Publications by authors named "Chuan Li"

685 Publications

Heterozygous Recurrent Mutations Inducing Dysfunction of Gene in Patients With Short Stature.

Front Cell Dev Biol 2021 14;9:661747. Epub 2021 Apr 14.

Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

Purpose: ROR2, a member of the ROR family, is essential for skeletal development as a receptor of Wnt5a. The present study aims to investigate the mutational spectrum of in children with short stature and to identify the underlying molecular mechanisms.

Methods: We retrospectively analyzed clinical phenotype and whole-exome sequencing (WES) data of 426 patients with short stature through mutation screening of . We subsequently examined the changes in protein expression and subcellular location in caused by the mutations. The mRNA expression of downstream signaling molecules of the Wnt5a-ROR2 pathway was also examined.

Results: We identified 12 mutations in in 21 patients, including 10 missense, one nonsense, and one frameshift. Among all missense variants, four recurrent missense variants [c.1675G > A(p.Gly559Ser), c.2212C > T(p.Arg738Cys), c.1930G > A(p.Asp644Asn), c.2117G > A(p.Arg706Gln)] were analyzed by experiments . The c.1675G > A mutation significantly altered the expression and the cellular localization of the ROR2 protein. The c.1675G > A mutation also caused a significantly decreased expression of c-Jun. In contrast, other missense variants did not confer any disruptive effect on the biological functions of ROR2.

Conclusion: We expanded the mutational spectrum of in patients with short stature. Functional experiments potentially revealed a novel molecular mechanism that the c.1675G > A mutation in might affect the expression of downstream Wnt5a-ROR2 pathway gene by disturbing the subcellular localization and expression of the protein.
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http://dx.doi.org/10.3389/fcell.2021.661747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080376PMC
April 2021

Case Report: Repeated Low-Dose Rituximab Treatment Is Effective in Relapsing Neuro Behçet's Disease.

Front Neurol 2021 15;12:595984. Epub 2021 Apr 15.

Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.

Neuro Behçet's disease (NBD) is a rare but most aggressive manifestation of Behçet's disease (BD) with a poor prognosis, and some patients even present a relapsing and treatment-resistant progressive course. In some relapsing NBD cases, traditional corticosteroids and immunosuppressive drugs show limited efficacy, while benefits of biological agents, such as anti-B-lymphocyte CD20 biological agent rituximab (RTX), gradually represent potential therapeutic advantages with clinical rapid remission and long-time maintenance. However, up to now, the optimal dosage of RTX in NBD is still elucidated. Here, we report two patients with relapsing NBD, despite continuous high dose steroids and sufficient azathioprine treatment, still presenting severe and relapsing meningoencephalitis or brainstem involvement. Repeated low-dose RTX (100 mg × 3/1 week apart, 100 mg repeated every 6 months) is then attempted with rapid recovery and sustained remission. The approach in our cases may expand therapeutic options and provide helpful references for relapsing NBD treatment.
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http://dx.doi.org/10.3389/fneur.2021.595984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081882PMC
April 2021

Pharmacokinetics-based identification of pseudoaldosterogenic compounds originating from Glycyrrhiza uralensis roots (Gancao) after dosing LianhuaQingwen capsule.

Acta Pharmacol Sin 2021 Apr 30. Epub 2021 Apr 30.

Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.

LianhuaQingwen capsule, prepared from an herbal combination, is officially recommended as treatment for COVID-19 in China. Of the serial pharmacokinetic investigations we designed to facilitate identifying LianhuaQingwen compounds that are likely to be therapeutically important, the current investigation focused on the component Glycyrrhiza uralensis roots (Gancao). Besides its function in COVID-19 treatment, Gancao is able to induce pseudoaldosteronism by inhibiting renal 11β-HSD2. Systemic and colon-luminal exposure to Gancao compounds were characterized in volunteers receiving LianhuaQingwen and by in vitro metabolism studies. Access of Gancao compounds to 11β-HSD2 was characterized using human/rat, in vitro transport, and plasma protein binding studies, while 11β-HSD2 inhibition was assessed using human kidney microsomes. LianhuaQingwen contained a total of 41 Gancao constituents (0.01-8.56 μmol/day). Although glycyrrhizin (1), licorice saponin G2 (2), and liquiritin/liquiritin apioside (21/22) were the major Gancao constituents in LianhuaQingwen, their poor intestinal absorption and access to colonic microbiota resulted in significant levels of their respective deglycosylated metabolites glycyrrhetic acid (8), 24-hydroxyglycyrrhetic acid (M2; a new Gancao metabolite), and liquiritigenin (27) in human plasma and feces after dosing. These circulating metabolites were glucuronized/sulfated in the liver and then excreted into bile. Hepatic oxidation of 8 also yielded M2. Circulating 8 and M2, having good membrane permeability, could access (via passive tubular reabsorption) and inhibit renal 11β-HSD2. Collectively, 1 and 2 were metabolically activated to the pseudoaldosterogenic compounds 8 and M2. This investigation, together with such investigations of other components, has implications for precisely defining therapeutic benefit of LianhuaQingwen and conditions for its safe use.
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http://dx.doi.org/10.1038/s41401-021-00651-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086230PMC
April 2021

Development of Apremilast Solid Dispersion Using TPGS and PVPVA with Enhanced Solubility and Bioavailability.

AAPS PharmSciTech 2021 Apr 23;22(4):142. Epub 2021 Apr 23.

College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou, 510632, China.

Apremilast (APST) is an effective inhibitor of phosphodieasterase 4 (PDE4) which is the first oral drug for the treatment of adult patients with active psoriatic arthritis. However, Apremilasts low solubility restricts its dissolution and bioavailability. In this study, APST solid dispersion with D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and Poly(1-vinylpyrrolidone-co-vinyl acetate) (PVPVA) was developed to improve the dissolution and bioavailability of APST by spray drying. A series of TPGS were synthesized to elucidate the effect of the ratio of monoester to diester on solubilizing capacity. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier transform infrared spectrophotometry (FT-IR) were used to characterize the solid dispersion, and the results showed that APST was amorphous in solid dispersion. In vitro dissolution study showed that the dissolution rate of solid dispersion in phosphate buffered saline (pH 6.8) was remarkably increased, reaching a release of 90% within 10 min. Moreover, in vivo pharmacokinetics study revealed that the bioavailability of solid dispersion in rats had significant improvement. In particular, its C and AUC were nearly 22- and 12.9-fold greater as compared to APST form B, respectively. In conclusion, APST solid dispersion with TPGS and PVPVA is an alternative drug delivery system to improve the solubility and oral bioavailability of APST.
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http://dx.doi.org/10.1208/s12249-021-02005-xDOI Listing
April 2021

Case Report: Multiple Vertebral Compression Fractures in 14-Year-Old Children With Multiple Myeloma.

Front Oncol 2021 25;11:662169. Epub 2021 Mar 25.

Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.

Multiple myeloma (MM) is a neoplastic disorder characterized by clonal proliferation of malignant plasma cells derived from B cells in bone marrow. Pediatric MM is rare with only approximately 0.3% of cases diagnosed before the age of 30. In this report, we present a 14 years old boy diagnosed as MM with multiple pathologic vertebral fractures. To our knowledge, our patient is the youngest Chinese case in the literature to present with MM. He was treated with bortezomib, dexamethasone, and cyclophosphamide followed by autologous hematopoietic stem cell transplantation with good clinical response. We hope to aid in the understanding of the pathophysiology and management of this condition.
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http://dx.doi.org/10.3389/fonc.2021.662169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044764PMC
March 2021

CT-Guided Microcoil Localization of Small Peripheral Pulmonary Nodules to Direct Video-Assisted Thoracoscopic Resection without the Aid of Intraoperative Fluoroscopy.

Korean J Radiol 2021 Apr 1. Epub 2021 Apr 1.

Department of Radiology, China-Japan Friendship Hospital, Beijing, China.

Objective: To evaluate the feasibility, safety, and effectiveness of CT-guided microcoil localization of solitary pulmonary nodules (SPNs) for guiding video-assisted thoracoscopic surgery (VATS).

Materials And Methods: Between June 2016 and October 2019, 454 consecutive patients with 501 SPNs who received CT-guided microcoil localization before VATS in our institution were enrolled. The diameter of the nodules was 0.93 ± 0.49 cm, and the shortest distance from the nodules to the pleura was 1.41 ± 0.95 cm. The distal end of the microcoil was placed less than 1 cm away from the nodule, and the proximal end was placed outside the visceral pleura. VATS was performed under the guidance of implanted microcoils without the aid of intraoperative fluoroscopy.

Results: All 501 nodules were marked with microcoils. The time required for microcoil localization was 12.8 ± 5.2 minutes. Microcoil localization-related complications occurred in 179 cases (39.4%). None of the complications required treatment. A total of 463 nodules were successfully resected under the guidance of implanted microcoils. VATS revealed 38 patients with dislocated microcoils, of which 28 underwent wedge resection (21 cases under the guidance of the bleeding points of pleural puncture, 7 cases through palpation), 5 underwent direct lobectomy, and the remaining 5 underwent a conversion to thoracotomy. In 4 cases, a portion of the microcoil remained in the lung parenchyma.

Conclusion: CT-guided microcoil localization of SPNs is safe and reliable. Marking the nodule and pleura simultaneously with microcoils can effectively guide the resection of SPNs using VATS without the aid of intraoperative fluoroscopy.
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http://dx.doi.org/10.3348/kjr.2020.0331DOI Listing
April 2021

The AMBRA1 E3 ligase adaptor regulates the stability of cyclin D.

Nature 2021 Apr 14;592(7856):794-798. Epub 2021 Apr 14.

Department of Pediatrics, Stanford University, Stanford, CA, USA.

The initiation of cell division integrates a large number of intra- and extracellular inputs. D-type cyclins (hereafter, cyclin D) couple these inputs to the initiation of DNA replication. Increased levels of cyclin D promote cell division by activating cyclin-dependent kinases 4 and 6 (hereafter, CDK4/6), which in turn phosphorylate and inactivate the retinoblastoma tumour suppressor. Accordingly, increased levels and activity of cyclin D-CDK4/6 complexes are strongly linked to unchecked cell proliferation and cancer. However, the mechanisms that regulate levels of cyclin D are incompletely understood. Here we show that autophagy and beclin 1 regulator 1 (AMBRA1) is the main regulator of the degradation of cyclin D. We identified AMBRA1 in a genome-wide screen to investigate the genetic basis of  the response to CDK4/6 inhibition. Loss of AMBRA1 results in high levels of cyclin D in cells and in mice, which promotes proliferation and decreases sensitivity to CDK4/6 inhibition. Mechanistically, AMBRA1 mediates ubiquitylation and proteasomal degradation of cyclin D as a substrate receptor for the cullin 4 E3 ligase complex. Loss of AMBRA1 enhances the growth of lung adenocarcinoma in a mouse model, and low levels of AMBRA1 correlate with worse survival in patients with lung adenocarcinoma. Thus, AMBRA1 regulates cellular levels of cyclin D, and contributes to cancer development and the response of cancer cells to CDK4/6 inhibitors.
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http://dx.doi.org/10.1038/s41586-021-03474-7DOI Listing
April 2021

Mettl14-Mediated mA Modification Facilitates Liver Regeneration by Maintaining Endoplasmic Reticulum Homeostasis.

Cell Mol Gastroenterol Hepatol 2021 Apr 10. Epub 2021 Apr 10.

Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, Chengdu, China; Department of Pathology, West China Hospital, Sichuan University, Chengdu, China.

Background & Aims: N-methyladenosine (mA), the most prevalent and dynamic posttranscriptional methylation modification of mammalian mRNA, is involved in various biological processes, but its role in liver regeneration has not been characterized.

Methods: We first conducted transcriptome-wide mA mRNA sequencing and characterized the expression pattern of mA in regenerating mouse liver. Next, we generated hepatocyte-specific Mettl3- or Mettl14-deficient mice and investigated their role in liver regeneration. A series of biochemical experiments in vitro and in vivo was further performed to investigate potential mechanisms.

Results: We identified an overwhelming proportion of mA-modified genes with initially up-regulated and subsequently down-regulated mA levels as liver regeneration progressed. Loss of Mettl14 but not of Mettl3 resulted in markedly disrupted liver regeneration, and Mettl14-ablated hepatocytes were arrested in the G1 phase of the cell cycle. Most strikingly, the Mettl14-ablated regenerating liver exhibited extensive parenchymal necrosis. mRNA transcripts, such as Hsp90b1, Erp29, Stt3a, P4hb, and Lman1, encoding proteins involved in polypeptide processing and the endoplasmic reticulum (ER) stress response, were mA-hypomethylated, and their mRNA and protein levels were subsequently decreased, resulting in unresolved ER stress, hepatocyte death, and inhibited proliferation.

Conclusions: We demonstrate the essential role of Mettl14 in facilitating liver regeneration by modulating polypeptide-processing proteins in the ER in an mA-dependent manner.
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http://dx.doi.org/10.1016/j.jcmgh.2021.04.001DOI Listing
April 2021

Exposure to biomass fuel is associated with high blood pressure and fasting blood glucose impairment in females in southern rural China.

Environ Res 2021 Apr 1:111072. Epub 2021 Apr 1.

Guangdong Provincial Center for Disease Control and Prevention, Guangdong, China. Electronic address:

Objectives: We sought to investigate the association between household exposure to biomass fuel and metabolic syndrome (MetS) and its components including blood pressure, triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG) and waist circumference among females in southern rural China.

Methods: We surveyed 1664 residents in the Chronic Disease and Risk Factors Surveillance, conducted in 14 districts of Guangdong province. We recorded the use of biomass fuel, MetS and its components, and other covariates by using a structured questionnaire. Logistic regression model and multivariate linear regression model were adopted for analysis.

Results: Exposure to biomass fuel was significantly associated with an increase of systolic blood pressure (SBP) (β: 2.15, 95% confidence interval: 0.13 to 4.17) and FBG (β: 0.19, 95% confidence interval: 0.01 to 0.37) in the adjusted and unadjusted models (all P< 0.05). Among participants with exposure to biomass fuel, being overweight or obese was associated with an increased risk of having hypertension (odds ratio: 3.19, 95% confidence interval: 2.13 to 4.76) and higher FBG levels (odds ratio: 2.10, 95% confidence interval: 1.46 to 3.02). Exposure to biomass fuel was significantly associated with a decrease of the prevalence of central obesity (P< 0.05). However, exposure to biomass fuel was not associated with MetS, diastolic blood pressure and TG (all P> 0.05).

Conclusions: Exposure to biomass fuel is associated with an increase in blood pressure and FBG levels, but not MetS per se. Efforts should be made to protect females in southern rural China from the adverse effects associated with biomass fuel pollution.
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http://dx.doi.org/10.1016/j.envres.2021.111072DOI Listing
April 2021

Abnormal upregulation of cardiovascular disease biomarker PLA2G7 induced by proinflammatory macrophages in COVID-19 patients.

Sci Rep 2021 03 24;11(1):6811. Epub 2021 Mar 24.

NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China.

High rate of cardiovascular disease (CVD) has been reported among patients with coronavirus disease 2019 (COVID-19). Importantly, CVD, as one of the comorbidities, could also increase the risks of the severity of COVID-19. Here we identified phospholipase A2 group VII (PLA2G7), a well-studied CVD biomarker, as a hub gene in COVID-19 though an integrated hypothesis-free genomic analysis on nasal swabs (n = 486) from patients with COVID-19. PLA2G7 was further found to be predominantly expressed by proinflammatory macrophages in lungs emerging with progression of COVID-19. In the validation stage, RNA level of PLA2G7 was identified in nasal swabs from both COVID-19 and pneumonia patients, other than health individuals. The positive rate of PLA2G7 were correlated with not only viral loads but also severity of pneumonia in non-COVID-19 patients. Serum protein levels of PLA2G7 were found to be elevated and beyond the normal limit in COVID-19 patients, especially among those re-positive patients. We identified and validated PLA2G7, a biomarker for CVD, was abnormally enhanced in COVID-19 at both nucleotide and protein aspects. These findings provided indications into the prevalence of cardiovascular involvements seen in patients with COVID-19. PLA2G7 could be a potential prognostic and therapeutic target in COVID-19.
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http://dx.doi.org/10.1038/s41598-021-85848-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990942PMC
March 2021

Prognostic significance of postoperative change of PALBI grade for patients with hepatocellular carcinoma after hepatectomy.

Medicine (Baltimore) 2021 Mar;100(11):e24476

Department of Liver Surgery & Liver Transplantation Center, West China Hospital of Sichuan University.

Abstract: The platelet-albumin-bilirubin (PALBI) grade plays critical role in evaluating liver function. However, the change of PALBI grade from the preoperative to postoperative period in predicting patient outcomes after hepatectomy remains unclear.A total of 489 HCC patients who underwent hepatectomy in West China Hospital between January, 2010 and June, 2016 were analyzed retrospectively.ΔPALBI grade was calculated by PALBI grade at the first postoperative month - preoperative PALBI grade.ΔPALBI >0 was considered as stable; otherwise, worse PALBI grade was considered. Kaplan- Meier method and Cox proportional hazard regression analyses were performed for survival analysis. Prognostic model was constructed by nomogram method.Three hundred forty two patients and 147 patients were classified into training group and validation group, respectively. In the training group, results from Cox model suggested that worse PALBI grade (HR 1.328, 95% CI 1.010-1.746, P = .042), tumor size (HR 1.460, 95% CI 1.058-2.015, P = .021), microvascular invasion (MVI, HR 1.802, 95% CI 1.205-2.695, P < .001), and high alpha-fetoprotein level (AFP, HR 1.364, 95% CI 1.044-1.781, P = .023) negatively influenced postoperative recurrence. Similarly, worse PALBI grade (HR 1.403, 95% CI 1.020-1.930, P = .038), tumor size (HR 1.708, 95% CI 1.157-2.520, P = .007), MVI (HR 1.914, 95% CI 1.375-2.663, P < .001), and presence of cirrhosis (HR 1.773, 95% CI 1.226-2.564, P = .002) had negatively impacts on overall survival. Patients with worse PALBI grade had worse recurrence free (RFS) and overall survival (OS). The prognostic model incorporating the change of PALBI grade constructed in training group and tested in the validation group could perform well in predicting the outcomes.Postoperative change of PALBI grade was independently risk factor related with prognosis. Prognostic model incorporating the change of PALBI grade might be a useful index to predict the prognosis of HCC patients following hepatectomy.
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http://dx.doi.org/10.1097/MD.0000000000024476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982202PMC
March 2021

Identifying the prognostic significance of B3GNT3 with PD-L1 expression in lung adenocarcinoma.

Transl Lung Cancer Res 2021 Feb;10(2):965-980

Department of Thoracic Surgery, Institute of Thoracic Oncology/West China Hospital, Sichuan University, Chengdu, China.

Background: As a novel treatment, programmed cell death protein 1 (PD-1) inhibitor appears to be less effective in tumors of lung adenocarcinoma patients with epidermal growth factor receptor () mutation. Beta-1,3-N-acetylglucosaminyltransferase 3 (B3GNT3) has reported to be associated with programmed death ligand 1 (PD-L1)/PD-1 interaction. However, the relationship between B3GNT3 and PD-L1 and its prognostic significance in.

Egfr: mutant status are still unknown.

Methods: B3GNT3 was identified through transcriptome sequencing and The Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) database. Flow cytometry and real-time polymerase chain reaction were performed to investigate the association between B3GNT3, PD-L1, and . Then, B3GNT3 and PD-L1 expression were evaluated by immunohistochemical analysis in 145 surgically resected primary lung adenocarcinomas. The relationships between survival and B3GNT3, PD-L1, and status were assessed, and the potential prognostic factors in patients with B3GNT3 expression were identified.

Results: We found that activation induced PD-L1 expression, and EGFR tyrosine kinase inhibitor (TKI) could reduce PD-L1 protein in EGFR-TKI-sensitive HCC827 and PC9 cell lines. Subsequent analysis showed that inhibitor could also lead to both decreased PD-L1 and B3GNT3 mRNA expression. A total of 145 lung adenocarcinoma patients were included. PD-L1 >1% and B3GNT3-positive expression in patients might contribute to worse prognosis in both overall survival (OS) [hazard ratio (HR), 2.63; 95% confidence interval (CI), 0.98-7.06; P=0.048] and disease-free survival (DFS) (HR, 3.04; 95% CI, 1.13-8.14; P=0.019), especially in the PD-L1 ≥50% group. However, when patients were negative for B3GNT3, PD-L1, and (or "triple negative"), there were significant decreases in OS (HR, 5.44; 95% CI, 0.99-29.83; P=0.029) and DFS (HR, 7.24; 95% CI, 1.32-39.73; P=0.008). Positive B3GNT3 expression was a significant risk factor associated with lower DFS (HR, 3.30; P=0.043).

Conclusions: Our results indicate that the B3GNT3 expression is tightly correlated with PD-L1 expression and mutation status. B3GNT3 is associated with poor prognosis in lung adenocarcinoma patients. Collectively, these findings may offer new insight into enhancing immune therapy efficacy for lung adenocarcinoma patients.
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http://dx.doi.org/10.21037/tlcr-21-146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947420PMC
February 2021

Genetic determinants of EGFR-Driven Lung Cancer Growth and Therapeutic Response In Vivo.

Cancer Discov 2021 Mar 11. Epub 2021 Mar 11.

Departments of Pathology and Internal Medicine (Section of Medical Oncology), Yale School of Medicine

In lung adenocarcinoma, oncogenic EGFR mutations co-occur with many tumor suppressor gene alterations, however the extent to which these contribute to tumor growth and response to therapy in vivo remains largely unknown. By quantifying the effects of inactivating ten putative tumor suppressor genes in a mouse model of EGFR-driven Trp53-deficient lung adenocarcinoma, we found that Apc, Rb1, or Rbm10 inactivation strongly promoted tumor growth. Unexpectedly, inactivation of Lkb1 or Setd2 - the strongest drivers of growth in a Kras-driven model - reduced EGFR-driven tumor growth. These results are consistent with mutational frequencies in human EGFR- and KRAS-driven lung adenocarcinomas. Furthermore, Keap1 inactivation reduced the sensitivity of EGFR-driven tumors to the EGFR inhibitor osimertinib and mutations in the KEAP1 pathway were associated with decreased time on tyrosine kinase inhibitor treatment in patients. Our study highlights how the impact of genetic alterations differ across oncogenic contexts and that the fitness landscape shifts upon treatment.
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http://dx.doi.org/10.1158/2159-8290.CD-20-1385DOI Listing
March 2021

Optimizing Surgical Procedures of Auricular Keloids According to Their Anatomic Morphological Features.

J Craniofac Surg 2021 Mar-Apr 01;32(2):723-725

Department of Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China.

Background: Aesthetic surgical reconstruction of auricular keloids is still a conundrum. This study introduces our experiences in analyzing the anatomic morphological features of auricular keloids, and devising optimized surgical procedures accordingly.

Methods: A total of 129 ears with auricular keloids were classified and operated. All patients were followed up for at least 12 months.

Results: According to their anatomic positions, auricular keloids were divided into 3 Groups (A, B, and C). The morphological features of keloids were further interpreted according to Chang-Park classification of earlobe keloids. The authors optimized surgical procedures according to the anatomic morphological features from a range of surgical techniques. The recurrence rate of Group C was statistically higher than Group A and B. There was no significant difference in recurrence rate between keloids treated with "primary suture" and "filleted flaps."

Conclusions: According to the anatomic positions and morphological features of auricular keloids, we could conveniently devise optimized surgical strategies to obtain aesthetic reconstruction of auricular keloids.
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http://dx.doi.org/10.1097/SCS.0000000000006972DOI Listing
March 2021

[Rapid and simultaneous determination of 10 active components of Psoraleae Fructus in beagle dog plasma using UPLC-MS/MS and its application in pharmacokinetic study].

Zhongguo Zhong Yao Za Zhi 2021 Jan;46(2):444-453

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences Beijing 100700, China State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences Shanghai 201203, China.

An UPLC-MS/MS method for rapid and simultaneous determination of psoralen, isopsoralen, apigenin, genistein, bavaisoflavone, neobavaisoflavone, bavachin, bavachinin, psoralenoside, and isopsoralenoside of Psoraleae Fructus in beagle dog plasma was established, and then the method was applied in the pharmacokinetic study after oral administration of Psoraleae Fructus extract to beagle dogs. The pharmacokinetic parameters were calculated by the software of WinNonlin. A Waters HSS-T3 column(2.1 mm×100 mm,1.8 μm)was used for liquid chromatography separation with acetonitrile-water(containing 0.004% formic acid) as the mobile phase for gradient elution.The mass spectrometry was detected using electrospray ion source(ESI) under multi-reaction monitoring mode(MRM), as well as positive ion mode. Analysis time only takes 8.5 min. The methodological study in terms of specificity, accuracy, precision, linear range, recovery, matrix effect, and stability, was validated. The LC-MS analysis method established in this experiment was simple, specific, accurate, reliable, and meet the requirement of pharmacokinetic study in plasma after administration of Psoraleae Fructus extract to beagle dogs. Six beagle dogs received intragastric administration of Psoraleae Fructus extract, T_(max) of 10 chemical components is 1.92-5.67 h; among them, C_(max) of psoralen, isopsoralen, psoralenoside and isopsoralenoside is 383-3 613 ng·mL~(-1), and AUC_(0-∞) is 3 556-18 949 ng·h·mL~(-1), t_(1/2) is 2.45-4.83 h. C_(max) of the remaining six compounds is 0.81-19.9 ng·mL~(-1), AUC_(0-∞ )is 6.54-178 ng·h·mL~(-1), t_(1/2) is 2.95-7.29 h. The UPLC-MS/MS analysis method established in this study was proved to be accurate and sensitive that it can be applied to the pharmacokinetic study of beagle dogs after oral administration of Psoraleae Fructus extract.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200629.204DOI Listing
January 2021

Combination of albumin-bilirubin grade and clinically significant portal hypertension predicts the prognosis of patients with hepatocellular carcinoma after liver resection.

Biosci Trends 2021 Mar 24;15(1):41-49. Epub 2021 Feb 24.

Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China.

There is little information concerning whether incorporating clinically significant portal hypertension (CSPH) into albumin-bilirubin (ALBI) grading could improve its predictive capacity. In this study, we investigated the predictive ability of ALBI grade plus CSPH (ALBI-P score) for patients with hepatocellular carcinoma (HCC) after liver resection. Data from 1,679 patients were retrospectively reviewed. The ALBI-P score was calculated from the ALBI grade and a point for CSPH (0 for absence of CSPH and 1 for presence of CSPH). Independent risk factors for recurrence-free survival (RFS) and overall survival (OS) were analyzed. Multivariate analysis suggested that the ALBI-P score was an independent risk factor for both postoperative recurrence (HR = 1.441, 95% CI = 1.328-1.563, P < 0.001) and mortality (HR = 1.332, 95% CI = 1.156-1.535, P < 0.001). Both the RFS and OS of patients with an ALBI-P score of 1 were significantly better than those of patients with ALBI-P scores of 2 and 3 (5-year RFS of 38.9%, 26.1%, and 14.7%, respectively, P < 0.001; 5-year OS of 52.7%, 42.6%, and 29.3%, P < 0.001). When the ALBI-P score and BCLC stage were combined, the ALBI-P-BCLC score showed the highest area under the receiver operating characteristic curve to predict both postoperative recurrence and mortality compared with BCLC stage alone, BCLC stage combined with ALBI grade, or platelet-albumin-bilirubin grade. These results suggested incorporating CSPH into the ALBI grade could strengthen its prognostic power. The ALBI-P score may serve as a surrogate marker to predict HCC patient outcomes after liver resection.
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http://dx.doi.org/10.5582/bst.2021.01064DOI Listing
March 2021

Dosimetric characteristics of accelerated partial breast irradiation by interstitial multicatheter brachytherapy with intraoperative free-hand implantation in the treatment of early breast cancer.

J Appl Clin Med Phys 2021 Mar 24;22(3):27-34. Epub 2021 Feb 24.

Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan.

Introduction: The aim of this study is to evaluate the characteristics of the dosimetry and the skin dose of interstitial brachytherapy by the use of the free-hand implantation technique toward the treatment of early breast cancer.

Materials & Methods: Seventeen patients diagnosed with early breast cancer were selected for the study. The implantation of the catheters for postoperative interstitial brachytherapy was performed using the free-hand technique. The total tumor dose to the tumor cavity plus 2 cm margin was 3400 cGy, twice daily for 10 fractions in 5 days. The dosage to the target and the organ at risk (OAR) were recorded for analysis. The skin dose of the patient and the phantom were measured with Gafchromic film (EBT3) and the results were compared with the skin dose calculated by the brachytherapy treatment planning system.

Results: The median conformal index is 94% (range 89%-99%), and the median homogeneity index is 71%. The median skin dose measured from the skin of the patients was 20.1% lower than the skin dose calculated from the treatment planning system and consistent with the phantom surface measurement experiment. There were no grade 3 or above acute toxicity recorded.

Conclusions: Interstitial brachytherapy by the use of the free-hand implantation technique for early breast cancer is feasible and avoids the need for a second surgical intervention. The calculated skin dose was overestimated by at least 20%. The results of this study may help in building a modification model for the prediction of skin toxicity in any future study.
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http://dx.doi.org/10.1002/acm2.13169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984496PMC
March 2021

Effect of a genetically engineered interferon-alpha versus traditional interferon-alpha in the treatment of moderate-to-severe COVID-19: a randomised clinical trial.

Ann Med 2021 12;53(1):391-401

Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.

Background: There are few effective therapies for coronavirus disease 2019 (COVID-19) upon the outbreak of the pandemic. To compare the effectiveness of a novel genetically engineered recombinant super-compound interferon (rSIFN-co) with traditional interferon-alpha added to baseline antiviral agents (lopinavir-ritonavir or umifenovir) for the treatment of moderate-to-severe COVID-19.

Method: In this multicenter randomized (1:1) trial, patients hospitalized with moderate-to-severe COVID-19 received either rSIFN-co nebulization or interferon-alpha nebulization added to baseline antiviral agents for no more than 28 days. The primary endpoint was the time to clinical improvement. Secondary endpoints included the overall rate of clinical improvement assessed on day 28, the time to radiological improvement and virus nucleic acid negative conversion.

Results: A total of 94 patients were included in the safety set (46 patients assigned to rSIFN-co group, 48 to interferon-alpha group). The time to clinical improvement was 11.5 days versus 14.0 days (95% CI 1.10 to 2.81,  = .019); the overall rate of clinical improvement on day 28 was 93.5% versus 77.1% (difference, 16.4%; 95% CI 3% to 30%); the time to radiological improvement was 8.0 days versus 10.0 days ( = .002), the time to virus nucleic acid negative conversion was 7.0 days versus 10.0 days ( = .018) in the rSIFN-co and interferon alpha arms, respectively. Adverse events were balanced with no deaths among groups.

Conclusions And Relevance: rSIFN-co was associated with a shorter time of clinical improvement than traditional interferon-alpha in the treatment of moderate-to-severe COVID-19 when combined with baseline antiviral agents. rSIFN-co therapy alone or combined with other antiviral therapy is worth to be further studied.Key messagesThere are few effective therapies for coronavirus disease 2019 (COVID-19) upon the outbreak of the pandemic. Interferon alphas, by inducing both innate and adaptive immune responses, have shown clinical efficacy in treating severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus.In this multicenter, head-to-head, randomized, clinical trial which included 94 participants with moderate-to-severe COVID-19, the rSIFN-co plus antiviral agents (lopinavir-ritonavir or umifenovir) was associated with a shorter time of clinical improvement than interferon-alpha plus antiviral agents.
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http://dx.doi.org/10.1080/07853890.2021.1890329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906612PMC
December 2021

A functional taxonomy of tumor suppression in oncogenic KRAS-driven lung cancer.

Cancer Discov 2021 Feb 19. Epub 2021 Feb 19.

Department of Genetics, Stanford University School of Medicine

Cancer genotyping has identified a large number of putative tumor suppressor genes. Carcinogenesis is a multi-step process, however the importance and specific roles of many of these genes during tumor initiation, growth and progression remain unknown. Here we use a multiplexed mouse model of oncogenic KRAS-driven lung cancer to quantify the impact of forty-eight known and putative tumor suppressor genes on diverse aspects of carcinogenesis at an unprecedented scale and resolution. We uncover many previously understudied functional tumor suppressors that constrain cancer in vivo. Inactivation of some genes substantially increased growth, while the inactivation of others increases tumor initiation and/or the emergence of exceptionally large tumors. These functional in vivo analyses revealed an unexpectedly complex landscape of tumor suppression that has implications for understanding cancer evolution, interpreting clinical cancer genome sequencing data, and directing approaches to limit tumor initiation and progression.
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http://dx.doi.org/10.1158/2159-8290.CD-20-1325DOI Listing
February 2021

The Block-and-Lock Strategy for Human Immunodeficiency Virus Cure: Lessons Learned from Didehydro-Cortistatin A.

J Infect Dis 2021 Feb;223(Supplement_1):46-53

Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, Florida, USA.

Antiretroviral therapy effectively controls human immunodeficiency virus (HIV) infection. However, a reservoir of latently infected cells persists under suppressive therapy, constituting a major barrier to an HIV cure. The block-and-lock approach to a functional cure aims at the transcriptional and epigenetic silencing of proviruses, blocking viral reactivation in the absence of therapy, preventing disease progression and transmission, despite the presence of detectable integrated proviruses. This approach has been put forward for exploration based on the activity of didehydro-cortistatin A, an inhibitor of the HIV transcriptional activator Tat. Here we review the mechanisms by which didehydro-cortistatin A inhibition of Tat's feedback loop transcriptional amplification results in epigenetic silencing of the HIV promoter, and we discuss the benefits and limitations of the block-and-lock approach for an HIV cure.
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http://dx.doi.org/10.1093/infdis/jiaa681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883021PMC
February 2021

Insulin-like growth factor-1 improves postoperative cognitive dysfunction following splenectomy in aged rats.

Exp Ther Med 2021 Mar 15;21(3):215. Epub 2021 Jan 15.

Department of Anesthesiology, Qingdao Municipal Hospital Affiliated to Qingdao University, Qingdao, Shandong 266071, P.R. China.

Postoperative cognitive dysfunction (POCD) is a serious complication following anesthesia and operations in aged patients undergoing surgical intervention. It is characterized by temporary or permanent cognitive decline, memory impairment and deterioration in language comprehension and social adaption ability. Therefore, the development of POCD prevention and treatment tools has become an area of interest. The current study assessed the therapeutic effects of insulin-like growth factor-1 (IGF-1) on POCD in aged rats and explored the underlying mechanisms. Model rats underwent splenectomy under 1.5-2% isoflurane and mechanical ventilation. IGF-1 (50 µg/kg) was diluted in normal saline and administered by abdominal hypodermic injection daily from the operation to day 7 post-operation. Following splenectomy, the animals showed marked cognitive impairment as determined by the Morris water maze test. Hippocampal protein levels of amyloid precursor protein (APP), β-site APP-cleaving enzyme-1 (BACE-1), amyloid-β (Aβ), capase3, Bax and Bcl-2 were assessed by immunoblotting. Neuronal apoptosis in the hippocampus was analyzed using a TUNEL assay. The results demonstrated that the levels of APP, BACE-1, Aβ, caspase3 and Bax were increased following splenectomy, while the levels of Bcl2 were reduced at days 1, 3 and 7 post-operation in aged rats. However, IGF-1 downregulated APP, BACE-1, Aβ, capase3 and Bax, and upregulated Bcl2 at these time points following splenectomy. TUNEL staining revealed that administration of IGF-1 significantly reduced neuronal apoptosis in the hippocampal CA1 region following splenectomy. These results indicated that IGF-1 decreased Aβ-protein production and inhibited neuronal apoptosis in the hippocampus following splenectomy, subsequently alleviating POCD.
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http://dx.doi.org/10.3892/etm.2021.9647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818527PMC
March 2021

The impact of thrombocytopenia on prognosis of HBV-related small hepatocellular carcinoma: a propensity score matching analysis.

World J Surg Oncol 2021 Feb 11;19(1):46. Epub 2021 Feb 11.

Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, 610041, China.

Background: Thrombocytopenia was reported both detrimental and advantageous to hepatocellular carcinoma (HCC). However, there is little evidence showing clearly the clinical value of preoperative thrombocytopenia on the surgical outcome of patients with small HCC. This retrospective study aimed at elucidating the correlation between preoperative thrombocytopenia and surgical outcome of small HCC patients within Milan criteria treated with liver resection.

Methods: Data of hepatitis B virus (HBV)-related small HCC patients were retrospectively analyzed, and we performed the propensity score matching (PSM) analysis to overcome the imbalance of clinicopathological features. Patients enrolled were subsequently categorized into two groups according to preoperative platelet counts: thrombocytopenia group and non-thrombocytopenia group. Survival outcomes of the patients in both groups were described with the Kaplan-Meier method, and the difference was compared with a log-rank test. Cox regression analysis was applied to identify the risk factors of surgical outcome.

Results: After PSM, the estimated 1-, 3-, and 5-year overall survival (OS) rates for small HCC patients in the thrombocytopenia group were 94.5%, 77.0%, and 57.6%, and 95.0%, 79.6%, and 68.0%, respectively, for small HCC patients in the non-thrombocytopenia group (P = 0.042). And the 1-, 3-, and 5-year estimated recurrence-free survival (RFS) rates for small HCC patients in the thrombocytopenia group were 70.4%, 51.0%, and 42.1%, and 83.8%, 63.7%, and 46.7%, respectively, for small HCC patients in the non-thrombocytopenia group (P = 0.035). Multivariate analysis indicated preoperative thrombocytopenia was a significant prognosticator of poor RFS (hazard ratio (HR) = 1.388, 95% confidence interval (CI) 1.028~1.874, P = 0.033).

Conclusion: Preoperative thrombocytopenia had an undesirable impact on the recurrence of small HCC patients treated with liver resection.
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http://dx.doi.org/10.1186/s12957-021-02160-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879633PMC
February 2021

FOXP1 Interacts with MyoD to Repress its Transcription and Myoblast Conversion.

J Cell Signal 2021 ;2(1):9-26

Department of Molecular Biosciences, the University of Texas at Austin, Austin TX 78712, USA.

Forkhead transcription factors (TFs) often dimerize outside their extensive family, whereas bHLH transcription factors typically dimerize with E12/E47. Based on structural similarities, we predicted that a member of the former, Forkhead Box P1 (FOXP1), might heterodimerize with a member of the latter, MYOD1 (MyoD). Data shown here support this hypothesis and further demonstrate the specificity of this forkhead/myogenic interaction among other myogenic regulatory factors. We found that FOXP1-MyoD heterodimerization compromises the ability of MyoD to bind to E-boxes and to transactivate E box- containing promoters. We observed that FOXP1 is required for the full ability of MyoD to convert fibroblasts into myotubules. We provide a model in which FOXP1 displaces ID and E12/E47 to repress MyoD during the proliferative phase of myoblast differentiation. These data identify FOXP1 as a hitherto unsuspected transcriptional repressor of MyoD. We suggest that isolation of paired E-box and forkhead sites within 1 turn helical spacings provides potential for cooperative interactions among heretofore distinct classes of transcription factors.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861563PMC
January 2021

Topological Transition of Superconductivity in Dirac Semimetal Nanowire Josephson Junctions.

Phys Rev Lett 2021 Jan;126(2):027001

State Key Laboratory for Mesoscopic Physics and Frontiers Science Center for Nano-optoelectronics, School of Physics, Peking University, Beijing 100871, China.

We report the topological transition by gate control in a Cd_{3}As_{2} Dirac semimetal nanowire Josephson junction with diameter of about 64 nm. In the electron branch, the quantum confinement effect enforces the surface band into a series of gapped subbands and thus nontopological states. In the hole branch, however, because the hole mean free path is smaller than the nanowire perimeter, the quantum confinement effect is inoperative and the topological property maintained. The superconductivity is enhanced by gate tuning from electron to hole conduction, manifested by a larger critical supercurrent and a larger critical magnetic field, which is attributed to the topological transition from gapped surface subbands to a gapless surface band. The gate-controlled topological transition of superconductivity should be valuable for manipulation of Majorana zero modes, providing a platform for future compatible and scalable design of topological qubits.
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http://dx.doi.org/10.1103/PhysRevLett.126.027001DOI Listing
January 2021

Characterization of lipid profiling in three parts (muscle, head and viscera) of tilapia (Oreochromis niloticus) using lipidomics with UPLC-ESI-Q-TOF-MS.

Food Chem 2021 Jun 11;347:129057. Epub 2021 Jan 11.

College of Food Science and Engineering, Hainan University, Haikou 570228, China; Hainan Provincial Engineering Research Centre of Aquatic Resources Efficient Utilization in the South China Sea, Haikou 570228, China; Key Laboratory of Food Nutrition and Functional Food of Hainan Province, Haikou 570228, China. Electronic address:

A lipidomic evaluation was performed on the tilapia muscle, head and viscera, including studying the composition, distribution and stereospecific characteristics of fatty acids and lipid species. The head and viscera lipids were significantly richer than the muscle lipids. Triacylglycerols were the predominant fraction (over 80% of total lipid in the muscle and head). Additionally, polyunsaturated fatty acids had higher percentages in phospholipids (30.35-52.05% of total fatty acids) than in triacylglycerols (18.11-25.15%). The C52:2 and C52:3 were the most abundant triacylglycerols, which indicates the potential application in infant food. Moreover, 622, 530 and 513 lipids were identified using ultraperformance liquid chromatography-quadrupole time-of-flight-mass spectrometry in the muscle, head and viscera, respectively. The three tilapia parts were distinguished using multivariate analysis. Five fatty acids and 33 lipid species were considered as the potential biomarkers. This comprehensive analysis will help to evaluate the lipid nutritional values and facilitate exploitation in tilapia consumption and processing.
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http://dx.doi.org/10.1016/j.foodchem.2021.129057DOI Listing
June 2021

Mild cognitive impairment in novel SPG11 mutation-related sporadic hereditary spastic paraplegia with thin corpus callosum: case series.

BMC Neurol 2021 Jan 11;21(1):12. Epub 2021 Jan 11.

Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi'an City, 710038, Shaanxi Province, China.

Background: SPG11 mutation-related autosomal recessive hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) is the most common cause in complicated forms of HSP, usually presenting comprehensive mental retardation on early-onset stage preceding spastic paraplegias in childhood. However, there are many instances of sporadic late-onset HSP-TCC cases with a negative family history, and potential mild cognitive deficits in multiple domains may be easily neglected and inaccurately described.

Methods: In this study, we performed next generation sequencing in four sporadic late-onset patients with HSP-TCC, and combined Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) to evaluate cognition of the patients.

Results: By evolutionary conservation and structural modeling analysis, we have revealed 4 novel pathogenic SPG11 mutations, and firstly confirmed mild cognitive impairment (MCI) with normal MMSE scores (≥27) and decreased MoCA scores (< 26) in these SPG11 mutation-related HSP-TCC patients, predominantly presenting impairment of executive function, delayed recall, abstraction and language.

Conclusions: The results expand the mutational spectrum of SPG11-associated HSP-TCC from sporadic cases, and confirm MCI with combination of decreased MoCA and normal MMSE assessment, suggesting that clinicians should consider doing a MoCA to detect MCI in patients with HSP, particularly those with HSP-TCC.
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http://dx.doi.org/10.1186/s12883-020-02040-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798194PMC
January 2021

Thymic Squamous Cell Carcinoma: A Population-Based Surveillance, Epidemiology, and End Result Analysis.

Front Oncol 2020 22;10:592023. Epub 2020 Dec 22.

Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.

Objectives: Thymic squamous cell carcinoma (TSCC) is a rare neoplasm that has been sparsely cited in the literature. The aim of this study was to determine disease characteristics and prognostic factors of patients in a Surveillance, Epidemiology, and End Results (SEER) analysis.

Methods: Cases from 1990-2016 were retrieved from the SEER database and demographics, treatments, and survival outcomes were analyzed.

Results: The TSCC accounted for 72.4% of the thymic carcinomas and 7.2% of thymic tumors. The 276 patients (165 men) selected for analysis had a median age of 65 (24-85) years, and 201 patients were diagnosed with Masaoka-Koga stage III/IV. The median survival of TSCC was 59 months with a 49.0% 5-year OS rate, a better prognosis than lymphoepithelioma-like carcinoma (32.1%) and undifferentiated carcinoma (33.3%). Multivariate analysis revealed the Masaoka-Koga stage (p = 0.003) and surgical types (complete resection, incomplete resection, and none; p < 0.001) were determinants of survival. Complete resection had the best prognosis with a 72.7% 5-year OS rate. Chemotherapy was an independent protective factor (HR = 0.555, 95% CI 0.347-0.886; p = 0.014) though poor survival was showed in univariate analysis. And the survival benefit of chemotherapy was validated in PSM analysis (3-year OS rate was 77.7% with chemotherapy 52.8% without chemotherapy; p = 0.014).

Conclusions: TSCC was frequently diagnosed in older patients with advanced Masaoka-Koga stage and had more favorable survival than other subtypes of thymic carcinomas. Complete resection is the preferred treatment. Masaoka-Koga stage and chemotherapy had a strong association with prognosis.
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http://dx.doi.org/10.3389/fonc.2020.592023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783386PMC
December 2020

Intracellular immune sensing promotes inflammation via gasdermin D-driven release of a lectin alarmin.

Nat Immunol 2021 02 4;22(2):154-165. Epub 2021 Jan 4.

Department of Immunology, University of Connecticut Health School of Medicine, Farmington, CT, USA.

Inflammatory caspase sensing of cytosolic lipopolysaccharide (LPS) triggers pyroptosis and the concurrent release of damage-associated molecular patterns (DAMPs). Collectively, DAMPs are key determinants that shape the aftermath of inflammatory cell death. However, the identity and function of the individual DAMPs released are poorly defined. Our proteomics study revealed that cytosolic LPS sensing triggered the release of galectin-1, a β-galactoside-binding lectin. Galectin-1 release is a common feature of inflammatory cell death, including necroptosis. In vivo studies using galectin-1-deficient mice, recombinant galectin-1 and galectin-1-neutralizing antibody showed that galectin-1 promotes inflammation and plays a detrimental role in LPS-induced lethality. Mechanistically, galectin-1 inhibition of CD45 (Ptprc) underlies its unfavorable role in endotoxin shock. Finally, we found increased galectin-1 in sera from human patients with sepsis. Overall, we uncovered galectin-1 as a bona fide DAMP released as a consequence of cytosolic LPS sensing, identifying a new outcome of inflammatory cell death.
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http://dx.doi.org/10.1038/s41590-020-00844-7DOI Listing
February 2021

A Newton-like iterative method implemented in the DelPhi for solving the nonlinear Poisson-Boltzmann equation.

Math Biosci Eng 2020 09;17(6):6259-6277

Department of Mathematics, University of Alabama, Tuscaloosa, AL 35487, USA.

DelPhi is a popular scientific program which numerically solves the Poisson-Boltzmann equation (PBE) for electrostatic potentials and energies of biomolecules immersed in water via finite difference method. It is well known for its accuracy, reliability, flexibility, and efficiency. In this work, a new edition of DelPhi that uses a novel Newton-like method to solve the nonlinear PBE, in addition to the already implemented Successive Over Relaxation (SOR) algorithm, is introduced. Our tests on various examples have shown that this new method is superior to the SOR method in terms of stability when solving the nonlinear PBE, being able to converge even for problems involving very strong nonlinearity.
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http://dx.doi.org/10.3934/mbe.2020331DOI Listing
September 2020

Analytical Evaluation and Experiment of the Dynamic Characteristics of Double-Thimble-Type Fiber Bragg Grating Temperature Sensors.

Micromachines (Basel) 2020 Dec 26;12(1). Epub 2020 Dec 26.

Faculty of Information Engineering and Automation, Kunming University of Science and Technology, Kunming 650500, China.

A double-thimble-type fiber Bragg grating (FBG) temperature sensor that isolates the stress strain is developed, and the three materials of air, grease, and copper thimble are employed for encapsulating. To investigate the effect of different encapsulation materials on the time constant of the sensors under dynamic conditions, the transient heat conduction mathematical model is built according to the lumped heat capacity (LHC) system and thermal equilibrium theory, and the time constant is solved by an analytical solution. Then, a proportional three-dimensional sensor simulation model is established and the transient heat transfer process is numerically solved by the finite element analysis method. To verify the models, an experimental system is established to test the response speed of the three-type sensor and the experimental data are compared with the analytical and numerical solution results. The results show that the dynamic response performance depends on the encapsulation material parameters; the response speed is faster than recovery speed; and the response speed of the air packaging sensor is more than 20% faster than that of the grease packaging sensor, and more than 30% faster than that of the copper packaging sensor. The smaller the heat storage capacity and the larger the heat transfer coefficient, the faster the sensor's response speed.
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http://dx.doi.org/10.3390/mi12010016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824047PMC
December 2020