Publications by authors named "Jianmin Wu"

214 Publications

A quadruple protection procedure for resuming pig production in small-scale ASFV-positive farms in China.

Curr Res Microb Sci 2021 Dec 26;2:100014. Epub 2020 Nov 26.

Laboratory of Molecular Virology and Immunology, Innovation Technology Center, Haid Research Institute, Guangdong Haid Group Co., Ltd, Guangzhou, China.

African swine fever (ASF) outbreak has caused serious economic losses in Asia since 2018. As ASF is a new emerging disease, many farmers hesitate to raise pigs before biosafety procedures were evaluated to be effective. To support small-scale farms in resuming pig production, a comprehensive procedure, called the quadruple protection procedure (QPP), was tested in 35 small farms which had been confirmed with African swine fever virus (ASFV). The QPP takes care of the farms' construction, environmental disinfection, regular immunization, and feed quality. Qualified daily management was supplemented as well. During a one-year survey four disinfectants and one piece of equipment were used in higher frequency. A 7- or 15-day empty period after the disinfection was suitable when it was combined with the rest of the protection measures from QPP. Totally 18,730 porkers and 3,006 sows were healthy by the end of the study with percentage of 100 and 98.8, respectively, indicating that QPP could protect pigs in small-scale farms from pathogens within China. This study developed an effective protective procedure system for small-scale farms to produce pigs under the risk of ASF outbreak.
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http://dx.doi.org/10.1016/j.crmicr.2020.100014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8610312PMC
December 2021

Lipid response of hepatocellular carcinoma cells to anticancer drug detected on nanostructure-assisted LDI-MS platform.

Talanta 2021 Dec 20;235:122817. Epub 2021 Aug 20.

Institution of Analytical Chemistry, Department of Chemistry, Zhejiang University, Hangzhou, 310058, China. Electronic address:

High heterogeneity of hepatocellular carcinoma (HCC) tumor has become an obstacle to select effective therapy for the treatment of HCC patients. Methods that can guide the decision on therapy choice for HCC treatment are highly demanded. Evaluating the drug response of heterogeneous tumor cells at the molecular level can help to reveal the toxicity mechanism of anticancer drugs and provide more information than current cell-based chemosensitivity assays. In the present work, nanostructure-assisted laser desorption/ionization mass spectrometry (NALDI-MS) was used to investigate the lipid response of HCC cells to anticancer drugs. Three types of HCC cells (LM3, Hep G2, Huh7) were treated with sorafenib, doxorubicin hydro-chloride, and cisplatin. We found that the lipid profiles of HCC cells changed a lot after the drug treatment, and the degree of lipid changes was related to the cell viability. Two pairs of fatty acids C16:1/C16:0 and C18:1/C18:0 were found to be strongly related to the viability of HCC cells after drug treatment, and were more sensitive than Methyl-thiazolyl tetrazolium (MTT) assay. Accordingly, they can act as sensitive and comprehensive indexes to evaluate the drug susceptibility of HCC cells. In addition, the peak ratio of several neighboring phospholipids displayed high correlation with drug response of specific cell subtype to specific drug. The ratio of neighboring lipids may be traced back to the activity of enzyme and gene expression which regulate the lipidomic pathway. This method provides drug response of heterogenous tumor cells at molecular level and could be a potential candidate to precise tumor chemosensitivity assay.
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http://dx.doi.org/10.1016/j.talanta.2021.122817DOI Listing
December 2021

The effect of biliary obstruction, biliary drainage and bile reinfusion on bile acid metabolism and gut microbiota in mice.

Liver Int 2021 Aug 30. Epub 2021 Aug 30.

The International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Shanghai, China.

Background & Aims: Preoperative obstructive jaundice is usually associated with higher post-operative mortality. Although external biliary drainage (EBD) has been widely used to relieve obstructive jaundice, the role of bile reinfusion after EBD is still controversial. The aim of our study was to study the effects of biliary obstruction, biliary drainage and bile reinfusion on bile acid metabolism and gut microbiota.

Methods: Firstly, we created a mice bile drainage collection (BDC) model to simulate the process of biliary obstruction, drainage and bile reinfusion. Then, we analysed the faecal, serum, liver and bile samples to investigate the effects of the process on bile acid profiles and gut microbiota. Finally, we evaluated the clinical effects of bile reinfusion.

Results: We evaluated the bile acid profiles of faeces, serum, liver and bile of normal mice. During biliary obstruction, secondary bile acids can still be produced, and increased in the liver and serum of mice. Compared with no bile reinfusion, bile reinfusion was beneficial to the recovery of T-ωMCA in the liver and bile, and can restore the colon crypt length shortened by biliary obstruction. Only Ruminococcus_1 proliferated when the biliary obstruction lasted for 12 days. In the clinic, bile reinfusion cannot accelerate the patient's perioperative recovery or prolong long-term survival.

Conclusion: We have successfully created a mice bile drainage collection model. Short-term bile reinfusion can partially benefit the recovery of the secondary bile acids in the liver and bile, but hardly benefit the patient's perioperative recovery or long-term survival. (247 words).
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http://dx.doi.org/10.1111/liv.15047DOI Listing
August 2021

Discovery of a Carbamoyl Phosphate Synthetase 1-Deficient HCC Subtype With Therapeutic Potential Through Integrative Genomic and Experimental Analysis.

Hepatology 2021 Dec 11;74(6):3249-3268. Epub 2021 Oct 11.

The International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.

Background And Aims: Metabolic reprogramming plays an important role in tumorigenesis. However, the metabolic types of different tumors are diverse and lack in-depth study. Here, through analysis of big databases and clinical samples, we identified a carbamoyl phosphate synthetase 1 (CPS1)-deficient hepatocellular carcinoma (HCC) subtype, explored tumorigenesis mechanism of this HCC subtype, and aimed to investigate metabolic reprogramming as a target for HCC prevention.

Approach And Results: A pan-cancer study involving differentially expressed metabolic genes of 7,764 tumor samples in 16 cancer types provided by The Cancer Genome Atlas (TCGA) demonstrated that urea cycle (UC) was liver-specific and was down-regulated in HCC. A large-scale gene expression data analysis including 2,596 HCC cases in 7 HCC cohorts from Database of HCC Expression Atlas and 17,444 HCC cases from in-house hepatectomy cohort identified a specific CPS1-deficent HCC subtype with poor clinical prognosis. In vitro and in vivo validation confirmed the crucial role of CPS1 in HCC. Liquid chromatography-mass spectrometry assay and Seahorse analysis revealed that UC disorder (UCD) led to the deceleration of the tricarboxylic acid cycle, whereas excess ammonia caused by CPS1 deficiency activated fatty acid oxidation (FAO) through phosphorylated adenosine monophosphate-activated protein kinase. Mechanistically, FAO provided sufficient ATP for cell proliferation and enhanced chemoresistance of HCC cells by activating forkhead box protein M1. Subcutaneous xenograft tumor models and patient-derived organoids were employed to identify that blocking FAO by etomoxir may provide therapeutic benefit to HCC patients with CPS1 deficiency.

Conclusions: In conclusion, our results prove a direct link between UCD and cancer stemness in HCC, define a CPS1-deficient HCC subtype through big-data mining, and provide insights for therapeutics for this type of HCC through targeting FAO.
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http://dx.doi.org/10.1002/hep.32088DOI Listing
December 2021

High-Throughput Salivary Metabolite Profiling on an Ultralow Noise Tip-Enhanced Laser Desorption Ionization Mass Spectrometry Platform for Noninvasive Diagnosis of Early Lung Cancer.

J Proteome Res 2021 09 3;20(9):4346-4356. Epub 2021 Aug 3.

Institution of Analytical Chemistry, Department of Chemistry, Zhejiang University, Hangzhou 310058, China.

Lung cancer (LC) is a widespread cancer that is the cause of the highest mortality rate accounting for 25% of all cancer deaths. To date, most LC patients are diagnosed at the advanced stage owing to the lack of obvious symptoms in the early stage and the limitations of current clinical diagnostic techniques. Therefore, developing a high throughput technique for early screening is of great importance. In this work, we established an effective and rapid salivary metabolic analysis platform for early LC diagnosis and combined metabolomics and transcriptomics to reveal the metabolic fluctuations correlated to LC. Saliva samples were collected from a total of 150 volunteers including 89 patients with early LC, 11 patients with advanced LC, and 50 healthy controls. The metabolic profiling of noninvasive samples was investigated on an ultralow noise TELDI-MS platform. In addition, data normalization methods were screened and assessed to overcome the MS signal variation caused by individual difference for biomarker mining. For untargeted metabolic profiling of saliva samples, around 264 peaks could be reliably detected in each sample. After multivariate analysis, 23 metabolites were sorted out and verified to be related to the dysfunction of the amino acid and nucleotide metabolism in early LC. Notably, transcriptomic data from online TCGA repository were utilized to support findings from the salivary metabolomics experiment, including the disorder of amino acid biosynthesis and amino acid metabolism. Based on the verified differential metabolites, early LC patients could be clearly distinguished from healthy controls with a sensitivity of 97.2% and a specificity of 92%. The ultralow noise TELDI-MS platform displayed satisfactory ability to explore salivary metabolite information and discover potential biomarkers that may help develop a noninvasive screening tool for early LC.
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http://dx.doi.org/10.1021/acs.jproteome.1c00310DOI Listing
September 2021

MA Demethylase ALKBH5 Regulates PD-L1 Expression and Tumor Immunoenvironment in Intrahepatic Cholangiocarcinoma.

Cancer Res 2021 Sep 23;81(18):4778-4793. Epub 2021 Jul 23.

Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

N-methyladenosine (mA) has been reported as an important mechanism of posttranscriptional regulation. Programmed death-ligand 1 (PD-L1) is a primary immune inhibitory molecule expressed on tumor cells that promotes immune evasion. Here we report ALKBH5 as an important mA demethylase that orchestrates PD-L1 expression in intrahepatic cholangiocarcinoma (ICC). Regulation of PD-L1 expression by ALKBH5 was confirmed in human ICC cell lines. Sequencing of the mA methylome identified PD-L1 mRNA as a direct target of mA modification whose levels were regulated by ALKBH5. Furthermore, ALKBH5 and PD-L1 mRNA were shown to interact. ALKBH5 deficiency enriched mA modification in the 3'UTR region of PD-L1 mRNA, thereby promoting its degradation in a YTHDF2-dependent manner. and , tumor-intrinsic ALKBH5 inhibited the expansion and cytotoxicity of T cells by sustaining tumor cell PD-L1 expression. The ALKBH5-PD-L1-regulating axis was further confirmed in human ICC specimens. Single-cell mass cytometry analysis unveiled a complex role of ALKBH5 in the tumor immune microenvironment by promoting the expression of PD-L1 on monocytes/macrophages and decreasing the infiltration of myeloid-derived suppressor-like cells. Analysis of specimens from patients receiving anti-PD1 immunotherapy suggested that tumors with strong nuclear expression patterns of ALKBH5 are more sensitive to anti-PD1 immunotherapy. Collectively, these results describe a new regulatory mechanism of PD-L1 by mRNA epigenetic modification by ALKBH5 and the potential role of ALKBH5 in immunotherapy response, which might provide insights for cancer immunotherapies. SIGNIFICANCE: This study identifies PD-L1 mRNA as a target of ALKBH5 and reveals a role for ALKBH5 in regulating the tumor immune microenvironment and immunotherapy efficacy.
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http://dx.doi.org/10.1158/0008-5472.CAN-21-0468DOI Listing
September 2021

Ultrasensitive and High Reproducible Detection of Urinary Metabolites Using the Tip-Contact Extraction Method Coupled with Negative LDI-MS.

J Proteome Res 2021 08 19;20(8):4022-4030. Epub 2021 Jul 19.

Institute of Analytical Chemistry, Department of Chemistry, Zhejiang University, Hangzhou 310058, P. R. China.

More and more evidence has proved that urinary metabolites can instantly reflect disease state. Therefore, ultra-sensitive and reproducible detection of urinary metabolites in a high-throughput way is urgently desirable for clinical diagnosis. Matrix-free laser desorption/ionization mass spectrometry (LDI-MS) is a high-throughput platform for metabolites detection, but it is encountered by severe interference from numerous salts in urine samples, because the crystallized urine salt on dried samples could result in poor reproducibility in LDI-MS detection. The present work proposed a tip-contact extraction (TCE) technique to eliminate interference from the urine salt. Vertical silicon nanowire arrays decorated with the fluorinated ethylene propylene film ([email protected]) could effectively extract metabolites from the urine sample dropping on its surface. High salt tolerance was observed in the subsequent LDI-MS detection of the metabolites extracted on the tip of [email protected] even in the presence of 1 M urea. Stable and reproducible mass spectra for non-target metabolic analysis were obtained in real urine samples with different dilution folds. Urinary metabolites collected from bladder cancer (BC) patients were reliably profiled by the TCE method coupled with negative LDI-MS. Based on this platform, potential metabolic biomarkers that can distinguish BC patients and normal controls were uncovered.
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http://dx.doi.org/10.1021/acs.jproteome.1c00340DOI Listing
August 2021

Modulation of Gut Microbiota to Enhance Effect of Checkpoint Inhibitor Immunotherapy.

Front Immunol 2021 29;12:669150. Epub 2021 Jun 29.

The International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.

Accumulating evidence demonstrated the crucial role of gut microbiota in many human diseases, including cancer. Checkpoint inhibitor therapy has emerged as a novel treatment and has been clinically accepted as a major therapeutic strategy for cancer. Gut microbiota is related to cancer and the effect of immune checkpoint inhibitors (ICIs), and supplement with specific bacterial species can restore or enhance the responses to the ICIs. Namely, specified bacteria can serve as the biomarkers for distinguishing the patient who will respond to ICIs and determine the effectiveness of ICIs, as well as predicting the efficacy of checkpoint inhibitor immunotherapy. Regardless of the significant findings, the relationship between gut microbiota and the effect of ICIs treatment needs a more thorough understanding to provide more effective therapeutic plans and reduce treatment complication. In this review, we summarized the role of gut microbiota played in immune system and cancer. We mainly focus on the relationship between gut microbiota and the checkpoint inhibitor immunotherapy.
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http://dx.doi.org/10.3389/fimmu.2021.669150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276067PMC
October 2021

Graphene quantum dot-decorated luminescent porous silicon dressing for theranostics of diabetic wounds.

Acta Biomater 2021 09 13;131:544-554. Epub 2021 Jul 13.

Institute of Analytical Chemistry, Department of Chemistry, Zhejiang University, Hangzhou 310058, China. Electronic address:

Diabetic wound healing is highly desirable but remains a great challenge owing to the continuous damage of excess reactive oxygen species (ROS) and degradation of therapeutic peptide drugs by over-expressed matrix metalloproteinase (MMP). Herein, we developed a stimuli-responsive smart dressing for theranostics of diabetic wounds using graphene quantum dots-decorated luminescent porous silicon ([email protected]), which was further loaded with peptide and embedded in chitosan (CS) film. The confinement of GQDs in nanochannels of PSi endowed [email protected] with efficient fluorescence resonance energy transfer (FRET) effect, leading to initial red fluorescence of PSi with complete quench of GQD's blue fluorescence. Furthermore, the decoration of GQDs on PSi surface significantly enhanced the loading capacity for peptide drugs including epidermal growth factor (EGF) and insulin (Ins) which can promote diabetic wounds healing. The peptides coloaded in [email protected] exhibited sustained release behavior and could be protected in presence of MMP owing to size exclusion of PSi's nanochannels. As HO-triggered oxidation of PSi lead to weakened FRET effect and degradation of PSi, [email protected] demonstrated HO-responsive ratiometric fluorescence change (from red PSi to blue GQDs) and drug release behavior. In combination with CS's degradation in the acidic and oxidation microenvironment, the smart dressing also showed stimuli-responsive drug release toward slightly acid and highly oxidative conditions in diabetic wounds. In vitro and in vivo results demonstrated the smart dressing enhanced the proliferation and migration of cells as well as significantly healed diabetic wounds. Real-time indicating of the exacerbation or healing of diabetic wounds was also realized using the rate of fluorescent discoloration of the dressing. STATEMENT OF SIGNIFICANCE: In this work, a dual luminescent nanomaterial was created by hosting graphene quantum dots (GQDs) in the nanochannel of porous silicon (PSi), which was further applied for theranostics of diabetic wound. The synergistic effect of the host-guest nanohybrid is significant. The GQDs can significantly improve the capacity for peptide drug loading and form a stimuli-response visual ratiometric sensor with luminescent PSi, which can also protect and sustain release of peptide drugs for effective diabetic wounds treatment. After embedded in a chitosan film, the smart dressing displayed HO-responsive visual ratiometric fluorescence change and drug release behavior. In vitro and in vivo results demonstrated the smart dressing enhanced the proliferation and migration of cells as well as significantly healed diabetic wounds.
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http://dx.doi.org/10.1016/j.actbio.2021.07.018DOI Listing
September 2021

DNA transposons mediate duplications via transposition-independent and -dependent mechanisms in metazoans.

Nat Commun 2021 07 13;12(1):4280. Epub 2021 Jul 13.

Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

Despite long being considered as "junk", transposable elements (TEs) are now accepted as catalysts of evolution. One example is Mutator-like elements (MULEs, one type of terminal inverted repeat DNA TEs, or TIR TEs) capturing sequences as Pack-MULEs in plants. However, their origination mechanism remains perplexing, and whether TIR TEs mediate duplication in animals is almost unexplored. Here we identify 370 Pack-TIRs in 100 animal reference genomes and one Pack-TIR (Ssk-FB4) family in fly populations. We find that single-copy Pack-TIRs are mostly generated via transposition-independent gap filling, and multicopy Pack-TIRs are likely generated by transposition after replication fork switching. We show that a proportion of Pack-TIRs are transcribed and often form chimeras with hosts. We also find that Ssk-FB4s represent a young protein family, as supported by proteomics and signatures of positive selection. Thus, TIR TEs catalyze new gene structures and new genes in animals via both transposition-independent and -dependent mechanisms.
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http://dx.doi.org/10.1038/s41467-021-24585-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277862PMC
July 2021

Viral Metagenome-Based Precision Surveillance of Pig Population at Large Scale Reveals Viromic Signatures of Sample Types and Influence of Farming Management on Pig Virome.

mSystems 2021 Jun 8;6(3):e0042021. Epub 2021 Jun 8.

Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, Jilin Province, China.

Pigs are a major meat source worldwide and a pillar of Chinese animal husbandry; hence, their health and safety are a prioritized concern of the national economy. Although pig viruses have been continuously investigated, the full extent of the pig virome has remained unknown and emerging viruses are still a major threat to the pig industry. Here, we report a comprehensive study to delineate the pig virome of 1,841 healthy weaned pigs from 45 commercial farms collected from 25 major pig-producing regions across China. A viromic sequence data set, named Pigs_VIRES, which matched 96,586 viral genes from at least 249 genera within 66 families and which almost tripled the number of previously published pig viromic genes, was established. The majority of the mammalian viruses were closely related to currently known ones. A comparison with previously published viromes of bovines, avians, and humans has revealed the distinct composition of Pigs_VIRES, which has provided characteristic viromic signatures of serum, pharyngeal, and anal samples that were significantly influenced by farming management and disease control measures. Taken together, Pigs_VIRES has revealed the most complete viromic data set of healthy pigs to date. The compiled data also provide useful guidance to pig viral disease control and prevention and the biosafety management of pig farms. Especially, the established viromic protocol has created a precision surveillance strategy to potentially innovate currently used surveillance methods of animal infectious diseases, particularly by making precision surveillance available to other animal species on a large scale or even during a nationwide surveillance campaign. Pigs are deeply involved in human lives; hence, their viruses are associated with public health. Here, we established the most comprehensive virome of healthy piglets to date, which provides a viromic baseline of weaned pigs for disease prevention and control, highlighting that longitudinal viromic monitoring is needed to better understand the dynamics of the virome in pig development and disease occurrence. The present study also shows how high standards of animal farm management with strict biosafety measures can significantly minimize the risk of introduction of pathogenic viruses into pig farms. Particularly, the viromic strategy established, i.e., high-throughput detection and analyses of various known and unknown pathogenic viruses in a single test at large scale, has completely innovated current surveillance measures in provision of timely and precise detection of all potentially existing pathogenic viruses and can be widely applied in other animal species.
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http://dx.doi.org/10.1128/mSystems.00420-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269232PMC
June 2021

Prophylactic Efficacy of Equine Immunoglobulin F(ab') Fragments Against Feline Parvovirus.

Appl Biochem Biotechnol 2021 Oct 4;193(10):3151-3162. Epub 2021 Jun 4.

Guangxi Key Laboratory of Veterinary Biotechnology, Guangxi Veterinary Research Institute, Nanning, 530001, China.

Feline parvovirus (FPV), a type of parvovirus prevalent worldwide, can cause foetal death and acute enteritis in adult cats with severe leukopenia, and yet there are no effective drugs to prevent or treat FPV. Here, the immune effects of two FPV vaccines on horses were compared. IgG was extracted from FPV-immunized horse sera. Equine F(ab') fragments were obtained from pepsin-digested IgG and then purified by protein-G column chromatography. The results showed that the inactivated FPV oil vaccine was more effective than the inactivated FPV propolis vaccine in helping healthy horses to produce hyper-immune serum. Four methods were tested, among which the optimized octanoic acid-ammonium sulphate precipitation method was proved to be the best process for extracting IgG. The optimal condition for preparing F(ab') by pepsin digestion was 30 °C for 3.5 h, and the content, purity and recovery of F(ab') were 8.64 mg/mL, 90.36% and 93.24%, respectively. Our equine immunoglobulin F(ab') fragments effectively neutralized activity in vitro against FPV, alleviated the clinical symptoms of FPV-infected cats, reduced the viral loads in the intestine and had prophylactic effects in FPV-infected cats. These results indicate that the F(ab') fragment prepared from inactivated FPV-immunized horses may be used as a prophylactic agent for diseases caused by FPV.
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http://dx.doi.org/10.1007/s12010-021-03591-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175436PMC
October 2021

Influence of atorvastatin on metabolic pattern of rats with pulmonary hypertension.

Aging (Albany NY) 2021 04 22;13(8):11954-11968. Epub 2021 Apr 22.

Department of Geriatrics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.

Background: Metabonomics has been widely used to analyze the initiation, progress, and development of diseases. However, application of metabonomics to explore the mechanism of pulmonary arterial hypertension (PAH) are poorly reported. This study aimed to investigate the influence of atorvastatin (Ato) on metabolic pattern of rats with pulmonary hypertension.

Methods: PAH animal model was established using monocrotaline (MCT). The mean pulmonary artery pressure (mPAP) and right ventricular hypertrophy index (RVHI) were measured. The microstructure of pulmonary arterioles was observed by HE staining. Nuclear magnetic resonance was used to detect and analyze the serum metabolites. The levels of glycogen synthase kinase-3β (GSK-3β), hexokinase 2 (HK-2), sterol regulatory element-binding protein 1c (SREBP-1c), and carnitine palmitoyltransferase I (CPT-1) in the lung tissues were measured.

Results: Ato significantly improved lung function by decreasing mPAP, RVHI, wall thickness, and wall area. Differences in metabolic patterns were observed among normal, PAH, and Ato group. The levels of GSK-3β and SREBP-1c were decreased, but HK-2 and CPT-1 were increased in the group PAH. Ato treatment markedly reversed the influence of MCT.

Conclusion: Ato significantly improved the pulmonary vascular remodeling and pulmonary hypertension of PAH rats due to its inhibition on Warburg effect and fatty acid β oxidation.
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http://dx.doi.org/10.18632/aging.202898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109122PMC
April 2021

A co-delivery platform for synergistic promotion of angiogenesis based on biodegradable, therapeutic and self-reporting luminescent porous silicon microparticles.

Biomaterials 2021 05 26;272:120772. Epub 2021 Mar 26.

Institute of Analytical Chemistry, Department of Chemistry, Zhejiang University, Hangzhou, 310058, China. Electronic address:

Insufficient angiogenesis happened in body defects such as ulceration, coronary heart disease, and chronic wounds constitutes a major challenge in tissue regeneration engineering. Owing to the poor bioactivity and maintenance of pro-angiogenic cells and factors during transplantation, new bioactive materials to tackle the barrier are highly desirable. Herein, we demonstrate a co-delivery platform for synergistic promotion of angiogenesis based on biodegradable, therapeutic, and self-reporting luminescent porous silicon (PSi) microparticles. The biodegradable and biocompatible PSi microparticles could quickly release therapeutic Si ions, which is bioactive to promote cell migration, tube formation, and angiogenic gene expression in vitro. To construct a highly efficient angiogenesis treatment platform, vascular endothelial growth factor (VEGF) was electrostatically adsorbed by PSi microparticles for effective drug loading and delivery. The dual therapeutic components (Si ions and VEGF) could release with the dissolution of Si skeleton, accompanying by the decay of photoluminescence (PL) intensity and blue shift of the maximum PL wavelength. Therefore, real-time drug release could be self-reported and assessed with the two-dimensional PL signal. The co-delivery of Si ions and VEGF displayed synergistic effect and highly efficient angiogenesis, which was evidenced by the enhancement of endothelial cell migration and tube formation in vitro with approximately 1.5-5 times higher than control. The blood vessel formation in vivo was also significantly improved as shown by the chick chorioallantoic membrane (CAM) model, in which the total length, size and junctions exhibited 2.1 ± 0.4, 4 ± 0.4, and 3.9 ± 0.3 times in comparison to control, respectively. The PSi and VEGF co-delivery system display great potential in tissue engineering as a biodegradable and self-reporting theranostic platform to promote angiogenesis.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120772DOI Listing
May 2021

Synergistic and On-Demand Release of Ag-AMPs Loaded on Porous Silicon Nanocarriers for Antibacteria and Wound Healing.

ACS Appl Mater Interfaces 2021 Apr 31;13(14):16127-16141. Epub 2021 Mar 31.

Institute of Analytical Chemistry, Department of Chemistry, Zhejiang University, Hangzhou 310058, China.

Due to the abuse of antibiotics, antimicrobial resistance is rapidly emerging and becoming a major global risk for public health. Thus, there is an urgent need for reducing the use of antibiotics, finding novel treatment approaches, and developing controllable release systems. In this work, a dual synergistic antibacterial platform with on-demand release ability based on silver nanoparticles (AgNPs) and antimicrobial peptide (AMP) coloaded porous silicon (PSi) was developed. The combination of AgNPs and AMPs (Tet-213, KRWWKWWRRC) exhibited an excellent synergistic antibacterial effect. As a carrier, porous silicon can efficiently load AgNPs and AMP under mild conditions and give the platform an on-demand release ability and a synergistic release effect. The AgNPs and AMP coloaded porous silicon microparticles ([email protected]) exhibited an acid pH and reactive oxygen species (ROS)-stimulated release of silver ions (Ag) and AMPs under bacterial infection conditions because of oxidation and desorption effects. Moreover, the release of the bactericide could be promoted by each other due to the interplay between AgNPs and Tet-213. antibacterial tests demonstrated that [email protected] inherited the intrinsic properties and synergistic antibacterial efficiency of both bactericides. In addition, wound dressing loaded with [email protected] showed outstanding bacteria-killing activity, accelerating wound-healing, and low biotoxicity in a-infected rat wound model. The present work demonstrated that PSiMPS might be an efficient platform for loading the antibiotic-free bactericide, which could synergistically and on-demand release to fight wound infection and promote wound healing.
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http://dx.doi.org/10.1021/acsami.1c02161DOI Listing
April 2021

FoxP3-miR-150-5p/3p suppresses ovarian tumorigenesis via an IGF1R/IRS1 pathway feedback loop.

Cell Death Dis 2021 03 15;12(3):275. Epub 2021 Mar 15.

Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China.

Ovarian cancer (OC) causes more deaths than any other gynecological cancer. Many cellular pathways have been elucidated to be associated with OC development and progression. Specifically, the insulin-like growth factor 1 receptor/insulin receptor substrate 1 (IGF1R/IRS1) pathway participates in OC development. Moreover, accumulating evidence has shown that microRNA deregulation contributes to tumor initiation and progression. Here, our study aimed to investigate the molecular functions and regulatory mechanisms of miR-150, specifically, in OC. We found that the expression of miR-150-5p/3p and their precursor, mir-150, was downregulated in OC tissues; lower mir-150 levels were associated with poor OC patient outcomes. Ectopic mir-150 expression inhibited OC cell growth and metastasis in vitro and in vivo. Furthermore, both IRS1 and IGF1R were confirmed as direct targets of miR-150-5p/3p, and the miR-150-IGF1R/IRS1 axis exerted antitumor effects via the PI3K/AKT/mTOR pathway. Forkhead box protein 3 (FoxP3) positively regulated the expression of miR-150-5p/3p by binding to the mir-150 promoter. In turn, the PI3K/AKT/mTOR pathway downregulated FoxP3 and miR-150-5p/3p. Taken together, these findings indicate that a complex FoxP3-miR-150-IGF1R/IRS1-PI3K/AKT/mTOR feedback loop regulates OC pathogenesis, providing a novel mechanism for miR-150 as a tumor suppressor miRNA in OC.
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http://dx.doi.org/10.1038/s41419-021-03554-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961150PMC
March 2021

Perfluorinated polymer modified vertical silicon nanowires as ultra low noise laser desorption ionization substrate for salivary metabolites profiling.

Talanta 2021 Apr 17;225:122022. Epub 2020 Dec 17.

Institution of Analytical Chemistry, Department of Chemistry, Zhejiang University, Hangzhou, 310058, China. Electronic address:

Metabolites in the body fluid are becoming a rich source of disease biomarkers. Developing an effective and high throughput detection and analysis platform of metabolites is of great importance for potential biomarker discovery and validation. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) has been successfully applied in rapid biomolecules detection in large scale. However, non-negligible background interference in low molecule-weight region still constitutes a main challenge even though various nanomaterials have been developed as an alternative to traditional organic matrix. In this work, a novel composite chip, silicon nanowires loaded with fluorinated ethylene propylene ([email protected]) was fabricated. It can serve as an excellent substrate for nanostructure-initiator mass spectrometry (NIMS) detection with ultra-low background noise in low molecular weight region (<500 Da). Ion desorption efficiency and internal energy transfer of [email protected] were studied using benzylpyridinium salt and tetraphenylboron salt as thermometer chemicals. The results indicated that a non-thermal desorption mechanism might be involved in the LDI process on [email protected] Owing to the higher LDI efficiency and low background interference of this novel substrate, the metabolic fingerprint of complex bio-fluids, such as human saliva, can be sensitively and stably acquired. As a proof of concept, [email protected] chip was successfully used in the detection of salivary metabolites. With the assistance of multivariate analysis, 22 metabolic candidates (p < 0.05) which can discriminate type 2 diabetes mellitus (2-DM) and healthy volunteers were found and identified. The role of these feature metabolites in the metabolic pathway involved in 2-DM was confirmed by literature mining. This work demonstrates that [email protected] NIMS might be served as an efficient and high throughput platform for metabolic biomarker exploration and clinical diagnosis.
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http://dx.doi.org/10.1016/j.talanta.2020.122022DOI Listing
April 2021

Capture and detection of urine bacteria using a microchannel silicon nanowire microfluidic chip coupled with MALDI-TOF MS.

Analyst 2021 Feb;146(4):1151-1156

Department of Chemistry, Zhejiang University, Hangzhou, 310058, China.

Fast bacterial identification in urine samples was achieved by capturing bacteria on a microchannel silicon nanowire microfluidic chip, followed by MALDI-TOF MS detection. Under the optimized conditions, bacteria with a concentration of 106 CFU mL-1 in urine samples could be identified without culture. If cultured for 4 hours, bacteria with a concentration as low as 103 CFU mL-1 were identified.
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http://dx.doi.org/10.1039/d0an02222eDOI Listing
February 2021

Rapid detection of SARS-CoV-2, replicating or non-replicating, using RT-PCR.

Int J Infect Dis 2021 Mar 21;104:471-473. Epub 2021 Jan 21.

Haid Research Institute, Guangdong HaidGroup Co., Ltd., Guangzhou, China. Electronic address:

To identify animals susceptible to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection or to determine whether SARS-CoV-2 contaminated meat is from a SARS-CoV-2-infected animal, a convenient and safe method was developed for rapid detection of SARS-CoV-2 in a replicating or non-replicating status in samples using reverse transcriptase-polymerase chain reaction (RT-PCR). This strategy can also be applied to develop assays for the detection of other viruses, either replicating or not.
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http://dx.doi.org/10.1016/j.ijid.2021.01.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825825PMC
March 2021

Reasons for discontinuing insulin and factors associated with insulin discontinuation in patients with type 2 diabetes mellitus: a real-world evidence study.

Clin Diabetes Endocrinol 2021 Jan 5;7(1). Epub 2021 Jan 5.

Division of Endocrinology, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, MA, 02115, USA.

Background: Evidence suggests that insulin therapy of patients with type 2 diabetes mellitus (T2DM) is frequently discontinued. However, the reasons for discontinuing insulin and factors associated with insulin discontinuation in this patient population are not well understood.

Methods: We conducted a retrospective cohort study of adults with T2DM prescribed insulin between 2010 and 2017 at Partners HealthCare. Reasons for discontinuing insulin and factors associated with insulin discontinuation were studied using electronic medical records (EMR) data. Natural language processing (NLP) was applied to identify reasons from unstructured clinical notes. Factors associated with insulin discontinuation were extracted from structured EMR data and evaluated using multivariable logistic regression.

Results: Among 7009 study patients, 2957 (42.2%) discontinued insulin within 12 months after study entry. Most patients who discontinued insulin (2121 / 71.7%) had reasons for discontinuation documented. The most common reasons were improving blood glucose control (33.2%), achieved weight loss (18.5%) and initiation of non-insulin diabetes medications (16.7%). In multivariable analysis adjusted for demographics and comorbidities, patients were more likely to discontinue either basal or bolus insulin if they were on a basal-bolus regimen (OR 1.6, 95% CI 1.3 to 1.8; p <  0.001) or were being seen by an endocrinologist (OR 2.6; 95% CI 2.2 to 3.0; p <  0.001).

Conclusions: In this large real-world evidence study conducted in an area with a high penetration of health insurance, insulin discontinuation countenanced by healthcare providers was common. In most cases it was linked to achievement of glycemic control, achieved weight loss and initiation of other diabetes medications. Factors associated with and stated reasons for insulin discontinuation were different from those previously described for non-adherence to insulin therapy, identifying it as a distinct clinical phenomenon.
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http://dx.doi.org/10.1186/s40842-020-00115-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786496PMC
January 2021

miR-340: A multifunctional role in human malignant diseases.

Int J Biol Sci 2021 1;17(1):236-246. Epub 2021 Jan 1.

Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou 325035, Zhejiang, P.R. China.

MicroRNAs (miRNAs) are a class of short non-coding RNAs of approximately 22 nucleotides in length, which function by binding to the 3' UTR sequences of their target mRNAs. It has been reported that dysregulated miRNAs play pivotal roles in numerous diseases, including cancers, such as gastric, breast, colorectal, ovarian, and other cancers. Recent research efforts have been devoted to translating these basic discoveries into clinical applications that could improve the therapeutic outcome in patients with cancer. Early studies have shown that miR-340 may act either as an oncogene or a tumor suppressor by targeting genes related to proliferation, apoptosis, and metastasis, as well as those associated with diagnosis, treatment, chemoresistance, and prognosis. miR-340 has been shown to have a role in other diseases, such as autoimmune diseases, acute stroke, and alcoholic steatohepatitis. Nevertheless, the roles of miR-340 in human malignancies are still unclear, and the associated mechanisms are complex, involving a variety of signaling pathways, such as Wnt/β-catenin and the JAK-STAT pathways. Herein, we review the crucial roles of miR-340 in human cancers through the analysis of the latest research studies, with the aim of clarifying miR-340 function in malignant disease diagnosis, treatment, and prognosis, and to propose further investigations.
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http://dx.doi.org/10.7150/ijbs.51123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757049PMC
January 2021

Corticosteroid dosing and opioid use are high in patients with SLE and remain elevated after belimumab initiation: a retrospective claims database analysis.

Lupus Sci Med 2020 12;7(1)

Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Objectives: To investigate corticosteroid and opioid use among patients with SLE and to examine the impact of belimumab initiation on the use of other SLE therapies.

Methods: We identified adult patients with SLE (International Classification of Diseases, 9th Revision/10th Revision 710.0 and M32) between 1 January 2012 and 31 May 2018 (earliest SLE diagnosis=index date) within MarketScan administrative claims data. Patients were followed from index date for a minimum of 12 months and until the earlier of disenrolment in their health plan or study end (31 May 2018). Corticosteroid utilisation, corticosteroid dose (in prednisone equivalents) and opioid utilisation (overall, by strength (weak, strong) and by duration (chronic use defined as >90 days of cumulative drug supply)) were measured during follow-up. Oral corticosteroid and opioid use were compared in the 6 months before and after initiation of belimumab.

Results: There were 49 413 patients with SLE eligible for analysis (mean (SD) age: 50.1 (14.0) years, 90.2% female). Of these, 68.5% received corticosteroids, and the average number of prescriptions was 4.59 (4.11) over the first 12 months of follow-up. Among patients with oral corticosteroids, average daily dose was 19.4 (14.2) mg and 59.6% had an average daily dose of ≥15 mg. Half (52.6%) had at least one opioid prescription and of these, 34.6% had chronic use over the first 12 months of follow-up. Among patients initiating belimumab during follow-up (n=1710), oral corticosteroid use decreased by 9.1% (p=0.001), and average daily dose decreased from 14.5 (18.4) mg to 11.9 (18.0) mg (p<0.001) in the 6 months after initiation compared with the 6 months prior. Initiation of belimumab had no impact on prevalence of opioid use.

Conclusions: A high proportion of patients with SLE are treated with corticosteroids to control SLE and opioid therapy to manage chronic pain. While there was no change in opioid use, oral corticosteroid use and dose intensity decreased following initiation of belimumab.
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http://dx.doi.org/10.1136/lupus-2020-000435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759957PMC
December 2020

ecDNA within tumors: a new mechanism that drives tumor heterogeneity and drug resistance.

Signal Transduct Target Ther 2020 11 24;5(1):277. Epub 2020 Nov 24.

Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, P.R. China.

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http://dx.doi.org/10.1038/s41392-020-00403-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686330PMC
November 2020

PINA 3.0: mining cancer interactome.

Nucleic Acids Res 2021 01;49(D1):D1351-D1357

Center for Cancer Bioinformatics, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, China.

Protein-protein interactions (PPIs) are crucial to mediate biological functions, and understanding PPIs in cancer type-specific context could help decipher the underlying molecular mechanisms of tumorigenesis and identify potential therapeutic options. Therefore, we update the Protein Interaction Network Analysis (PINA) platform to version 3.0, to integrate the unified human interactome with RNA-seq transcriptomes and mass spectrometry-based proteomes across tens of cancer types. A number of new analytical utilities were developed to help characterize the cancer context for a PPI network, which includes inferring proteins with expression specificity and identifying candidate prognosis biomarkers, putative cancer drivers, and therapeutic targets for a specific cancer type; as well as identifying pairs of co-expressing interacting proteins across cancer types. Furthermore, a brand-new web interface has been designed to integrate these new utilities within an interactive network visualization environment, which allows users to quickly and comprehensively investigate the roles of human interacting proteins in a cancer type-specific context. PINA is freely available at https://omics.bjcancer.org/pina/.
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http://dx.doi.org/10.1093/nar/gkaa1075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779002PMC
January 2021

Dietary nutrients shape gut microbes and intestinal mucosa via epigenetic modifications.

Crit Rev Food Sci Nutr 2020 Oct 12:1-15. Epub 2020 Oct 12.

State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China.

The imbalance of intestinal microecology firstly impairs intestinal mucosa barrier and function, then further damages the functions and homeostasis of distal organs, leading to systemic diseases. Nutrients, transplantation of bacteria flora and modes of life can shape gut microbiota and intestinal mucosa barrier and mitigate stress. Current researches demonstrate that dynamic epigenetic modifications of intestinal tissue strongly mediate the crosstalk between gut microbes and gut mucosa barrier. and species can synthesize folate to increase DNA methylation and mRNA N6-methyladenosine (m6A) of gut, which ensures intestinal normal development. , and can induce histone acylation modifications by butyrate to enhance the development and immune balance of gut. Herein, we summarizes the present scientific understanding of how dietary nutrients shape gut microbiota and further regulate intestinal mucosa functions via epigenetic modifications, which will shed light on manipulation of gut microbiota by dietary nutrients, for prevention or clinical treatment of intestinal diseases.
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http://dx.doi.org/10.1080/10408398.2020.1828813DOI Listing
October 2020

DPHL: A DIA Pan-human Protein Mass Spectrometry Library for Robust Biomarker Discovery.

Genomics Proteomics Bioinformatics 2020 04 12;18(2):104-119. Epub 2020 Aug 12.

Department of Anatomical Pathology, Singapore General Hospital, Singapore 169608, Singapore.

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipeline and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to generate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.
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http://dx.doi.org/10.1016/j.gpb.2019.11.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646093PMC
April 2020

5-Aza-2-deoxycytidine inhibits osteolysis induced by titanium particles by regulating RANKL/OPG ratio.

Biochem Biophys Res Commun 2020 08 17;529(3):629-634. Epub 2020 Jul 17.

Department of Orthopaedics, The Fourth Affiliated Hospital of Harbin Medical University, 150006, Harbin, China. Electronic address:

Periprosthetic osteolysis (PIO) caused by wear particles is the main cause of implant failure, which is regulated by nuclear factor κ B receptor activator ligand (RANKL)/osteoprotegerin (OPG) system. At present, there is a lack of effective drugs to prevent or treat PIO. Previous studies have confirmed that DNA methylation is closely related to postmenopausal osteoporosis and can affect the expression of OPG and RANKL. However, the relationship between DNA methylation and PIO is not clear. In this study, we investigated the inhibitory effect of 5-Aza-2-deoxycytidine (AzadC) on osteolysis induced by titanium particles in a mouse model. This inhibition mechanism is achieved by changing the ratio of RANKL/OPG in the osteolysis model. In conclusion, there is a relationship between DNA methylation and PIO. AzadC has a certain inhibitory effect on osteolysis induced by titanium particles. Regulating DNA methylation may be a new way to treat PIO. Our findings lay a foundation for epigenetic understanding and intervention of osteolysis.
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http://dx.doi.org/10.1016/j.bbrc.2020.05.192DOI Listing
August 2020

Use of a magnetic covalent organic framework material with a large specific surface area as an effective adsorbent for the extraction and determination of six fluoroquinolone antibiotics by HPLC in milk sample.

J Sep Sci 2020 Oct 9;43(19):3775-3784. Epub 2020 Aug 9.

School of Chemistry and Materials Science of Shanxi Normal University, Key Laboratory of Magnetic Molecules and Magnetic Information Materials (Shanxi Normal University) Ministry of Education, Linfen, Shanxi, P. R. China.

A magnetic covalent organic framework material was synthesized with a core-shell structure using a simple solvothermal method. It was prepared with Fe O as the magnetic core, covalent organic framework as the shell, which synthesized from 1,3,5-triformylphloroglucinol and p-phenylenediamine by Schiff base reaction. Transmission electron microscopy, Fourier transform infrared spectroscopy, powder X-ray diffraction, vibrating sample magnetometry, and nitrogen adsorption-desorption were used to characterize magnetic adsorbent. It has showed a large specific surface area (505.6 m /g), which can provide many adsorption sites. Moreover, the saturation magnetization value was 48.4 emu/g enough to be separated by external magnet. Six kinds of fluoroquinolones (enoxacin, fleroxacin, ofloxacin, norfloxacin, pefloxacin, and lomefloxacin) were extracted by magnetic solid phase extraction with the magnetic adsorbent. High-performance liquid chromatography detects the entire adsorption and desorption process to further evaluate the optimal extraction and desorption conditions. Under the optimal chromatographic conditions, this method showed a low detection limit (0.05 to 0.20 μg/L), good linearity in the range of 0.5 to 200 μg/L, and the enrichment factor reaches 115.5-127.3. The spiked recovery of the fluoroquinolones in milk sample ranged from 90.4 to 101.2%.
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http://dx.doi.org/10.1002/jssc.202000616DOI Listing
October 2020

Precision Oncology in Surgery: Patient Selection for Operable Pancreatic Cancer.

Ann Surg 2020 08;272(2):366-376

Department of Surgery, Universitätsklinikum Erlangen, Erlangen, Germany.

Objective: We aimed to define preoperative clinical and molecular characteristics that would allow better patient selection for operative resection.

Background: Although we use molecular selection methods for systemic targeted therapies, these principles are not applied to surgical oncology. Improving patient selection is of vital importance for the operative treatment of pancreatic cancer (pancreatic ductal adenocarcinoma). Although surgery is the only chance of long-term survival, 80% still succumb to the disease and approximately 30% die within 1 year, often sooner than those that have unresected local disease.

Method: In 3 independent pancreatic ductal adenocarcinoma cohorts (total participants = 1184) the relationship between aberrant expression of prometastatic proteins S100A2 and S100A4 and survival was assessed. A preoperative nomogram based on clinical variables available before surgery and expression of these proteins was constructed and compared to traditional measures, and a postoperative nomogram.

Results: High expression of either S100A2 or S100A4 was independent poor prognostic factors in a training cohort of 518 participants. These results were validated in 2 independent patient cohorts (Glasgow, n = 198; Germany, n = 468). Aberrant biomarker expression stratified the cohorts into 3 distinct prognostic groups. A preoperative nomogram incorporating S100A2 and S100A4 expression predicted survival and nomograms derived using postoperative clinicopathological variables.

Conclusions: Of those patients with a poor preoperative nomogram score, approximately 50% of patients died within a year of resection. Nomograms have the potential to improve selection for surgery and neoadjuvant therapy, avoiding surgery in aggressive disease, and justifying more extensive resections in biologically favorable disease.
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http://dx.doi.org/10.1097/SLA.0000000000003143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373491PMC
August 2020
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