Publications by authors named "Liang Cheng"

1,602 Publications

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Prioritizing Disease-Related Microbes Based on the Topological Properties of a Comprehensive Network.

Front Microbiol 2021 8;12:685549. Epub 2021 Jul 8.

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.

Many microbes are parasitic within the human body, engaging in various physiological processes and playing an important role in human diseases. The discovery of new microbe-disease associations aids our understanding of disease pathogenesis. Computational methods can be applied in such investigations, thereby avoiding the time-consuming and laborious nature of experimental methods. In this study, we constructed a comprehensive microbe-disease network by integrating known microbe-disease associations from three large-scale databases (Peryton, Disbiome, and gutMDisorder), and extended the random walk with restart to the network for prioritizing unknown microbe-disease associations. The area under the curve values of the leave-one-out cross-validation and the fivefold cross-validation exceeded 0.9370 and 0.9366, respectively, indicating the high performance of this method. Despite being widely studied diseases, in case studies of inflammatory bowel disease, asthma, and obesity, some prioritized disease-related microbes were validated by recent literature. This suggested that our method is effective at prioritizing novel disease-related microbes and may offer further insight into disease pathogenesis.
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http://dx.doi.org/10.3389/fmicb.2021.685549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315281PMC
July 2021

Modified layered hand-sewn cervical end-to-side anastomosis for minimally invasive McKeown esophagectomy.

J Surg Oncol 2021 Jul 26. Epub 2021 Jul 26.

Department of Thoracic Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.

Background: Minimally invasive McKeown esophagectomy (MIE McKeown) with cervical anastomosis is a widely used approach for the treatment of esophageal cancer (EC). Anastomotic leak is one of the most serious complications following esophagectomy. This study aimed to summarize the anastomosis procedure and assess the clinical outcomes of our modified layered hand-sewn cervical end-to-side anastomosis for cervical anastomosis during MIE McKeown.

Methods: We retrospectively reviewed clinical data of 508 consecutive EC patients who underwent MIE McKeown using the modified layered hand-sewn cervical end-to-side anastomosis between June 2016 and June 2020.

Results: The incidence of anastomotic leakage in our cohort was 2.0%. The postoperative stricture rate was 6.9% and the incidence of other postoperative complications was less than 9.3%. The mean time for setting up MIE McKeown was approximately 211.0 min and the average duration of postoperative hospital stay was 9.1 days.

Conclusion: This modified layered hand-sewn cervical end-to-side anastomosis is a safe and effective method for MIE McKeown with a low incidence of anastomotic leakage, anastomotic stricture, or other postoperative complications.
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http://dx.doi.org/10.1002/jso.26622DOI Listing
July 2021

Prostate Cancer in 2021: Novelties in Prognostic and Therapeutic Biomarker Evaluation.

Cancers (Basel) 2021 Jul 11;13(14). Epub 2021 Jul 11.

Section of Pathological Anatomy, United Hospitals, School of Medicine, Polytechnic University of the Marche Region, Via Conca 71, 60126 Ancona, Italy.

The 2021 novelties in prognostic and therapeutic tissue markers in patients with prostate cancer (PCa) can be subdivided into two major groups. The first group is related to prognostic markers based on morphological and immunohistochemical evaluations. The novelties in this group can then be subdivided into two subgroups, one involving morphologic evaluation only, i.e., , and the other involving both morphologic and immunohistochemical evaluations, i.e., . Grading concerns androgen-dependent PCa, while AVPCa represents a late phase in its natural history, when it becomes androgen-independent. The novelties of the other major group are related to molecular markers predicting significant disease or response to therapy. This group mainly includes novelties in the molecular evaluation of PCa in tissue material and liquid biopsies.
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http://dx.doi.org/10.3390/cancers13143471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307279PMC
July 2021

Amine-Assisted Delaminated 2D TiCT MXenes for High Specific Capacitance in Neutral Aqueous Electrolytes.

ACS Appl Mater Interfaces 2021 Jul 23. Epub 2021 Jul 23.

Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, Jiangsu 215123, P. R. China.

Electrochemical capacitors using neutral aqueous electrolytes are safer and cheaper and allow diverse current collectors compared with the counterparts using organic or acidic/alkaline electrolytes. Two-dimensional (2D) MXenes have been demonstrated as the high-capacitive materials with high rate performance. However, MXene electrodes often exhibit a limited capacitance in neutral electrolytes, where the reversible electrochemical reactions rely greatly on the structural and surface properties of MXenes depending on their synthesis methods. Herein, a simple and highly efficient strategy, which combines HF etching of TiAlC powder and subsequent amine-assisted delamination at a low temperature, is developed to synthesize 2D TiCT MXenes. The comprehensive results demonstrate that the enlarged interlayer spacing and the presence of more -O-containing functional groups synergistically contribute to the improvement of capacitive performance in neutral electrolytes. The 2D TiCT MXenes show excellent electrochemical performance in various neutral electrolytes, and a high specific gravimetric capacitance of 149.8 F/g is achieved in 1.0 M LiSO. Furthermore, the flexible solid-state supercapacitors (SCs) with a neutral PVA/LiCl gel electrolyte possess a superior areal capacitance (163.1 mF/cm) and high energy density (17.6 μWh/cm at 0.07 mW/cm), together with high user safety. This work provides a promising guideline of synthesis strategy for high-capacitive MXenes used in neutral electrolytes, which may promote the development of safe and flexible power sources with a high energy density.
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http://dx.doi.org/10.1021/acsami.1c06161DOI Listing
July 2021

Cancer Subtype Identification by Consensus Guided Graph Autoencoders.

Bioinformatics 2021 Jul 20. Epub 2021 Jul 20.

College of Computer Science and Electronic Engineering, Hunan University, Changsha, 410082, China.

Motivation: Cancer subtype identification aims to divide cancer patients into subgroups with distinct clinical phenotypes and facilitate the development for subgroup specific therapies. The massive amount of multi-omics datasets accumulated in the public databases have provided unprecedented opportunities to fulfill this task. As a result, great computational efforts have been made to accurately identify cancer subtypes via integrative analysis of these multi-omics datasets.

Results: In this paper, we propose a Consensus Guided Graph Autoencoder (CGGA) to effectively identify cancer subtypes. First, we learn for each omic a new feature matrix by using graph autoencoders, where both structure information and node features can be effectively incorporated during the learning process. Second, we learn a set of omic-specific similarity matrices together with a consensus matrix based on the features obtained in the first step. The learned omic-specific similarity matrices are then fed back to the graph autoencoders to guide the feature learning. By iterating the two steps above, our method obtains a final consensus similarity matrix for cancer subtyping. To comprehensively evaluate the prediction performance of our method, we compare CGGA with several approaches ranging from general-purpose multi-view clustering algorithms to multi-omics-specific integrative methods. The experimental results on both generic datasets and cancer datasets confirm the superiority of our method. Moreover, we validate the effectiveness of our method in leveraging multi-omics datasets to identify cancer subtypes. In addition, we investigate the clinical implications of the obtained clusters for glioblastoma and provide new insights into the treatment for patients with different subtypes.

Availability: The source code of our method is freely available at https://github.com/alcs417/CGGA.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btab535DOI Listing
July 2021

Briefings in functional genomics special section editorial: analysis of integrated multiple omics data.

Brief Funct Genomics 2021 Jul;20(4):196-197

Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu 610054, China.

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http://dx.doi.org/10.1093/bfgp/elab033DOI Listing
July 2021

Digital whole mount sections of the prostate: heading towards new ways of communicating with clinicians and patients without microscope.

Minerva Urol Nephrol 2021 Jul 15. Epub 2021 Jul 15.

Section of Pathological Anatomy, School of Medicine, United Hospitals, Polytechnic University of the Marche Region, Ancona, Italy -

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http://dx.doi.org/10.23736/S2724-6051.21.04552-3DOI Listing
July 2021

Somatic-Type Yolk Sac Tumor Arising as a Predominant Component of Bladder Urothelial Carcinoma.

Int J Surg Pathol 2021 Jul 13:10668969211030688. Epub 2021 Jul 13.

12250Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA.

Germ cell differentiation has been described in association with somatic tumors arising from several organ systems; rare cases arising from urothelium have been reported. Here we present a 62-year-old male with a remote history of lung cancer, a left adrenal gland mass, and a 5.6 cm left bladder wall mass; cystoscopy demonstrated a large papillary mass on the left anterior bladder wall. A transurethral resection specimen was sent for review in consultation and showed extensive papillary structures with thin fibrovascular cores lined by neoplastic cells with clear cytoplasm. These neoplastic cells were diffusely positive for pancytokeratin, CDX2 (caudal-type homebox 2), SALL4 (sal-like transcription factor 4), glypican-3, AFP (alpha-fetoprotein), while negative for PAX-8 (paired box gene 8), NKX3.1 (NK3 homeobox 1), PSA (prostate specific antigen), TTF-1 (thyroid transcription factor 1), Napsin A, inhibin, and OCT4 (octamer-binding transcription factor 4). Conventional urothelial conventional carcinoma and focal squamous differentiation were also identified as minor components. Urothelial carcinoma was focally positive for GATA3 (GATA-binding protein 3) and p63; SALL4 and glypican-3 were negative. Overall findings supported a yolk sac tumor with a smaller component of squamous cell carcinoma (<1%). Subsequent cystectomy showed similar morphologic features and immunoprofile in addition to foci of urothelial carcinoma and urothelial carcinoma in situ. No chromosome 12p abnormalities were identified by fluorescent in-situ hybridization study. A diagnosis of yolk sac tumor derived from urothelial carcinoma was made. Yolk sac tumor should be considered in the differential diagnosis of a high-grade urothelial carcinoma, particularly when glandular or other unusual architectural patterns are present. A somatic origin with underlying genomic instability similar to what has been described in the uterus and ovaries is suggested.
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http://dx.doi.org/10.1177/10668969211030688DOI Listing
July 2021

Metastatic urothelial carcinoma to the brain, spinal cord and spine: A contemporary multi-institutional clinicopathologic analysis of 24 cases.

Pathol Res Pract 2021 Jul 1;224:153537. Epub 2021 Jul 1.

Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA; Department of Urology, Emory University School of Medicine, Atlanta, GA 30322, USA; Department of Pathology, Veterans Affairs Medical Center, Decatur, GA 30033, USA; Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA. Electronic address:

Only case reports and small series of metastatic urothelial carcinoma (UCa) to the central nervous system (CNS) or spine have been published. We identified 24 cases at our institutions. The mean patient age was 64 years (range: 41-78 years) with a male predominance. Nineteen (79%) cases involved the brain, 3 (13%) and 2 (8%) cases involved the spinal cord and spine, respectively. Most cases (79%) were a single mass with a mean size of 2.8 cm (range: 0.9-5.5 cm). With the exception of 3 cases demonstrating micropapillary UCa, all metastases showed morphologic features of conventional UCa. Prior to CNS and spinal metastases, there was a history of UCa involving only the bladder in 16 (67%) patients, ureter in 1 (4%) patient, and kidney/renal pelvis in 1 (4%) patient. In 1 additional patient (4%) each, the primary tumor involved both bladder and ureter, bladder and kidney/renal pelvis, and ureter and kidney/renal pelvis, respectively. Three (13%) patients had no known primary site. In two patients, the diagnosis of primary UCa was made concurrently as the CNS metastasis, and ranged up to 30 years in other patients. Follow-up was available in 14 patients with a mean duration of 7 months (range: 0-23 months), and 4 patients died of disease. Both clinicians and pathologists should be aware that concurrent or late CNS or spine metastases may occur and could present as a solitary mass even over a decade after the initial diagnosis.
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http://dx.doi.org/10.1016/j.prp.2021.153537DOI Listing
July 2021

Identification of gene signature associated with type 2 diabetes mellitus by integrating mutation and expression data.

Curr Gene Ther 2021 Jul 7. Epub 2021 Jul 7.

NHC and CAMS Key Laboratory of Molecular Probe and Targeted Theranostics, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, China.

Type 2 diabetes mellitus (T2DM) is a chronic disease. The molecular diagnosis should be helpful for the treatment of T2DM patients. With the development of sequencing technology, a large number of differentially expressed genes were identified from expression data. However, the method of machine learning can only identify the local optimal solution as the signature. The mutation information obtained by inheritance can better reflect the relationship between genes and diseases. Therefore, we need to integrate mutation information to more accurately identify the signature. To this end, we integrated genome-wide association study (GWAS) data and expression data, combined with expression quantitative trait loci (eQTL) technology to get T2DM predictive signature (T2DMSig-10). Firstly, we used GWAS data to obtain a list of T2DM susceptible loci. Then, we used eQTL technology to obtain risk single nucleotide polymorphisms (SNPs), and combined with the pancreatic β-cells gene expression data to obtain 10 protein-coding genes. Next, we combined these genes with equal weights. After receiver operating characteristic (ROC), single-gene removal and increase method, gene ontology function enrichment and protein-protein interaction network were used to verify the results that showed that T2DMSig-10 had an excellent predictive effect on T2DM (AUC=0.99), and was highly robust. In short, we obtained the predictive signature of T2DM, and further verified it.
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http://dx.doi.org/10.2174/1566523221666210707140839DOI Listing
July 2021

Supramolecular wrapped sandwich like SW-SiN hybrid sheets as advanced filler toward reducing fire risks and enhancing thermal conductivity of thermoplastic polyurethanes.

J Colloid Interface Sci 2021 Jun 29;603:844-855. Epub 2021 Jun 29.

State Key Laboratory of Fire Science, CAS Key Laboratory of Soft Matter Chemistry, University of Science and Technology of China, Hefei 230026, China. Electronic address:

A sandwich-like melamine/phytic acid/silicon nitride hybrid (SW-SiN) sheets were prepared by supramolecular wrapping as the hybrid flame retardants for thermoplastic polyurethane (TPU). The introduction of SiN sheets as a template could not only induce the generation of two-dimensional phytic/melamine (PAMA) capping layers, but also produce the synergistic flame-retardant effect on TPU composites. Cone test showed that heat release rate (HRR), smoke production rate (SPR) and total smoke production (TSP) values of TPU were decreased obviously by adding SW-SiN. TG-IR test indicated the dramatic inhibition of aromatic compound, hydrocarbons, CO and HCN release. Besides, the thermal conductivity of composites was obviously improved by adding SW-SiN. This work may provide better reference for developing multi-functional TPU composites for diverse application.
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http://dx.doi.org/10.1016/j.jcis.2021.06.153DOI Listing
June 2021

Immunohistochemical Characterization of 120 Testicular Sex Cord-Stromal Tumors With an Emphasis on the Diagnostic Utility of SOX9, FOXL2, and SF-1.

Am J Surg Pathol 2021 Mar 22. Epub 2021 Mar 22.

*Department of Pathology and Laboratory Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto †Department of Pathology, Stanford Medical Center, Stanford, CA ‡Department of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH §Department of Pathology, Indiana University School of Medicine, Indianapolis, IN.

Sex cord-stromal tumors (SCSTs) account for the second most common category of testicular neoplasms and include several entities that may show overlapping morphologies and present diagnostic challenges. We analyzed a cohort of 120 testicular SCSTs and investigated the diagnostic utility of SRY-box transcription factor 9 (SOX9), forkhead box protein L2 (FOXL2), and steroidogenic factor 1 (SF-1) immunohistochemical stains. The results were compared with the more commonly used SCST markers, inhibin α, calretinin, and Wilms' tumor 1 (WT1). SF-1 was overall the most sensitive stain (91%), followed by inhibin α (70%), calretinin (52%), FOXL2 (50%), SOX9 (47%), and WT1 (37%), but sensitivities varied by tumor type. SOX9 and calretinin were more commonly positive in sex cord elements versus stromal elements (62% vs. 27% and 47% vs. 9%, respectively), whereas FOXL2 was more commonly positive in stromal elements versus sex cord elements (100% vs. 55%) when excluding Leydig cell tumors from the stromal category. Although no individual stain was diagnostically specific, some immunophenotypic patterns were noted that may help in the subclassification of SCSTs. We conclude that SOX9, FOXL2, and SF-1 are useful immunohistochemical stains for confirming sex cord-stromal differentiation in testicular tumors and provide increased sensitivity as well as additional diagnostic information, especially when combined with the more commonly used inhibin α, calretinin, and WT1 immunostains. Although morphology is paramount for subclassification of SCSTs, knowledge of certain immunohistochemical patterns may be helpful for diagnostically challenging cases.
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http://dx.doi.org/10.1097/PAS.0000000000001704DOI Listing
March 2021

Enantiospecific Detection of D-Amino Acid through Synergistic Upconversion Energy Transfer.

Angew Chem Int Ed Engl 2021 Jul 5. Epub 2021 Jul 5.

SZU-NUS Collaborative Innovation Center for Optoelectronic Science & Technology, International Collaborative Laboratory of 2D Materials for Optoelectronics Science and Technology of Ministry of Education, Institute of Microscale Optoelectronics, Shenzhen University, Shenzhen, 518060, China.

D-amino acids (DAAs) are indispensable in regulating diverse metabolic pathways. Selective and sensitive detection of DAAs is crucial for understanding the complexity of metabolic processes and managing associated diseases. However, current DAA detection strategies mainly rely on bulky instrumentation or electrochemical probes, limiting their cellular and animal applications. Here we report an enzyme-coupled nanoprobe that can detect enantiospecific DAAs through synergistic energy transfer. This nanoprobe offers near-infrared upconversion capability, a wide dynamic detection range, and a detection limit of 2.2 μM, providing a versatile platform for in vivo noninvasive detection of DAAs with high enantioselectivity. These results potentially allow real-time monitoring of biomolecular handedness in living animals, as well as developing antipsychotic treatment strategies.
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http://dx.doi.org/10.1002/anie.202105297DOI Listing
July 2021

The Coronavirus Disease 2019 (COVID-19) Pandemic's Impact on Social Interaction in Pathology.

Arch Pathol Lab Med 2021 Jun 25. Epub 2021 Jun 25.

Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy.

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http://dx.doi.org/10.5858/arpa.2021-0221-LEDOI Listing
June 2021

Low-grade oncocytic tumour expands the spectrum of renal oncocytic tumours and deserves separate classification: a review of 23 cases from a single tertiary institute.

J Clin Pathol 2021 Jun 24. Epub 2021 Jun 24.

Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA

Aims: Low-grade oncocytic tumour (LOT) has recently been introduced as a potential distinct entity.

Methods: At the Indiana University department of pathology, primary renal epithelial neoplasms between 2005 and 2020 were searched after appropriate institutional review board permissions.

Results: Twenty-three cases (male/female ratio 14/9) with a median age of 66 (23-84 years) were identified. The majority of patients underwent partial nephrectomy (15/23, 65%), with a median tumour size of 4.0 cm (2.2-10.5 cm). Only one case had infiltration beyond the kidney (perinephric fat). Solid/diffuse proliferation of tightly packed oncocytic tumour cells and occasional tubule formations, with an abrupt edematous change in the stroma with loosely connected small clusters of tumour cells. Along with diffuse CK7 expression with lack of CD117 in all cases, vimentin was positive in 8/23 cases (35%, 5 focal). CD10 was expressed in 6/13 (46%, 4 focal). Alpha-Methylacyl-CoA Racemase (AMACR) was positive in 5/8 (63%) cases. Focal but intense cytoplasmic colloidal iron stain was present in 3/20 (15%) cases. Luminal or cytoplasmic/perinuclear precipitation was observed in 8/20 (40%) cases. Succinate Dehydrogenase B (SDHB) was performed in 6 cases, with all retained expression.

Conclusions: LOT is a clinically indolent and potentially benign entity with distinguishable morphology and immunohistochemical profile that can be performed and be easily interpreted in most of surgical pathology settings. Additional studies with larger cohorts, comprehensive molecular evaluation and longer follow-up are needed to definitively recognise these tumours as a separate entity and to further address the possibility of active surveillance options in eligible patients.
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http://dx.doi.org/10.1136/jclinpath-2021-207478DOI Listing
June 2021

Highly differentiated follicular thyroid-type carcinoma of the ovary reconsidered.

J Clin Pathol 2021 Jun 23. Epub 2021 Jun 23.

Pathology & Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.

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http://dx.doi.org/10.1136/jclinpath-2021-207447DOI Listing
June 2021

Ex vivo and in vivo fluorescence detection and imaging of adenosine triphosphate.

J Nanobiotechnology 2021 Jun 22;19(1):187. Epub 2021 Jun 22.

Laboratory of Nanoscale Biochemical Analysis, Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou, 215123, China.

Background: Ex vivo and in vivo detection and imaging of adenosine triphosphate (ATP) is critically important for the diagnosis and treatment of diseases, which still remains challenges up to present.

Results: We herein demonstrate that ATP could be fluorescently detected and imaged ex vivo and in vivo. In particular, we fabricate a kind of fluorescent ATP probes, which are made of titanium carbide (TC) nanosheets modified with the ROX-tagged ATP-aptamer (TC/Apt). In the constructed TC/Apt, TC shows superior quenching efficiency against ROX (e.g., ~ 97%). While in the presence of ATP, ROX-tagged aptamer is released from TC surface, leading to the recovery of fluorescence of ROX under the 545-nm excitation. Consequently, a wide dynamic range from 1 μM to 1.5 mM ATP and a high sensitivity with a limit of detection (LOD) down to 0.2 μM ATP can be readily achieved by the prepared TC/Apt. We further demonstrate that the as-prepared TC/Apt probe is feasible for accurate discrimination of ATP in different samples including living cells, body fluids (e.g., mouse serum, mouse urine and human serum) and mouse tumor models.

Conclusions: Fluorescence detection and imaging of ATP could be readily achieved in living cells, body fluids (e.g., urine and serum), as well as mouse tumor model through a new kind of fluorescent ATP nanoprobes, offering new powerful tools for the treatment of diseases related to abnormal fluctuation of ATP concentration.
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http://dx.doi.org/10.1186/s12951-021-00930-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220756PMC
June 2021

Inorganic nanomaterials with rapid clearance for biomedical applications.

Chem Soc Rev 2021 Aug 22;50(15):8669-8742. Epub 2021 Jun 22.

Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu Province, China.

Inorganic nanomaterials that have inherently exceptional physicochemical properties (e.g., catalytic, optical, thermal, electrical, or magnetic performance) that can provide desirable functionality (e.g., drug delivery, diagnostics, imaging, or therapy) have considerable potential for application in the field of biomedicine. However, toxicity can be caused by the long-term, non-specific accumulation of these inorganic nanomaterials in healthy tissues, preventing their large-scale clinical utilization. Over the past several decades, the emergence of biodegradable and clearable inorganic nanomaterials has offered the potential to prevent such long-term toxicity. In addition, a comprehensive understanding of the design of such nanomaterials and their metabolic pathways within the body is essential for enabling the expansion of theranostic applications for various diseases and advancing clinical trials. Thus, it is of critical importance to develop biodegradable and clearable inorganic nanomaterials for biomedical applications. This review systematically summarizes the recent progress of biodegradable and clearable inorganic nanomaterials, particularly for application in cancer theranostics and other disease therapies. The future prospects and opportunities in this rapidly growing biomedical field are also discussed. We believe that this timely and comprehensive review will stimulate and guide additional in-depth studies in the area of inorganic nanomedicine, as rapid in vivo clearance and degradation is likely to be a prerequisite for the future clinical translation of inorganic nanomaterials with unique properties and functionality.
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http://dx.doi.org/10.1039/d0cs00461hDOI Listing
August 2021

Targeting WD repeat domain 5 enhances chemosensitivity and inhibits proliferation and programmed death-ligand 1 expression in bladder cancer.

J Exp Clin Cancer Res 2021 Jun 21;40(1):203. Epub 2021 Jun 21.

Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107th Yanjiangxi Road, Guangzhou, China.

Background: Chemotherapy and/or immunotherapy are first-line treatments for advanced muscle-invasive bladder cancer (BCa), but the unsatisfactory objective response rate to these treatments yields poor 5-year patient survival. Discovery of therapeutic targets essential for BCa maintenance is critical to improve therapy response in clinic. This study evaluated the role of targeting WD repeat domain 5 (WDR5) with the small molecule compound OICR-9429 and whether it could be used to treat bladder cancer.

Methods: We analysed the expression and clinical prognosis of WDR5 in a TCGA cohort. The pharmacological role of OICR-9429 was further investigated in vitro and in vivo. RNA sequencing, western blot, and chromatin immunoprecipitation (ChIP) were utilized to explored the mechanism underlying OICR-9429-induced WDR5 inhibition.

Results: First, we found that WDR5 expression was upregulated in BCa and was associated with histologic grade, metastasis status, histologic subtype, and molecular subtype. High WDR5 expression level was also correlated with shorter overall survival (OS) in BCa. The WDR5 inhibitor OICR-9429 reduced cell viability by decreasing H3K4me3 levels but not WDR5 levels in T24, UM-UC-3, and TCCSUP BCa cells. OICR-9429 suppressed the proliferation of BCa cells by blocking the G1/S phase transition. Next, OICR-9429 enhanced apoptosis and chemosensitivity to cisplatin in BCa cells. In addition, OICR-9429 independently inhibited the motility and metastatic behaviour of BCa cells. In vivo experiments further revealed that OICR-9429 suppressed tumour growth, enhanced chemosensitivity, and reduced the toxicity of cisplatin in BCa. Notably, WDR5 was positively correlated with programmed death-ligand 1 (PD-L1) expression, and OICR-9429 suppressed immune evasion by blocking PD-L1 induced by IFN-γ. Mechanistically, some cell cycle-, antiapoptosis-, DNA repair-, metastasis-, and immune evasion-related genes, including BIRC5, XRCC2, CCNB1, CCNE2, PLK1, AURKA, FOXM1, and PD-L1 were identified to be directly regulated by OICR-9429 in a H3K4me3-dependent manner.

Conclusions: Our novel finding is that the WDR5 inhibitor, OICR-9429, suppressed proliferation, metastasis and PD-L1-based immune evasion while enhancing apoptosis and chemosensitivity to cisplatin in BCa by blocking the WDR5-MLL complex mediating H3K4me3 in target genes. Hence, our findings offer insight into a multipotential anticancer compound, OICR-9429, which enhances the antitumour effect of cisplatin or immunotherapy in BCa.
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http://dx.doi.org/10.1186/s13046-021-01989-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215817PMC
June 2021

Local Random Pattern Flap Coverage for Implant Exposure following Open Reduction Internal Fixation via Extensile Lateral Approach to the Calcaneus.

BMC Musculoskelet Disord 2021 Jun 21;22(1):567. Epub 2021 Jun 21.

Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan road, Shanghai, 200233, China.

Background: Skin necrosis and implant exposure most often appear at the corner of Extensile Lateral Approach for open reduction and internal fixation (ORIF) for displaced intra-articular fracture of the calcaneus. Flap transfer is often used for coverage of this implant exposure. We introduced a new simple local random pattern flap to cover the implant exposure.

Methods: From March 2017 to March 2020, 12 patients with implant exposure after ORIF for displaced intra-articular fracture of the calcaneus were treated with this procedure. The sizes of the defects ranged from 2 × 2 cm to 5 × 2 cm. A local random pattern flap was designed according to the defect size. The lower edge of the flap was along with the wound upper edge and extended distally. The upper horizontal incision of the flap was made at the lateral malleolus level with a length of 5-7 cm depending on the wound defect. Then the random pattern flap was elevated and transferred to cover the defect area.

Results: The mean follow-up duration was 6.3 months (ranging 4-13 months). All 12 flaps were uneventfully healed and all patients were able to wear shoes, and no debulking procedures were required.

Conclusion: The local random pattern flap could be a choice for surgeons when implant exposure at the corner of Extensile Lateral Approach to the Calcaneus occurs.
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http://dx.doi.org/10.1186/s12891-021-04427-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218457PMC
June 2021

Regional water security evaluation with risk control model and its application in Jiangsu Province, China.

Environ Sci Pollut Res Int 2021 Jun 17. Epub 2021 Jun 17.

Nanjing Hydraulic Research Institute, Nanjing, 210029, Jiangsu, China.

To reduce losses from the various disasters, regional water security evaluation and risk control model is studied. The model is built upon different kinds of indices in water security system, proceeding from the whole structure and its parts of evaluation, forewarning and decision making analysis. Based on China's national conditions, this study firstly advances an evaluation index system of regional water security, which includes three subsystems of water resource security, water environment security, and water disaster control security. Secondly, fuzzy analytic hierarchy process based on accelerating genetic algorithm (AGA-FAHP) combines with entropy weight method (EW) to determine the objective weights of evaluation indexes. The subjective and objective weights can be integrated by the principle of minimum relative information entropy. The subsystem weights are obtained by using AGA-FAHP. Then regional water security evaluation model is established. Thirdly, the comparison judging method is adopted to divide warning degree of water security with the comprehensive evaluation index and forewarning standards, and then the local conditions for proposing planning schemes. Finally, decision making analysis is employed to find the effective indices based on projection pursuit technique with the ideal point method in multi-index decision. This study takes Jiangsu province, China as an example. The evaluation results from 2000 to 2015 show that the development trend of water security is increasing on the whole except in several individual years. Risk forewarning doesn't take place in recent years. But risk is always there. So, project and non-project measures are proposed for the corresponding forewarning levels. From light warnings for three times and moderate warning for once in 2000, 2001, 2002, and 2004, index 1, 3, 4, 11, 13, 17, and 18 are selected as the effective indices to decision making analysis in common. Then, the solution schemes are given as the processing method accordingly. This conclusion is reasonable and its method is practical that match the reality. It suggests that the presented model is feasible with theory and application, which can offer advice in regional water security management to some extent.
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http://dx.doi.org/10.1007/s11356-021-14547-5DOI Listing
June 2021

The Genitourinary Pathology Society Update on Classification of Variant Histologies, T1 Substaging, Molecular Taxonomy, and Immunotherapy and PD-L1 Testing Implications of Urothelial Cancers.

Adv Anat Pathol 2021 Jul;28(4):196-208

Department of Pathology, West German Cancer Center/University Hospital Essen, University of Duisburg-Essen, Duisburg.

The Genitourinary Pathology Society (GUPS) undertook a critical review of the recent advances in bladder cancer focusing on important topics of high interest for the practicing surgical pathologist and urologist. This review represents the second of 2 manuscripts ensuing from this effort. Herein, we address the effective reporting of bladder cancer, focusing particularly on newly published data since the last 2016 World Health Organization (WHO) classification. In addition, this review focuses on the importance of reporting bladder cancer with divergent differentiation and variant (subtypes of urothelial carcinoma) histologies and the potential impact on patient care. We provide new recommendations for reporting pT1 staging in diagnostic pathology. Furthermore, we explore molecular evolution and classification, emphasizing aspects that impact the understanding of important concepts relevant to reporting and management of patients.
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http://dx.doi.org/10.1097/PAP.0000000000000309DOI Listing
July 2021

The Genitourinary Pathology Society Update on Classification and Grading of Flat and Papillary Urothelial Neoplasia With New Reporting Recommendations and Approach to Lesions With Mixed and Early Patterns of Neoplasia.

Adv Anat Pathol 2021 Jul;28(4):179-195

Medicine.

The Genitourinary Pathology Society (GUPS) undertook a critical review of the recent advances in bladder neoplasia with a focus on issues relevant to the practicing surgical pathologist for the understanding and effective reporting of bladder cancer, emphasizing particularly on the newly accumulated evidence post-2016 World Health Organization (WHO) classification. The work is presented in 2 manuscripts. Here, in the first, we revisit the nomenclature and classification system used for grading flat and papillary urothelial lesions centering on clinical relevance, and on dilemmas related to application in routine reporting. As patients of noninvasive bladder cancer frequently undergo cystoscopy and biopsy in their typically prolonged clinical course and for surveillance of disease, we discuss morphologies presented in these scenarios which may not have readily applicable diagnostic terms in the WHO classification. The topic of inverted patterns in urothelial neoplasia, particularly when prominent or exclusive, and beyond inverted papilloma has not been addressed formally in the WHO classification. Herein we provide a through review and suggest guidelines for when and how to report such lesions. In promulgating these GUPS recommendations, we aim to provide clarity on the clinical application of these not so uncommon diagnostically challenging situations encountered in routine practice, while also importantly advocating consistent terminology which would inform future work.
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http://dx.doi.org/10.1097/PAP.0000000000000308DOI Listing
July 2021

Incidentally discovered myelolipomatous adrenal adenomas, including six cases presenting with hypercortisolism.

Pathol Res Pract 2021 Jun 6;224:153508. Epub 2021 Jun 6.

Department of Pathology, Indiana University, Indianapolis, IN, 46202, USA.

Most adrenal incidentalomas are non-functioning adenomas that require no treatment. The presence of a myelolipomatous component of adrenal incidentalomas is a rare, but well-known occurrence in both hyperplastic and neoplastic lesions of the adrenal cortex. Although the improvements in abdominal imaging have increased identification of myelolipomatous adrenal cortical adenomas radiologically, due to the rarity of this lesion, the clinical pathological features of these lesions are unclear and can sometimes cause diagnostic difficulty. Eleven patients had surgeries at The University of Texas MD Anderson Cancer Center. Four additional cases were provided from an external collaborator. Of the 15 cases, there were 5 male and 10 female patients, with a median age of 52 years (mean 54 years, range 28-84 years). Clinical presentation included adrenal incidentaloma (n = 9), Cushing syndrome (n = 4, including 1 as a part of Carney complex), and subclinical Cushing syndrome (n = 2, including 1 with bilateral macronodular adrenal hyperplasia). In this study, we present the clinicopathologic features of fifteen myelolipomatous adrenal adenomas, the largest series published thus far.
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http://dx.doi.org/10.1016/j.prp.2021.153508DOI Listing
June 2021

Colorectal cancer with microsatellite instability: Right-sided location and signet ring cell histology are associated with nodal metastases, and extranodal extension influences disease-free survival.

Pathol Res Pract 2021 Jun 8;224:153519. Epub 2021 Jun 8.

Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy. Electronic address:

Colorectal cancer (CRC) with microsatellite instability (MSI) accounts for 15-18 % of all CRCs and represents the category with the best prognosis. This study aimed at determining any possible clinical/pathological features associated with a higher risk of nodal metastasization in MSI-CRC, and at defining any possible prognostic moderators in this setting. All surgically resected CRCs of the last 20 years (mono-institutional series) with a PCR-based diagnosis of MSI, with and without nodal metastasis, have been retrieved for histological review, which was performed following WHO guidelines. Furthermore, the most important prognostic moderators have been investigated with a survival analysis. The study of 33 cases of MSI-CRCs with nodal metastasis highlighted a high fidelity of histology maintenance between primary tumors and matched nodal metastases. At survival analysis, the strongest prognostic variable in MSI-CRCs with nodal metastasis was the extranodal extension (multivariate analysis, HR: 14.4, 95 %CI: 1.46-140.9, p = 0.022). Furthermore, through a comparison between nodal positive (33 cases) and nodal negative (71 cases) MSI-CRCs, right-sided location (p < 0.0001), pT4 stage (p = 0.0004) and signet-ring histology (p = 0.0089) emerged as parameters more commonly associated with nodal metastasization. These findings shed new light on the biology of MSI-CRC and can be of help for the prognostic stratification of MSI-CRC patients.
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http://dx.doi.org/10.1016/j.prp.2021.153519DOI Listing
June 2021

Single-cell RNA sequencing of human femoral head .

Aging (Albany NY) 2021 06 10;13(11):15595-15619. Epub 2021 Jun 10.

Center for System Biology, Data Sciences, and Reproductive Health, School of Basic Medical Science, Central South University, Yuelu, Changsha 410013, China.

The homeostasis of bone metabolism depends on the coupling and precise regulation of various types of cells in bone tissue. However, the communication and interaction between bone tissue cells at the single-cell level remains poorly understood. Thus, we performed single-cell RNA sequencing (scRNA-seq) on the primary human femoral head tissue cells (FHTCs). Nine cell types were identified in 26,574 primary human FHTCs, including granulocytes, T cells, monocytes, B cells, red blood cells, osteoblastic lineage cells, endothelial cells, endothelial progenitor cells (EPCs) and plasmacytoid dendritic cells. We identified () and () as novel bone metabolism-related genes. Additionally, we found that several subtypes of monocytes, T cells and B cells were related to bone metabolism. Cell-cell communication analysis showed that collagen, chemokine, transforming growth factor and their ligands have significant roles in the crosstalks between FHTCs. In particular, EPCs communicated with osteoblastic lineage cells closely via the "COL2A1-ITGB1" interaction pair. Collectively, this study provided an initial characterization of the cellular composition of the human FHTCs and the complex crosstalks between them at the single-cell level. It is a unique starting resource for in-depth insights into bone metabolism.
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http://dx.doi.org/10.18632/aging.203124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221309PMC
June 2021

Mg(OH) nanoparticles enhance the antibacterial activities of macrophages by activating the reactive oxygen species.

J Biomed Mater Res A 2021 Jun 10. Epub 2021 Jun 10.

Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China.

Infection often causes disastrous consequences in all fields of clinical medicine, especially orthopedics. Hence, critical efforts are being made to engineer novel nanomaterials for the treatment of orthopedic infections due to the high biocompatibility and antibacterial properties they possess. The purpose of this study was to investigate the antibacterial effects of magnesium hydroxide (Mg(OH) ) nanoparticles (NPs) in vitro and determine their possible mechanisms of action. In this study, Escherichia coli was selected as the pathogenic bacteria and it was found that Mg(OH) NPs significantly inhibited the growth of E. coli by promoting nucleic acid leakage, inhibiting protein synthesis, and suppressing the metabolic activity. The minimum inhibitory concentration for these bacteria was determined to be 4.4 μg/ml. In vitro flow cytometry and immunofluorescence tests indicated that Mg(OH) NPs induced the macrophages to generate reactive oxygen species to kill the bacteria. To understand the mechanisms involved in this process, western blotting was performed and it was found that Mg(OH) NPs activated the phosphatidylinositol-3-kinase/serine-threonine kinase (PI3K/Akt) signaling pathway of macrophages to enhance their phagocytosis with no obvious cytotoxicity. Thus, Mg(OH) NPs are a suitable choice to develop promising agents or coating materials for the treatment of clinically widespread infections in view of their safety, biocompatibility, and powerful antibacterial properties.
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http://dx.doi.org/10.1002/jbm.a.37219DOI Listing
June 2021

A Light-Controllable Chemical Modulation of m A RNA Methylation.

Angew Chem Int Ed Engl 2021 Jun 9. Epub 2021 Jun 9.

Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Key Laboratory of Molecular Recognition and Function, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.

Bioactive small molecules with photo-removable protecting groups have provided spatial and temporal control of corresponding biological effects. We present the design, synthesis, computational and experimental evaluation of the first photo-activatable small-molecule methyltransferase agonist. By blocking the functional N-H group on MPCH with a photo-removable ortho-nitrobenzyl moiety, we have developed a promising photo-caged compound that had completely concealed its biological activity. Short UV light exposure of cells treated with that caged molecule in a few minutes resulted in a considerable hypermethylation of m A modification in transcriptome RNAs, implicating a rapid release of the parent active compound. This study validates for the first time the photo-activatable small organic molecular concept in the field of RNA epigenetic research, which represents a novel tool in spatiotemporal and cellular modulation approaches.
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http://dx.doi.org/10.1002/anie.202103854DOI Listing
June 2021
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