Publications by authors named "Jian Lin"

830 Publications

Case Report: Subacute thyroiditis after receiving inactivated SARS-CoV-2 vaccine (BBIBP-CorV).

Front Med (Lausanne) 2022 22;9:918721. Epub 2022 Jul 22.

Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.

Background: Subacute thyroiditis, an inflammatory disease, has been reported caused by vaccines in rare cases. In the context of the coronavirus disease 19 pandemic, various SARS-CoV-2 vaccines have been developed and may be potential triggers for subacute thyroiditis.

Case Presentation: We report a case of subacute thyroiditis 3 days after receiving the second dose of inactivated SARS-CoV-2 vaccine (BBIBP-CorV). The patient did not report a previous history of thyroid disease, upper respiratory tract infection, or COVID-19. Physical examination, laboratory testing, ultrasonography, and radioactive iodine uptake were consistent with subacute thyroiditis. During follow-up, the patient recovered from symptoms and signs, and imaging changes except for hypothyroidism, requiring an ongoing thyroxine replacement.

Conclusions: Inactivated SARS-CoV-2 vaccine may be a causal trigger leading to subacute thyroiditis. Clinicians should be aware of subacute thyroiditis as a possible thyroid-related side effect of an inactivated SARS-CoV-2 vaccine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmed.2022.918721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355607PMC
July 2022

ETS-1 facilitates Th1 cell-mediated mucosal inflammation in inflammatory bowel diseases through upregulating CIRBP.

J Autoimmun 2022 Aug 1;132:102872. Epub 2022 Aug 1.

Center for Inflammatory Bowel Disease Research and Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China; Division of Immunology, School of Basic Medical Sciences; Department of Gastroenterology, The First Affiliated Hospital and Clinical Medicine College, Henan University of Science and Technology, Luoyang, 471003, China; Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, 450014, China. Electronic address:

Background & Aims: As a susceptibility gene for human inflammatory bowel diseases (IBD), how avian erythroblastosis virus E26 oncogene homolog-1 (ETS-1) modulates intestinal mucosal immune response remains unclear. Here we studied the potential roles of ETS-1 in the pathogenesis of IBD.

Methods: ETS-1 expression was examined in IBD patients. CD45RBCD4 T cell-transfer colitis, dextran sulfate sodium (DSS)-induced colitis, and azomethane (AOM)/DSS-induced colitis-associated cancer (CAC) models were constructed to probe the function of ETS-1 in vivo. RNA-sequencing of CD4 T cells from Ets-1 transgenic (Tg) mice was performed to decipher the key differentially expressed genes. Adenovirus transduction was conducted to verify the therapeutic potentials of ETS-1 in vivo.

Results: ETS-1 expression was significantly increased in CD4 T cells from active IBD patients compared with healthy controls, which was upregulated by TNF-α but markedly suppressed by anti-TNF-α mAb therapy. More severe colitis was observed in Rag1 mice reconstituted with Ets-1CD45RBCD4 T cells or in Ets-1 Tg mice after DSS exposure compared with controls, characterized by higher TNF-α and IFN-γ expression in inflamed colon. Ets-1 Tg mice were more prone to develop AOM/DSS-induced CAC, and bone marrow chimeras further proved that lamina propria immune cells but not intestinal epithelial cells contributed to the development of colitis. RNA-sequencing and luciferase analysis revealed cold-inducible RNA-binding protein (CIRBP) as a functional target of ETS-1 to promote Th1 cell-driven immune response. Consistently, intraperitoneal administration of adenovirus-m-cirbp-shRNA ameliorated trinitrobenzene sulfonic acid (TNBS)-induced colitis of Ets-1 Tg mice.

Conclusions: Our data identify that ETS-1 is highly expressed in IBD patients and promotes Th1-driven mucosal inflammation through CIRBP. CIRBP may serve as a novel therapeutic target for treatment of human IBD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaut.2022.102872DOI Listing
August 2022

Enhancing photosensitivity the assembly of a uranyl coordination polymer.

Chem Commun (Camb) 2022 Jul 29. Epub 2022 Jul 29.

School of Nuclear Science and Technology, Xi'an Jiaotong University, No. 28, West Xianning Road, Xi'an, 710049, P. R. China.

Synergistic assembly of uranyl centres and luminescent 2,6-bis(pyrazol-1-yl)pyridine-4-carboxylates (bppCOOH) gives rise to a uranyl coordination polymer, namely U-bppCOO, which exhibits a luminescence quenching response toward UV or X-ray irradiation doses. Notably, the photosensitivity of U-bppCOO has been significantly enhanced metal-ligand assembly compared with that of the naked bppCOOH ligand.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d2cc02985eDOI Listing
July 2022

Enhanced assessment of human dynamic stability by eliminating the effect of body height: modeling and experiment study.

Comput Methods Biomech Biomed Engin 2022 Jul 28:1-11. Epub 2022 Jul 28.

Department of Biomedical Engineering, Key Laboratory of Biomedical Engineering of MOE, Zhejiang University, Hangzhou, China.

Margin of stability (MOS) is one of the essential indices for evaluating dynamic stability. However, there are indications that MOS was affected by body height and its application in identifying factors on dynamic stability other than body height is restricted. An inverted pendulum model was used to simulate human walking and investigate the relevance between MOS and body height. Eventually, a height-independent index in dynamic stability assessment (named as Angled Margin of Stability, AMOS) was proposed. For testing, fifteen healthy young volunteers performed walking trials with normal arm swing, holding arms, and anti-normal arm swing. Kinematic parameters were recorded using a gait analysis system with a Microsoft Kinect V2.0 and instrumented walkway. Both simulation and test results show that MOS had a significant correlation with height during walking with normal arm swing, while AMOS had no such significant correlation. Walking with normal arm swing produced significantly larger AMOS than holding arms and anti-normal arm swing. However, no significant difference showed up in MOS between normal arm swing and holding arms. The results suggest that AMOS is not affected by body height and has the potential to identify the variations in dynamic stability caused by physiological factors other than body height.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10255842.2022.2104606DOI Listing
July 2022

Multimodule characterization of immune subgroups in intrahepatic cholangiocarcinoma reveals distinct therapeutic vulnerabilities.

J Immunother Cancer 2022 Jul;10(7)

Jinshan Hospital Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China

Background: Immune microenvironment is well recognized as a critical regulator across cancer types, despite its complex roles in different disease conditions. Intrahepatic cholangiocarcinoma (iCCA) is characterized by a tumor-reactive milieu, emphasizing a deep insight into its immunogenomic profile to provide prognostic and therapeutic implications.

Methods: We performed genomic, transcriptomic, and proteomic characterization of 255 paired iCCA and adjacent liver tissues. We validated our findings through H&E staining (n=177), multiplex immunostaining (n=188), single-cell RNA sequencing (scRNA-seq) (n=10), functional studies, and transposon-based mouse models.

Results: Integrated multimodule data identified three immune subgroups with distinct clinical, genetic, and molecular features, designated as IG1 (immune-suppressive, 25.1%), IG2 (immune-exclusion, 42.7%), and IG3 (immune-activated, 32.2%). IG1 was characterized by excessive infiltration of neutrophils and immature dendritic cells (DCs). The hallmark of IG2 was the relatively higher tumor-proliferative activity and tumor purity. IG3 exhibited an enrichment of adaptive immune cells, natural killer cells, and activated DCs. These immune subgroups were significantly associated with prognosis and validated in two independent cohorts. Tumors with mutations were enriched in IG1 and associated with myeloid inflammation-dominated immunosuppression. Although tumor mutation burden was relatively higher in IG2, loss of heterozygosity in human leucocyte antigen and defects in antigen presentation undermined the recognition of neoantigens, contributing to immune-exclusion behavior. Pathological analysis confirmed that tumor-infiltrating lymphocytes and tertiary lymphoid structures were both predominant in IG3. Hepatitis B virus (HBV)-related samples tended to be under-represented in IG1, and scRNA-seq analyses implied that HBV infection indeed alleviated myeloid inflammation and reinvigorated antitumor immunity.

Conclusions: Our study elucidates that the immunogenomic traits of iCCA are intrinsically heterogeneous among patients, posing great challenge and opportunity for the application of personalized immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jitc-2022-004892DOI Listing
July 2022

Impact of sarcopenia on outcomes of patients undergoing liver resection for hepatocellular carcinoma.

J Cachexia Sarcopenia Muscle 2022 Jul 19. Epub 2022 Jul 19.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Background: Previous studies have indicated that sarcopenia is associated with poor post-operative outcomes in liver cancer patients, but the studies are limited by confounding from mixed diseases, retrospective data, and non-standardized measurement methods. At present, there is no research with both muscle mass and strength as predictors for hepatocellular carcinoma (HCC) outcomes. We studied the impact of sarcopenia on post-operative outcomes in HCC patients in a cohort study designed according to the European Working Group on Sarcopenia in Older People standards.

Methods: A total of 781 consecutive patients admitted to our centre were registered from May 2020 to August 2021. All participants submitted questionnaires and underwent handgrip strength, chair stand test, physical performance, and computed tomographic evaluation. Then, they were divided into three groups according to muscle mass and strength: Group A (reduced muscle mass and strength), Group B (reduced muscle strength or reduced muscle mass), and Group C (normal muscle mass and strength). The baseline data and post-operative outcomes were compared and analysed. The primary outcome variable in this study was the presence of a major post-operative complication, and the secondary outcome was the 90-day re-admission rate.

Results: A total of 155 patients [median age, 60.00 (IQR, 51.00-66.00) years; 20 females (12.90%)] were included after strict exclusion. The mean (SD) BMI was 23.37 ± 0.23 kg/m . The mean (SD) SMI of all participants was 47.05 ± 0.79 cm /m , and the mean (SD) handgrip strength was 32.84 ± 0.69 kg. Among them, 77 (49.68%) patients underwent laparoscopic hepatectomy, and 73 (47.10%) patients received major hepatectomy. Regarding the post-operative results, Group A had a higher rate of major complications [40.91% (9 of 22) vs. 11.94% (8 of 67) in Group B and 6.06 (4 of 66) in Group C; P = 0.001], higher rate of blood transfusion (77.27% vs. 46.27% in Group B and 42.42% in Group C; P = 0.015), higher hospitalization expenses (P = 0.001), and longer hospital stay (P < 0.001). There was no difference in 90-day re-admission rates among the three groups. Sarcopenia (hazard ratio, 10.735; 95% CI, 2.547-45.244; P = 0.001) and open surgery (hazard ratio, 4.528; 95% CI, 1.425-14.387; P = 0.010) were independent risk factors associated with major complications.

Conclusions: Sarcopenia is associated with adverse outcomes after liver resection for HCC. It should be evaluated upon admission to classify high-risk patients and reduce the risk of major complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcsm.13040DOI Listing
July 2022

Geospatial immune heterogeneity reflects the diverse tumor-immune interactions in intrahepatic cholangiocarcinoma.

Cancer Discov 2022 Jul 19. Epub 2022 Jul 19.

Liver Cancer Institute, Zhong Shan Hospital and Shanghai Medical School, Fudan University,, Shanghai, China.

Intrahepatic cholangiocarcinoma (iCCA) exhibits extensive intratumoral heterogeneity and extremely high mortality rate. Here, we performed WES, RNA-seq, TCR-seq and multiplexed immunofluorescence on 207 tumor regions from 45 iCCA patients. Over half of iCCA displayed intratumoral heterogeneity of immune infiltration, and iCCA were classified into sparsely, heterogeneously, and highly infiltrated subgroups with distinct immunogenomic characteristics. Sparsely infiltrated tumors displayed active copy number loss of clonal neoantigens and heterogeneous immune infiltration played an important role in the subclonal evolution across tumor subregions. Highly infiltrated tumors were characterized by extensive immune activation and similar TCR repertoire across tumor subregions, but counteracted with T cell exhaustion and pervasive antigen presentation defects. Notably, FGFR2 mutations and fusions correlated with low mutation burden and reduced immune infiltration. Our work sculpted the dynamic tumor-immune interactions and developed a robust classification system to divide iCCA patients into high and low immune evasion groups with different prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/2159-8290.CD-21-1640DOI Listing
July 2022

YY1 accelerates oral squamous cell carcinoma progression through long non-coding RNA Kcnq1ot1/microRNA-506-3p/SYPL1 axis.

J Ovarian Res 2022 Jul 1;15(1):77. Epub 2022 Jul 1.

Center for Drug Research and Development, Guangzhou Key Laboratory of Construction and Application of New Drug Screening Model Systems, Key Laboratory of New Drug Discovery and Evaluation of Ordinary Universities of Guangdong Province, Guangdong Pharmaceutical University, No. 280, Waihuan East Road, Guangzhou, 510006, Guangdong, China.

Objective: Ying Yang1 (YY1) has already been discussed in oral squamous cell carcinoma (OSCC), but the knowledge about its mediation on long non-coding RNA KCNQ1 overlapping transcript 1/microRNA-506-3p/synaptophysin like 1 (Kcnq1ot/miR-506-3p/SYPL1) axis in OSCC is still in its infancy. Hence, this article aims to explain the mechanism of YY1/Kcnq1ot1/miR-506-3p/SYPL1 axis in OSCC development.

Methods: YY1, Kcnq1ot1, miR-506-3p and SYPL1 expression levels were determined in OSCC tissues. The potential relation among YY1, Kcnq1ot1, miR-506-3p and SYPL1 was explored. Cell progression was observed to figure out the actions of depleted YY1, Kcnq1ot1 and SYPL1 and restored miR-506-3p in OSCC. OSCC tumorigenic ability in mice was examined.

Results: Elevated YY1, Kcnq1ot1 and SYPL1 and reduced miR-506-3p were manifested in OSCC. YY1 promoted Kcnq1ot1 transcription and up-regulated Kcnq1ot1 expression, thereby promoting OSCC cell procession. Silencing Kcnq1ot1 or elevating miR-506-3p delayed OSCC cell progression and silencing Kcnq1ot1 impeded tumorigenic ability of OSCC cells in mice. YY1-mediated Kcnq1ot1 sponged miR-506-3p to target SYPL1.

Conclusion: YY1 promotes OSCC cell progression via up-regulating Kcnq1ot1 to sponge miR-506-3p to elevate SYPL1, guiding a novel way to treat OSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13048-022-01000-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250217PMC
July 2022

C. elegans monitor energy status via the AMPK pathway to trigger innate immune responses against bacterial pathogens.

Commun Biol 2022 Jun 30;5(1):643. Epub 2022 Jun 30.

State Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, National Engineering Research Center of Microbial Pesticides, Huazhong Agricultural University, Wuhan, 430070, China.

Pathogen recognition and the triggering of host innate immune system are critical to understanding pathogen-host interaction. Cellular surveillance systems have been identified as an important strategy for the identification of microbial infection. In the present study, using Bacillus thuringiensis-Caenorhabditis elegans as a model, we found an approach for surveillance systems to sense pathogens. We report that Bacillus thuringiensis Cry5Ba, a typical pore-forming toxin, caused mitochondrial damage and energy imbalance by triggering potassium ion leakage, instead of directly targeting mitochondria. Interestingly, we find C. elegans can monitor intracellular energy status to trigger innate immune responses via AMP-activated protein kinase (AMPK), secreting multiple effectors to defend against pathogenic attacks. Our study indicates that the imbalance of energy status is a prevalent side effect of pathogen infection. Furthermore, the AMPK-dependent surveillance system may serve as a practicable strategy for the host to recognize and defense against pathogens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s42003-022-03589-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9246835PMC
June 2022

Transient MPTP exposure at a sensitive developmental window altered gut microbiome and led to male-biased motor and social behavioral deficits in adult zebrafish.

Neurotoxicology 2022 07 27;91:360-368. Epub 2022 Jun 27.

School of Public Health and Management, Wenzhou Medical University, Wenzhou 325035, PR China; The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou 325035, PR China. Electronic address:

Zebrafish is an economical alternative model for developmental neurotoxicity (DNT) testing. DNT studies in zebrafish have been focused on acute effects; few studies explore enduring neurotoxicity in adults. More recently, gut microbiome has emerged as an important modulator between chemical exposure and neurotoxicity, rendering its necessity to be included in DNT testing. The present study used a well-known dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as a model chemical to explore long-lasting neurotoxicity in adults after transient exposure during early development. We demonstrated that transient MPTP exposure at 1 μM during a sensitive developmental window of 48-96 h post-fertilization (hpf) altered gut microbiome and led to male-biased locomotion and behavioral deficits in adult fish. The locomotion deficit was manifested as hypoactivity observed in adult males under light conditions or specifically the reduction of fast swim bouts. The social behavioral deficits were characterized by the reduced number of times fish crossed the mirror zone in the mirror response assay and the reduced percent time fish spent at the area proximal to conspecific fish shoal in the social preference test. Gut microbiome analysis revealed that transient MPTP exposure during early development might render fish more susceptible to the colonization of the pathogenic Vibrio. In conclusion, our study revealed that transient MPTP exposure during early development could lead to long-lasting neurotoxicity in adult fish and cause altered gut microbiome composition in both larval and adult fish.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuro.2022.06.008DOI Listing
July 2022

Evaluation of the MeltPro Myco Assay for the Identification of Non-Tuberculous Mycobacteria.

Infect Drug Resist 2022 22;15:3287-3293. Epub 2022 Jun 22.

Institute of Tuberculosis Control and Prevention, Fujian Center for Disease Control and Prevention, Fuzhou, People's Republic of China.

Purpose: The purpose of this study was to evaluate a new commercial kit for species identification and compare its results with that of the commonly used GenoType Mycobacterium CM assay. In addition, we were committed to identifying the main frequent species of nontuberculous mycobacteria (NTM) in Fujian.

Methods: A total of 261 clinical strains, collected at the Center for Disease Control and Prevention of Fujian Province, China, were preliminarily identified as NTM based on p-nitrobenzoic acid (PNB) growth test. The genomic DNA of all 261 strains was extracted and subjected to species identification using MeltPro Myco assay and GenoType Mycobacterium CM assay. The results of the latter were used as a control to calculate the positive agreement, negative agreement, agreement and the total agreement of the former. For samples with inconsistent detection results, sequencing was performed for verification.

Results: Compared to GenoType Mycobacterium CM assay, the total agreement of MeltPro Myco assay was 96.55% (252/261 strains). Both the positive and negative agreement of MeltPro Myco assay in identifying , and mixed infections were higher than 99.00%, but the positive agreement of was relatively low at only 33.33%. In Fujian, the predominant strain of NTM was (64.36%, 130/202 strains), followed by (19.31%, 39/202 strains), (4.46%, 9/202 strains), and (3.96%, 8/202 strains).

Conclusion: The reliability of MeltPro Myco assay for identifying mycobacterium species was strongly demonstrated in this study, which greatly supports its usage for the clinical identification of mycobacteria. The present study also showed that the distribution of mycobacteria in Fujian, China, was significantly different from that in other regions and provided important data for future epidemiological study of NTM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/IDR.S369160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234190PMC
June 2022

Zirconium-oxo Nodes of MOFs with Tunable Electronic Properties Provide Effective ⋅OH Species for Enhanced Methane Hydroxylation.

Angew Chem Int Ed Engl 2022 Jun 29:e202205077. Epub 2022 Jun 29.

CAS Key Laboratory of Science and Technology on Applied Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian, 116023, China.

Direct conversion of methane to high value-added oxygenates under mild conditions has attracted extensive interest. However, the over-oxidation of target products is usually unavoidable due to the easily excessive activation of C-H bond on the sites of supported metal species. Here, we identified the most efficient Zr-oxo nodes of UiO-66 metal-organic frameworks (MOFs) catalysts for the selective oxidation of methane with H O . These nodes were modified by three types of benzene 1, 4-dicarboxylates (NH -BDC, H BDC, and NO -BDC). Detailed characterizations and DFT calculations revealed that these ligands can effectively tune the electronic properties of Zr-oxo nodes and the H BDC ligand led to optimal electronic density of Zr-oxo nodes in UiO-66. Thus the UiO-66-H catalyst promoted the formation of ⋅OH species that adsorbed on Zr-oxo nodes, and facilitated the activation of methane with a lower energy barrier and subsequent conversion to hydroxylation oxygenates with 100 % selectivity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.202205077DOI Listing
June 2022

Characterization of Developmental Neurobehavioral Toxicity in a Zebrafish MPTP-Induced Model: A Novel Mechanism Involving Anemia.

ACS Chem Neurosci 2022 07 27;13(13):1877-1890. Epub 2022 Jun 27.

School of Public Health and Preventive Medicine, Wenzhou Medical University, Wenzhou 325035, China.

Zebrafish represent an economical alternative to rodents for developmental neurotoxicity (DNT) testing. Mechanistic understanding is the key to successfully translating zebrafish findings to humans. In the present study, we used a well-known dopaminergic (DA) neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as a model chemical to uncover the molecular pathways for observed DNT effects. To enhance the specificity of potential molecular targets, we restricted our exposure to a concentration that is nonteratogenic yet exhibits high DNT effects and an exposure window sensitive to MPTP. Our DNT assessment based on a battery of motor and social behavioral tests revealed an effective concentration of 1 μM and a sensitive window of 48-96 h postfertilization (hpf) for MPTP-induced hypoactivity. It is worth noting that this hypoactivity persisted into later larval development until 28 dpf. We observed increased cell apoptosis, oxidative stress, and decreased ATP levels in larvae immediately after exposure at 96 hpf. Significant reductions of DA neurons were found in the retina at 72, 96, and 120 hpf. No visible deformity was found in motoneurons at 72, 96, and 120 hpf. Transcriptome analysis uncovered a novel pathway manifested by significant upregulation of genes enriched with erythropoiesis. Sensitive window exposure of MPTP and other DA neurotoxins rotenone and paraquat exhibited a concentration-dependent effect on transcriptional changes of embryonic hemoglobins and anemia. Given that anemia is a significant risk factor for Parkinson's disease and MPTP is known to cause parkinsonism in humans, we concluded that anemia resulting from dysregulation of primitive erythropoiesis during embryonic development might serve as a common mechanism underlying DA neurotoxin-induced DNT effects between zebrafish and humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acschemneuro.2c00089DOI Listing
July 2022

Investigation of CYP3A induction by PF-05251749 in early clinical development: comparison of linear slope physiologically based pharmacokinetic prediction and biomarker response.

Clin Transl Sci 2022 Jun 21. Epub 2022 Jun 21.

Clinical Pharmacology, Early Clinical Development, Worldwide Research, Development and Medical, Pfizer Inc., Cambridge, Massachusetts, USA.

PF-05251749 is a dual inhibitor of casein kinase 1 δ/ε under clinical development to treat disruption of circadian rhythm in Alzheimer's and Parkinson's diseases. In vitro, PF-05251749 (0.3-100 μM) induced CYP3A in cryopreserved human hepatocytes, demonstrating non-saturable, dose-dependent CYP3A mRNA increases, with induction slopes in the range 0.036-0.39 μM . In a multiple-dose study (B8001002) in healthy participants, CYP3A activity was explored by measuring changes in 4β-hydroxycholesterol/cholesterol ratio. Following repeated oral administration of PF-05251749, up to 400 mg q.d., no significant changes were observed in 4β-hydroxycholesterol/cholesterol ratio; this ratio increased significantly (~1.5-fold) following administration of PF-05251749 at 750 mg q.d., suggesting potential CYP3A induction at this dose. Physiologically based pharmacokinetic (PBPK) models were developed to characterize the observed clinical pharmacokinetics (PK) of PF-05251749 at 400 and 750 mg q.d.; the PBPK induction model was calibrated using the in vitro linear fit induction slope, with rifampin as reference compound (Ind  = 8, EC  = 0.32 μM). Clinical trial simulation following co-administration of PF-05251749, 400 mg q.d. with oral midazolam 2 mg, predicted no significant drug interaction risk. PBPK model predicted weak drug interaction following co-administration of PF-05251749, 750 mg q.d. with midazolam 2 mg. In conclusion, good agreement was obtained between CYP3A drug interaction risk predicted using linear-slope PBPK model and exploratory biomarker trends. This agreement between two orthogonal approaches enabled assessment of drug interaction risks of PF-05251749 in early clinical development, in the absence of a clinical drug-drug interaction study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cts.13352DOI Listing
June 2022

Use of the O-Z Flap to Repair Scalp Defects After Cancer Tumor Resection.

J Craniofac Surg 2022 May 26;33(3):892-894. Epub 2021 Oct 26.

Ningbo City First Hospital, Ningbo, China.

Background: Large benign and malignant tumors in the scalp cannot be sutured directly after resection. Instead, skin grafting or skin flap repair is the most commonly used techniques. Local tissue depression and lack of hair growth are some of the drawbacks associated with these techniques. The use of a modified local flap (the O-Z flap) may effectively overcome these issues.

Objective: To explore the application of O-Z flap in wound repair after excision of benign and malignant tumors of the scalp.

Methods: Between April 2016 and November 2017, the authors treated 6 patients with scalp tumors. They underwent round or oval radical tumor resection with negative margins. Tumor specimens were diagnosed by cryosection during operation. According to the wound defect size and location, surrounding scalp looseness, and hair distribution, 2 rotating flaps in opposite directions were formed on the left and right sides or front and back of the wound. Subsequently, the skin flaps were rotated in opposite directions to repair the wound.

Results: The scalp tumors comprised 2 cases of basal cell carcinoma, 2 cases of squamous cell carcinoma, 1 case of hair sheath carcinoma, and 1 case of epidermoid cyst. After complete tumor resection, the wound defect area was between 3.0 cm × 3.5 cm and 5.0 cm × 6.0 cm. After operation, approximately 6% of the tip of the skin flap was necrotized. The wounds healed after 4 weeks of dressing treatment. All skin flaps survived in stage I and no complications occurred. All patients were followed up for 3 to 12 months; the scalps were in good condition and no tumor recurrence was found.

Conclusions: The use of the O-Z flap to repair scalp wounds offers flexible design, good blood circulation, uniform tension, and good hair growth after operation; thus, this technique is suitable for wound repair following scalp tumor resection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SCS.0000000000008300DOI Listing
May 2022

The Ion Channel-Related Gene Signatures Correlated With Diagnosis, Prognosis, and Individualized Treatment in Patients With Clear Cell Renal Cell Carcinoma.

Front Pharmacol 2022 1;13:889142. Epub 2022 Jun 1.

National Urological Cancer Center, Department of Urology, Institute of Urology, Clinical Research Cooperation Network of Urology of the Peking University First Hospital, The Peking University First Hospital, Peking University, Beijing and the Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.

Early detection and precise prognostic evaluation of clear cell renal cell carcinoma (ccRCC) are crucial for patient life expectancy. Ion channel-related genes (ICRGs) are of great diagnostic and prognostic value as components that maintain the normal structure of the kidney. Therefore, we systematically explored the diagnostic, prognostic, and therapeutic value of ICRGs in ccRCC using the multi-database. RNA transcriptome profiles and clinical data of ccRCC patients were extracted and integrated from public databases including The Cancer Genome Atlas, ICGC, GEO, and E-MTAB databases. Ion channel-related genes were obtained from the literature collection. The diagnostic signature was performed using the LASSO and SVM-REF analyses. Meanwhile, the prognostic signature was conducted using the LASSO analyses. Molecular subtyping was performed using the ConsensusClusterPlus and the corresponding therapeutic targets were evaluated using the pRRophetic package. In addition, a prognostic nomogram was constructed based on the results of cox regression analyses. We successfully constructed diagnostic signatures for five ICRGs and prognostic signatures for 10 ICRGs with AUC values greater than 0.7, showing good predictive performance. Based on the median risk score, we found that high-risk patients had a significantly worse prognosis. We also divided ccRCC patients into two clusters according to prognostic ICRGs, and there was a significant survival outcome between the two clusters and different sensitivity to diverse clinical therapeutic strategies. Meanwhile, we constructed a nomogram based on clinical molecules and signatures, and its predictive efficacy was better than the signature or the present tumor-node-metastasis staging system. In this study, we established useful signatures for early detection, prognosis evaluation, and individualized treatment for ccRCC. Moreover, KCNJ16 deserves to be explored comprehensively in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2022.889142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9198310PMC
June 2022

Single-Cell Transcriptomics Uncover Key Regulators of Skin Regeneration in Human Long-Term Mechanical Stretch-Mediated Expansion Therapy.

Front Cell Dev Biol 2022 30;10:865983. Epub 2022 May 30.

Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Tissue expansion is a commonly performed therapy to grow extra skin for reconstruction. While mechanical stretch-induced epidermal changes have been extensively studied in rodents and cell culture, little is known about the mechanobiology of the human epidermis . Here, we employed single-cell RNA sequencing to interrogate the changes in the human epidermis during long-term tissue expansion therapy in clinical settings. We also verified the main findings at the protein level by immunofluorescence analysis of independent clinical samples. Our data show that the expanding human skin epidermis maintained a cellular composition and lineage trajectory that are similar to its non-expanding neighbor, suggesting the cellular heterogeneity of long-term expanded samples differs from the early response to the expansion. Also, a decrease in proliferative cells due to the decayed regenerative competency was detected. On the other hand, profound transcriptional changes are detected for epidermal stem cells in the expanding skin versus their non-expanding peers. These include significantly enriched signatures of C-FOS, EMT, and mTOR pathways and upregulation of AREG and SERPINB2 genes. CellChat associated ligand-receptor pairs and signaling pathways were revealed. Together, our data present a single-cell atlas of human epidermal changes in long-term tissue expansion therapy, suggesting that transcriptional change in epidermal stem cells is the major mechanism underlying long-term human skin expansion therapy. We also identified novel therapeutic targets to promote human skin expansion efficiency in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2022.865983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9195629PMC
May 2022

The Pharmacokinetics, Metabolism, and Clearance Mechanisms of Abrocitinib, a Selective Janus Kinase Inhibitor, in Humans.

Drug Metab Dispos 2022 Aug 14;50(8):1106-1118. Epub 2022 Jun 14.

Medicine Design (M.E.D), Inflammation and Immunology (T.H.L., J.-B.T.), and Clinical Pharmacology (C.B.), Pfizer Inc., Cambridge, Massachusetts; Medicine Design (J.N.B., A.C.D., A.K.-A., R.S., G.S.W., J.L., T.C.G.) and Clinical Pharmacology (S.T.), Pfizer Inc., Groton, Connecticut; and Clinical Pharmacology, Pfizer Inc., New York, New York (B.K.M.)

Abrocitinib is an oral once-daily Janus kinase 1 selective inhibitor being developed for the treatment of moderate-to-severe atopic dermatitis. This study examined the disposition of abrocitinib in male participants following oral and intravenous administration using accelerator mass spectroscopy methodology to estimate pharmacokinetic parameters and characterize metabolite (M) profiles. The results indicated abrocitinib had a systemic clearance of 64.2 L/h, a steady-state volume of distribution of 100 L, extent of absorption >90%, time to maximum plasma concentration of ∼0.5 hours, and absolute oral bioavailability of 60%. The half-life of both abrocitinib and total radioactivity was similar, with no indication of metabolite accumulation. Abrocitinib was the main circulating drug species in plasma (∼26%), with 3 major monohydroxylated metabolites (M1, M2, and M4) at >10%. Oxidative metabolism was the primary route of elimination for abrocitinib, with the greatest disposition of radioactivity shown in the urine (∼85%). In vitro phenotyping indicated abrocitinib cytochrome P450 fraction of metabolism assignments of 0.53 for CYP2C19, 0.30 for CYP2C9, 0.11 for CYP3A4, and ∼0.06 for CYP2B6. The principal systemic metabolites M1, M2, and M4 were primarily cleared renally. Abrocitinib, M1, and M2 showed pharmacology with similar Janus kinase 1 selectivity, whereas M4 was inactive. SIGNIFICANCE STATEMENT: This study provides a detailed understanding of the disposition and metabolism of abrocitinib, a Janus kinase inhibitor for atopic dermatitis, in humans, as well as characterization of clearance pathways and pharmacokinetics of abrocitinib and its metabolites.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1124/dmd.122.000829DOI Listing
August 2022

Dichotomous roles of neutrophils in modulating pathogenic and repair processes of inflammatory bowel diseases.

Precis Clin Med 2021 Dec 15;4(4):246-257. Epub 2021 Nov 15.

Center for Inflammatory Bowel Disease Research, the Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.

Neutrophils are considered as complex innate immune cells and play a critical role in maintaining intestinal mucosal homeostasis. They exert robust pro-inflammatory effects and recruit other immune cells in the acute phase of pathogen infection and intestinal inflammation, but paradoxically, they also limit exogenous microbial invasion and facilitate mucosal restoration. Hyperactivation or dysfunction of neutrophils results in abnormal immune responses, leading to multiple autoimmune and inflammatory diseases including systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel diseases (IBD). As a refractory intestinal inflammatory disease, the pathogenesis and progression of IBD are associated with complicated immune response processes in which neutrophils are profoundly involved. However, the consensus on potential roles of neutrophils in modulating pathogenic and repair processes of IBD remains not fully understood. Accumulated infiltrating neutrophils cross the epithelial barrier and contribute to microbial dysbiosis, aggravated intestinal architectural damage, compromised resolution of intestinal inflammation and increased risk of thrombosis during IBD. Paradoxically, activated neutrophils are also associated with effective elimination of invaded microbiota, promoted angiogenesis and tissue restoration of gut mucosa in IBD. Here, we discuss the beneficial and detrimental roles of neutrophils in the onset and resolution of intestinal mucosal inflammation, hoping to provide a precise overview of neutrophil functions in the pathogenesis of IBD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/pcmedi/pbab025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8982532PMC
December 2021

LDL receptor-related protein 1 (LRP1), a novel target for opening the blood-labyrinth barrier (BLB).

Signal Transduct Target Ther 2022 06 10;7(1):175. Epub 2022 Jun 10.

College of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Beijing, China.

Inner ear disorders are a cluster of diseases that cause hearing loss in more than 1.5 billion people worldwide. However, the presence of the blood-labyrinth barrier (BLB) on the surface of the inner ear capillaries greatly hinders the effectiveness of systemic drugs for prevention and intervention due to the low permeability, which restricts the entry of most drug compounds from the bloodstream into the inner ear tissue. Here, we report the finding of a novel receptor, low-density lipoprotein receptor-related protein 1 (LRP1), that is expressed on the BLB, as a potential target for shuttling therapeutics across this barrier. As a proof-of-concept, we developed an LRP1-binding peptide, IETP2, and covalently conjugated a series of model small-molecule compounds to it, including potential drugs and imaging agents. All compounds were successfully delivered into the inner ear and inner ear lymph, indicating that targeting the receptor LRP1 is a promising strategy to enhance the permeability of the BLB. The discovery of the receptor LRP1 will illuminate developing strategies for crossing the BLB and for improving systemic drug delivery for inner ear disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41392-022-00995-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9184653PMC
June 2022

Brain structural connectivity sub typing in unilateral temporal lobe epilepsy.

Brain Imaging Behav 2022 Jun 8. Epub 2022 Jun 8.

Department of Neurology, General Hospital of Southern Theater Command, No. 111 of Liuhua Road, Yuexiu District, Guangzhou, 510010, China.

To categorize and clinically characterize subtypes of brain structural connectivity patterns in unilateral temporal lobe epilepsy (TLE). Voxel based morphometry (VBM) and surfaced based morphometry (SBM) analysis were used to detect brain structural alterations associated with TLE from MRI data. Principal component analysis (PCA) was performed to identify subtypes of brain structural connectivity patterns. Correlation analysis was used to explore associations between PC scores and clinical characteristics. A total of 59 patients with TLE and 100 healthy adults were included in this study. Widespread cortical atrophy was shown in both left and right TLE (P < 0.05, FWE corrected). Six principal components (PCs) that explained more than 70% of the variance were extracted for left and right TLE, reflecting patterns of brain structural connectivity. PCs representing perisylvian connectivity were positively correlated with verbal IQ (left TLE: r = 0.696, P < 0.001; right TLE: r = 0.484, P = 0.012) and total IQ (left TLE r = 0.608, P < 0.001) and negatively correlated with disease duration (r = -0.448, P = 0.009). In left TLE, the PC in the ipsilateral mesial temporal region was negatively correlated with age at onset (r = -0.382, P = 0.028). In right TLE, the PC representing the default mode network was negatively correlated with number of antiepileptic drugs (r = -0.407, P = 0.039). This study categorized subtypes of unilateral TLE based on brain structural connectivity patterns. Findings may provide insight into seizure pathways, the pathophysiology of epilepsy, including comorbidities such as cognitive impairment, and help predict treatment outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11682-022-00691-0DOI Listing
June 2022

Risk Factors for Tigecycline-Associated Hepatotoxicity in Patients in the Intensive Care Units of 2 Tertiary Hospitals: A Retrospective Study.

J Clin Pharmacol 2022 Jun 7. Epub 2022 Jun 7.

Department of Critical Care Medicine, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital South Branch, Fujian Provincial Jinshan Hospital, Fuzhou, Fujian Province, China.

Tigecycline is a broad-spectrum antibacterial agent. As the incidence of multidrug-resistant bacterial infections has increased in intensive care units (ICUs) over the past decades, tigecycline is often used in ICUs. Information about tigecycline-associated hepatotoxicity in ICU patients is limited. To investigate the potential risk factors for tigecycline-associated hepatotoxicity in ICU patients, 148 patients from 2 centers who had received tigecycline for at least 4 days were retrospectively analyzed. Hepatotoxicity was classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (5.0) grading system. As a result, 33.8% of patients experienced hepatotoxicity events in the ICU. The multivariate analysis showed that an albumin concentration <25 g/L at baseline (odds ratio, 3.714; 95%CI, 1.082-12.744; P = .037) and treatment duration (odds ratio, 1.094; 95%CI, 1.032-1.160; P = .003) were significantly correlated with tigecycline-associated hepatotoxicity. The median time to onset of hepatotoxicity was 8.0 days. The median duration ICU stay and the in-hospital mortality rate were not different between the hepatotoxicity group and the nonhepatotoxicity group (33.5 days (interquartile range, 21.0-72.0) vs 31.0 days (interquartile range, 21-62.5), P = .850; 38.0% vs 43.8%; P = .504). Therefore, close monitoring of liver function is recommended for patients with baseline albumin concentrations <25 g/L or for patients who receive tigecycline therapy for >8 days.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcph.2099DOI Listing
June 2022

Characterization of lncRNA Profiles of Plasma-Derived Exosomes From Type 1 Diabetes Mellitus.

Front Endocrinol (Lausanne) 2022 12;13:822221. Epub 2022 May 12.

National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.

Backgrounds: Exosomes contain several types of transcripts, including long non-coding RNAs (lncRNAs), and have been shown to exert important effects in human diseases. However, the roles of exosomal lncRNAs in type 1 diabetes mellitus (T1DM) have not been well investigated. In the present study, we characterized the plasma-derived exosomal lncRNAs expression profiles of T1DM and predict their potential function in the pathogenesis of T1DM.

Material And Methods: Exosomal lncRNA expression profiles were detected by Illumina Hiseq platform (T1DM subjects N=10; age-, sex- matched Control subjects N=10). Six exosomal lncRNAs were selected to validate their expression level by using quantitative real-time PCR (qRT-PCR) (T1DM subjects N=30; age-, sex- matched Control subjects N=30). Bioinformatics analysis approaches were carried out to explore the potential biological function of differentially expressed lncRNAs.

Results: A total of 162 differentially expressed exosomal lncRNAs were identified in T1DM patients compared with control subjects, among which 77 up-regulated and 85 down-regulated. The expression level of the selected six lncRNAs didn't show significant difference in the following qRT-PCR analysis. Gene Ontology analysis enriched terms such as activation of phospholipase D activity, neuronal cell body membrane, and calcium sensitive guanylate cyclase activator activity for cis-acting genes of lncRNAs, and metal ion binding for trans-acting genes. The most enriched Kyoto Encyclopedia of Genes and Genomes pathways for the lncRNAs were associated with oxidative phosphorylation and Parkinson's disease for cis-acting genes, and pathways in cancer as well as focal adhesion for trans-acting genes.

Conclusions: This study characterized the lncRNA profiles of plasma-derived exosomes from T1DM for the first time and these results highlighted the potential role of exosomal lncRNAs in T1DM pathogenesis. A better understanding of exosomal lncRNA profiling will provide novel insights into its molecular mechanisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2022.822221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9135040PMC
May 2022

Immune Responses Induced by Recombinant Expressing the PEDV Spike Protein Targeted at Microfold Cells.

Vet Sci 2022 Apr 25;9(5). Epub 2022 Apr 25.

College of Veterinary Medicine, Nanjing Agricultural University, Weigang 1, Nanjing 210095, China.

(), a probiotic bacterium and feeding additive, is widely used for heterologous antigen expression and protective immunisation. Porcine epidemic diarrhoea virus (PEDV) invades swine via mucosal tissue. To enhance the mucosal immune response to PEDV, we modified to express a PEDV antigen and used it as a mucosal vaccine delivery system. Initially, we constructed a recombinant strain () that expressed the PEDV spike protein and L-Lectin-β-GF, with the goal of inducing mucosal secretory immunoglobulin A (sIgA) and anti-PEDV serum immunoglobulin G (IgG) production, as well as to increase the number of microfold cells (M cells). Following the oral administration of to mice, the small intestinal PEDV-specific sIgA expression levels significantly increased, as well as the increased number of adhered to M cells. Moreover, we found that mice administered exhibited markedly higher percentages of CD4 and CD8 T cells in the mesenteric lymph nodes and spleen compared to the control mice. Furthermore, we found that intestinal mucosa sIgA and serum anti-PEDV IgG levels were higher in mice orally immunised with , suggesting that the mice could be more resistant to PEDV. In this study, we developed a novel oral vaccine to prevent porcine diarrhoea epidemics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/vetsci9050211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9143571PMC
April 2022

The missing heritability in type 1 diabetes.

Diabetes Obes Metab 2022 May 23. Epub 2022 May 23.

National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.

Type 1 diabetes (T1D) is a complex autoimmune disease characterized by an absolute deficiency of insulin. It affects more than 20 million people worldwide and imposes an enormous financial burden on patients. The underlying pathogenic mechanisms of T1D are still obscure, but it is widely accepted that both genetics and the environment play an important role in its onset and development. Previous studies have identified more than 60 susceptible loci associated with T1D, explaining approximately 80%-85% of the heritability. However, most identified variants confer only small increases in risk, which restricts their potential clinical application. In addition, there is still a so-called 'missing heritability' phenomenon. While the gap between known heritability and true heritability in T1D is small compared with that in other complex traits and disorders, further elucidation of T1D genetics has the potential to bring novel insights into its aetiology and provide new therapeutic targets. Many hypotheses have been proposed to explain the missing heritability, including variants remaining to be found (variants with small effect sizes, rare variants and structural variants) and interactions (gene-gene and gene-environment interactions; e.g. epigenetic effects). In the following review, we introduce the possible sources of missing heritability and discuss the existing related knowledge in the context of T1D.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/dom.14777DOI Listing
May 2022

Development of novel-nanobody-based lateral-flow immunochromatographic strip test for rapid detection of recombinant human interferon α2b.

J Pharm Anal 2022 Apr 8;12(2):308-316. Epub 2021 Jul 8.

National Institutes for Food and Drug Control, Beijing, 100050, China.

Recombinant human interferon α2b (rhIFNα2b) is widely used as an antiviral therapy agent for the treatment of hepatitis B and hepatitis C. The current identification test for rhIFNα2b is complex. In this study, an anti-rhIFNα2b nanobody was discovered and used for the development of a rapid lateral flow strip for the identification of rhIFNα2b. RhIFNα2b was used to immunize an alpaca, which established a phage nanobody library. After five steps of enrichment, the nanobody I22, which specifically bound rhIFNα2b, was isolated and inserted into the prokaryotic expression vector pET28a. After subsequent purification, the physicochemical properties of the nanobody were determined. A semiquantitative detection and rapid identification assay of rhIFNα2b was developed using this novel nanobody. To develop a rapid test, the nanobody I22 was coupled with a colloidal gold to produce lateral-flow test strips. The developed rhIFNα2b detection assay had a limit of detection of 1 μg/mL. The isolation of I22 and successful construction of a lateral-flow immunochromatographic test strip demonstrated the feasibility of performing ligand-binding assays on a lateral-flow test strip using recombinant protein products. The principle of this novel assay is generally applicable for the rapid testing of other commercial products, with a great potential for routine use in detecting counterfeit recombinant protein products.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpha.2021.07.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9091920PMC
April 2022

Publisher Correction: Single-cell transcriptomic analysis suggests two molecularly distinct subtypes of intrahepatic cholangiocarcinoma.

Nat Commun 2022 May 17;13(1):2848. Epub 2022 May 17.

Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-022-30599-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114109PMC
May 2022

Isolating Single and Few Atoms for Enhanced Catalysis.

Adv Mater 2022 May 16:e2201796. Epub 2022 May 16.

School of Science, RMIT University, Melbourne, VIC, 3000, Australia.

Atomically dispersed metal catalysts have triggered great interest in the field of catalysis owing to their unique features. The isolated single or few metal atoms can be anchored on substrates via chemical bonding or space confinement to maximize atom utilization efficiency. The key challenge lies in precisely regulating the geometric and electronic structure of active metal centers, thus significantly influencing the catalytic properties. Although several review papers were published on the preparation, characterization, and application of single-atom catalysts (SACs), the comprehensive understanding of SACs, dual-atom catalysts (DACs), and atomic clusters has never been systematically summarized. In this review, recent advances in the engineering of local environments of state-of-the-art SACs, DACs, and atomic clusters for enhanced catalytic performance are highlighted. Firstly, various synthesis approaches for SACs, DACs, and atomic clusters are presented, focusing on how to stabilize single or few atoms on appropriate supports. Then, special attention is focused on the elucidation of local environments in terms of electronic state and coordination structure. Furthermore, a comprehensive summary of isolated single and few atoms for the applications of thermocatalysis, electrocatalysis, and photocatalysis is provided and discussed, with an emphasis on structure-performance relationships. Finally, the potential challenges and future opportunities in this emerging field are offered for guiding the design of isolated metal catalysts for enhanced catalysis. This review will pave the way to regulate the microenvironment of the active site for boosted catalytic processes. This article is protected by copyright. All rights reserved.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adma.202201796DOI Listing
May 2022

rs3806265 and rs4612666 of the Gene Are Associated With the Titer of Glutamic Acid Decarboxylase Antibody in Type 1 Diabetes.

Front Endocrinol (Lausanne) 2022 21;13:835054. Epub 2022 Apr 21.

National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.

Background And Aims: The NLRP3 gene is reportedly associated with several autoimmune diseases. However, in the Chinese Han population, whether NLRP3 polymorphisms are associated with type 1 diabetes (T1D) is unclear. Therefore, this study examined the associations of rs3806265 and rs4612666 of the NLRP3 gene with T1D susceptibility and the clinical characteristics of Chinese Han T1D patients.

Methods: In total, 510 classic T1D patients and 531 healthy controls from the Chinese Han population were recruited for a case-control study. rs3806265 and rs4612666 of the NLRP3 gene were genotyped by MassARRAY. Logistic regression analysis and the chi-square test were used to compare the distributions of the alleles and genotypes of rs3806265 and rs4612666. The relationships between rs3806265 and rs4612666 and the clinical characteristics of T1D patients were analyzed by Kruskal-Wallis one-way ANOVA. Student's t test was used to analyze normally distributed data. Bonferroni correction was used for multiple comparisons.

Results: 1) rs3806265 was associated with glutamic acid decarboxylase antibody (GADA) titers (P = 0.02), and patients with the CC genotype had higher GADA titers than patients with the TT genotype. 2) rs4612666 was also associated with GADA titers (P=0.041). Compared with patients with the CC genotype, patients with the TT genotype had higher GADA titers. 3) rs3806265 and rs4612666 of the NLRP3 gene were not significantly associated with T1D susceptibility under different genetic models.

Conclusion: rs3806265 and rs4612666 of the NLRP3 gene were significantly associated with GADA titers in Chinese Han T1D patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2022.835054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9068986PMC
May 2022

Hydrolytically Stable Zr-Based Metal-Organic Framework as a Highly Sensitive and Selective Luminescent Sensor of Radionuclides.

Inorg Chem 2022 May 5;61(19):7467-7476. Epub 2022 May 5.

School of Nuclear Science and Technology, Xi'an Jiaotong University, No. 28, West Xianning Road, Xi'an 710049, P. R. China.

Effective detections of radionuclides including uranium and its predominant fission products, for example, iodine, are highly desired owing to their radiotoxicity and potential threat to human health. However, traditional analytical techniques of radionuclides are instrument-demanding, and chemosensors targeted for sensitization of radionuclides remain limited. In this regard, we report a sensitive and selective sensor of UO and I based on the unique quenching behavior of a luminescent Zr-based metal-organic framework, ZrO(OH)(OH)(HO)(TCPE)·(HO)(CHNO) (). Immobilization of the luminescent tetrakis(4-carboxyphenyl)ethylene (TCPE) linkers by Zr nodes enhances the photoluminescence quantum yield of , which facilitates the effective sensing of radionuclides in a "turn-off" manner. Moreover, can sensitively and selectively recognize UO and I ions with the lowest limits of detection of 0.67 and 0.87 μg/kg, respectively, of which the former one is much lower than the permissible value (30 μg/L) defined by the U.S. EPA. In addition, features excellent hydrolytic stability and can withstand pH conditions ranging from 3 to 11. To facilitate real-world applications, we have further fabricated polyvinylidene fluoride-integrating as luminescence-based sensor membranes for on-site sensing of UO and I.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.inorgchem.2c00545DOI Listing
May 2022
-->