Publications by authors named "Jianping Xie"

405 Publications

Pemphigus Herpetiformis-Type Drug Reaction Caused by Programmed Cell Death Protein-1 Inhibitor Treatment.

Clin Cosmet Investig Dermatol 2021 27;14:1125-1129. Epub 2021 Aug 27.

Department of Dermatology, The Fifth People's Hospital of Hainan Province, Branch of National Clinical Research Center for Skin and Immune Disease, Haikou, 570206, People's Republic of China.

Reports of immune-related adverse events caused by programmed cell death protein-1 inhibitor are becoming increasingly frequent. Herein, we report the first case of pemphigus herpetiformis-type drug reaction presented after the treatment of tislelizumab (6 cycles) in a primary non-small cell lung carcinoma patient. A 56-year-old Chinese man was referred to our department for pruritic annulare erythema and blister for two weeks. Histological finding revealed blister formation in the epidermis and eosinophilic infiltration in the blister fluid. Direct immunofluorescence showed intercellular deposition of IgG and C3 within the lower part of epidermis. Serum anti-intercellular antibodies were positive at 1:100 dilution. Based on history and clinicopathological correlation, herpetiformis-type drug-induced pemphigus was diagnosed, which was possibly be induced by tislelizumab. To the best to our knowledge, there is no report of pemphigus herpetiformis-type drug-induced reaction associated with programmed cell death protein-1 inhibitor treatment.
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http://dx.doi.org/10.2147/CCID.S330354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407525PMC
August 2021

Mycobacterium tuberculosis PE17 (Rv1646) promotes host cell apoptosis via host chromatin remodeling mediated by reduced H3K9me3 occupancy.

Microb Pathog 2021 Oct 13;159:105147. Epub 2021 Aug 13.

Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Ecoenvironments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University, Beibei, Chongqing, 400715, China. Electronic address:

Tuberculosis caused by Mycobacterium tuberculosis remains a serious global public health threat. M. tuberculosis PE and PPE proteins are closely involved in pathogen-host interaction. To explore the predicted function of the M. tuberculosis PE17 (Rv1646), we heterologously expressed PE17 in a non-pathogenic Mycobacterium smegmatis strain (Ms_PE17). PE17 can reduce the survival of M. smegmatis within macrophages associated with altering the transcription levels of inflammatory cytokines IL1β, IL6, TNFα, and IL10 in Ms_PE17 infected macrophages through JNK signaling. Furthermore, macrophages apoptosis was increased upon Ms_PE17 infection in a caspases-dependent manner, accompanied by the activation of the Endoplasmic Reticulum stress IRE1α/ASK1/JNK signaling pathway. This can be largely interpreted by the epigenetic changes through reduced H3K9me3 chromatin occupancy post Ms_PE17 infection. To our knowledge, this is the first report that PE17 altered the macrophages apoptosis via H3K9me3 mediated chromatin remodeling.
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http://dx.doi.org/10.1016/j.micpath.2021.105147DOI Listing
October 2021

Thymic MALT lymphoma mimicking parathyroid adenoma uptake on Tc-MIBI parathyroid scintigraphy.

Hell J Nucl Med 2021 May-Aug;24(2):157-158. Epub 2021 Aug 6.

Department of Nuclear Medicine, The Affiliated Hospital of North Sichuan Medical College, No.1, Maoyuan South Road, 637000 Nanchong, Sichuan province, P.R.China.

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http://dx.doi.org/10.1967/s002449912357DOI Listing
August 2021

Heterogeneous radioiodine uptake in breast fibroadenoma: A case report.

Hell J Nucl Med 2021 May-Aug;24(2):155-156. Epub 2021 Aug 6.

Department of Nuclear Medicine, Affiliated Hospital of North Sichuan Medical College, No.1, Maoyuan South Road,637000 Nanchong, Sichuan province, P. R. China.

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http://dx.doi.org/10.1967/s002449912356DOI Listing
August 2021

Mycobacterium tuberculosis RKIP (Rv2140c) dephosphorylates ERK/NF-κB upstream signaling molecules to subvert macrophage innate immune response.

Infect Genet Evol 2021 Oct 30;94:105019. Epub 2021 Jul 30.

Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Ecoenvironments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University, Beibei, Chongqing 400715, China. Electronic address:

Mycobacterium tuberculosis (Mtb) survival and virulence largely reside on its ability to manipulate the host immune response. We have previously shown that M. tuberculosis Raf kinase inhibitor protein (RKIP) Rv2140c regulates diverse phosphorylation events in M. smegmatis. However, its role during infection is unknown. In this report, we show that Rv2140c can mimic the mammalian RKIP function. Rv2140c inhibit the activation of extracellular signal-regulated kinase (ERK) and nuclear factor κB (NF-κB) via decreasing the phosphorylation capacity of upstream mediators MEK1, ERK1/2, and IKKα/β, thus leading to a reduction in pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. This effect can be reversed by RKIP inhibitor locostatin. Furthermore Rv2140c mediates apoptosis associated with activation of caspases cascades. This modulation enhances the intracellular survival of M. smegmatis within macrophage. We propose that Rv2140c is a multifunctional virulence factor and a promising novel anti-Tuberculosis drug target.
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http://dx.doi.org/10.1016/j.meegid.2021.105019DOI Listing
October 2021

The Evaluation and Validation of Blood-Derived Novel Biomarkers for Precise and Rapid Diagnosis of Tuberculosis in Areas With High-TB Burden.

Front Microbiol 2021 14;12:650567. Epub 2021 Jun 14.

State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-Environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Institute of Modern Biopharmaceuticals, Southwest University, Chongqing, China.

Tuberculosis (TB) remains a highly contagious public health threat. Precise and prompt diagnosis and monitoring of treatment responses are urgently needed for clinics. To pursue novel and satisfied host blood-derived biomarkers, we streamlined a bioinformatic pipeline by integrating differentially expressed genes, a gene co-expression network, and short time-series analysis to mine the published transcriptomes derived from whole blood of TB patients in the GEO database, followed by validating the diagnostic performance of biomarkers in both independent datasets and blood samples of Chinese patients using quantitative real-time PCR (qRT-PCR). We found that four genes, namely UBE2L6 (Ubiquitin/ISG15-conjugating enzyme E2 L6), BATF2 (Basic leucine zipper transcriptional factor ATF-like), SERPING1 (Plasma protease C1 inhibitor), and VAMP5 (Vesicle-associated membrane protein 5), had high diagnostic value for active TB. The transcription levels of these four gene combinations can reach up to 88% sensitivity and 78% specificity (average) for the diagnosis of active TB; the highest sensitivity can achieve 100% by parallel of BATF2 and VAMP5, and the highest specificity can reach 89.5% through a combination of SERPIG1, UBE2L6, and VAMP5, which were significantly higher than 75.3% sensitivity and 69.1% specificity by T-SPOT.TB in the same patients. Quite unexpectedly, the gene set can assess the efficacy of anti-TB response and differentiate active TB from Latent TB infection. The data demonstrated these four biomarkers might have great potency and advantage over IGRAs in the diagnosis of TB.
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http://dx.doi.org/10.3389/fmicb.2021.650567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236956PMC
June 2021

Interaction of porcine circovirus-like virus P1 capsid protein with host proteins.

BMC Vet Res 2021 Jun 26;17(1):227. Epub 2021 Jun 26.

Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Nanjing, Jiangsu, China.

Background: Porcine circovirus-like virus P1 is a relatively new kind of virus that is closely related to the post-weaning multisystemic wasting syndrome, congenital tremors, and abortions in swine. The molecular mechanisms of P1 virus infection and pathogenesis are fully unknown. To analyze P1 and its host interactions, we used a yeast two-hybrid (Y2H) assay to identify cellular proteins interacting with the Cap of the P1 virus. In this study, the Cap of the P1 virus exhibited no self-activation and toxicity to yeast cells and was used as bait to screen the Y2H library prepared from the pancreas tissue.

Results: Five cellular proteins (EEP, Ral GDS, Bcl-2-L-12, CPS1, and one not identified) were found to interact with P1 Cap. The interaction between Cap and Ral GDS was confirmed by co-immunoprecipitation.

Conclusions: Our data are likely to support the future investigation of the underlying mechanism of P1 infection and pathogenesis.
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http://dx.doi.org/10.1186/s12917-021-02926-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235626PMC
June 2021

Molecular reactivity of thiolate-protected noble metal nanoclusters: synthesis, self-assembly, and applications.

Chem Sci 2020 Nov 23;12(1):99-127. Epub 2020 Nov 23.

Department of Chemical and Biomolecular Engineering, National University of Singapore 4 Engineering Drive 4 Singapore 117585

Thiolate-protected noble metal (, Au and Ag) nanoclusters (NCs) are ultra-small particles with a core size of less than 3 nm. Due to the strong quantum confinement effects and diverse atomic packing modes in this ultra-small size regime, noble metal NCs exhibit numerous molecule-like optical, magnetic, and electronic properties, making them an emerging family of "metallic molecules". Based on such molecule-like structures and properties, an individual noble metal NC behaves as a molecular entity in many chemical reactions, and exhibits structurally sensitive molecular reactivity to various ions, molecules, and other metal NCs. Although this molecular reactivity determines the application of NCs in various fields such as sensors, biomedicine, and catalysis, there is still a lack of systematic summary of the molecular interaction/reaction fundamentals of noble metal NCs at the molecular and atomic levels in the current literature. Here, we discuss the latest progress in understanding and exploiting the molecular interactions/reactions of noble metal NCs in their synthesis, self-assembly and application scenarios, based on the typical M(0)@M(i)-SR core-shell structure scheme, where M and SR are the metal atom and thiolate ligand, respectively. In particular, the continuous development of synthesis and characterization techniques has enabled noble metal NCs to be produced with molecular purity and atomically precise structural resolution. Such molecular purity and atomically precise structure, coupled with the great help of theoretical calculations, have revealed the active sites in various structural hierarchies of noble metal NCs (, M(0) core, M-S interface, and SR ligand) for their molecular interactions/reactions. The anatomy of such molecular interactions/reactions of noble metal NCs in synthesis, self-assembly, and applications (, sensors, biomedicine, and catalysis) constitutes another center of our discussion. The basis and practicality of the molecular interactions/reactions of noble metal NCs exemplified in this may increase the acceptance of metal NCs in various fields.
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http://dx.doi.org/10.1039/d0sc04620eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178751PMC
November 2020

Association of central obesity with hepatocellular carcinoma in patients with chronic hepatitis B receiving antiviral therapy.

Aliment Pharmacol Ther 2021 08 22;54(3):329-338. Epub 2021 Jun 22.

Guangzhou, China.

Background: Obesity is typically associated with metabolic dysfunction, but its impact on hepatocellular carcinoma (HCC) remains unclear in patients with chronic hepatitis B (CHB).

Aim: To study the effect of obesity on HCC development in patients with CHB receiving antiviral therapy.

Methods: We included patients from a Chinese multicentre, prospective, observational, treated CHB cohort in this study. General obesity was evaluated by body-mass index (BMI). Central obesity was evaluated by waist circumference, waist-to-hip ratio and waist-to-height ratio.

Results: A total of 5754 nucleos(t)ide analogue treated patients were enrolled in the analysis. The 5-year cumulative incidence of HCC was 2.9%. Waist-to-height ratio performed better in predicting HCC development than BMI, waist circumference or waist-to-hip ratio. Patients with central obesity (defined as waist-to-height ratio >0.5) had significantly higher 5-year incidence of HCC than those without central obesity in the overall population (3.9% vs 2.1%, hazard ratio [HR]: 2.06, P = 0.0001) and 745 propensity score matched pairs (4.7% vs 2.3%, HR: 2.04, P = 0.026), respectively. Besides cirrhosis status and aMAP HCC risk score, central obesity was also independently associated with HCC risk (HR: 1.63, P = 0.013). Waist-to-height ratio gain within 1 year was associated with a significantly higher HCC risk with an adjusted HR value of 1.88 (95% confidence interval: 1.12-3.13, P = 0.017).

Conclusions: Central obesity, evaluated by the waist-to-height ratio, was associated with a twofold increase in HCC risk among CHB patients receiving antiviral treatment, highlighting the important role of abnormal metabolic function in the progression of liver disease.
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http://dx.doi.org/10.1111/apt.16469DOI Listing
August 2021

HLA complex group 11 is involved in colorectal carcinoma cisplatin resistance via the miR-214-5p/SOX4 axis.

Oncol Lett 2021 Jul 19;22(1):535. Epub 2021 May 19.

Department of Clinical Laboratory, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang Central Hospital, Xiangyang, Hubei 441000, P.R. China.

The aim of the present study was to investigate the roles and potential mechanisms of long non-coding RNA HLA complex group 11 (HCG11) in colorectal carcinoma. Reverse transcription-quantitative PCR was used to detect HCG11 expression in clinical tissues and survival analysis was performed to identify its prognostic value. In order to investigate its specific biological functions in colorectal carcinoma, the transfection technique was used for the knockdown and overexpression of HCG11. Dual-luciferase reporter gene and RNA pull-down assays were used to identify the binding association between HCG11 and microRNA (miR)-214-5p. Western blot analysis was used to detect the mechanism of epithelial-mesenchymal transition (EMT) regulation in tumor cells in the pathway downstream of HCG11. HCG11 level was high in colorectal carcinoma tissues, which was associated with poor patient prognosis; however, chemotherapy may prevent the upregulation of HCG11 in colorectal carcinoma. HCG11-knockdown suppressed the proliferation, migration and chemotherapeutic sensitivity of colorectal carcinoma cells, whereas HCG11-overexpression enhanced chemotherapeutic sensitivity. miR-214-5p was revealed to be a target gene, and upon direct interaction, a negative regulator of HCG11 in colorectal carcinoma cells. Inhibition of miR-214-5p reversed the restriction of HCG11 on the malignant activity of colorectal carcinoma cells, while miR-214-5p mediated the chemotherapy-related intracellular EMT pathway. In conclusion, HCG11 is a vital oncogene of colorectal carcinoma involved in mediating the chemotherapeutic resistance of tumors.
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http://dx.doi.org/10.3892/ol.2021.12796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157335PMC
July 2021

Revealing the etching process of water-soluble Au nanoclusters at the molecular level.

Nat Commun 2021 05 28;12(1):3212. Epub 2021 May 28.

Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore, 117585, Singapore.

Etching (often considered as decomposition) is one of the key considerations in the synthesis, storage, and application of metal nanoparticles. However, the underlying chemistry of their etching process still remains elusive. Here, we use real-time electrospray ionization mass spectrometry to study the reaction dynamics and size/structure evolution of all the stable intermediates during the etching of water-soluble thiolate-protected gold nanoclusters (Au NCs), which reveal an unusual "recombination" process in the oxidative reaction environment after the initial decomposition process. Interestingly, the sizes of NC species grow larger and their ligand-to-metal ratios become higher during this recombination process, which are distinctly different from that observed in the reductive growth of Au NCs (e.g., lower ligand-to-metal ratios with increasing sizes). The etching chemistry revealed in this study provides molecular-level understandings on how metal nanoparticles transform under the oxidative reaction environment, providing efficient synthetic strategies for new NC species through the etching reactions.
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http://dx.doi.org/10.1038/s41467-021-23568-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163824PMC
May 2021

The frequency and dynamics of CD4 mucosal-associated invariant T (MAIT) cells in active pulmonary tuberculosis.

Cell Immunol 2021 Jul 20;365:104381. Epub 2021 May 20.

Shanghai Clinical Research Center for Tuberculosis, Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address:

MAIT cells are unconventional innate-like T lymphocytes contributing to host immune protection against Mycobacteria tuberculosis (Mtb) infection. CD4 MAIT cells play a major role in immune protection against tuberculosis (TB), however, the role of CD4 MAIT cells was elusive due to their low abundance. We firstly investigated the frequency and functions of CD4 MAIT cells in pulmonary tuberculosis (PTB) patients before and after anti-TB treatment. We found that the frequency of Mtb-reactive CD4 MAIT cells and IFN-γ, granzyme B (GrzB), CD69 expression on them were increased while LAG-3 cells of them were decreased in PTB patients. After the treatment, the frequency of Mtb-reactive CD4 MAIT cells and CD69, IFN-γ, GrzB expression on them were decreased while LAG-3 increased. The results indicated the expression profile is distinct between CD4 MAIT cells and CD4 MAIT cells in PTB patients, the increased IFN-γ and GrzB expression of CD4 MAIT cells play a role in anti-TB immunity.
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http://dx.doi.org/10.1016/j.cellimm.2021.104381DOI Listing
July 2021

Mycobacterium tuberculosis effector PPE36 attenuates host cytokine storm damage via inhibiting macrophage M1 polarization.

J Cell Physiol 2021 May 7. Epub 2021 May 7.

State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Institute of Modern Biopharmaceuticals, Southwest University, Chongqing, China.

Tuberculosis caused by Mycobacterium tuberculosis remains a serious global public health threat. Macrophage polarization is crucial for the innate immunity against M. tuberculosis. However, how M. tuberculosis interferes with macrophage polarization is elusive. We demonstrated here that M. tuberculosis PPE36 (Rv2108) blocked macrophage M1 polarization, preventing the cytokine storm, and alleviating inflammatory damage to mouse immune organs. PPE36 inhibited the polarization of THP-1 cell differentiation to M1 macrophages, reduced mitochondrial dehydrogenase activity, inhibited the expression of CD16, and repressed the expression of pro-inflammatory cytokines IL-6 and TNF-α, as well as chemokines CXCL9, CXCL10, CCL3, and CCL5. Intriguingly, in the mouse infection model, PPE36 significantly alleviated the inflammatory damage of immune organs caused by a cytokine storm. Furthermore, we found that PPE36 inhibited the polarization of macrophages into mature M1 macrophages by suppressing the ERK signaling. The study provided novel insights into the function and mechanism of action of M. tuberculosis effector PPE36 both at the cellular and animal level.
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http://dx.doi.org/10.1002/jcp.30411DOI Listing
May 2021

Tauroursodeoxycholic acid prevents Burkholderia pseudomallei-induced endoplasmic reticulum stress and is protective during melioidosis in mice.

BMC Microbiol 2021 05 4;21(1):137. Epub 2021 May 4.

Department of Clinical Microbiology and Immunology, College of Pharmacy and Medical Laboratory, Army Medical University (Third Military Medical University), Chongqing, 400038, China.

Background: Burkholderia pseudomallei, a facultative intracellular bacterium, is the aetiological agent of melioidosis that is responsible for up to 40% sepsis-related mortality in epidemic areas. However, no effective vaccine is available currently, and the drug resistance is also a major problem in the treatment of melioidosis. Therefore, finding new clinical treatment strategies in melioidosis is extremely urgent.

Results: We demonstrated that tauroursodeoxycholic acid (TUDCA), a clinically available endoplasmic reticulum (ER) stress inhibitor, can promote B. pseudomallei clearance both in vivo and in vitro. In this study, we investigated the effects of TUDCA on the survival of melioidosis mice, and found that treatment with TUDCA significantly decreased intracellular survival of B. pseudomallei. Mechanistically, we found that B. pseudomallei induced apoptosis and activated IRE1 and PERK signaling ways of ER stress in RAW264.7 macrophages. TUDCA treatment could reduce B. pseudomallei-induced ER stress in vitro, and TUDCA is protective in vivo.

Conclusion: Taken together, our study has demonstrated that B. pseudomallei infection results in ER stress-induced apoptosis, and TUDCA enhances the clearance of B. pseudomallei by inhibiting ER stress-induced apoptosis both in vivo and in vitro, suggesting that TUDCA could be used as a potentially alternative treatment for melioidosis.
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http://dx.doi.org/10.1186/s12866-021-02199-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094575PMC
May 2021

[Research progress on the relationship between the Raf murine sarcoma viral oncogene homolog B gene mutation and lymph node metastasis of papillary thyroid carcinoma].

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2021 Feb;38(1):191-195

Department of Nuclear Medicine, the Affiliated Hospital of North Sichuan Medical College, Nanchong, P.R.China.

In recent years, with the improvement of the sensitivity of examination equipment and the change of people's living environment and diet, the rate of thyroid cancer has risen rapidly, which has increased nearly five folds in 10 years. The pathogenesis, clinical manifestation, biological behavior, treatment and prognosis of thyroid carcinoma of different pathological types are obviously different. Papillary thyroid carcinoma (PTC) can develop at any age, which accounts for about 90% of thyroid cancer. It progresses slowly and has favourable prognosis, but lymph node metastasis appears easily. Whether PTC is accompanied by lymph node metastasis has an important impact on its prognosis and outcome. The Raf murine sarcoma viral oncogene homolog B(BRAF)gene mutation plays a crucial role in PTC lymph node metastasis. Having an in-depth understanding of the specific role and mechanism of BRAF gene mutation in PTC is expected to provide new ideas for diagnosis and treatment of PTC.
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http://dx.doi.org/10.7507/1001-5515.202006040DOI Listing
February 2021

Active destruction of pyrite passivation by ozone oxidation of a biotic leaching system.

Chemosphere 2021 Aug 19;277:130335. Epub 2021 Mar 19.

School of Minerals Processing & Bioengineering, Central South University, Changsha, Hunan, China; Key Lab of Biohydrometallurgy of Ministry of Education, Changsha, Hunan, China.

Although pyrite bio-dissolution plays an important role in the processing of sulfide ores, the formation of passivation film inhibited the further dissolution of sulfide ores. In order to enhance the dissolution of sulfide ores, a novel method for destroying the passivation film using ozone was proposed and verified. The generated passivation film inhibiting pyrite dissolution in the presence of Leptospirillum ferrooxidans and Acidithiobacillus thiooxidans was studied. The X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) results indicate that a passivation film mainly consisting of jarosite and polysulfide (S/S) might be formed during biotic stage, which can be eliminated with the introduction of ozone (2 g/min) in 30 min. Electrochemical results show that ozone significantly increased the electrochemical reactivity of passivated pyrite, further proving that ozone enhanced the dissolution of passivated pyrite through destroying the passivation layer. Hence, a bi-stage method for dissolution of sulfide ores can be proposed.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130335DOI Listing
August 2021

Insight into the emerging role of SARS-CoV-2 nonstructural and accessory proteins in modulation of multiple mechanisms of host innate defense.

Bosn J Basic Med Sci 2021 Oct 1;21(5):515-527. Epub 2021 Oct 1.

Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Al Jouf, Saudi Arabia.

Coronavirus disease-19 (COVID-19) is an extremely infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has become a major global health concern. The induction of a coordinated immune response is crucial to the elimination of any pathogenic infection. However, SARS-CoV-2 can modulate the host immune system to favor viral adaptation and persistence within the host. The virus can counteract type I interferon (IFN-I) production, attenuating IFN-I signaling pathway activation and disrupting antigen presentation. Simultaneously, SARS-CoV-2 infection can enhance apoptosis and the production of inflammatory mediators, which ultimately results in increased disease severity. SARS-CoV-2 produces an array of effector molecules, including nonstructural proteins (NSPs) and open-reading frames (ORFs) accessory proteins. We describe the complex molecular interplay of SARS-CoV-2 NSPs and accessory proteins with the host's signaling mediating immune evasion in the current review. In addition, the crucial role played by immunomodulation therapy to address immune evasion is discussed. Thus, the current review can provide new directions for the development of vaccines and specific therapies.
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http://dx.doi.org/10.17305/bjbms.2020.5543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381213PMC
October 2021

Evidence for 2-Methoxyestradiol-Mediated Inhibition of Receptor Tyrosine Kinase RON in the Management of Prostate Cancer.

Int J Mol Sci 2021 Feb 12;22(4). Epub 2021 Feb 12.

Department of Molecular Medicine, University of Texas Health, San Antonio, TX 78229, USA.

2-Methoxyestradiol (2-ME) possesses anti-tumorigenic activities in multiple tumor models with acceptable tolerability profile in humans. Incomplete understanding of the mechanism has hindered its development as an anti-tumorigenic compound. We have identified for the first-time macrophage stimulatory protein 1 receptor (MST1R) as a potential target of 2-ME in prostate cancer cells. Human tissue validation studies show that MST1R (a.k.a RON) protein levels are significantly elevated in prostate cancer tissues compared to adjacent normal/benign glands. Serum levels of macrophage stimulatory protein (MSP), a ligand for RON, is not only associated with the risk of disease recurrence, but also significantly elevated in samples from African American patients. 2-ME treatment inhibited mechanical properties such as adhesion and elasticity that are associated with epithelial mesenchymal transition by downregulating mRNA expression and protein levels of MST1R in prostate cancer cell lines. Intervention with 2-ME significantly reduced tumor burden in mice. Notably, global metabolomic profiling studies identified significantly higher circulating levels of bile acids in castrated animals that were decreased with 2-ME intervention. In summary, findings presented in this manuscript identified MSP as a potential marker for predicting biochemical recurrence and suggest repurposing 2-ME to target RON signaling may be a potential therapeutic modality for prostate cancer.
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http://dx.doi.org/10.3390/ijms22041852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918140PMC
February 2021

Mycobacterium tuberculosis PPE10 (Rv0442c) alters host cell apoptosis and cytokine profile via linear ubiquitin chain assembly complex HOIP-NF-κB signaling axis.

Int Immunopharmacol 2021 May 2;94:107363. Epub 2021 Mar 2.

State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-Environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Institute of Modern Biopharmaceuticals, Southwest University, Chongqing, PR China. Electronic address:

Tuberculosis caused by Mycobacterium tuberculosis infection remains one of the top ten causes of deaths worldwide. M. tuberculosis genome devoted 10% capacity for highly repeated PE/PPE genes family. To explore the role of PPE10 in host-pathogen interaction, PPE10 encoding gene Rv0442c was heterologously expressed in the nonpathogenic M. smegmatis strain. PPE10 altered the bacterial cell surface properties, colony morphology, and biofilm formation. Ms_PPE10 showed more resistance to stress conditions such as diamide, and low pH, as well as higher survival within the macrophage. Moreover, the host's cell apoptosis was regulated via decreased expression of caspases, IL-1, IL-6, and TNF-α through the Linear Ubiquitin Chain Assembly Complex (LUBAC) HOIP-NF-κB signaling axis. The study revealed novel insights into the mechanism of action of the PPE family.
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http://dx.doi.org/10.1016/j.intimp.2020.107363DOI Listing
May 2021

The role of Mfd in Mycobacterium tuberculosis physiology and underlying regulatory network.

Microbiol Res 2021 May 3;246:126718. Epub 2021 Feb 3.

Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Ministry of Education Eco-Environment of the Three Gorges Reservoir Region, Ministry of Education, Chongqing Municipal Key Laboratory of Karst Environment, School of Life Sciences, Southwest University, Beibei, Chongqing, 400715, China. Electronic address:

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis with millions of deaths annually, remains one of the most formidable pathogen to global public health. As the most successful intracellular pathogens, Mtb can spatiotemporally coordinate the transcription and translation timely to reconcile the inevitable transcription-replication conflicts. Mutation frequency decline (Mfd) is a bacterial ATP-dependent DNA translocase that couples DNA repair to transcription via hydrolyzing ATP as energy, which preferentially acts on the damaged DNA transcribed strand to rescue stalled RNAP or dissociate RNAP to terminate the transcription depending on impediment severity, mitigating the damage to bacteria. In addition to the traditional damage repair effect, Mfd may also promote bacteria mutagenesis under stresses and boost the drug resistance. Mfd is widespread among bacteria and intensively studied, but there are very few studies in Mycobacteria, especially Mtb. In this review, the structure, function and mechanism characteristics of Mfd in Mtb (MtbMfd, Rv1020) are explored, with emphasis on the regulatory network of MtbMfd and its potential as a prime target for antibiotic drugs against tuberculosis.
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http://dx.doi.org/10.1016/j.micres.2021.126718DOI Listing
May 2021

Depressive Symptoms, Sleep Quality and Diet During the 2019 Novel Coronavirus Epidemic in China: A Survey of Medical Students.

Front Public Health 2020 26;8:588578. Epub 2021 Jan 26.

School of Basic Medical Sciences, Kunming Medical University, Kunming, China.

The psychological condition of medical students may be influenced by the 2019 novel coronavirus (COVID-19) outbreak. This study investigated the prevalence and influencing factors of depressive symptoms, poor sleep quality and poor diet in students at Kunming Medical University during the early part of the COVID-19 outbreak. A cross-sectional study was used from a questionnaire survey in February 2020. Of a total of 1,026 study participants, the prevalence of depressive symptoms, poor sleep quality, and poor diet was, respectively, 22.4, 33.2, and 17.4%. Male students and students with a low degree of focus on COVID-19 had a high risk of depressive symptoms. A high percentage of females and students in the fifth grade, as well as students with high levels of concern about the negative impact of COVID-19 on their education or employment, comprised those with poor sleep quality. Students in the fifth grade and students with high levels of concern about the negative impact of COVID-19 on their education or employment were more likely to report poor diet. This study suggests the importance of monitoring medical students' depressive state during the COVID-19 outbreak, and universities are encouraged to institute policies and programs to provide educational counseling and psychological support to help students to cope with these problems.
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http://dx.doi.org/10.3389/fpubh.2020.588578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870982PMC
February 2021

Mycobacterium tuberculosis Rv1515c antigen enhances survival of M. smegmatis within macrophages by disrupting the host defence.

Microb Pathog 2021 Apr 3;153:104778. Epub 2021 Feb 3.

State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Institute of Modern Biopharmaceuticals, Southwest University, Chongqing, China. Electronic address:

Mycobacterium tuberculosis (Mtb) infection is the major cause of tuberculosis. Mtb regions of difference (RD) genes are vital for survival of the pathogen within hosts and for the attenuation of the bacillus Calmette-Guérin vaccine. However, the function of most RD proteins largely remains unexplored. In the present study, we focused on Rv1515c, an RD6 member from M. tuberculosis, and characterised it as a cell surface-associated protein that functions in disrupting the cytokine profile and promoting endoplasmic reticulum stress-mediated apoptosis. Rv1515c expression in M. smegmatis, a nonpathogenic species, resulted in enhanced resistance of the bacterium to various in vitro stressors (such as low pH, sodium dodecyl sulfate, oxidative pressure, and nitrogen intermediate) and its cellular survival within macrophages. Our study is the first to identify the role of Rv1515c in the physiology and pathogenesis of mycobacterium.
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http://dx.doi.org/10.1016/j.micpath.2021.104778DOI Listing
April 2021

Rv0580c Impedes the Intracellular Survival of Recombinant Mycobacteria, Manipulates the Cytokines, and Induces ER Stress and Apoptosis in Host Macrophages via NF-κB and p38/JNK Signaling.

Pathogens 2021 Feb 1;10(2). Epub 2021 Feb 1.

Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-environment and Bio-resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Science, Southwest University, Beibei, Chongqing 400715, China.

The () genome encodes a large number of hypothetical proteins, which need to investigate their role in physiology, virulence, pathogenesis, and host interaction. To explore the role of hypothetical protein Rv0580c, we constructed the recombinant () strain, which expressed the Rv0580c protein heterologously. We observed that Rv0580c expressing strain (Ms_Rv0580c) altered the colony morphology and increased the cell wall permeability, leading to this recombinant strain becoming susceptible to acidic stress, oxidative stress, cell wall-perturbing stress, and multiple antibiotics. The intracellular survival of Ms_Rv0580c was reduced in THP-1 macrophages. Ms_Rv0580c up-regulated the IFN-γ expression via NF-κB and JNK signaling, and down-regulated IL-10 expression via NF-κB signaling in THP-1 macrophages as compared to control. Moreover, Ms_Rv0580c up-regulated the expression of and ER stress marker genes via the NF-κB/JNK axis and JNK/p38 axis, respectively, and boosted the mitochondria-independent apoptosis in macrophages, which might be lead to eliminate the intracellular bacilli. This study explores the crucial role of Rv0580c protein in the physiology and novel host-pathogen interactions of mycobacteria.
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http://dx.doi.org/10.3390/pathogens10020143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912736PMC
February 2021

Ligand Design in Ligand-Protected Gold Nanoclusters.

Small 2021 07 28;17(27):e2004381. Epub 2021 Jan 28.

Joint School of National University of Singapore and Tianjin University, International Campus of Tianjin University, Binhai New City, Fuzhou, 350207, P. R. China.

The design of surface ligands is crucial for ligand-protected gold nanoclusters (Au NCs). Besides providing good protection for Au NCs, the surface ligands also play the following two important roles: i) as the outermost layer of Au NCs, the ligands will directly interact with the exterior environment (e.g., solvents, molecules and cells) influencing Au NCs in various applications; and ii) the interfacial chemistry between ligands and gold atoms can determine the structures, as well as the physical and chemical properties of Au NCs. A delicate ligand design in Au NCs (or other metal NCs) needs to consider the covalent bonds between ligands and gold atoms (e.g., gold-sulfur (Au-S) and gold-phosphorus (Au-P) bond), the physics forces between ligands (e.g., hydrophobic and van der Waals forces), and the ionic forces between the functional groups of ligands (e.g., carboxylic (COOH) and amine group (NH )); which form the underlying chemistry and discussion focus of this review article. Here, detailed discussions on the effects of surface ligands (e.g., thiolate, phosphine, and alkynyl ligands; or hydrophobic and hydrophilic ligands) on the synthesis, structures, and properties of Au NCs; highlighting the design principles in the surface engineering of Au NCs for diverse emerging applications, are provided.
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http://dx.doi.org/10.1002/smll.202004381DOI Listing
July 2021

Multiscale Assembly of [AgS ] Tetrahedrons into Hierarchical Ag-S Networks for Robust Photonic Water.

Adv Mater 2021 Feb 21;33(8):e2006459. Epub 2021 Jan 21.

Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore, 117585, Singapore.

There is an urgent need to assemble ultrasmall metal chalcogenides (with atomic precision) into functional materials with the required anisotropy and uniformity, on a micro- or even macroscale. Here, a delicate yet simple chemistry is developed to produce a silver-sulfur network microplate with a high monodispersity in size and morphology. Spanning from the atomic, molecular, to nanometer, to micrometer scale, the key structural evolution of the obtained microplates includes 2D confinement growth, edge-sharing growth mode, and thermodynamically driven layer-by-layer stacking, all of which are derived from the [AgS ] tetrahedron unit. The key to such a high hierarchical, complex, and accurate assembly is the dense deprotonated ligand layer on the surface of the microplates, forming an infinite surface with high negative charge density. This feature operates at an orderly distance to allow further hierarchical self-assembly on the microscale to generate columnar assemblies composed of microplate components, thereby endowing the feature of the 1D photonic reflector to water (i.e., photonic water). The reflective color of the resulting photonic water is highly dependent on the thickness of the building blocks (i.e., silver-sulfur microplates), and the coexistent order and fluidity help to form robust photonic water.
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http://dx.doi.org/10.1002/adma.202006459DOI Listing
February 2021

Mycobacteriophage SWU1-Functionalized magnetic particles for facile bioluminescent detection of Mycobacterium smegmatis.

Anal Chim Acta 2021 Feb 8;1145:17-25. Epub 2020 Dec 8.

Key Laboratory of Luminescence Analysis and Molecular Sensing (Ministry of Education), College of Pharmaceutical Sciences, Southwest University, Chongqing, 400716, China. Electronic address:

Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis, ranks one of the most dangerous pathogens for its large deaths toll. Due to its characteristic extremely slow growth, the conventional culture-based protocol cannot meet the requirement for the efficient diagnosis of M. tuberculosis-induced tuberculosis. With our previously isolated mycobacteriophage SWU1, we tried to develop a mycobacteriophage-based protocol for detecting Mycobacterium genus. In this work, Mycobacterium smegmatis (M. smegmatis) was used as a model due to its similar physiological features as pathogenic M. tuberculosis, much faster growth and nonpathogenic property. Mycobacteriophage SWU1-functionalized magnetic particles (SWU1-MPs) were used as highly efficient separation carriers for the viable host M. smegmatis. After a replication cycle of approximate 60 min, the cells of M. smegmatis were disrupted by the progeny mycobacteriophages to release intracellular adenosine triphosphate (ATP). The bioluminescent (BL) signal of released ATP was collected to quantitate the amount of M. smegmatis. For the developed protocol, the detection range is 5.0 × 10 to 5.0 × 10 CFU mL, and the detection limit is 3.8 × 10 CFU mL (S/N = 3). Furthermore, the protocol can exclude the potential interference of 3 non-pathogenic mycobacteria and 6 other bacterial species. It has been successfully applied to quantitate M. smegmatis in human urine, human saliva, and human serum. The results demonstrate its application potential for a simple, fast, and specific diagnosis of M. tuberculosis infection.
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http://dx.doi.org/10.1016/j.aca.2020.12.009DOI Listing
February 2021

Ginsenoside Rb1 exerts antidepressant-like effects via suppression inflammation and activation of AKT pathway.

Neurosci Lett 2021 01 24;744:135561. Epub 2020 Dec 24.

School of Pharmaceutical Sciences, Department of Zoology & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, PR China; Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan 650500, PR China. Electronic address:

Depression-like behaviors caused by chronic stress are related to inflammation and microglia activation. Antidepressant therapy may contribute to inhibiting inflammation responses and microglia activation. Ginsenoside Rb1 (GRb1) is known to display antidepressant-like effect on chronic unpredictable mild stress-induced depressive rats. However, the antidepressant-like effects of GRb1 on chronic restraint stress (CRS) mice and the potential anti-inflammatory mechanisms are unclear. Here, we focused on the molecular mechanisms related to inhibition of inflammation response and the protection on microglia. Our results showed that GRb1 had an antidepressant effects via relieving the depression-like behaviors in CRS model. Furthermore, GRb1 increased the protein expressions of brain-derived neurotrophic factor and phospho- protein kinase B/ protein kinase B (p-AKT/AKT), and decreased the protein expressions of interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α) and ionized calcium binding adapter molecule 1 in hippocampus, reduced the levels IL-1β and TNF-α in serum. Finally, GRb1 lowered the protein expressions of IL-1β and TNF-α in BV-2 microglia induced by lipopolysaccharides. Taken together, the results indicate that GRb1 prevents CRS-induced depression-like behaviors in mice, which may be related to anti-inflammatory effects in hippocampus, serum and microglia and activation of AKT pathway.
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http://dx.doi.org/10.1016/j.neulet.2020.135561DOI Listing
January 2021

Stimulation of soil respiration by elevated CO is enhanced under nitrogen limitation in a decade-long grassland study.

Proc Natl Acad Sci U S A 2020 12 14;117(52):33317-33324. Epub 2020 Dec 14.

State Key Joint Laboratory of Environment Simulation and Pollution Control, School of Environment, Tsinghua University, 100084 Beijing, China;

Whether and how CO and nitrogen (N) availability interact to influence carbon (C) cycling processes such as soil respiration remains a question of considerable uncertainty in projecting future C-climate feedbacks, which are strongly influenced by multiple global change drivers, including elevated atmospheric CO concentrations (eCO) and increased N deposition. However, because decades of research on the responses of ecosystems to eCO and N enrichment have been done largely independently, their interactive effects on soil respiratory CO efflux remain unresolved. Here, we show that in a multifactor free-air CO enrichment experiment, BioCON (Biodiversity, CO, and N deposition) in Minnesota, the positive response of soil respiration to eCO gradually strengthened at ambient (low) N supply but not enriched (high) N supply for the 12-y experimental period from 1998 to 2009. In contrast to earlier years, eCO stimulated soil respiration twice as much at low than at high N supply from 2006 to 2009. In parallel, microbial C degradation genes were significantly boosted by eCO at low but not high N supply. Incorporating those functional genes into a coupled C-N ecosystem model reduced model parameter uncertainty and improved the projections of the effects of different CO and N levels on soil respiration. If our observed results generalize to other ecosystems, they imply widely positive effects of eCO on soil respiration even in infertile systems.
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http://dx.doi.org/10.1073/pnas.2002780117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7777058PMC
December 2020

Genomic and proteomic portrait of a novel mycobacteriophage SWU2 isolated from China.

Infect Genet Evol 2021 01 3;87:104665. Epub 2020 Dec 3.

Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, Chongqing Municipal Key Laboratory of Karst Environment, School of Life Sciences, Southwest University, Beibei, Chongqing 400715, China. Electronic address:

Phage therapy, especially combination with antibiotics, was revitalized to control the antibiotics resistance. Mycobacteriophage, the phage of mycobacterium with the most notorious Mycobacterium tuberculosis (M. tuberculosis), was intensively explored. A novel mycobacteriophage SWU2 was isolated from a soil sample collected at Nanchang city, Jiangxi province, China, by using Mycolicibacterium smegmatis (M. smegmatis) mc 155 as the host. Phage morphology and biology were characterized. Phage structure proteins were analyzed by LC-MS/MS. The putative functions of phage proteins and multi-genome comparison were performed with bioinformatics. The transmission electron microscopy result indicated that this phage belongs to Siphoviridae of Caudovirales. Plaques of SWU2 appeared clear but small. In a one-step growth test, we demonstrated that SWU2 had a latent period of 30 min and a logarithmic phase of 120 min. Among the 76 predicted Open Reading Frames (ORFs), 9 ORFs were identified as phage structure proteins of SWU2. The assembled phage genome size is 50,013 bp, with 62.7% of G + C content. SWU2 genome sequence shares 88% identity with Mycobacterium phages HINdeR and Timshel, differing in substitutions, insertions and deletions in SWU2. Phylogenetic tree revealed that SWU2 is grouped into A7 sub-cluster. There are several substitutions, insertions and deletions in SWU2 genome in comparison with close cousin phages HINdeR and Timshel. The new phage adds another dimension of abundance to the mycobacteriophages.
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http://dx.doi.org/10.1016/j.meegid.2020.104665DOI Listing
January 2021

Pasteur-like Separation of Silver Nanocluster Racemates by Conglomerate Crystallization.

ACS Cent Sci 2020 Nov 22;6(11):1862-1865. Epub 2020 Oct 22.

Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585.

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http://dx.doi.org/10.1021/acscentsci.0c01301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706071PMC
November 2020
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