Publications by authors named "Xiaoli Ma"

353 Publications

A 4/8 Subtype α-Conotoxin Vt1.27 Inhibits N-Type Calcium Channels With Potent Anti-Allodynic Effect.

Front Pharmacol 2022 29;13:881732. Epub 2022 Apr 29.

Beijing Institute of Biotechnology, Beijing, China.

A novel 4/8 subtype α-conotoxin, Vt1.27 (NCCMFHTCPIDYSRFNC-NH), was identified from in the South China Sea by RACE methods. The peptide was synthesized and structurally characterized. Similar to other α-conotoxins that target neuronal nicotinic acetylcholine receptor (nAChR) subtypes, Vt1.27 inhibited the rat α3β2 nAChR subtype (IC = 1160 nM) and was inactive at voltage-gated sodium and potassium channels in rat sensory neurons. However, Vt1.27 inhibited high voltage-activated N-type (Ca2.2) calcium channels expressed in HEK293T cells with an IC of 398 nM. An alanine scan of the peptide showed that residues Phe, Pro, Ile, and Ser contribute significantly to the inhibitory activity of Vt1.27. The molecular dockings indicate that Vt1.27 inhibits the transmembrane region of Ca2.2, which is different from that of ω-conotoxins. Furthermore, Vt1.27 exhibited potent anti-allodynic effect in rat partial sciatic nerve injury (PNL) and chronic constriction injury (CCI) pain models at 10 nmol/kg level with the intramuscular injection. The pain threshold elevation of Vt1.27 groups was higher than that of α-conotoxin Vc1.1 in CCI rat models. These findings expand our knowledge of targets of α-conotoxins and potentially provide a potent, anti-allodynic peptide for the treatment of neuropathic pain.
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http://dx.doi.org/10.3389/fphar.2022.881732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9230573PMC
April 2022

Safety and efficacy of vebicorvir administered with entecavir in treatment-naïve patients with chronic hepatitis B virus infection.

J Hepatol 2022 Jun 10. Epub 2022 Jun 10.

Toronto Liver Centre, Toronto, Canada.

Background And Aims: Nucleos(t)ide reverse transcriptase inhibitors do not completely suppress hepatitis B virus (HBV) DNA in chronic HBV infection (cHBV). Vebicorvir (VBR) is an investigational core inhibitor which interferes with multiple aspects of HBV replication. This phase 2 trial (NCT03577171) evaluated the efficacy and safety of VBR in combination with entecavir (ETV) in treatment-naïve patients with cHBV.

Methods: Hepatitis B "e" antigen positive, treatment-naïve patients without cirrhosis were randomised 1:1 in a double-blind manner, to once-daily VBR 300 mg+ETV 0.5 mg or placebo (PBO)+ETV for 24 weeks (W). The primary endpoint was change in mean log HBV DNA from Baseline to W12 and W24.

Results: All patients in both treatment groups (PBO+ETV: 12/12; VBR+ETV: 13/13) completed the study. At W12, VBR+ETV led to a greater mean (SD) reduction from Baseline in log IU/mL HBV DNA (-4.45 [1.03]) vs PBO+ETV (-3.30 [1.18]; p=0.0077). At W24, VBR+ETV led to a greater reduction from Baseline in log IU/mL HBV DNA (-5.33 [1.59]) vs PBO+ETV (-4.20 [0.98]; p=0.0084). Greater mean reductions in pregenomic RNA were observed at W12 and W24 in patients receiving VBR+ETV vs PBO+ETV (p<0.0001 and p<0.0001). Changes in viral antigens were similar in both groups. No drug interaction between VBR and ETV was observed. Two patients experienced HBV DNA rebound during treatment, with no resistance breakthrough detected. Safety of VBR+ETV was similar to PBO+ETV. All treatment-emergent adverse events and laboratory abnormalities were Grade 1/2. There were no deaths, serious AEs, or evidence of drug-induced liver injury.

Conclusions: In this 24-week study, VBR+ETV provided additive antiviral activity over PBO+ETV in treatment-naïve patients with cHBV with a favourable safety and tolerability profile.

Lay Summary: Hepatitis B is a long-lasting viral infection of the liver. This study demonstrates that vebicorvir (a core inhibitor) with entecavir is generally safe, well tolerated, and demonstrates greater antiviral activity compared with entecavir alone in treatment-naïve patients chronically infected with hepatitis B virus. This study supports continued evaluation of vebicorvir in the treatment of chronic hepatitis B.

Clinical Trial Number: NCT03577171.
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http://dx.doi.org/10.1016/j.jhep.2022.05.027DOI Listing
June 2022

The transcription factor TOX is involved in the regulation of T-cell exhaustion in neuroblastoma.

Immunol Lett 2022 Jun 9;248:16-25. Epub 2022 Jun 9.

Laboratory of Tumor Immunology, Beijing Pediatric Research Institute, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing 100045, China; Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China. Electronic address:

T-cell exhaustion is one of the key reasons for attenuated T-cell cytotoxicity against tumours. At both the expression and epigenetic levels, a number of genes, including the transcription factor TOX, are believed to be implicated in regulating T-cell exhaustion. In the present study, we found that in NB patients, the ratio of exhausted T cells, featuring upregulated PD-1 and Tim-3, was increased. Meanwhile, the expression of inhibitory surface receptors, including Lag-3, CD160, VISTA and KLRG1, was also increased, but this was accompanied by a reduced ability to release the effector molecules IL-2, IFN-γ, TNF-α and Granzyme B in CD3+ T cells from NB patients. It is noteworthy that NB-derived memory T cells (Tm) showed more obvious exhausted characteristics than other T cells. Moreover, the T cells from NB patients possessed a higher potential for exhaustion conversion upon in vitro TCR stimulation in our time-course culture experiment. In NB patients, T-cell exhaustion was demonstrated to correlate with the elevated expression of TOX in freshly sorted CD3+ T cells as well as in anti-CD3 stimulated PBMCs. Most importantly, our data supported the idea that the hypomethylation of the TOX promoter may be one of the initiators that regulates TOX expression and enables TOX to play a crucial role in T-cell exhaustion reprogramming in NB patients.
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http://dx.doi.org/10.1016/j.imlet.2022.06.004DOI Listing
June 2022

Long noncoding RNA Sh2d3c promotes manganese-induced neuronal apoptosis through the mmu-miR-675-5p/Chmp4b/Bax axis.

Toxicol Lett 2022 Jun 8;365:24-35. Epub 2022 Jun 8.

Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi, China; Guangxi Key Laboratory of Environment and Health Research, Guangxi Medical University, Nanning 530021, Guangxi, China; Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education, Nanning 530021, Guangxi, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning 530021, Guangxi, China. Electronic address:

Environmental excessive manganese (Mn) exposure can cause neurotoxicity and neurodegenerative diseases. Long noncoding RNAs (lncRNAs) have been shown to affect the development of neurodegenerative diseases. However, whether lncRNAs are also linked to Mn-induced neurotoxicity has not been reported. In this study, we explored the role of lncRNAs in Mn-induced neurotoxicity and its mechanisms. LncSh2d3c was identified to be the significantly increased lncRNA in Mn-exposed N2a cells. Knockdown of lncSh2d3c increased the cell viability and inhibited cell apoptosis. Mechanistically, lncSh2d3c acted as a sponge for mmu-miR-675-5p, thereby preventing the inhibitory effect of mmu-miR-675-5p on Chmp4b. The binding potency of lncSh2d3c/mmu-miR-675-5p and mmu-miR-675-5p/Chmp4b was verified by RNA antisense purification (RAP) and luciferase reporter assays. Furthermore, we also found that the lncSh2d3c/mmu-miR-675-5p/Chmp4b/Bax axis might be associated with the learning ability and memory of mice after Mn exposure. These results revealed a novel mechanism of Mn-induced neuronal apoptosis through the lncSh2d3c/mmu-miR-675-5p/Chmp4b/Bax axis and suggested that lncSh2d3c may act as a key regulatory factor in Mn-induced neurotoxicity.
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http://dx.doi.org/10.1016/j.toxlet.2022.06.002DOI Listing
June 2022

Excellent upconversion luminescence and temperature sensing performance of CdMoO:Er,Yb phosphors.

Dalton Trans 2022 Jun 7;51(22):8749-8756. Epub 2022 Jun 7.

School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu, 273165, P. R. China.

In this paper, Er/Yb co-doped CdMoO phosphors were prepared by a traditional high temperature solid state reaction method. Based on the 3D network structure of the CdMoO host and the efficient Er/Yb upconversion luminescence combinations, excellent green emission properties were observed when the prepared sample is irradiated with a laser at about 980 nm. For optical temperature sensors based on the fluorescence intensity ratio (FIR), the prepared phosphors have excellent sensitivity to temperature in the range of 293 to 473 K. With increasing environmental temperatures, the absolute sensitivity of the CdMoO:0.02Er,0.08Yb sample reached a maximum at about 473 K ( = 1.388% K). The calculated relative sensitivity of the optical temperature sensor was = 1.631% K at 293 K. This is due to the sensitive thermally coupled energy levels (TCLs) of the Er ions (H and S) in the CdMoO structure. Therefore, it is shown that the prepared CdMoO:0.02Er,0.08Yb phosphor has excellent applications in non-contact optical temperature measurement.
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http://dx.doi.org/10.1039/d2dt01029aDOI Listing
June 2022

The α5-nAChR/PD-L1 axis facilitates lung adenocarcinoma cell migration and invasion.

Hum Cell 2022 Jul 20;35(4):1207-1218. Epub 2022 May 20.

Department of Medical Laboratory, Weifang Medical University, Weifang, 261053, China.

α5 nicotinic acetylcholine receptor (α5-nAChR) is associated with the progression of smoking-related lung adenocarcinoma (LUAD), but the molecular mechanism is unclear. Programmed death ligand 1 (PD-L1) is encoded by the CD274 gene, which not only inhibits the immune system, but also plays a unique role in tumor growth and metastasis. Here, we gained important insights into the underlying mechanism between α5-nAChR and PD-L1 in LUAD progression. α5-nAChR was overexpressed in various histological subtypes, cancer stages and metastasis statuses of LUAD. The group that coexpressed α5-nAChR and PD-L1 had a worse prognosis than the other subgroups at different stages of LUAD lymph node metastasis. The expression of α5-nAChR and PD-L1 was associated with epithelial-mesenchymal transition (EMT) marker CDH2. In vitro, α5-nAChR mediated nicotine-induced PD-L1 expression via STAT3 and the expression of EMT markers. Downregulation of α5-nAChR and/or PD-L1 inhibited EMT marker expression, cell proliferation, migration and invasion compared to silencing α5-nAChR or PD-L1 alone in LUAD cells. Furthermore, α5-nAChR expression was associated with PD-L1 and EMT marker expression in mouse xenograft models. These results highlight that α5-nAChR mediates STAT3/PD-L1 signaling, which contributes to cell migration and invasion. Therefore, our study may reveal a new interaction between α5-nAChR and PD-L1 that is involved in tumor cell growth and progression in LUAD, which may be a promising target for NSCLC diagnosis and immunotherapy.
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http://dx.doi.org/10.1007/s13577-022-00709-1DOI Listing
July 2022

Technological and computational advances driving high-throughput oncology.

Trends Cell Biol 2022 May 13. Epub 2022 May 13.

Institute of Bioengineering, School of Engineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland. Electronic address:

Engineering and computational advances have opened many new avenues in cancer research, particularly when being exploited in interdisciplinary approaches. For example, the combination of microfluidics, novel sequencing technologies, and computational analyses has been crucial to enable single-cell assays, giving a detailed picture of tumor heterogeneity for the very first time. In a similar way, these 'tech' disciplines have been elementary for generating large data sets in multidimensional cancer 'omics' approaches, cell-cell interaction screens, 3D tumor models, and tissue level analyses. In this review we summarize the most important technology and computational developments that have been or will be instrumental for transitioning classical cancer research to a large data-driven, high-throughput, high-content discipline across all biological scales.
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http://dx.doi.org/10.1016/j.tcb.2022.04.008DOI Listing
May 2022

Network Pharmacology and Bioinformatics Analyses Identify Intersection Genes of Vitamin D3 and COVID-19 as Potential Therapeutic Targets.

Front Pharmacol 2022 28;13:874637. Epub 2022 Apr 28.

Research Center of Basic Medicine, Jinan Central Hospital, Shandong University, Jinan, China.

The persistent pandemic of coronavirus disease 2019 (COVID-19), the discovery of gastrointestinal transmission routes and the possible susceptibility of cancer patients to COVID-19 have forced us to search for effective pathways against stomach adenocarcinoma (STAD)/COVID-19. Vitamin D3 (VD3) is a steroid hormone with antiviral, anti-inflammatory and immunomodulatory properties. This study aimed to evaluate the possible functional role and potential mechanisms of action of VD3 as an anti-COVID-19 and anti- STAD. Clinicopathological analysis, enrichment analysis and protein interaction analysis using bioinformatics and network pharmacology methods. Validate the binding activity of VD3 to core pharmacological targets and viral crystal structures using molecular docking. We revealed the clinical characteristics of STAD/COVID-19 patients. We also demonstrated that VD3 may be anti- STAD/COVID-19 through antiviral, anti-inflammatory, and immunomodulatory pathways. Molecular docking results showed that VD3 binds well to the relevant targets of COVID-19, including the spike RBD/ACE2 complex and main protease (Mpro, also known as 3CLpro). We also identified five core pharmacological targets of VD3 in anti-STAD/COVID-19 and validated the binding activity of VD3 to PAI1 by molecular docking. This study reveals for the first time that VD3 may act on disease target gene through inflammatory and viral related signaling pathways and biological functions for the therapy of STAD/COVID-19. This may provide a new idea for the use of VD3 in the treatment of STAD/COVID-19.
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http://dx.doi.org/10.3389/fphar.2022.874637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9095980PMC
April 2022

Safety and efficacy of vebicorvir in virologically suppressed patients with chronic hepatitis B virus infection.

J Hepatol 2022 Apr 20. Epub 2022 Apr 20.

Toronto Liver Centre, Toronto, Canada.

Background & Aims: HBV nucleos(t)ide reverse transcriptase inhibitors (NrtIs) do not completely suppress HBV replication. Previous reports indicate persistent viremia during NrtI treatment despite HBV DNA being undetectable. HBV core inhibitors may enhance viral suppression when combined with NrtIs. This phase II trial (NCT03576066) evaluated the efficacy and safety of the investigational core inhibitor, vebicorvir (VBR), in virologically- suppressed patients on NrtIs.

Methods: Non-cirrhotic, NrtI-suppressed patients with chronic HBV were randomised to VBR 300 mg once daily or matching placebo (PBO) for 24 weeks. Treatment was stratified by hepatitis B e antigen (HBeAg) status. The primary endpoint was change from Baseline in serum HBeAg or hepatitis B surface antigen (HBsAg) after 24 weeks.

Results: Of 73 patients enrolled, 47 were HBeAg positive and 26 were HBeAg negative. In HBeAg-positive and -negative patients, there were no differences in the change from Baseline at Week 24 for HBsAg or HBeAg. Using a novel, high-sensitivity assay to detect HBV DNA, a greater proportion of patients with detectable HBV DNA at Baseline achieved undetectable HBV DNA at Week 24 in the VBR+NrtI vs. PBO+NrtI group. In HBeAg-positive patients, a greater change from Baseline in HBV pregenomic (pg)RNA was observed at Week 24 with VBR+NrtI vs. PBO+NrtI. Treatment-emergent adverse events (TEAEs) in VBR+NrtI patients included upper respiratory tract infection, nausea, and pruritus. No serious adverse events, Grade 4 TEAEs, or deaths were reported.

Conclusions: In this 24-week study, VBR+NrtI demonstrated a favourable safety and tolerability profile. While there were no significant changes in viral antigen levels, enhanced viral suppression was demonstrated by greater changes in DNA and pgRNA with the addition of VBR compared to NrtI alone.

Clinical Trials Number: NCT03576066.

Lay Summary: Core inhibitors represent a novel approach for the treatment of chronic hepatitis B virus (HBV) infection, with mechanisms of action distinct from existing treatments. In this study, vebicorvir added to existing therapy reduced HBV replication to a greater extent than existing treatment and was generally safe and well tolerated.
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http://dx.doi.org/10.1016/j.jhep.2022.04.005DOI Listing
April 2022

Organoaluminum hydrides catalyzed hydroboration of carbonates, esters, carboxylic acids, and carbon dioxide.

Dalton Trans 2022 May 3;51(17):6756-6765. Epub 2022 May 3.

Dr. P. H. W. Roesky, Institut für Anorganische Chemie, Georg-August-Universität Göttin-gen, Tammannnstr. 4, 37077 Göttingen, Germany.

The reductive functionalization of the CO unit of carbonates, carboxylic acids, esters, and CO, respectively has received great attention since its introduction. This method is often used industrially for the synthesis of high value-added energy products in chemistry. This opens up a new way forward to reduce greenhouse gases and the consumption of traditional energy sources. Herein, we report an earth-abundant, cheap, and readily available aluminum dihydride, which can catalyze the reduction of a range of carbonates, esters, carboxylic acids, and CO, respectively in the presence of pinacolborane as a reducing agent. Moreover, we demonstrate that the reaction can proceed to obtain good yield products under mild conditions, with low catalyst loading and solvent-free reactions. The mechanism of the catalytic reduction of carbonates has been investigated.
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http://dx.doi.org/10.1039/d2dt00785aDOI Listing
May 2022

CRISPR/Cas9-Mediated Transgenesis of the Masu Salmon (Oncorhynchus masou) elovl2 Gene Improves n-3 Fatty Acid Content in Channel Catfish (Ictalurus punctatus).

Mar Biotechnol (NY) 2022 Jun 13;24(3):513-523. Epub 2022 Apr 13.

School of Fisheries, Aquaculture and Aquatic Sciences, Auburn University, Auburn, AL, 36849, USA.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs), particularly eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3), play a very important role in human health. Channel catfish (Ictalurus punctatus) is one of the leading freshwater aquaculture species in the USA, but has low levels of EPA and DHA compared to some fish such as salmon. To improve EPA and DHA content, a modification of the n-3 PUFA biosynthetic pathway was achieved through the insertion of an elovl2 transgene isolated from masu salmon (Oncorhynchus masou) driven by a carp β-actin promoter using a two-hit by gRNA and two oligos with a targeting plasmid (2H2OP) CRISPR/Cas9 approach. Integration rate of the transgene was high (37.5%) and detected in twelve different tissues of P transgenic fish with tissue-specific gene expression. Liver and muscle had relative high gene expression (13.4- and 9.2-fold change, respectively). Fatty acid analysis showed DHA content in the muscle from transgenic fish was 1.62-fold higher than in non-transgenic fish (P < 0.05). Additionally, total n-3 PUFAs and omega-6 polyunsaturated fatty acids (n-6 PUFAs) increased to 1.41-fold and 1.50-fold, respectively, suggesting the β-actin-elovl2 transgene improved biosynthesis of PUFAs in channel catfish as a whole. The n-9 fatty acid level decreased in the transgenic fish compared to the control. Morphometric analysis showed that there were significant differences between injected fish with sgRNAs (including positive and negative fish) and sham-injected controls (P < 0.001). Potential off-target effects are likely the major factor responsible for morphological deformities. Optimization of sgRNA design to maximize activity and reduce off-target effects of CRISPR/Cas9 should be examined in future transgenic research, but this research shows a promising first step in the improvement of n-3 PUFAs in channel catfish.
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http://dx.doi.org/10.1007/s10126-022-10110-6DOI Listing
June 2022

Transcriptome expression profiles associated with diabetic nephropathy development.

Mol Cell Biochem 2022 Jul 31;477(7):1931-1946. Epub 2022 Mar 31.

Department of Endocrinology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China.

The objective of this study was to identify different transcriptome expression profiles involved in the pathogenesis of diabetic nephropathy (DN) and to illustrate the diagnostic and therapeutic potential of mRNAs, long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) in DN progression. The participants were divided into four groups: normoalbuminuria (group DM), microalbuminuria (group A2), macroalbuminuria (group A3) and healthy controls (group N). There were three individuals in each group for sequencing. Transcriptome sequencing analysis was performed on the peripheral blood of all the participants to identify the differential expression of mRNAs, lncRNAs, and circRNAs between intervention groups and controls. The functional enrichment analysis, the short time-series expression miner (STEM) program, and the miRNA-circRNA-mRNA network were further conducted. To verify the reproducibility of transcriptome sequencing, 10 and 30 blood samples were collected from the control and diseased groups, respectively. Four candidate biomarkers were selected from differentially expressed circRNAs (circ_0005379, circ_0002024, and circ_0000567, and circ_0001017) and their concentrations in the blood were measured using quantitative PCR (qPCR). In the comparison of A2 with N, 549 mRNAs, 1259 lncRNAs, and 12 circRNAs were screened. In the comparison of A3 with N, 1217 mRNAs, 1613 lncRNAs, and 24 circRNAs were screened. Moreover, in the comparison of diabetes mellitus (DM) with N, 948 mRNAs, 1495 lncRNAs, and 25 circRNAs were screened. Functional enrichment analysis showed that differentially expressed mRNAs were related to insulin secretion, insulin resistance, and inflammation, while differentially expressed lncRNAs were mainly associated with crossover junction endodeoxyribonuclease activity. In STEM analysis, a total of 481 mRNAs and 152 differential expression circRNAs showed a significant tendency. The key relationships in the miRNA-circRNA-mRNA network were identified, such as hsa-miR-103a-3p-circ_0005379-PTEN, hsa-miR-497-5p-circ_0002024-IGF1R and hsa-miR-1269a-circ_0000567-SOX6. In addition, qPCR showed consistent results with RNA sequencing. We found that differentially expressed mRNAs, lncRNAs, and circRNAs participated in DN development. Circ_0005379, circ_0002024, and circ_0000567 could be adopted as potential biomarkers for DN.
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http://dx.doi.org/10.1007/s11010-022-04420-5DOI Listing
July 2022

Interleukin-15 enhanced the survival of human γδT cells by regulating the expression of Mcl-1 in neuroblastoma.

Cell Death Discov 2022 Mar 29;8(1):139. Epub 2022 Mar 29.

Laboratory of Tumor Immunology, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.

Neuroblastoma (NB) is the most common extracranial solid tumor and the treatment efficacy of high-risk NB is unsatisfactory. γδT-cell-based adoptive cell transfer is a promising approach for high-risk NB treatment. Our previous study has revealed that γδT cells in NB patients exhibit a poor proliferation activity and a decreased anti-tumor capacity in vitro. In the present study, we found that IL-15 could effectively enhance the proliferation of NB γδT cells, to a level that remains lower than healthy controls though. In addition, IL-15-fostered NB γδT cells robustly boosted cell survival against apoptosis induced by cytokines depletion. Our data revealed that Mcl-1 was a key anti-apoptotic protein in IL-15-fostered γδT cells during cytokine withdrawal and its expression was regulated via the activation of STAT5 and ERK. In addition, IL-2 and IL-15-fostered γδT cells harbored higher levels of tumoricidal capacity which is also beneficial for γδ T-cell based immune therapy in NB. Understanding the survival control of γδT cells in a sub-optimal cytokine supportive microenvironment will expedite the clinical application of γδT cells for immunotherapy.
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http://dx.doi.org/10.1038/s41420-022-00942-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8964681PMC
March 2022

Engineering Interlayer Electron-Phonon Coupling in WS/BN Heterostructures.

Nano Lett 2022 Apr 16;22(7):2725-2733. Epub 2022 Mar 16.

State Key Laboratory for Artificial Microstructure and Mesoscopic Physics, Frontiers Science Center for Nano-optoelectronics, School of Physics, Peking University, Beijing 100871, People's Republic of China.

In van der Waals (vdW) heterostructures, the interlayer electron-phonon coupling (EPC) provides one unique channel to nonlocally engineer these elementary particles. However, limited by the stringent occurrence conditions, the efficient engineering of interlayer EPC remains elusive. Here we report a multitier engineering of interlayer EPC in WS/boron nitride (BN) heterostructures, including isotope enrichments of BN substrates, temperature, and high-pressure tuning. The hyperfine isotope dependence of Raman intensities was unambiguously revealed. In combination with theoretical calculations, we anticipate that WS/BN supercells could induce Brillouin-zone-folded phonons that contribute to the interlayer coupling, leading to a complex nature of broad Raman peaks. We further demonstrate the significance of a previously unexplored parameter, the interlayer spacing. By varying the temperature and high pressure, we effectively manipulated the strengths of EPC with on/off capabilities, indicating critical thresholds of the layer-layer spacing for activating and strengthening interlayer EPC. Our findings provide new opportunities to engineer vdW heterostructures with controlled interlayer coupling.
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http://dx.doi.org/10.1021/acs.nanolett.1c04598DOI Listing
April 2022

In Reply to LC-MS/MS Peptide Assay Validation: A Plea for Robust Stability Studies.

Clin Chem 2022 May;68(5):729-731

Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China.

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http://dx.doi.org/10.1093/clinchem/hvac038DOI Listing
May 2022

An automated magnetic bead extraction method for measuring plasma metanephrines and 3-methoxytyramine using liquid chromatography tandem mass spectrometry.

Anal Bioanal Chem 2022 May 2;414(11):3541-3549. Epub 2022 Mar 2.

Department of Clinical Laboratory, Dongcheng District, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, No. 1 Shuaifu Yuan, Beijing, 100730, People's Republic of China.

Liquid chromatography tandem mass spectrometry (LC-MS/MS) is used routinely in clinical diagnostics; however, automating the sample pretreatment is challenging. We established and evaluated an automated method based on the magnetic bead extraction principle (MBE) to measure normetanephrine (NMN), metanephrine (MN), and 3-methoxytyramine (3-MT). The target analytes were extracted, purified, and concentrated using different solvents and chemical bond-modified magnetic beads transferred via a magnetic bar. The linearity, recovery, matrix effect, and precision of MBE were evaluated thoroughly, and compared with traditional solid-phase extraction (SPE) using 131 plasma samples. The chromatography peaks of metanephrines and 3-MT, extracted via MBE, are symmetrical, without interfering peaks. The linearity was excellent with correlation coefficient (r) > 0.99. The MBE exhibited good reproducibility with within-run coefficient variations (CVs) of 1.96-2.00%, 4.06-5.75%, and 3.89-4.90% for MN, NMN, and 3-MT, respectively. The total CVs for MN, NMN, and 3-MT were 1.96-2.80%, 5.12-5.75%, and 5.44-6.27%, respectively. The relative recoveries for MN, NMN, and 3-MT varied between 93.5 and 107.4%, whereas their biases were all within 10%. The results for MN, NMN, and 3-MT extracted via MBE compared with SPE exhibited excellent correlation, with r > 0.99; the mean bias% for MN, NMN, and 3-MT were small (-2.9%, -3.2%, and -3.2%, respectively). In conclusion, the automated MBE method for measuring plasma metanephrines and 3-MT can be applied in future routine clinical diagnostics, and the MBE principle may indicate a new era for LC-MS/MS in clinical application.
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http://dx.doi.org/10.1007/s00216-022-03984-xDOI Listing
May 2022

High-throughput analysis of total homocysteine and methylmalonic acid with the efficiency to separate succinic acid in serum and urine via liquid chromatography tandem mass spectrometry.

J Chromatogr B Analyt Technol Biomed Life Sci 2022 Feb 11;1193:123135. Epub 2022 Feb 11.

Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China. Electronic address:

Vitamin B12 (VB12) deficiency may lead to hyperhomocysteinemia and methylmalonic acidemia development which are risk factors of cardiovascular disease and nervous system impairment, respectively. However, few analytical methods are available to simultaneously quantify total homocysteine (tHcy) and methylmalonic acid (MMA) due to complex analytical requirements, such as sensitivity at nanomolar concentration, separation performance for succinic acid (SA), an endogenous isomer of MMA, and retention properties for polar compounds. Therefore, we developed and validated a simple and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of tHcy and MMA with the efficient separation of SA in human serum and urine. The clinical performance of the assay was validated according to CLSI C62-A guidelines. The recovery for serum tHcy was 95.2-105.8%, urine tHcy was 98.1-111.5%, serum MMA was 94.6-99.4%, and urine MMA was 101.6-105.6%. In addition, the LC-MS/MS method was found to be reliable based on the value of inter-assay imprecision and total imprecision coefficient variation (CV), matrix effect, and carryover. Standards and samples were stable in -20 °C for at least 2 months. The limits of quantifications (LOQs) were 0.074 nmol/mL for tHcy and 0.040 nmol/mL for MMA, which are suitable for detecting tHcy and MMA concentrations in human serum and urine. The concentration of tHcy and MMA in samples collected from 148 subjects were measured using this method. The results suggested that the concentrations of serum tHcy and MMA considerably differed between VB12 sufficient and deficient groups. Serum tHcy and serum MMA concentrations were inversely correlated with VB12 status. Our method represents a rapid technique for estimating tHcy and MMA concentrations in serum and urine samples without the need for derivatization and may be used to assess VB12 status in clinical applications.
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http://dx.doi.org/10.1016/j.jchromb.2022.123135DOI Listing
February 2022

Does learning different script systems affect configural visual processing? ERP evidence from early readers of Chinese and German.

Psychophysiology 2022 06 12;59(6):e14006. Epub 2022 Feb 12.

Institut für Psychologie, Humboldt-Universität zu Berlin, Berlin, Germany.

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http://dx.doi.org/10.1111/psyp.14006DOI Listing
June 2022

The role of α5-nicotinic acetylcholine receptor/NLRP3 signaling pathway in lung adenocarcinoma cell proliferation and migration.

Toxicology 2022 03 4;469:153120. Epub 2022 Feb 4.

Research Center of Basic Medicine, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan Shandong, 250013, China; Department of Medical Laboratory, Weifang Medical University, Weifang, 261000, China; Central Hospital Affiliated to Shandong First Medical University, Jinan, 250013, China. Electronic address:

α5-nicotinic acetylcholine receptor (α5-nAChR) is involved in tobacco smoking-induced lung carcinogenesis. Increasing evidence has highlighted the importance of inflammation in lung cancer and a strong relationship between smoking and the NLR family pyrin domain containing protein 3 (NLRP3) inflammasome. However, it is unclear whether an inflammation-related effect of α5-nAChR contributes to cigarette smoking-related lung cancer. Here, we identified a functional link between α5-nAChR and NLRP3 inflammasome activation in lung adenocarcinoma (LUAD). The expression of α5-nAChR was correlated with the expression of NLRP3 via STAT3 in LUAD tissues. In vitro, nicotine increased the levels of α5-nAChR, p-STAT3, and NLRP3 inflammasome expression, accompanied by the expression of caspase-1, IL-1β and IL-18. Nicotine-induced activation of p-STAT3 and NLRP3 inflammasome signaling were inhibited by the silencing of α5-nAChR. STAT3 binds to the NLRP3 promoter and α5-nAChR mediates NLRP3 expression via STAT3. Functionally, the combination of nicotine and LPS/ATP could significantly enhance cell proliferation and migration compared to nicotine or LPS/ATP alone. Furthermore, the functional link between α5-nAChR and NLRP3 was confirmed in chicken embryo chorioallantoic membrane (CAM) and mouse xenograft models. Together, these findings reveal a novel nicotine-mediated signaling pathway: nicotine promotes lung cell proliferation and migration via the α5-nAChR/STAT3/NLRP3 axis in lung cancer.
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http://dx.doi.org/10.1016/j.tox.2022.153120DOI Listing
March 2022

DEC1 promotes progression of Helicobacter pylori-positive gastric cancer by regulating Akt/NF-κB pathway.

J Cell Mol Med 2022 04 4;26(7):1943-1954. Epub 2022 Feb 4.

Research Center of Basic Medicine, Jinan Central Hospital, Shandong First Medical University, Jinan, China.

Helicobacter pylori (H. pylori) infection plays a crucial role in the initiation and progression of gastric cancer (GC). Differentiated embryo-chondrocyte expressed gene 1 (DEC1) is dysregulated in some cancers and may regulate cell proliferation in specific contexts. Of note, DEC1 is emerging as one of the important factors regulating cellular responses in microenvironment. However, the triggers and precise regulation mechanism for DEC1 during inflammatory carcinoma transformation of GC are unclear. In this study, we identified DEC1 was upregulated in both H. pylori-infected gastric tissues and GC cells. DEC1 expression was positively associated with H. pylori infection status and GC progression. DEC1-positive expression indicated a poorer prognosis in H. pylori-positive GC. DEC1 was required for H. pylori-induced GC cells proliferation. Mechanistically, H. pylori infection significantly activated Akt/NF-κB signal pathway and this induction depend on DEC1 expression level in GC cells. Importantly, their interaction pathway was further verified by H. pylori-positive gastritis mice model. Taken together, our findings identified a novel function of DEC1 in GC. H. pylori infection induce DEC1 expression, and which leading to the progression of GC through activating Akt/ NF-κB signalling pathway. Blocking DEC1/Akt/NF-κB, therefore, presents a promising novel therapeutic strategy for H. pylori-positive GC.
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http://dx.doi.org/10.1111/jcmm.17219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8980912PMC
April 2022

Suppressing Effect of Na/Ca Exchanger (NCX) Inhibitors on the Growth of Melanoma Cells.

Int J Mol Sci 2022 Jan 14;23(2). Epub 2022 Jan 14.

Department of Pharmacology and Chemical Biology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China.

The role of calcium ion (Ca) signaling in tumorigenicity has received increasing attention in melanoma research. Previous Ca signaling studies focused on Ca entry routes, but rarely explored the role of Ca extrusion. Functioning of the Na/Ca exchanger (NCX) on the plasma membrane is the major way of Ca extrusion, but very few associations between NCX and melanoma have been reported. Here, we explored whether pharmacological modulation of the NCX could suppress melanoma and promise new therapeutic strategies. Methods included cell viability assay, Ca imaging, immunoblotting, and cell death analysis. The NCX inhibitors SN-6 and YM-244769 were used to selectively block reverse operation of the NCX. Bepridil, KB-R7943, and CB-DMB blocked either reverse or forward NCX operation. We found that blocking the reverse NCX with SN-6 or YM-244769 (5-100 μM) did not affect melanoma cells or increase cytosolic Ca. Bepridil, KB-R7943, and CB-DMB all significantly suppressed melanoma cells with IC values of 3-20 μM. Bepridil and KB-R7943 elevated intracellular Ca level of melanoma. Bepridil-induced melanoma cell death came from cell cycle arrest and enhanced apoptosis, which were all attenuated by the Ca chelator BAPTA-AM. As compared with melanoma, normal melanocytes had lower NCX1 expression and were less sensitive to the cytotoxicity of bepridil. In conclusion, blockade of the forward but not the reverse NCX leads to Ca-related cell death in melanoma and the NCX is a potential drug target for cancer therapy.
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http://dx.doi.org/10.3390/ijms23020901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8780355PMC
January 2022

Transcriptomic and Metabolomic Profiling in Induced Gastric Cancer Identified Prognosis- and Immunotherapy-Relevant Gene Signatures.

Front Cell Dev Biol 2021 24;9:769409. Epub 2021 Dec 24.

Research Center of Basic Medicine, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Chronic (HP) infection is considered the major cause of non-cardia gastric cancer (GC). However, how HP infection influences the metabolism and further regulates the progression of GC remains unknown. We comprehensively evaluated the metabolic pattern of HP-positive (HP+) GC samples using transcriptomic data and correlated these patterns with tumor microenvironment (TME)-infiltrating characteristics. The metabolic score was constructed to quantify metabolic patterns of individual tumors using principal component analysis (PCA) algorithms. The expression alterations of key metabolism-related genes (MRGs) and downstream metabolites were validated by PCR and untargeted metabolomics analysis. Two distinct metabolic patterns and differential metabolic scores were identified in HP+ GC, which had various biological pathways in common and were associated with clinical outcomes. TME-infiltrating profiles under both patterns were highly consistent with the immunophenotype. Furthermore, the analysis indicated that a low metabolic score was correlated with an increased EMT subtype, immunosuppression status, and worse survival. Importantly, we identified that the expression of five MRGs, GSS, GMPPA, OGDH, SGPP2, and PIK3CA, was remarkably correlated with HP infection, patient survival, and therapy response. Furthermore, the carbohydrate metabolism and citric acid may be downstream regulators of the function of metabolic genes in HP-induced GC. Our findings suggest that there is cross talk between metabolism and immune promotion during HP infection. MRG-specific transcriptional alterations may serve as predictive biomarkers of survival outcomes and potential targets for treatment of patients with HP-induced GC.
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http://dx.doi.org/10.3389/fcell.2021.769409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8740065PMC
December 2021

Combining Organic Fertilizer With Controlled-Release Urea to Reduce Nitrogen Leaching and Promote Wheat Yields.

Front Plant Sci 2021 24;12:802137. Epub 2021 Dec 24.

Shandong Provincial Key Laboratory of Water and Soil Conservation and Environmental Protection, College of Resources and Environment/College of Agricultural and Forestry Science, Linyi University, Linyi, China.

Soil deterioration, low nitrogen use efficiency (NUE), and environmental risks caused by excessive chemical N fertilizer use are key factors restricting sustainable agriculture. It is extremely critical to develop effective N management strategies that consider both environmental and agronomic benefits. From 2017 to 2019, a field experiment was conducted to assess the effects of combinations of organic fertilizers (OF, provided at 30, 50, and 70% of the total applied N) and controlled-release urea (CU) on the NUE, N leaching and wheat yield compared with the effects of urea and CU. The results suggested that OF released N slowly in the early stage and showed a significant residual effect, while CU released N quickly in the first 2 months. The OF substitutes with 30-50% CU increased wheat yield by 4.2-9.2%, while the 70%OF+30%CU treatment showed no significant difference relative to the urea treatment. The average maximum apparent NUE recovery (50.4%) was achieved under the 50%OF+50%CU treatment, but the partial factor productivity was not affected by the N type. As the OF application rate increased, the total carbon content increased, and the total N value decreased. The -N and -N concentrations in the OF+CU treatments were lower before the jointing stage but higher from the grain-filling to mature stages than those in the urea treatment. -N and -N were mainly concentrated in the 0-60-cm layer soil by OF substitution, and N leaching to the 60-100-cm soil layer was significantly reduced. Hence, the results suggest that the combination of 30-50% OF with CU synchronizes absorption with availability due to a period of increased N availability in soils and proved to be the best strategy for simultaneously increasing wheat production and reducing N leaching.
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http://dx.doi.org/10.3389/fpls.2021.802137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8740327PMC
December 2021

α5-nAChR associated with Ly6E modulates cell migration via TGF-β1/Smad signaling in non-small cell lung cancer.

Carcinogenesis 2022 May;43(4):393-404

Research Center of Basic Medicine, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

The α5-nicotinic acetylcholine receptor (α5-nAChR) is closely associated with nicotine-related lung cancer, offering a novel perspective for investigating the molecular pathogenesis of this disease. However, the mechanism by which α5-nAChR functions in lung carcinogenesis remains to be elucidated. Lymphocyte antigen 6 (Ly6) proteins, like snake three-finger alpha toxins such as α-bungarotoxin, can modulate nAChR signaling. Ly6E, a member of the Ly6 family, is a biomarker of poor prognosis in smoking-induced lung carcinogenesis and is involved in the regulation of TGF-β1/Smad signaling. Here, we explored the underlying mechanisms linking α5-nAChR and Ly6E in non-small cell lung cancer (NSCLC). The expression of α5-nAChR was correlated with Ly6 expression, smoking status and lower survival in NSCLC tissues. In vitro, α5-nAChR mediated Ly6E, the phosphorylation of the TGF-β1 downstream molecule Smad3 (pSmad3, a key mediator of TGF-β1 signaling), the epithelial-mesenchymal transition (EMT) markers Zeb1, N-cadherin and vimentin expression in NSCLC cells. The downregulation of Ly6E reduced α5-nAChR, pSmad3, Zeb1, N-cadherin and vimentin expression. Functionally, silencing both α5-nAChR and Ly6E significantly inhibited cell migration compared to silencing α5-nAChR or Ly6E alone. Furthermore, the functional effects of α5-nAchR and Ly6E were confirmed in chicken embryo chorioallantoic membrane (CAM) and mouse xenograft models. Therefore, our findings uncover a new interaction between α5-nAChR and Ly6E that inhibits cancer cell migration by modulating the TGF-β1/Smad signaling pathway in NSCLC, which may serve as a novel target for therapeutic intervention.
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http://dx.doi.org/10.1093/carcin/bgac003DOI Listing
May 2022

Case Report : Li-Fraumeni Syndrome with Central Nervous System Tumors in Two Siblings.

BMC Pediatr 2021 12 27;21(1):588. Epub 2021 Dec 27.

Medical Oncology Department, Pediatric Oncology Center, Beijing Children's Hospital, National Center for Children's Health, Beijing Key Laboratory of Pediatric Hematology Ocology, Key Laboratory of Major Diseases in Children, Ministry of Education, Hematology Oncology Center, Capital Medical University, Beijing, 100045, China.

Background: Li-Fraumeni syndrome (LFS) is a rare autosomal dominant cancer predisposition syndrome caused by germline TP53 gene mutations. It is characterized by high risk of early-onset cancer, and has been confirmed as associated with multiple tumors clinically. So pediatricians should be more alert to LFS in children with tumors. Choroid plexus carcinoma (CPC) is a rare, malignant tumor which account for less than 1% of all central nervous system (CNS) tumors. However, when such tumorigenesis occurs, it is important to be vigilant for the presence of LFS.

Case Presentation: The first patient is a 32-month-old boy admitted for convulsions and then was found intracranial space-occupying lesion. Underwent operation, he was diagnosis as choroid plexus carcinoma (WHO Grade III). After 5 months, his elder sister, a 13-year-old girl, was brought to emergency department for confusion and intermittent convulsions. Surgery was performed immediately after head CT examination found the lesion. The pathology result indicated glioblastoma. Because the siblings of the same family have successively suffered from malignant tumors, we performed genetic testing on this family. TP53 gene mutation occurred in both children of these two cases from their father, and their other brother was not spared either. So the two siblings both met the diagnostic criteria of LFS. Then they all received systematic anti-tumor therapy, and follow-up hitherto.

Conclusion: Here we reported a rare LFS case that two siblings were inherited the same TP53 germline mutations from their father. They suffered from choroid plexus carcinoma and glioblastoma and were finally diagnosed with LFS. In this LFS family, the primary tumors of the two children were both central nervous system tumors, which were not reported in the previous literature. It is suggested that clinicians should be alert to LFS related tumors, which is helpful for early diagnosis. Timely detection of TP53 gene is an important way for early diagnosis of LFS, especially in children with tumor. The incidence of secondary tumor in LFS patients is significantly higher, and other family members of the LFS patient also have an increased risk of suffering from the tumors. Therefore, early diagnosis and timely tumor surveillance can obtain better therapeutic effect and prognosis for both proband and their family.
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http://dx.doi.org/10.1186/s12887-021-03070-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8711161PMC
December 2021

The 3/4- and 3/6-Subfamily Variants of α-Conotoxins GI and MI Exhibit Potent Inhibitory Activity against Muscular Nicotinic Acetylcholine Receptors.

Mar Drugs 2021 Dec 14;19(12). Epub 2021 Dec 14.

Beijing Institute of Biotechnology, Beijing 100071, China.

α-Conotoxins GI and MI belong to the 3/5 subfamily of α-conotoxins and potently inhibit muscular nicotinic acetylcholine receptors (nAChRs). To date, no 3/4- or 3/6-subfamily α-conotoxins have been reported to inhibit muscular nAChRs. In the present study, a series of new 3/4-, 3/6-, and 3/7-subfamily GI and MI variants were synthesized and functionally characterized by modifications of loop2. The results show that the 3/4-subfamily GI variant GI[∆8G]-II and the 3/6-subfamily variants GI[+13A], GI[+13R], and GI[+13K] displayed potent inhibition of muscular nAChRs expressed in oocytes, with an IC of 45.4-73.4 nM, similar to or slightly lower than that of wild-type GI (42.0 nM). The toxicity of these GI variants in mice appeared to be about a half to a quarter of that of wild-type GI. At the same time, the 3/7-subfamily GI variants showed significantly lower in vitro potency and toxicity. On the other hand, similar to the 3/6-subfamily GI variants, the 3/6-subfamily MI variants MI[+14R] and MI[+14K] were also active after the addition of a basic amino acid, Arg or Lys, in loop2, but the activity was not maintained for the 3/4-subfamily MI variant MI[∆9G]. Interestingly, the disulfide bond connectivity "C1-C4, C2-C3" in the 3/4-subfamily variant GI[∆8G]-II was significantly more potent than the "C1-C3, C2-C4" connectivity found in wild-type GI and MI, suggesting that disulfide bond connectivity is easily affected in the rigid 3/4-subfamily α-conotoxins and that the disulfide bonds significantly impact the variants' function. This work is the first to demonstrate that 3/4- and 3/6-subfamily α-conotoxins potently inhibit muscular nAChRs, expanding our knowledge of α-conotoxins and providing new motifs for their further modifications.
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http://dx.doi.org/10.3390/md19120705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704989PMC
December 2021

Oxidative stress suppression in . by peptides from dogfish skin regulation of transcription factors DAF-16 and HSF-1.

Food Funct 2022 Jan 24;13(2):716-724. Epub 2022 Jan 24.

College of Life Science, Shanxi University, Taiyuan 030006, PR China.

Functional peptides were obtained enzymatic hydrolysis of smooth dogfish () skin. The enzyme-assisted process was optimized to achieve high yield of smooth dogfish skin peptides (SDSP). Fractions of SDSP (MW < 2 kDa, 2-5 kDa, 5-10 kDa and >10 kDa) showed antioxidant activities. The peptides <2 kDa (SDSP) significantly improved motility, reduced ROS and HO levels of , and increased its resistance to oxidative stress compared to the other peptide fractions. function of SDSP could be explained by their capacity to increase the expression of stress-response genes. The enhanced resistance to oxidative stress mediated by SDSP was dependent on DAF-16 and HSF-1. The amino acid residues and sequences of SDSP were characterized and revealed a higher content of hydrophobic polar amino acid contents. This study (especially the investigation) explored new potent antioxidant peptides derived from dogfish skin.
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http://dx.doi.org/10.1039/d1fo02271gDOI Listing
January 2022

Enriched clonal hematopoiesis in seniors with dietary vitamin C inadequacy.

Clin Nutr ESPEN 2021 12 30;46:179-184. Epub 2021 Oct 30.

Beijing Lu Daopei Institute of Hematology, Beijing, China; Division of Laboratory Medicine, Hebei Yanda Lu Daopei Hospital, Langfang, China; Division of Pathology & Laboratory Medicine, Beijing Lu Daopei Hospital, Beijing, China. Electronic address:

Background: The anti-cancer effect of vitamin C (VC) has long been speculated, but studies yielded inconsistency. Recent studies reported that supraphysiological concentration of VC have therapeutic or prevention effects for myeloid malignancies with certain mutation signatures. There was a notable proportion of DAT (i.e., DNMT3A, ASXL1, and TET2) and dozens of other genes that mutate in age-related clonal hematopoiesis (ARCH).

Methods And Results: Through analyzing the plasma VC concentration and mutations of 21 genes in 215 senior volunteers, we revealed that ARCH is significantly associated with dietary plasma VC concentrations, especially TET2 mutations and non-DAT mutations.

Conclusion: This study firstly disclosed the significant association between VC inadequacy and ARCH in the senior population. It provides evidence that physiological VC concentration has ARCH prevention effect. It will illuminate future explorations on the oral VC supplement in maintaining sound hematopoiesis, reversal ARCH, adjuvant therapy for myeloid malignancies, and prevention of other ARCH related comorbidities.
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http://dx.doi.org/10.1016/j.clnesp.2021.10.014DOI Listing
December 2021

High positively charged FeO nanocomposites for efficient and recyclable demulsification of hexadecane-water micro-emulsion.

Chemosphere 2022 Mar 26;291(Pt 3):133050. Epub 2021 Nov 26.

College of Chemistry and Chemical Engineering, Xinjiang Normal University, Urumqi, 830054, China; Xinjiang Key Laboratory of Energy Storage and Photoelectrocatalytic Materials, Xinjiang Normal University, Urumqi, 830054, China. Electronic address:

Oily wastewater not only causes major environmental issues, but also threatens human health. Magnetic nanoparticles (MNPs) are an attractively alternative commercial demulsifiers for their recyclability and high surface area. The wettability and surface charge of magnetic materials are significant factors in oily wastewater treatment. However, the specific influence of surface charge on the demulsification performance has not been rigorously investigated. Herein, a series of MNPs coated by dimethyl-diallyl-ammonium chloride (PDDA) and fulvic acid (FA) (FeO/FA/PDDA) with different surface positive charges were synthesized by adjusting the PDDA concentrations and applied in demulsification of hexadecane-water micro-emulsion. The oil-water separation efficiency (Es) was enhanced gradually with increasing the surface positive charge of demulsifiers. Derjaguin-Landau-Verwey-Overbeek (DLVO) theory confirmed that with increasing surface positive potential, the electrostatic attraction between demulsifiers and oil droplets increased, and thus, Es increased. In addition, the superior Es of FeO/FA MNPs for hexadecyl trimethyl ammonium bromide (CTAB)-stabilized micro-emulsions and FeO/FA/PDDA MNPs for sodium dodecyl sulfate (SDS)-stabilized micro-emulsions further confirmed that electrostatic force was critical in demulsification. The high positively charged FeO/FA/PDDA MNPs can be used as an efficient and recyclable demulsifier for hexadecane-water micro-emulsion. This study provides a theoretical basis for designing demulsifiers.
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http://dx.doi.org/10.1016/j.chemosphere.2021.133050DOI Listing
March 2022

Carbon-Based Nanocomposite Smart Sensors for the Rapid Detection of Mycotoxins.

Nanomaterials (Basel) 2021 Oct 26;11(11). Epub 2021 Oct 26.

Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi 830046, China.

Carbon-based nanomaterials have become the subject of intensive interest because their intriguing physical and chemical properties are different from those of their bulk counterparts, leading to novel applications in smart sensors. Mycotoxins are secondary metabolites with different structures and toxic effects produced by fungi. Mycotoxins have low molecular weights and highly diverse molecular structures, which can induce a spectrum of biological effects in humans and animals even at low concentrations. A tremendous amount of biosensor platforms based on various carbon nanocomposites have been developed for the determination of mycotoxins. Therefore, the contents of this review are based on a balanced combination of our own studies and selected research studies performed by academic groups worldwide. We first address the vital preparation methods of biorecognition unit (antibodies, aptamers, molecularly imprinted polymers)-functionalized carbon-based nanomaterials for sensing mycotoxins. Then, we summarize various types of smart sensors for the detection of mycotoxins. We expect future research on smart sensors to show a significant impact on the detection of mycotoxins in food products.
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http://dx.doi.org/10.3390/nano11112851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621137PMC
October 2021
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