Publications by authors named "Yu Xiao"

1,217 Publications

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Sequential drug delivery of vancomycin and rhBMP-2 via pore-closed PLGA microparticles embedded photo-crosslinked chitosan hydrogel for enhanced osteointegration.

Authors:
Wei Song Yu Xiao

Int J Biol Macromol 2021 Apr 7. Epub 2021 Apr 7.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No.14, Section 3, Ren Min Nan Rd., Chengdu 610041, Sichuan, China. Electronic address:

As generally accepted, inhibiting the bacterial invasion at initial stage and promoting the behavior of related osteogenesis cells afterwards is crucial to achieve favorable osteointegration after dental implantation. In this study, a novel combined structured hydrogel composed of chitosan and pore-closed poly(lactic-co-glycolic acid) microparticles was prepared and characterized. In vitro and in-vivo studies have identified that this biocompatible material can rapidly release vancomycin at initial 2 days and then sustainedly release recombinant human bone morphogenetic protein-2 for about 12 days, thus respectively accomplish antibacterial and osteogenesis functions. This sequential drug release system can be used as a promising coating material to improve the surface conditions of dental implant to enhance the osteointegration after surgery.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.03.181DOI Listing
April 2021

Cultivation of compound ability of postgraduates with medical professional degree: the importance of double tutor system.

Postgrad Med J 2021 Apr 9. Epub 2021 Apr 9.

Department of Psychiatry, Shantou University Mental Health Center, Shantou, China.

As we all know, medical postgraduate education is very important for training high-quality clinicians, and can have a long-term impact on the promotion of the global health service system. In recent years, following the example of developed countries in Europe and America, the Chinese government has reformed the training mode of medical postgraduates and implemented the double tutor system. Although this system will bring many positive effects in theory, the difficulties encountered in implementing this system are real and need the joint efforts of schools, tutors and students to solve them. This article closely follows the background of the current era, compares the differences between Chinese and foreign graduate training modes, and emphatically discusses the significance and problems of the double tutor system in the postgraduate education reform in China.
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http://dx.doi.org/10.1136/postgradmedj-2021-139779DOI Listing
April 2021

Pollen PCP-B peptides unlock a stigma peptide-receptor kinase gating mechanism for pollination.

Science 2021 Apr;372(6538):171-175

School of Life Sciences, East China Normal University, Shanghai, China.

Sexual reproduction in angiosperms relies on precise communications between the pollen and pistil. The molecular mechanisms underlying these communications remain elusive. We established that in , a stigmatic gatekeeper, the ANJEA-FERONIA (ANJ-FER) receptor kinase complex, perceives the RAPID ALKALINIZATION FACTOR peptides RALF23 and RALF33 to induce reactive oxygen species (ROS) production in the stigma papillae, whereas pollination reduces stigmatic ROS, allowing pollen hydration. Upon pollination, the POLLEN COAT PROTEIN B-class peptides (PCP-Bs) compete with RALF23/33 for binding to the ANJ-FER complex, leading to a decline of stigmatic ROS that facilitates pollen hydration. Our results elucidate a molecular gating mechanism in which distinct peptide classes from pollen compete with stigma peptides for interaction with a stigmatic receptor kinase complex, allowing the pollen to hydrate and germinate.
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http://dx.doi.org/10.1126/science.abc6107DOI Listing
April 2021

In vitro expansion of pancreatic islet clusters facilitated by hormones and chemicals.

Cell Discov 2020 Apr 7;6(1):20. Epub 2020 Apr 7.

Key Laboratory Experimental Teratology of the Ministry of Education and Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Shandong University, 250012, Jinan, Shandong, China.

Tissue regeneration, such as pancreatic islet tissue propagation in vitro, could serve as a promising strategy for diabetes therapy and personalised drug testing. However, such a strategy has not been realised yet. Propagation could be divided into two steps, in vitro expansion and repeated passaging. Even the first step of the in vitro islet expansion has not been achieved to date. Here, we describe a method that enables the expansion of islet clusters isolated from pregnant mice or wild-type rats by employing a combination of specific regeneration factors and chemical compounds in vitro. The expanded islet clusters expressed insulin, glucagon and somatostatin, which are markers corresponding to pancreatic β cells, α cells and δ cells, respectively. These different types of cells grouped together, were spatially organised and functioned similarly to primary islets. Further mechanistic analysis revealed that forskolin in our recipe contributed to renewal and regeneration, whereas exendin-4 was essential for preserving islet cell identity. Our results provide a novel method for the in vitro expansion of islet clusters, which is an important step forward in developing future protocols and media used for islet tissue propagation in vitro. Such method is important for future regenerative diabetes therapies and personalised medicines using large amounts of pancreatic islets derived from the same person.
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http://dx.doi.org/10.1038/s41421-020-0159-xDOI Listing
April 2020

Deletion of renal Nedd4-2 abolishes the effect of high sodium intake (HS) on Kir4.1, ENaC and NCC, and causes hypokalemia during HS.

Am J Physiol Renal Physiol 2021 Apr 5. Epub 2021 Apr 5.

Pharmacology, New York Medical College, United States.

Nedd4-2 regulates the expression of Kir4.1, thiazide-sensitive Na-Cl-cotransporter (NCC) and epithelial Na channel (ENaC) in aldosterone-sensitive-distal-nephron (ASDN) and Nedd4-2-deletion causes salt-sensitive hypertension. We now examine whether Nedd4-2-deletion compromises the effect of high salt (HS) on Kir4.1, NCC, ENaC and renal K excretion. Immunoblotting showed that HS decreased the expression of Kir4.1, Ca-activated-big-conductance K-channel subunit-a (BKa), ENaCb, ENaCg, total NCC (tNCC) and phosphor-NCC (pNCC at Thr) in Nedd4l mice while these effects were absent in kidney-specific Nedd4-2-knockout (Ks-Nedd4-2 KO) mice. Patch-clamp experiments showed that neither HS nor low salt (LS) had effect on Kir4.1/Kir5.1 currents of the distal convoluted tubule (DCT) in Nedd4-2-deficient mice while we confirmed that HS inhibited and LS increased Kir4.1/Kir5.1 activity in Nedd4l mice. Nedd4-2-deletion increased ENaC currents in the ASDN and this increase was more robust in the cortical-collecting-duct (CCD) than in the DCT. Also, HS-induced inhibition of ENaC currents in the ASDN was absent in Nedd4-2-deficient mice. Renal clearance experiments showed that HS intake for two-weeks increased the basal level of renal K excretion and caused hypokalemia in Ks-Nedd4-2-KO mice but not in Nedd4l mice. In contrast, plasma Na concentrations were similar in Nedd4l and Ks-Nedd4-2 KO mice on HS. We conclude that Nedd4-2 plays an important role in mediating inhibitory effect of HS on the Kir4.1, ENaC and NCC; and is essential for maintaining a normal renal K excretion and plasma K ranges during long-term HS.
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http://dx.doi.org/10.1152/ajprenal.00555.2020DOI Listing
April 2021

Ligand recognition, unconventional activation, and G protein coupling of the prostaglandin E receptor EP2 subtype.

Sci Adv 2021 Apr 2;7(14). Epub 2021 Apr 2.

Department of Biophysics and Department of Pathology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.

Selective modulation of the heterotrimeric G protein α S subunit-coupled prostaglandin E (PGE) receptor EP2 subtype is a promising therapeutic strategy for osteoporosis, ocular hypertension, neurodegenerative diseases, and cardiovascular disorders. Here, we report the cryo-electron microscopy structure of the EP2-G complex with its endogenous agonist PGE and two synthesized agonists, taprenepag and evatanepag (CP-533536). These structures revealed distinct features of EP2 within the EP receptor family in terms of its unconventional receptor activation and G protein coupling mechanisms, including activation in the absence of a typical W "toggle switch" and coupling to G via helix 8. Moreover, inspection of the agonist-bound EP2 structures uncovered key motifs governing ligand selectivity. Our study provides important knowledge for agonist recognition and activation mechanisms of EP2 and will facilitate the rational design of drugs targeting the PGE signaling system.
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http://dx.doi.org/10.1126/sciadv.abf1268DOI Listing
April 2021

Fast computational depth segmentation using orthogonal fringe patterns without pattern sequence changing.

J Opt Soc Am A Opt Image Sci Vis 2021 Apr;38(4):564-572

The recently proposed omnidirectional depth segmentation method (ODSM) has advantages over traditional depth segmentation in terms of robustness and computational costs. However, this method uses at least six fringe patterns and changes their sequences multiple times to perform depth segmentation, which limits its segmentation speed and increases computational complexity. This paper proposes a fast computational depth segmentation (FCDS) method in which only five patterns are used for object segmentation at different depths into isolated regions without the requirement of pattern sequence changing. Phase singularity points are fully utilized due to their significance as depth segmentation markers to extract segmenting lines used for depth determination. Meanwhile, a modified Fourier transform algorithm (MFTA) is introduced to calculate the wrapped phase sequences, which uses two groups of orthogonal phase-shifting fringe patterns and a DC component pattern (five in total). The segmenting lines along orthogonal directions can be extracted with the FCDS method without changing the fringe sequences, which not only solves the problem of phase insensitivity but reduces the calculation costs. Besides, the problem of mis-segmentation is solved with an optimization algorithm for depth segmenting lines and successfully segments objects with abrupt depth changes. The simulation results demonstrate the effectiveness and precision of the proposed method. The experimental results prove the success of the proposed method for segmenting objects of similar color with a segmentation speed that is up to a 120% increase relative to previous methods.
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http://dx.doi.org/10.1364/JOSAA.414326DOI Listing
April 2021

PRDX2 Protects Against Atherosclerosis by Regulating the Phenotype and Function of the Vascular Smooth Muscle Cell.

Front Cardiovasc Med 2021 11;8:624796. Epub 2021 Mar 11.

Department of Pathology and Forensic Medicine, College of Basic Medical Sciences, Dalian Medical University, Dalian, China.

Peroxiredoxin 2 (PRDX2), an inhibitor of reactive oxygen species (ROS), is potentially involved in the progression of atherosclerosis (AS). The aim of this study was to explore the role and mechanism of PRDX2 in AS. The expression of PRDX2 was evaluated in 14 human carotid artery tissues with or without AS. The results showed that the positive reaction of PRDX2 was observed in the carotid artery vascular smooth muscle cells (CAVSMCs). To assess the mechanism by which PRDX2 may function in AS, the CAVSMCs were transfected with pEX4-PRDX2 and si-PRDX2. The catalase, hydrogen peroxide (HO) scavenger, was used to further confirm that PRDX2-induced inhibitory effects might be mediated through reducing ROS levels. Phenotype alteration and functional testing included transcription testing, immunostaining, and expression studies. The drug of MAPK signaling pathway inhibitors SB203580, SP600125, and PD98059 was used to evaluate the underlying mechanism. In this study, we found that the protein level of PRDX2 and the level of HO were higher in the human AS carotid artery tissues than in the normal carotid artery tissues, accompanied with the activation of MAPK signaling pathway. The up-regulation of PRDX2 in the CAVSMCs significantly decreased the expression of ROS, collagen type I (COL I), collagen type III (COL III), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) and inhibited the proliferation, migration, and transformation of the CAVSMCs. The up-regulation of PRDX2 reversed the effect of the CAVSMCs treated with tumor necrosis factor-α (TNF-α). In addition, PRDX2 down-regulation promoted the protein levels of p-p38, p-JNK, and p-ERK, which was confirmed in relevant MAPK inhibitor treatment experiments. Our results suggest a protective role of PRDX2, as a scavenger of ROS, in AS progression through inhibiting the VSMC phenotype alteration and function MAPK signaling pathway.
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http://dx.doi.org/10.3389/fcvm.2021.624796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006347PMC
March 2021

Androgen receptor splice variant 7 detected by immunohistochemical is an independent poor prognostic marker in men receiving adjuvant androgen-deprivation therapy after radical prostatectomy.

Biomark Res 2021 Mar 31;9(1):23. Epub 2021 Mar 31.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Background: To evaluate the predictive value of AR-V7 expression detected by immunohistochemical (IHC) in the prognosis of prostate cancer patients receiving adjuvant hormonal therapy (AHT) following radical prostatectomy (RP).

Methods: We retrospectively collected data of 110 patients with prostate cancer receiving RP, followed by AHT, from Tongji hospital. IHC analysis of AR-V7 expression was performed in a retrospective cohort.

Results: In total, 110 patients were enrolled, of whom 21 patients (19.1%) were AR-V7-positive and 89 patients (80.9%) were AR-V7-negative. No significant differences in baseline characteristics were found between the two groups. AR-V7-positive patients had shorter progression-free survival (PFS) (HR: 4.26; 95% CI, 1.55 to 11.68; P = 0.003), shorter cancer-special survival (CSS) (HR: 22.47; 95% CI, 2.912 to 173.4; P = 0.003) and shorter overall survival (OS) (HR: 6.61; 95% CI, 1.40 to 31.20; P = 0.017) compared to AR-V7-negative patients. In multivariate analysis, AR-V7 is an independent risk factor for shorter PFS (HR, 3.76; 95% CI, 1.63 to 8.70; P = 0.002), shorter CSS (HR: 9.17; 95% CI, 1.48 to 55.56; P = 0.017) and shorter OS (HR: 4.81; 95% CI, 1.28 to 17.86; P = 0.020).

Conclusion: The presence of AR-V7 in prostate cancer tissue is independently associated with an unfavorable prognosis for PFS, OS and CSS in patients who received AHT.
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http://dx.doi.org/10.1186/s40364-021-00276-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011087PMC
March 2021

Comparison of Thulium Laser Resection of Bladder Tumors and Conventional Transurethral Resection of Bladder Tumors for Non-Muscle-Invasive Bladder Cancer.

Urol Int 2021 Mar 30:1-6. Epub 2021 Mar 30.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Introduction: The thulium laser resection of bladder tumors (TmLRBT) was increasingly used in the treatment of non-muscle-invasive bladder cancer (NMIBC) recently, and here we report the relevant outcomes of our institution to evaluate its efficacy and safety.

Methods: We retrospectively collected the data of NMIBC patients who underwent either TmLRBT or transurethral resection of bladder tumor (TURBT). The baseline characteristics and perioperative outcomes were compared in these 2 groups.

Results: The TmLRBT had a higher rate of detrusor identification than TURBT (97.4 vs. 87.6%, p = 0.001). After screening, 134 patients who underwent TmLRBT and 152 patients who received TURBT were enrolled in the analysis, and their baseline characteristics were similar. During the TURBT, 24 (15.8%) obturator nerve reflexes and 9 (5.9%) bladder perforations occurred, while none happened during the TmLRBT. After surgery, TmLRBT patients had fewer postoperative gross hematuria (38.1 vs. 96.7%, p < 0.001) and postoperative irrigation (27.6 vs. 92.7%, p < 0.001), and its irrigation duration was significantly shorter (2.3 vs. 3.3 day, p < 0.001). During the follow-up, no significant difference in the recurrence rate was detected (p = 0.315).

Conclusions: TmLRBT is a safer technique than conventional TURBT in the treatment of NMIBC, and it could offer better specimens for pathologic assessment while the cancer control was not compromised.
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http://dx.doi.org/10.1159/000514042DOI Listing
March 2021

Generation of two induced pluripotent stem cell lines from blood cells of a prostate cancer patient carrying germline mutation in CHEK2.

Stem Cell Res 2021 Mar 18;53:102299. Epub 2021 Mar 18.

Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China; Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan, China; Human Genetics Resource Preservation Center of Wuhan University, Wuhan, China. Electronic address:

Germline mutations of CHEK2 have been reported in various types of disease including breast cancer, ovarian cancer, colorectal cancer and prostate cancer. We generated two iPSC lines ZNHi001-A and ZNHi001-B from a prostate cancer patient carrying germline mutation in CHEK2 (c.667C>T, also p.R223C) which may increase the risk of prostate cancer. Pluripotency and multi-lineage differentiation capacity of the two iPSC lines were confirmed by gene expression and teratoma assay. The generated iPSC lines carrying specific CHEK2 mutation might be a useful resource to study the pathogenic mechanism and develop potential therapeutic strategy of prostate cancer.
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http://dx.doi.org/10.1016/j.scr.2021.102299DOI Listing
March 2021

Genetic characteristics and prognostic implications of m1A regulators in pancreatic cancer.

Biosci Rep 2021 Apr;41(4)

Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.

Studies have identified the methylation of N1 adenosine (m1A), an RNA modification, playing an important role in the progression of the tumorigenesis. The present study aimed to analyze the genetic characteristics and prognostic value of m1A regulators in pancreatic cancer. In the present study, data on gene mutations, single-nucleotide variants (SNVs), and copy number variation (CNV) were obtained from 363 patients with pancreatic cancer in the Cancer Genome Atlas (TCGA) database, and survival analysis was performed using the logarithmic rank test and Cox regression model. The chi-squared test was used to examine the relationship between the changes in m1A regulatory factors and clinicopathological characteristics. And we used ICGC database to verify the reliability of prognostic markers. The results show that changes in m1A-regulating genes are related to clinical stage and that the expression of some m1A-regulating genes is positively correlated with CNV. In addition, the low expression of the 'eraser' gene ALKBH1 is related to the poor prognosis of patients with pancreatic cancer, and its expression level has important clinical significance for patients with pancreatic adenocarcinoma (PAAD). Mechanistically, ALKBH1 may participate in the occurrence and development of pancreatic cancer through mTOR and ErbB signaling pathway. The expression of m1A-regulating genes can be used as a prognostic marker for pancreatic cancer. These findings provide valuable clues for us to understand the epigenetics of m1A in pancreatic cancer.
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http://dx.doi.org/10.1042/BSR20210337DOI Listing
April 2021

PTP-MEG2 regulates quantal size and fusion pore opening through two distinct structural bases and substrates.

EMBO Rep 2021 Mar 25:e52141. Epub 2021 Mar 25.

Key Laboratory Experimental Teratology of the Ministry of Education and Department of Physiology, Shandong University School of Medicine, Jinan, China.

Tyrosine phosphorylation of secretion machinery proteins is a crucial regulatory mechanism for exocytosis. However, the participation of protein tyrosine phosphatases (PTPs) in different exocytosis stages has not been defined. Here we demonstrate that PTP-MEG2 controls multiple steps of catecholamine secretion. Biochemical and crystallographic analyses reveal key residues that govern the interaction between PTP-MEG2 and its substrate, a peptide containing the phosphorylated NSF-pY site, specify PTP-MEG2 substrate selectivity, and modulate the fusion of catecholamine-containing vesicles. Unexpectedly, delineation of PTP-MEG2 mutants along with the NSF binding interface reveals that PTP-MEG2 controls the fusion pore opening through NSF independent mechanisms. Utilizing bioinformatics search and biochemical and electrochemical screening approaches, we uncover that PTP-MEG2 regulates the opening and extension of the fusion pore by dephosphorylating the DYNAMIN2-pY and MUNC18-1-pY sites. Further structural and biochemical analyses confirmed the interaction of PTP-MEG2 with MUNC18-1-pY or DYNAMIN2-pY through a distinct structural basis compared with that of the NSF-pY site. Our studies thus provide mechanistic insights in complex exocytosis processes.
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http://dx.doi.org/10.15252/embr.202052141DOI Listing
March 2021

Promising role of long non-coding RNA PCAT6 in malignancies.

Biomed Pharmacother 2021 May 26;137:111402. Epub 2021 Feb 26.

Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou 450052, China; Henan Key Laboratory of Digestive Organ Transplantation, Zhengzhou 450052, China. Electronic address:

Long non-coding RNAs (lncRNAs), a newly identified class of non-coding RNA (ncRNA), are defined as RNA molecules at least 200 nucleotides in length that are not translated into proteins. LncRNAs contribute to a wide range of biological processes and are master regulators of disease occurrence, development, and response to therapy in human malignancies. The lncRNA prostate cancer‑associated transcript 6 (PCAT6) is upregulated in various human malignancies, including lung cancer, hepatocellular carcinoma, cervical cancer, osteosarcoma, glioblastoma, colorectal cancer, breast cancer, gastric cancer, gastrointestinal stromal tumors, and pancreatic ductal adenocarcinoma. High expression of PCAT6 is closely correlated with aggressive clinicopathological characteristics and poor prognosis in cancer patients, suggesting it is an oncogenic lncRNA. PCAT6 overexpression also facilitates cell proliferation, invasion, and migration while attenuating apoptosis, indicating that it might serve as a new prognostic biomarker and therapeutic target for malignancies. Here, we discuss the molecular mechanisms, regulatory functions, and potential clinical applications of PCAT6 in cancer.
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http://dx.doi.org/10.1016/j.biopha.2021.111402DOI Listing
May 2021

FENDRR: A pivotal, cancer-related, long non-coding RNA.

Biomed Pharmacother 2021 May 16;137:111390. Epub 2021 Feb 16.

Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou 450052, China; Henan Key Laboratory of Digestive Organ Transplantation, Zhengzhou 450052, China. Electronic address:

Long non-coding RNAs (lncRNAs) have more than 200 nucleotides and do not encode proteins. Based on numerous studies, lncRNAs have emerged as new and crucial regulators of biological function and have been implicated in the pathogenesis of a variety of diseases, especially cancers. Specific lncRNAs have been identified as novel molecular biomarkers for cancer diagnosis, prognosis, and treatment efficacy. Fetal-lethal non-coding developmental regulatory RNA (FENDRR, also known as FOXF1-AS1) is a novel lncRNA that is located at chr3q13.31 and has four exons and 3099 nucleotides, and its genomic site is located at chr3q13.31. FENDRR is abnormally expressed in a variety of cancers and is significantly associated with different clinical characteristics. In addition, FENDRR has shown potential as a biomarker for cancer diagnosis, prognosis, and treatment. In this review, we summarize the current understanding of FENDRR and its mechanistic role in cancer progression. We also discuss recent insights into the clinical significance of FENDRR for cancer diagnosis, prognosis, and treatment.
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http://dx.doi.org/10.1016/j.biopha.2021.111390DOI Listing
May 2021

Managing capacity for virtual and office appointments in chronic care.

Health Care Manag Sci 2021 Mar 24. Epub 2021 Mar 24.

Industrial and Manufacturing Systems Engineering, University of Michigan-Dearborn, Dearborn, MI, 48128, USA.

Patients living with a chronic disease often require regular appointments and treatments. Due to the constraints on the availability of office appointments and the capacity of physicians, access to chronic care can be limited; consequently, patients may fail to receive the recommended care suggested by clinical guidelines. Virtual appointments can provide a cost-effective alternative to traditional office appointments for managing chronic conditions. Advances in information technology infrastructure, communication, and connected medical devices are enabling providers to evaluate, diagnose, and treat patients remotely. In this study, we build a capacity allocation model to study the use of virtual appointments in a chronic care setting. We consider a cohort of patients receiving chronic care and model the flow of the patients between office and virtual appointments using an open migration network. We formulate the planning of capacity needed for office and virtual appointments with a newsvendor model to maximize long-run average earnings. We consider differences in treatment and diagnosis effectiveness for office and virtual appointments. We derive optimal capacity allocation policies and implement numerical experiments. With the model developed, capacity decisions for office and virtual appointments can be made more systematically with the consideration of patient disease progressions.
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http://dx.doi.org/10.1007/s10729-021-09546-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987515PMC
March 2021

Pentagonal BC monolayer with extremely high theoretical capacity for Li-/Na-ion batteries.

Phys Chem Chem Phys 2021 Mar;23(10):6278-6285

State Key Laboratory of Reliability and Intelligence of Electrical Equipment, Hebei University of Technology, Tianjin 300130, China. and School of Materials Science and Engineering, Hebei University of Technology, Tianjin 300130, China.

Recently, two-dimensional (2-D) materials with a Penta-atomic-configuration such as Penta-graphene have received considerable attention because of their potential applications in electronics, spintronics and ion batteries. Previously, Penta-graphene has been proposed as an excellent anode material for Li-/Na-ion batteries with a high theoretical capacity (1489 mA h g-1). Here, based on the first-principles calculations, we report that a new 2-D material namely Penta-B2C can become another excellent anode material with even higher theoretical capacity for Li-/Na-ion batteries than Penta-graphene. Our results demonstrate that Li/Na atoms can be stably adsorbed on Penta-B2C. Meanwhile, Penta-B2C shows metallic conductivity during the adsorption. Most strikingly, the theoretical capacities of Penta-B2C are as high as 1594 for Li and 2391 mA h g-1 for Na, which are superior to those of the most known 2-D anode materials. Especially, the Na theoretical capacity of Penta-B2C sets a new record among known 2-D anode materials. In addition, Penta-B2C possesses relatively low open-circuit voltage and a low diffusion barrier for ions, which are vital for anode materials. These results highly promise that Penta-B2C can be an excellent anode material with a fast charge/discharge rate and extremely high theoretical capacity for Li-/Na-ion batteries.
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http://dx.doi.org/10.1039/d0cp06363kDOI Listing
March 2021

RPN2 Predicts Poor Prognosis and Promotes Bladder Cancer Growth and Metastasis via the PI3K-Akt Pathway.

Onco Targets Ther 2021 3;14:1643-1657. Epub 2021 Mar 3.

Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China.

Background: Ribophorin II (RPN2) is a highly conserved glycoprotein involved in the N-linked glycosylation of multiple proteins. RPN2 was reported to be associated with malignant phenotype in several tumors. However, the function of RPN2 in bladder cancer (BCa) remains unclear.

Methods: Expression of RPN2 in BCa and adjacent tissues was compared by bioinformatics analysis, immunohistochemistry, and Western blotting. qRT-PCR was performed to explore the correlation between RPN2 expression and various clinical features in 38 patients. We assessed the effects of RPN2 on the biological activity of BCa both in vitro and in vivo, and explored its potential mechanisms based on gene set enrichment analysis (GSEA).

Results: We found that RPN2 was highly expressed in human BCa compared with normal adjacent tissues. There was a significant positive correlation between higher RPN2 mRNA levels and tumor T stage, lymph node (LN) metastasis and the degree of pathological differentiation in 38 patients with BCa. We further demonstrated that RPN2 silencing inhibited the growth and metastasis of BCa both in vitro and in vivo. Western blotting revealed that RPN2 knockdown suppressed epithelial-mesenchymal transition (EMT) and inhibited the PI3K-Akt pathway.

Conclusion: These data suggest that RPN2 functions as an oncogene to promote tumor development and is a promising prognostic factor and therapeutic target in BCa.
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http://dx.doi.org/10.2147/OTT.S300480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953128PMC
March 2021

The inhibitory effect of melatonin on human prostate cancer.

Cell Commun Signal 2021 Mar 15;19(1):34. Epub 2021 Mar 15.

Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China.

Prostate cancer (PCa) is one of the most commonly diagnosed human cancers in males. Nearly 191,930 new cases and 33,330 new deaths of PCa are estimated in 2020. Androgen and androgen receptor pathways played essential roles in the pathogenesis of PCa. Androgen depletion therapy is the most used therapies for primary PCa patients. However, due to the high relapse and mortality of PCa, developing novel noninvasive therapies have become the focus of research. Melatonin is an indole-like neurohormone mainly produced in the human pineal gland with a prominent anti-oxidant property. The anti-tumor ability of melatonin has been substantially confirmed and several related articles have also reported the inhibitory effect of melatonin on PCa, while reviews of this inhibitory effect of melatonin on PCa in recent 10 years are absent. Therefore, we systematically discuss the relationship between melatonin disruption and the risk of PCa, the mechanism of how melatonin inhibited PCa, and the synergistic benefits of melatonin and other drugs to summarize current understandings about the function of melatonin in suppressing human prostate cancer. We also raise several unsolved issues that need to be resolved to translate currently non-clinical trials of melatonin for clinic use. We hope this literature review could provide a solid theoretical basis for the future utilization of melatonin in preventing, diagnosing and treating human prostate cancer. Video abstract.
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http://dx.doi.org/10.1186/s12964-021-00723-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962396PMC
March 2021

Pyrococcus furiosus Argonaute coupled with modified ligase chain reaction for detection of SARS-CoV-2 and HPV.

Talanta 2021 May 11;227:122154. Epub 2021 Feb 11.

State Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, Hubei Key Laboratory of Industrial Biotechnology, School of Life Sciences, Hubei University, Wuhan, Hubei, PR China. Electronic address:

Infectious diseases caused by viruses such as SARS-CoV-2 and HPV have greatly endangered human health. The nucleic acid detection is essential for the early diagnosis of diseases. Here, we propose a method called PLCR (PfAgo coupled with modified Ligase Chain Reaction for nucleic acid detection) which utilizes PfAgo to only use DNA guides longer than 14-mer to specifically cleave DNA and LCR to precisely distinguish single-base mismatch. PLCR can detect DNA or RNA without PCR at attomolar sensitivities, distinguish single base mutation between the genome of wild type SARS-CoV-2 and its mutant spike D614G, effectively distinguish the novel coronavirus from other coronaviruses and finally achieve multiplexed detection in 70 min. Additionally, LCR products can be directly used as DNA guides without additional input guides to simplify primer design. With desirable sensitivity, specificity and simplicity, the method can be extended for detecting other pathogenic microorganisms.
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http://dx.doi.org/10.1016/j.talanta.2021.122154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875706PMC
May 2021

Atrial Fibrillation and Outcomes After Transcatheter or Surgical Aortic Valve Replacement (from the PARTNER 3 Trial).

Am J Cardiol 2021 Mar 7. Epub 2021 Mar 7.

Cardiovascular Research Foundation, New York, New York; NewYork-Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York. Electronic address:

The prognostic impact of preexisting atrial fibrillation or flutter (AF) in low-risk patients with severe aortic stenosis treated with transcatheter (TAVR) or surgical aortic valve replacement (SAVR) remains unknown. In this sub-analysis of the PARTNER 3 trial of patients with severe aortic stenosis at low surgical risk randomized 1:1 to TAVR versus SAVR, clinical outcomes were analyzed at 2 years according to AF status. Among 948 patients included in the analysis (452 [47.7%] in the SAVR vs 496 [52.3%] in the TAVR arm), 168 (17.6%) patients had AF [88/452 (19.5%) and 80/496 (16.1%) treated with SAVR and TAVR, respectively]. At 2 years, patients with AF had higher unadjusted rates of the composite outcome of death, stroke or rehospitalization (21.2% vs 12.9%, p = 0.007) and rehospitalization alone (15.3% vs 9.4%, p = 0.03) but not all cause death (3.8% vs 2.6%, p = 0.45) or stroke (4.8% vs 2.6%, p = 0.12). In adjusted analyses, patients with AF had a higher risk for the composite outcome of death, stroke or rehospitalization (hazard ratio [HR] 1.80, 95% confidence interval [CI] 1.20-2.71, p = 0.0046) and rehospitalization alone (HR 1.8, 95% CI 0.12-2.9, p = 0.015), but not death or stroke. There was no interaction between treatment modality and AF on the composite outcome (Pinter = 0.83). In conclusion, preexisting AF in patients with severe AS at low surgical risk was associated with increased risk of the composite outcome of death, stroke or rehospitalization at 2 years, irrespective of treatment modality.
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http://dx.doi.org/10.1016/j.amjcard.2021.02.040DOI Listing
March 2021

Hexavalent TRAIL fusion protein eftozanermin alfa optimally clusters apoptosis-inducing TRAIL receptors to induce on-target antitumor activity in solid tumors.

Cancer Res 2021 Mar 9. Epub 2021 Mar 9.

Oncology Discovery, AbbVie Inc.

TNF Receptor Apoptosis-Inducing Ligand (TRAIL) can activate cell surface death receptors resulting in potent tumor cell death via induction of the extrinsic apoptosis pathway. Eftozanermin alfa (ABBV-621) is a second-generation TRAIL receptor agonist engineered as an IgG1-Fc mutant backbone linked to two sets of trimeric native single chain TRAIL receptor binding domain monomers. This hexavalent agonistic fusion protein binds to the death-inducing DR4 and DR5 receptors with nanomolar affinity to drive on-target biological activity with enhanced caspase-8 aggregation and DISC formation independent of FcγR-mediated cross-linking, and without clinical signs or pathological evidence of toxicity in non-rodent species. ABBV-621 induced cell death in approximately 36% (45/126) of solid cancer cell lines in vitro at sub-nanomolar concentrations. An in vivo patient-derived xenograft (PDX) screen of ABBV-621 activity across 15 different tumor indications resulted in an overall response (OR) of 29% (47/162). Although DR4 (TNFSFR10A) and/or DR5 (TNFSFR10B) expression levels did not predict the level of response to ABBV-621 activity in vivo, KRAS mutations were associated with elevated TNFSFR10A and TNFSFR10B and were enriched in ABBV-621 responsive colorectal carcinoma (CRC) PDX models. To build upon the OR of ABBV-621 monotherapy in CRC (45%; 10/22) and pancreatic cancer (35%; 7/20), we subsequently demonstrated that inherent resistance to ABBV-621 treatment could be overcome in combination with chemotherapeutics or with selective inhibitors of BCL-XL. In summary, these data provide a pre-clinical rationale for the ongoing Phase-1 clinical trial (NCT03082209) evaluating the activity of ABBV-621 in cancer patients.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-2178DOI Listing
March 2021

E3 ubiquitin ligase RNF126 affects bladder cancer progression through regulation of PTEN stability.

Cell Death Dis 2021 Mar 4;12(3):239. Epub 2021 Mar 4.

Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.

E3 ubiquitin ligase RNF126 (ring finger protein 126) is highly expressed in various cancers and strongly associated with tumorigenesis. However, its specific function in bladder cancer (BCa) is still debatable. Here, we found that RNF126 was significantly upregulated in BCa tissue by TCGA database, and our studies indicated that downregulation of RNF126 significantly inhibited cell proliferation and metastasis through the EGFR/PI3K/AKT signaling pathway in BCa cells. Furthermore, we identified PTEN, an inhibitor of the PI3K/AKT signaling pathway, as a novel substrate for RNF126. By co-immunoprecipitation assays, we proved that RNF126 directly interacts with PTEN. Predominantly, PTEN binds to the C-terminal containing the RING domain of RNF126. The in vivo ubiquitination assay showed that RNF126 specifically regulates PTEN stability through poly-ubiquitination. Furthermore, PTEN knockdown restored cell proliferation, metastasis, and tumor formation of BCa cells inhibited by RNF126 silencing in vitro and in vivo. In conclusion, these results identified RNF126 as an oncogene that functions through ubiquitination and degradation of PTEN in BCa.
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http://dx.doi.org/10.1038/s41419-021-03521-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933351PMC
March 2021

Breast cancer proliferation and deterioration-associated metabolic heterogeneity changes induced by exposure of bisphenol S, a widespread replacement of bisphenol A.

J Hazard Mater 2021 Feb 19;414:125391. Epub 2021 Feb 19.

State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong SAR, China. Electronic address:

Exposure to bisphenol A (BPA) is considered to be associated with the increased incidence of breast cancer. As a widespread replacement of BPA, the effect of bisphenol S (BPS) on breast tumor programming has not been studied. We reported that BPS exposure significantly promoted proliferation and deterioration of breast tumor by nonmonotonic dose response. The mechanisms were investigated by molecular biology and mass spectrometry-based lipidomics, proteomics and imaging. BPS exposure induced the spatially intratumor heterogeneity of morphology-driven lipids and proteins. The more significant proliferation resulted from BPS-10 (10 μg/kg body weight /day) exposure was evidenced by the variations of spatial distribution of lipids related to ceramide-sphingomyelin signaling pathway, proteins related to chromosomal stability and cell proliferation in central necrotic regions of breast tumor. In contrast, the BPS-100 exposure obviously accelerated deterioration of breast tumor by the variations of spatial distribution of proteins that were associated with the stability of nucleic acid structure in peripheral neoplastic regions. Accordingly, dysregulation of metabolism and protein function as well as DNA methylation and hypoxic tumor microenvironment could be applied to predict the possibility of tumorigenesis, proliferation and metastasis that might be caused by other bisphenol analogs.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125391DOI Listing
February 2021

Author Correction: CTCF interacts with the lytic HSV-1 genome to promote viral transcription.

Sci Rep 2021 Feb 25;11(1):5039. Epub 2021 Feb 25.

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Kunming, 650223, China.

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http://dx.doi.org/10.1038/s41598-021-84469-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907186PMC
February 2021

Deficiency for Lcn8 causes epididymal sperm maturation defects in mice.

Biochem Biophys Res Commun 2021 Apr 22;548:7-13. Epub 2021 Feb 22.

School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan, 250100, PR China. Electronic address:

Lipocalin family members, LCN8 and LCN9, are specifically expressed in the initial segment of mouse caput epididymis. However, the biological functions of the molecules in vivo are yet to be clarified. In this study, CRISPR/Cas9 technology was used to generate Lcn8 and Lcn9 knockout mice, respectively. Lcn8 and Lcn9 male mice showed normal spermatogenesis and fertility. In the cauda epididymis of Lcn8 male mice, morphologically abnormal sperm was increased significantly, the proportion of progressive motility sperm was decreased, the proportion of immobilized sperm was elevated, and the sperm spontaneous acrosome reaction (AR) frequency was increased. Conversely, the knockout of Lcn9 did not have any effect on the ratio of morphologically abnormal sperm, sperm motility, and sperm spontaneous AR frequencies. These results demonstrated the role of LCN8 in maintaining the sperm quality in the epididymis, and suggested that the deficiency of LCN8 leads to epididymal sperm maturation defects.
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http://dx.doi.org/10.1016/j.bbrc.2021.02.052DOI Listing
April 2021

Dysregulation of circulating follicular helper T cells in type 2 diabetic patients with diabetic retinopathy.

Immunol Res 2021 Feb 24. Epub 2021 Feb 24.

Zhongshan Ophthalmic Center, SunYat-Sen University, Guangzhou, Guangdong, China.

Inflammation is known to be involved in the progression of diabetic retinopathy. Follicular helper T cells (Tfh) play critical roles in the differentiation of long-live plasma cells and production of antibodies, whereas circulating CD4CXCR5 T cells may act as a counterpart to measure Tfh cell disorders. In this study, we investigated whether Tfh could be involved in the development of diabetic retinopathy (DR) by assessing circulating Tfh cells in peripheral blood. Data showed that serum levels of total IgG and IgA were both significantly increased in type 2 diabetes mellitus (T2DM) patients with proliferative diabetic retinopathy (PDR) than with non-PDR. Also, B cell activation and differentiation were both enhanced in T2DM patients with PDR. Little changes were detected in levels of Th1, Th2, and Th17 cells. As indicated by elevated serum levels and supernatant from cultured PBMC of IL-21, we found increased circulating Tfh cells in PDR patients with dysregulated subsets. This study suggests the involvement of circulating Tfh cells in DR and, in particular, the pathogenesis of PDR.
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http://dx.doi.org/10.1007/s12026-021-09182-8DOI Listing
February 2021

Author Correction: Cryo-EM structure of trimeric Mycobacterium smegmatis succinate dehydrogenase with a membrane-anchor SdhF.

Nat Commun 2021 Feb 23;12(1):1370. Epub 2021 Feb 23.

State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, 300353, Tianjin, China.

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http://dx.doi.org/10.1038/s41467-021-21616-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902622PMC
February 2021

Lateral Gradient Ambidextrous Optical Reflection in Self-Organized Left-Handed Chiral Nematic Cellulose Nanocrystals Films.

Front Bioeng Biotechnol 2021 5;9:608965. Epub 2021 Feb 5.

State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, Jilin University, Changchun, China.

Artificial photonic materials displaying ordered reflected color patterns are desirable in the field of photonic technologies, however, it is challenging to realize. Here we present that self-assembly of cellulose nanocrystals (CNC) in a tilted cuvette leads to the formation of rainbow color CNC films. We show that the self-organized CNC films enable simultaneous reflection of left-handed circularly polarized (LCP) and right-handed circularly polarized (RCP) light with lateral gradient transmittance ratio (LCP/RCP: 8.7-0.9) and the maximum reflectance value up to 72%. This unique ambidextrous optical reflection arises from left-handed chiral photonic architectures with lateral gradient photonic bandgaps and nematic-like defects at the film-substrate interface and between left-handed photonic bandgap layers acting as a half-wavelength retarder. We demonstrate that the tilted angle self-assembly method provides a feasible step toward color patterning of CNC-based photonic films capable of ambidextrous optical reflection.
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http://dx.doi.org/10.3389/fbioe.2021.608965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892906PMC
February 2021

High levels of soluble CD25 in COVID-19 severity suggest a divergence between anti-viral and pro-inflammatory T-cell responses.

Clin Transl Immunology 2021 15;10(2):e1251. Epub 2021 Feb 15.

The University of Queensland Diamantina Institute Faculty of Medicine The University of Queensland Brisbane QLD Australia.

Objectives: We aimed to gain an understanding of the paradox of the immunity in COVID-19 patients with T cells showing both functional defects and hyperactivation and enhanced proliferation.

Methods: A total of 280 hospitalised patients with COVID-19 were evaluated for cytokine profiles and clinical features including viral shedding. A mouse model of acute infection by lymphocytic choriomeningitis virus (LCMV) was applied to dissect the relationship between immunological, virological and pathological features. The results from the mouse model were validated by published data set of single-cell RNA sequencing (scRNA-seq) of immune cells in bronchoalveolar lavage fluid (BALF) of COVID-19 patients.

Results: The levels of soluble CD25 (sCD25), IL-6, IL-8, IL-10 and TNF-α were higher in severe COVID-19 patients than non-severe cases, but only sCD25 was identified as an independent risk factor for disease severity by multivariable binary logistic regression analysis and showed a positive association with the duration of viral shedding. In agreement with the clinical observation, LCMV-infected mice with high levels of sCD25 demonstrated insufficient anti-viral response and delayed viral clearance. The elevation of sCD25 in mice was mainly contributed by the expansion of CD25CD8 T cells that also expressed the highest level of PD-1 with pro-inflammatory potential. The counterpart human CD25PD-1 T cells were expanded in BALF of COVID-19 patients with severe disease compared to those with modest disease.

Conclusion: These results suggest that high levels of sCD25 in COVID-19 patients probably result from insufficient anti-viral immunity and indicate an expansion of pro-inflammatory T cells that contribute to disease severity.
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http://dx.doi.org/10.1002/cti2.1251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883478PMC
February 2021