui, College of Veterinary Medicine, Yangzhou University, Yangzhou, China.

Prolactin (PRL) is a pituitary hormone that regulates multiple physiological processes. However, the mechanisms of PLR synthesis have not been fully elucidated. The aims of the present study were to study the functions and the related mechanisms of miR-375 regulating PRL synthesis. We initially found that miR-375 mainly expressed in the lactotrophs of mouse pituitary gland. To identify the function of miR-375 in the pituitary gland, the miR-375 knockout mice were generated by using Crispr/Cas9 technique. The results showed that miR-375 knockout resulted in the decline of pituitary PRL mRNA and protein levels by 75.7% and 60.4% respectively, and the serum PRL level reduced about 46.1%, but had no significant effect on FSH, LH and TSH. Further, we identified that Estrogen receptor 1 (alpha) (Esr1) was a downstream molecule of miR-375. The real-time PCR and western blot results showed that ESR1 mRNA and protein levels markedly decreased by 40.9% and 42.9% in the miR-375 knockout mouse pituitary, and these were subsequently confirmed by the in vitro study using transfections of miR-375 mimics and inhibitors in pituitary lactotroph GH4 cells. Further, Rasd1 was predicted by bioinformatic tools and proved to be the direct target of miR-375 in lactotrophs using dual-luciferase reporter assay. Rasd1-siRNA transfection results revealed the negative effect of Rasd1 in regulating ESR1. Collectively, the results presented here demonstrate that miR-375 positively modulates PRL synthesis through Rasd1 and Esr1, which are crucial for understanding the regulating mechanisms of pituitary hormone synthesis.
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http://dx.doi.org/10.1530/JOE-20-0001DOI Listing
May 2021

Novel variant of associated with mild evaluation of related disorder in a Chinese family.

Clin Chem Lab Med 2021 May 19. Epub 2021 May 19.

Department of Clinical Laboratory, The Second Hospital of Hebei Medical University, Shijiazhuang, P. R. China.

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http://dx.doi.org/10.1515/cclm-2021-0205DOI Listing
May 2021

Enhancing the static green up-conversion luminescence of NaY(MoO):Yb/Er microcrystals an annealing strategy for anti-counterfeiting applications.

Dalton Trans 2021 Jun;50(22):7826-7834

College of Science, Xi'an University of Architecture and Technology, Xi'an 710055, China.

The majority of the fabrication procedures of lanthanide-doped materials involve thermal treatment that often results in crystallite regrowth, stabilizing the specific crystal structure and resulting in luminescence enhancement. The efficiency and intensity of up-conversion luminescence are closely related to the structure and synthesis process of the materials. Herein, well-crystallized and pure tetragonal NaY(MoO4)2 microcrystals with a uniform octahedral shape have been successfully synthesized via an environmentally friendly hydrothermal method, followed by annealing treatment. The phases, structures, morphologies, and compositions of the synthesized products annealed at 500-1000 °C remain unchanged, indicating high thermal stability. Furthermore, the NaY(MoO4)2:Yb3+/Er3+ microcrystals exhibit strong green emission when irradiated using infrared (980 nm) or ultraviolet (378 nm) wavelengths. Upon 980 nm excitation, up to 37-fold luminescence enhancement is achieved when the samples are annealed at about 700 °C. Interestingly, the high colour purity of the strong green emission is not only independent of the dopant concentration and heat treatment temperature, but it is also independent of the excitation conditions, including power and wavelength, and this makes it particularly suitable as a green safety signal light and luminescent security ink in paintings. As-prepared safety inks with NaY(MoO4)2:Yb3+/Er3+ microcrystals were used for visual fingerprint recognition printed on A4 paper with three-level fingerprint security features, significantly increasing the difficulty of illegal imitation and enhancing the levels of anti-counterfeiting.
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http://dx.doi.org/10.1039/d1dt00948fDOI Listing
June 2021

Untargeted and targeted gingival metabolome in rodents reveal metabolic links between high-fat diet-induced obesity and periodontitis.

J Clin Periodontol 2021 May 17. Epub 2021 May 17.

Department of Periodontics, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.

Aim: To characterize gingival metabolome in high-fat diet (HFD)-induced obesity in mice with/without periodontitis.

Methods: HFD-induced obesity mouse model was established by 16-week feeding, and a lean control group was fed with low-fat diet (n = 21/group). Both models were induced for periodontitis on the left sides by molar ligation for 10 days, whereas the right sides were used as controls. Gingival metabolome and arginine metabolism were analysed by non-targeted/targeted liquid chromatography-mass spectrometry.

Results: Of 2247 reference features, presence of periodontitis altered 165 in lean versus 885 in HFD mice; and HFD altered 525 in absence versus 1435 in presence of periodontitis. Compared with healthy condition, periodontitis and HFD had distinct effects on gingival metabolome. Metabolomic impacts of periodontitis were generally greater in HFD mice versus lean controls. K-medoids clustering showed that HFD amplified the impacts of periodontitis on gingival metabolome in both intensity and extensity. Ten metabolic pathways were enriched, including 2 specific to periodontitis, 5 specific to HFD and 3 shared ones. Targeted validation on arginine metabolism confirmed the additive effects between HFD and periodontitis.

Conclusion: The obese population consuming excessive HFD display amplified metabolic response to periodontitis, presenting a metabolic susceptibility to exacerbated periodontal destruction.
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http://dx.doi.org/10.1111/jcpe.13486DOI Listing
May 2021

SGK1 mutations in DLBCL generate hyperstable protein neoisoforms that promote AKT independence.

Blood 2021 May 14. Epub 2021 May 14.

University of Cambridge, Cambridge, United Kingdom.

Serum and Glucocorticoid-regulated Kinase-1 (SGK1) is one of the most frequently mutated genes in Diffuse Large B Cell Lymphoma (DLBCL). However, little is known about its function or the consequence of its mutation. The frequent finding of truncating mutations has led to the widespread assumption that these represent loss-of-function variants and accordingly, that SGK1 must act as a tumour suppressor. Here we show that instead, the most common SGK1 mutations lead to production of aberrantly spliced mRNA neoisoforms in which translation is initiated from downstream methionines. The resulting N-terminal truncated protein isoforms show increased expression due to the exclusion of an N-terminal degradation domain. However, they retain a functional kinase domain, the over-expression of which renders cells resistant to AKT inhibition in part due to increased phosphorylation of GSK3B. These findings challenge the prevailing assumption that SGK1 is a tumour suppressor gene in DLBCL and provide the impetus to explore further the pharmacological inhibition of SGK1 as a therapeutic strategy for DLBCL.
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http://dx.doi.org/10.1182/blood.2020010432DOI Listing
May 2021

Realizing the role of N-acyl-homoserine lactone-mediated quorum sensing in nitrification and denitrification: A review.

Chemosphere 2021 Jul 15;274:129970. Epub 2021 Feb 15.

CAS Key Laboratory of Environmental Biotechnology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

Nitrification and denitrification are crucial processes in the nitrogen cycle, a vital microbially driven biogeochemical cycle. N-acyl-homoserine lactone (AHL)-mediated quorum sensing (QS) is widespread in bacteria and plays a key role in their physiological status. Recently, there has been an increase in research into how the AHL-mediated QS system is involved in nitrification and denitrification. Consequentially, the AHL-mediated QS system has been considered a promising regulatory approach in nitrogen metabolism processes, with high potential for real-world applications. In this review, the universal presence of QS in nitrifiers and denitrifiers is summarized. Many microorganisms taking part in nitrification and denitrification harbor QS genes, and they may produce AHLs with different chain lengths. The phenotypes and processes affected by QS in real-world applications are also reviewed. In wastewater bioreactors, QS could affect nitrogen metabolism efficiency, granule aggregation, and biofilm formation. Furthermore, methods commonly used to identify the existence and functions of QS, including physiological tests, genetic manipulation and omics analyses are discussed.
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http://dx.doi.org/10.1016/j.chemosphere.2021.129970DOI Listing
July 2021

JWX-A0108, a positive allosteric modulator of α7 nAChR, attenuates cognitive deficits in APP/PS1 mice by suppressing NF-κB-mediated inflammation.

Int Immunopharmacol 2021 May 8;96:107726. Epub 2021 May 8.

Department of Pharmacology, Qingdao University School of Pharmacy, Qingdao 266000, China. Electronic address:

Neuroinflammation plays an early and prominent role in the pathology of Alzheimer's disease (AD). Studies have shown that cholinergic lesion is a contributor for the pathophysiology of AD. The α7 nicotinic acetylcholine receptors (nAChRs), a subtype of nAChRs, are abundantly expressed in the brain regions related to cognition and memory, such as hippocampus and frontal cortex. The α7 nAChR is rapidly activated and desensitized by agonists. JWX-A0108 is a type I positive allosteric modulator (PAM) of α7 nAChR, which mainly enhances agonist-evoked peak currents. Here, we used the Morris Water Maze to evaluate the effect of JWX-A0108 on cognition and memory functions in APP/PS1 mice, and the mechanism related to anti-inflammatory effect. The results showed that JWX-A0108 could improve the learning and memory function of APP/PS1 transgenic mice in Morris water maze, decrease the expression of IL-1β, TNF-α, IL-6 in the brain and lower the phosphorylation level of IκBα (Ser32/36) and NF-κB p65 (Ser536), decrease the expression of Iba1, the microglia activation marker. Nissl staining showed that the CA3 and DG regions of hippocampus were damaged in APP/PS1 mice, which was improved by JWX-A0108. All of these effects of JWX-A0108 were reversed by MLA (α7 nAChR specific blocker). Taken together, the results reveal that JWX-A0108 improved the learning and memory function of APP/PS1 mice by enhancing the anti-inflammatory effect of the endogenous choline system through α7 nAChR, inhibited the activation of the NF-κB signaling pathway by inhibiting IκB phosphorylation, and ultimately inhibited inflammatory responses.
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http://dx.doi.org/10.1016/j.intimp.2021.107726DOI Listing
May 2021

Astragaloside alleviates alcoholic fatty liver disease by suppressing oxidative stress.

Kaohsiung J Med Sci 2021 May 11. Epub 2021 May 11.

Department of Preclinical Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, China.

Alcoholic fatty liver disease (AFLD) is the most common liver disease and can progress to fatal liver cirrhosis and carcinoma, affecting millions of patients worldwide. The functions of astragaloside on the cardiovascular system have been elucidated. However, its role in AFLD is unclear. Ethanol-treated AML-12 cells were used as a cell model of alcoholic fatty liver. Real-time quantitative reverse transcription-PCR and Western blotting detected genes and proteins expressions. Reactive oxygen species (ROS), triglyceride, total cholesterol, low-density lipoprotein, albumin, ferritin, bilirubin, superoxide dismutase, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were examined using commercial kits. Lipid accumulation was assessed by Oil red O staining. MTT and flow cytometry measured cell viability and apoptosis. JC-1 was used to analyze mitochondrial membrane potential. A rat model of AFLD was established by treating rats with ethanol. Astragaloside suppressed ethanol-induced lipid accumulation, oxidative stress, and the production of AST and ALT in AML-12 cells. Ethanol induced TNF-α and reduced IL-10 expression, which were reversed by astragaloside. Ethanol promoted Bax expression and cytochrome C release and inhibited Bcl-2 and ATP expression. Astragaloside hampered these apoptosis effects in AML-12 cells. Impaired mitochondrial membrane potential was recovered by astragaloside. However, all these astragaloside-mediated beneficial effects were abolished by the ROS inducer pyocyanin. Ethanol-induced activation of NF-κB signaling was suppressed by astragaloside in vitro and in vivo, suggesting that astragaloside inhibited oxidative stress by suppressing the activation of NF-κB signaling, thus improving liver function and alleviating AFLD in rats. Our study elucidates the pharmacological mechanism of astragaloside and provides potential therapeutic strategies for AFLD.
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http://dx.doi.org/10.1002/kjm2.12390DOI Listing
May 2021

Rapid synthesis and characterization of silver-loaded graphene oxide nanomaterials and their antibacterial applications.

R Soc Open Sci 2021 Feb 24;8(2):201744. Epub 2021 Feb 24.

College of Chemistry and Environmental Engineering, Chongqing University of Arts and Sciences, Yongchuan 402160, People's Republic of China.

With the promising potential application of Ag/graphene-based nanomaterials in medicine and engineering materials, the large-scale production has attracted great interest of researchers on the basis of green synthesis. In this study, water-soluble silver/graphene oxide (Ag/GO) nanomaterials were synthesized under ultrasound-assisted conditions. The structural characteristics of Ag/GO were confirmed by Fourier transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy, scanning electron microscopy and energy dispersion spectroscopy, respectively. The results showed the silver particles (AgNPs) obtained by reduction were attached to the surface of GO, and there was a strong interaction between AgNPs and GO. The antibacterial activity was primarily evaluated by the plate method and hole punching method. Antibacterial tests indicated that Ag/GO could inhibit the growth of Gram-negative and Gram-positive bacteria, special for the .
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http://dx.doi.org/10.1098/rsos.201744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074688PMC
February 2021