Publications by authors named "Tao Xie"

391 Publications

Homeostatic growth of dynamic covalent polymer network toward ultrafast direct soft lithography.

Sci Adv 2021 Oct 20;7(43):eabi7360. Epub 2021 Oct 20.

Ningbo Research Institute of Zhejiang University, Ningbo 315100, China.

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http://dx.doi.org/10.1126/sciadv.abi7360DOI Listing
October 2021

Intrinsic and acquired drug resistance to LSD1 inhibitors in small cell lung cancer occurs through a TEAD4-driven transcriptional state.

Mol Oncol 2021 Oct 20. Epub 2021 Oct 20.

Oncology Research Discovery, Pfizer Worldwide Research and Development, 10777 Science Center Dr, San Diego, CA, 92121, USA.

Small cell lung cancer (SCLC) is a heterogeneous disease, consisting of intra-tumoral and inter-tumoral neuroendocrine (ASCL1 and/or NEUROD1), mesenchymal-like, and YAP-driven transcriptional states. Lysine-specific demethylase 1 (LSD1; also known as KDM1A) inhibitors have recently been progressed to clinical trials in SCLC based on a promising preclinical anti-tumor activity. A potential clinical limitation of LSD1 inhibitors is the heterogeneous drug responses that have been observed in SCLC cell lines and patient-derived models. Based on these observations, we studied molecular and transcriptional signatures that predict patient response to this class of drug. Employing SCLC patient-derived transcriptional signatures, we define that SCLC cell lines sensitive to LSD1 inhibitors are enriched in neuroendocrine transcriptional markers, whereas cell lines enriched in a mesenchymal-like transcriptional program demonstrate intrinsic resistance to LSD1 inhibitors. We have identified a reversible, adaptive resistance mechanism to LSD1 inhibitors through epigenetic reprogramming to a TEAD4-driven mesenchymal-like state. Our data suggest that only a segment of SCLC patients, with a defined neuroendocrine differentiation state, will likely benefit from LSD1 inhibitors. It provides novel evidence for the selection of a TEAD4-driven mesenchymal-like subpopulation resistant to LSD1 inhibitors in SCLC patients that may require effective drug combinations to sustain effective clinical responses.
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http://dx.doi.org/10.1002/1878-0261.13124DOI Listing
October 2021

Rapid digital light 3D printing enabled by a soft and deformable hydrogel separation interface.

Nat Commun 2021 Oct 18;12(1):6070. Epub 2021 Oct 18.

Ningbo Research Institute Zhejiang University, Ningbo, 315807, China.

The low productivity of typical 3D printing is a major hurdle for its utilization in large-scale manufacturing. Innovative techniques have been developed to break the limitation of printing speed, however, sophisticated facilities or costly consumables are required, which still substantially restricts the economic efficiency. Here we report that a common stereolithographic 3D printing facility can achieve a very high printing speed (400 mm/h) using a green and inexpensive hydrogel as a separation interface against the cured part. In sharp contrast to other techniques, the unique separation mechanism relies on the large recoverable deformation along the thickness direction of the hydrogel interface during the layer-wise printing. The hydrogel needs to be extraordinarily soft and unusually thick to remarkably reduce the adhesion force which is a key factor for achieving rapid 3D printing. This technique shows excellent printing stability even for fabricating large continuous solid structures, which is extremely challenging for other rapid 3D printing techniques. The printing process is highly robust for fabricating diversified materials with various functions. With the advantages mentioned above, the presented technique is believed to make a large impact on large-scale manufacturing.
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http://dx.doi.org/10.1038/s41467-021-26386-6DOI Listing
October 2021

Severity of Downgaze Palsy in the Context of Disease Duration Could Estimate Survival Duration in Patients With Progressive Supranuclear Palsy.

Front Neurol 2021 28;12:736784. Epub 2021 Sep 28.

Department of Ophthalmology, University of Chicago Medicine, Chicago, IL, United States.

It is an unmet need to estimate survival duration for patients with progressive supranuclear palsy (PSP). The objective of this study was to identify factors associated with the survival duration in patients with PSP. We followed up 23 patients with probable PSP-RS (Richardson syndrome) or PSP-P (parkinsonism) in our PSP center until death from 2011 to 2019. We prospectively and quantitatively rated their downgaze palsy whenever first noticed in our clinic. This was utilized along with the disease duration, motor function, medication use for parkinsonism, sex, age at onset of PSP, comorbid pulmonary and cardiovascular diseases, and the total survival duration from the onset of PSP to death for prediction analysis. A well-fitted linear regression model and a multivariant Cox model were applied to identify predicting factors for total survival duration. All patients had the specific hummingbird sign on brain MRI for PSP when downgaze palsy was documented. We found that the severity of downgaze palsy and the disease duration at the assessment were consistently correlated with the total survival duration in both models. The total survival duration could be further estimated by a formed regression equation. We conclude that severity and time to develop downgaze palsy could help to estimate the total survival duration in patients with probable PSP-RS and PSP-P, the major forms of PSP, which has significant clinical applications in clinical counseling and trial enrollment.
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http://dx.doi.org/10.3389/fneur.2021.736784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505535PMC
September 2021

A Parachlorella kessleri (Trebouxiophyceae, Chlorophyta) Strain Tolerant to High Concentration of Calcium Chloride.

J Eukaryot Microbiol 2021 Oct 7:e12872. Epub 2021 Oct 7.

School of Life Science, Shanxi Key Laboratory for Research and Development of Regional Plants, Shanxi University, Taiyuan, 030006, China.

Members of coccoid green algae have been documented in various extreme environments. In this article, a unicellular green alga was found to slowly grow in high concentration (3.6 g/L) and pure calcium chloride solution in the lab. It was successfully cultured and a taxonomic study combined approaches of morphological and molecular methods was conducted to determine its classification attribution, which was followed by a preliminary physiology research to explore its unique tolerance characteristics against calcium chloride stress. The strain was identified as Parachlorella kessleri by very similar morphology and the same phylogenetic position. The morphological differences among the three species in genus Parachlorella were then discussed and the characteristic traits of absent or thin mucilaginous envelop and mantel-shaped chloroplast for Parachlorella kessleri were supported. In addition, the almost strictly spherical shape of adult cells could further distinguish the Parachlorella kessleri from the other two species. The tolerant characteristics to CaCl stress for this strain were confirmed and the limit concentration was revealed as between 2,000 to 4,000 times than the standard BG11 culture concentration. Therefore, this Parachlorella kessleri strain is expected to be a good material to explore the mechanism of resistance to calcium ions stress for eukaryotic microbiology.
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http://dx.doi.org/10.1111/jeu.12872DOI Listing
October 2021

Ultrafast Digital Fabrication of Designable Architectured Liquid Crystalline Elastomer.

Adv Mater 2021 Oct 2:e2105597. Epub 2021 Oct 2.

State Key Laboratory of Chemical Engineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, China.

The muscle-like activities of liquid crystalline elastomers (LCEs) offer great potential for designing future soft machines. Their motion complexity, however, relies on inflexible and cumbersome mesogen alignment techniques. Here, a digital photocuring method for ultrafast template-free fabrication of LCE artificial muscles capable of designable complex motions is reported. This method utilizes the intrinsic light attenuation in the through-plane direction to create mesogen alignment for reversible bending action. To turn this simple actuation into complex motions, the principles of muscles are borrowed which realize diverse motions through the cooperative actions of otherwise simple contraction/expansion of individual muscle bundles. Specifically, the spatiotemporal digital light is utilized to design LCE architectures composed of strategically arranged bending modules. As such, LCE capable of highly designable motions can be fabricated within 25 s light curing without employing any physical alignment templates, which offers an attractive option toward designing functionally diverse soft machines.
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http://dx.doi.org/10.1002/adma.202105597DOI Listing
October 2021

Apigenin increases radiosensitivity of glioma stem cells by attenuating HIF-1α-mediated glycolysis.

Med Oncol 2021 Sep 23;38(11):131. Epub 2021 Sep 23.

College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.

Apigenin, a natural flavonoid compound present in a variety of edible plants and health foods, has an anti-tumor effect and inhibits hypoxia inducible factor-lα (HIF-1α) expression in hypertrophic cardiac tissues. However, whether or not apigenin has a radiosensitization effect on glioma stem cells (GSCs) is unknown. Our present study aimed to investigate the effect of apigenin and its possible mechanisms. The human GSCs SU3 and its radioresistance line SU3-5R were treated with apigenin, radiation, or their combination, and the cell proliferation, migration, colony formation, and intracellular lactic acid and glycolytic related protein expressions were determined. Additionally, a cell model with hypoxia-induced HIF-1α expression was used and treated with apigenin. The current results displayed that the combination of apigenin and radiation could synergically reduce the viability, colony formation, and migration of the both GSCs. Moreover, this combination could also decrease the radiation-induced increments of glycolytic production lactic acid in the both GSCs and related protein expressions, including HIF-1α, glucose transporter (GLUT)-1/3, nuclear factor kappa B (NF-κB) p65, and pyruvate kinase isozyme type M2 (PKM2). Further study confirmed that after treatment of hypoxia-cultured SU3 or SU3-5R cells with apigenin, the expression levels of HIF-1α, GLUT-1/3, NF-κB p65, and PKM2 proteins were reduced. These results demonstrated that apigenin could increase the radiosensitivity of GSCs and its radiosensitization mechanisms were attributable to the attenuation of glycolysis, which might result from the inhibition of HIF-1α expression and subsequent reductions of GLUT-1/3, NF-κB, and PKM2 expressions.
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http://dx.doi.org/10.1007/s12032-021-01586-8DOI Listing
September 2021

High cellulose diet promotes intestinal motility through regulating intestinal immune homeostasis and serotonin biosynthesis.

Biol Chem 2021 Sep 20. Epub 2021 Sep 20.

Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Guangzhou510282, China.

It is widely accepted dietary fiber intimately linked to inflammatory and nervous diseases, which often been described with altered gastrointestinal (GI) motility. However, how dose dietary fiber modulate inflammation and crosstalk influence GI function has not been explained in detail. We found fiber-free diet reduced intestinal motility, accompanied by upregulated proinflammatory immunocytes and inflammatory cytokines in colon of mice. We also discovered high-cellulose diet increased synthesis of serotonin and expression of neurotrophic factors, both of that have been reported involved in promoting intestinal motility. In addition, metabolomics analysis showed increased tryptophan metabolites in high-cellulose diet mice, which happened to be required for serotonin biosynthesis. Further analysis revealed high-cellulose diet changed the composition of gut microbiota, in particular by altering the ratio of Firmicutes to Bacteroidetes, consequently, concentration of short-chain fatty acids (SCFAs), especially acetate. Orally administration of acetate confirmed its modulating to serotonin synthesis, neurotrophic factors expression and immunocyte differentiation through regulating histone deacetylase (HDAC3) activity in colon. Together, our results demonstrated high-cellulose diet promote intestinal motility through regulating intestinal homeostasis and enteric nervous system by increasing acetate production and HDAC3 inhibition. Thus, rich cellulose diet or acetate supplement can be considered as dietary advice to improve clinically intestinal motility insufficiency.
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http://dx.doi.org/10.1515/hsz-2021-0216DOI Listing
September 2021

The Use of Micro Retractor in Endoscopic Endonasal Posterior Pseudocapsule Resection of Pituitary Macroadenoma. Technical Note.

Front Oncol 2021 13;11:714342. Epub 2021 Aug 13.

Department of Neurosurgery, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: The endoscopic endonasal approach and extra-pseudocapsule resection may be the main progress in modern pituitary surgery. However, for pituitary macroadenomas, discerning the pseudocapsule in the posterior plane of the tumor may be difficult. When the anterior-inferior debulking is performed, the early subsidence of the thinning normal pituitary gland and enlarged diaphragm may obstruct the surgical dissection view.

Method: We describe the technique of using a micro retractor for the endoscopic endonasal posterior pseudocapsule resection of pituitary macroadenomas. This micro retractor that was 2 mm in width was placed at the 12 o'clock position on the nostrils, and the end was fixed in the flexible arms of the self-retaining retractor system. The head of the micro retractor elevated the herniated diaphragm sellae in order to continue the posterior pseudocapsule resection of the pituitary macroadenoma.

Result: The technique was performed very easily and no complication was observed.

Conclusion: The use of this micro retractor can increase the view of the posterior margin of the adenomas to facilitate the pseudocapsule dissection.
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http://dx.doi.org/10.3389/fonc.2021.714342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414968PMC
August 2021

Pan-Cancer Analysis of Genomic and Prognostic Characteristics Associated With Coronavirus Disease 2019 Regulators.

Front Med (Lausanne) 2021 11;8:662460. Epub 2021 Aug 11.

Department of Radiation Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, Guangzhou, China.

Cancer patients are alleged to have poor coronavirus disease 2019 (COVID-19) outcomes. However, no systematic or comprehensive analyses of the role and mechanisms of COVID-19 receptor-related regulators in cancer are available. We comprehensively evaluated the genomic alterations and their clinical relevance of six COVID-19 receptor-related regulators [transmembrane serine protease 2 (TMPRSS2), angiotensinogen (AGT), angiotensin-converting enzyme 1 (ACE1), solute carrier family 6 member 19 (SLC6A19), angiotensin-converting enzyme 2 (ACE2), and angiotensin II receptor type 2 (AGTR2)] across a broad spectrum of solid tumors. RNA-seq data, single nucleotide variation data, copy number variation data, methylation data, and miRNA-mRNA interaction network data from The Cancer Genome Atlas (TCGA) of 33 solid tumors were analyzed. We assessed the sensitivities of drugs targeting COVID-19 receptor-related regulators, using information from the Cancer Therapeutics Response Portal database. We found that there are widespread genetic alterations of COVID-19 regulators and that their expression levels were significantly correlated with the activity of cancer hallmark-related pathways. Moreover, COVID-19 receptor-related regulators may be used as prognostic biomarkers. By mining the genomics of drug sensitivities in cancer databases, we discovered a number of potential drugs that may target COVID-19 receptor-related regulators. This study revealed the genomic alterations and clinical characteristics of COVID-19 receptor-related regulators across 33 cancers, which may clarify the potential mechanism between COVID-19 receptor-related regulators and tumorigenesis and provide a novel approach for cancer treatments.
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http://dx.doi.org/10.3389/fmed.2021.662460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385656PMC
August 2021

Comparative transcriptome analysis of a fan-shaped inflorescence in pineapple using RNA-seq.

Genomics 2021 Aug 26;113(6):3653-3665. Epub 2021 Aug 26.

Key Laboratory of Biology and Germplasm Enhancement of Horticultural Crops in South China, Ministry of Agriculture, South China Agricultural University, Guangzhou 510642, China. Electronic address:

Pineapple plant usually has a capitulum. However, a fan-shaped inflorescence was exceptionally evolved in pineapple, having multiple crown buds. In order to reveal the molecular mechanisms of the formation of the fan-shaped inflorescence, fruit traits and the transcriptional differences between the fan-shaped inflorescence and the wild-shaped inflorescence pineapples were analyzed in three tissues, i.e., the flower stem apex, the base of the inflorescence, and the inflorescence axis. The weight (i.e., individual yield) of fan-shaped fruit is 4.5 times that of wild-shaped fruit;and non-significant difference in soluble solids, soluble sugar, titratable acid, and Vitamin C was found. Between the fan-shaped inflorescence and wild-shaped inflorescence, a total of 5370 differentially expressed genes were identified across the three tissues. Of these genes, there were 489 overlapping differentially expressed genes in all three tissue comparisons. Between the two pineapples, functional analysis indicated that 444 transcription factors and 206 inflorescence development-related genes were differentially expressed in at least one tissue comparison, while 45 transcription factors and 21 inflorescence development-related genes were overlapped across three tissues. Among the 489 overlapping differentially expressed genes in the three tissue comparisons, excluding the inflorescence development-related genes and transcription factors, 80 of them revealed a higher percentage of involvement in the biological processes relating to response to auxin, and reproductive processes. RNA-seq value and real-time quantitative PCR analysis exhibited the similar gene expression patterns in the three tissues. Our result provided novel cues for understanding the molecular mechanisms of the formation of the fan-shaped inflorescence in pineapple, making a valuable resource for the study of plant breeding and the speciation of pineapple.
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http://dx.doi.org/10.1016/j.ygeno.2021.08.022DOI Listing
August 2021

PARP Inhibitors Display Differential Efficacy in Models of Mutant High-Grade Serous Ovarian Cancer.

Int J Mol Sci 2021 Aug 7;22(16). Epub 2021 Aug 7.

Translational Oncology Group, School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW 2007, Australia.

Several poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors are now in clinical use for tumours with defects in BReast CAncer genes or that result in deficient homologous recombination repair (HRR). Use of olaparib, niraparib or rucaparib for the treatment of high-grade serous ovarian cancer, including in the maintenance setting, has extended both progression free and overall survival for women with this malignancy. While different PARP inhibitors (PARPis) are mechanistically similar, differences are apparent in their chemical structures, toxicity profiles, PARP trapping abilities and polypharmacological landscapes. We have treated ovarian cancer cell line models of known status, including the paired cell lines PEO1 and PEO4, and UWB1.289 and UWB1.289+BRCA1, with five PARPis (olaparib, niraparib, rucaparib, talazoparib and veliparib) and observed differences between PARPis in both cell viability and cell survival. A cell line model of acquired resistance to veliparib showed increased resistance to the other four PARPis tested, suggesting that acquired resistance to one PARPi may not be able to be rescued by another. Lastly, as a proof of principle, HRR proficient ovarian cancer cells were sensitised to PARPis by depletion of . In the future, guidelines will need to emerge to assist clinicians in matching specific PARPis to specific patients and tumours.
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http://dx.doi.org/10.3390/ijms22168506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395221PMC
August 2021

Spatial Disparities in Access to Healthcare Professionals in Sichuan: Evidence from County-Level Data.

Healthcare (Basel) 2021 Aug 16;9(8). Epub 2021 Aug 16.

School of Public Policy and Administration, Xi'an Jiaotong University, Xi'an 710049, China.

As a southwestern province of China, Sichuan is confronted with geographical disparities in access to healthcare professionals because of its complex terrain, uneven population distribution and huge economic gaps between regions. With 10-year data, this study aims to explore the county-level spatial disparities in access to different types of healthcare professionals (licensed doctors, registered nurses, pharmacists, technologists and interns) in Sichuan using temporal and spatial analysis methods. The time-series results showed that the quantity of all types of healthcare professionals increased, especially the registered nurses, while huge spatial disparities exist in the distribution of healthcare professionals in Sichuan. The local Moran's I calculations showed that high-high clusters (significantly high healthcare professional quantity in a group of counties) were detected in Chengdu (capital of Sichuan) and relatively rich areas, while low-low clusters (significantly low healthcare professional quantity in a group of counties) were usually found near the mountain areas, namely, Tsinling Mountains and Hengduan Mountains. The findings may deserve considerations in making region-oriented policies in educating and attracting more healthcare professionals to the disadvantaged areas.
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http://dx.doi.org/10.3390/healthcare9081053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394835PMC
August 2021

Position-Related Paroxysmal Facial Twitching.

Mov Disord Clin Pract 2021 Jul 15;8(5):807-808. Epub 2021 May 15.

Division of Neuroradiology, Department of Radiology University of Chicago Medicine Chicago Illinois USA.

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http://dx.doi.org/10.1002/mdc3.13219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287172PMC
July 2021

LncRNA LINC00473 promoted colorectal cancer cell proliferation and invasion by targeting miR-195 expression.

Am J Transl Res 2021 15;13(6):6066-6075. Epub 2021 Jun 15.

Department of General Surgery, Rizhao People's Hospital Rizhao 276800, Shandong, China.

Long noncoding RNAs (lncRNAs) have been shown to play crucial roles in cancer development. However, the role of LINC00473 in colorectal cancer has not been explored. In our study, we showed that LINC00473 expression was upregulated in colorectal cancer samples compared to nontumor samples. The expression of LINC00473 in colorectal cancer tissues from patients with distant metastasis was higher than that from cases without distant metastasis. The higher expression level of LINC00473 was positively correlated with advanced clinical stage. The elevated expression of LINC00473 accelerated colorectal cancer cell proliferation, cell cycle progression and invasion. Moreover, overexpression of LINC00473 induced epithelial to mesenchymal (EMT) progression in HT29 and SW480 cells. Ectopic expression of LINC00473 suppressed miR-195 expression in colorectal cancer cells. miR-195 expression was downregulated in colorectal cancer samples compared with nontumor samples. The expression of miR-195 in colorectal cancer tissues from patients with distant metastasis was lower than that from cases without distant metastasis. The lower expression level of miR-195 was positively correlated with advanced clinical stage. In addition, we showed that the expression of miR-195 was negatively correlated with the LINC00473 expression level in colorectal cancer tissues. LINC00473 accelerated colorectal cancer cell proliferation and cell cycle progression and regulated EMT progression by regulating miR-195 expression. These data suggested that LINC00473 induced cell proliferation, cell cycle progression and EMT progression by acting as a ceRNA for miR-195 in colorectal cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290708PMC
June 2021

Variable Induction of Pro-Inflammatory Cytokines by Commercial SARS CoV-2 Spike Protein Reagents: Potential Impacts of LPS on In Vitro Modeling and Pathogenic Mechanisms In Vivo.

Int J Mol Sci 2021 Jul 14;22(14). Epub 2021 Jul 14.

Division of Biotechnology Review and Research II, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.

Proinflammatory cytokine production following infection with severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) is associated with poor clinical outcomes. Like SARS CoV-1, SARS CoV-2 enters host cells via its spike protein, which attaches to angiotensin-converting enzyme 2 (ACE2). As SARS CoV-1 spike protein is reported to induce cytokine production, we hypothesized that this pathway could be a shared mechanism underlying pathogenic immune responses. We herein compared the capabilities of Middle East Respiratory Syndrome (MERS), SARS CoV-1 and SARS CoV-2 spike proteins to induce cytokine expression in human peripheral blood mononuclear cells (PBMC). We observed that only specific commercial lots of SARS CoV-2 induce cytokine production. Surprisingly, recombinant SARS CoV-2 spike proteins from different vendors and batches exhibited different patterns of cytokine induction, and these activities were not inhibited by blockade of spike protein-ACE2 binding using either soluble ACE2 or neutralizing anti-S1 antibody. Moreover, commercial spike protein reagents contained varying levels of lipopolysaccharide (LPS), which correlated directly with their abilities to induce cytokine production. The LPS inhibitor, polymyxin B, blocked this cytokine induction activity. In addition, SARS CoV-2 spike protein avidly bound soluble LPS in vitro, rendering it a cytokine inducer. These results not only suggest caution in monitoring the purity of SARS CoV-2 spike protein reagents, but they indicate the possibility that interactions of SARS CoV-2 spike protein with LPS from commensal bacteria in virally infected mucosal tissues could promote pathogenic inflammatory cytokine production.
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http://dx.doi.org/10.3390/ijms22147540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305765PMC
July 2021

Pan-cancer analyses reveal genomics and clinical characteristics of the melatonergic regulators in cancer.

J Pineal Res 2021 Oct 5;71(3):e12758. Epub 2021 Sep 5.

Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, Guangzhou Institute of Respiratory Disease, Guangzhou, China.

Melatonin, an endogenous hormone, plays protective roles in cancer. In addition to regulating circadian rhythms, sleep, and neuroendocrine activity, melatonin functions in various survival pathways. However, the mechanisms of melatonin regulation in cancer remain unknown. In the present study, we performed a comprehensive characterization of melatonin regulators in 9125 tumor samples across 33 cancer types using multi-omic data from The Cancer Genome Atlas and Cancer Cell Line Encyclopedia. In the genomic landscape, we identified the heterozygous amplification of AANAT and GPR50, and heterozygous deletion of PER3, CYP2C19, and MTNR1A as the dominant alteration events. Expression analysis revealed methylation-mediated downregulation of melatonergic regulator expression. In addition, we found that melatonergic regulator expression could be used to predict patient survival in various cancers. In depth, microRNA (miRNA) analysis revealed an miRNA-mRNA interaction network, and the deregulated miRNAs were involved in melatonin secretion and metabolism by targeting circadian clock genes. Pathway analysis showed that melatonergic regulators were associated with inhibition of apoptosis, the cell cycle, the DNA damage response, and activation of RAS/MAPK and RTK signaling pathways. Importantly, by mining the Genomics of Drug Sensitivity in Cancer database, we discovered a number of potential drugs that might target melatonergic regulators. In summary, this study revealed the genomic alteration and clinical characteristics of melatonergic regulators across 33 cancers, which might clarify the relationship between melatonin and tumorigenesis. Our findings also might provide a novel approach for the clinical treatment of cancers.
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http://dx.doi.org/10.1111/jpi.12758DOI Listing
October 2021

Autonomous Off-Equilibrium Morphing Pathways of a Supramolecular Shape-Memory Polymer.

Adv Mater 2021 Aug 18;33(34):e2102473. Epub 2021 Jul 18.

State Key Laboratory of Chemical Engineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, China.

The diverse morphing behaviors of living creatures arise from their unlimited pathways. In contrast, the equilibrium-driven morphing pathways of common synthetic shape-shifting materials are very limited. For a shape-memory polymer (SMP), its recovery from the temporary shape(s) to the permanent shape typically requires external stimulation and follows a single fixed route. Herein, a covalently crosslinked SMP is designed with ample ureidopyrimidinone (UPy) supramolecular moieties in the network. The UPy units endow the SMP with strong time-temperature dependency, which is explored as a mechanism for spatio-temporal programming of autonomous shape-shifting pathways. In particular, the use of digitally controlled photothermal heating provides versatility in control via an off-equilibrium mechanism. In addition, cooling/heating across its glass transition introduces a locking/unlocking mechanism for its temporal morphing. The benefits of these unique features are demonstrated by multi-shape-transformation, an "invisible"-color-based clock, a time-temperature indicator, and sequence-programmable 4D printing.
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http://dx.doi.org/10.1002/adma.202102473DOI Listing
August 2021

Best Practices in the Clinical Management of Progressive Supranuclear Palsy and Corticobasal Syndrome: A Consensus Statement of the CurePSP Centers of Care.

Front Neurol 2021 1;12:694872. Epub 2021 Jul 1.

Neurology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.

Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS; the most common phenotype of corticobasal degeneration) are tauopathies with a relentless course, usually starting in the mid-60s and leading to death after an average of 7 years. There is as yet no specific or disease-modifying treatment. Clinical deficits in PSP are numerous, involve the entire neuraxis, and present as several discrete phenotypes. They center on rigidity, bradykinesia, postural instability, gait freezing, supranuclear ocular motor impairment, dysarthria, dysphagia, incontinence, sleep disorders, frontal cognitive dysfunction, and a variety of behavioral changes. CBS presents with prominent and usually asymmetric dystonia, apraxia, myoclonus, pyramidal signs, and cortical sensory loss. The symptoms and deficits of PSP and CBS are amenable to a variety of treatment strategies but most physicians, including many neurologists, are reluctant to care for patients with these conditions because of unfamiliarity with their multiplicity of interacting symptoms and deficits. CurePSP, the organization devoted to support, research, and education for PSP and CBS, created its CurePSP Centers of Care network in North America in 2017 to improve patient access to clinical expertise and develop collaborations. The directors of the 25 centers have created this consensus document outlining best practices in the management of PSP and CBS. They formed a writing committee for each of 12 sub-topics. A 4-member Steering Committee collated and edited the contributions. The result was returned to the entire cohort of authors for further comments, which were considered for incorporation by the Steering Committee. The authors hope that this publication will serve as a convenient guide for all clinicians caring for patients with PSP and CBS and that it will improve care for patients with these devastating but manageable disorders.
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http://dx.doi.org/10.3389/fneur.2021.694872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284317PMC
July 2021

Transparent origami glass.

Nat Commun 2021 Jul 12;12(1):4261. Epub 2021 Jul 12.

State Key Laboratory of Chemical Engineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, People's Republic of China.

The art of origami has emerged as an engineering tool with ever increasing potential, but the technique is typically limited to soft and deformable materials. Glass is indispensable in many applications, but its processing options are limited by its brittle nature and the requirement to achieve optical transparency. We report a strategy that allows making three dimensional transparent glass with origami techniques. Our process starts from a dynamic covalent polymer matrix with homogeneously dispersed silica nanoparticles. Particle cavitation and dynamic bond exchange offer two complementary plasticity mechanisms that allow the nanocomposite to be permanently folded into designable geometries. Further pyrolysis and sintering convert it into transparent three dimensional glass. Our method expands the scope of glass shaping and potentially opens up its utilities in unexplored territories.
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http://dx.doi.org/10.1038/s41467-021-24559-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275568PMC
July 2021

Suppresses Tumor Progression by Inhibiting the PI3K/AKT Signaling Pathway in Prostate Cancer.

Front Cell Dev Biol 2021 25;9:678967. Epub 2021 Jun 25.

Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Background: SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily C member 1 () protein is a potential tumor suppressor in various cancers. However, its role in prostate cancer (PCa) remains controversial. The aim of this study was to determine the biological function of in PCa and explore the underlying regulatory mechanisms.

Methods: The expression of was validated in PCa tissues by immunohistochemistry. Meanwhile, function experiments were used to evaluate the regulatory role on cell proliferation and metastasis in PCa cells with depletion both and . The expression levels of relevant proteins were detected by Western blotting.

Results: Our finding showed that was significantly downregulated in prostate adenocarcinoma, with a higher Gleason score (GS) than that in low GS. The decreased expression of was significantly correlated with a higher GS and poor prognosis. Additionally, we found that silencing of dramatically accelerated cell proliferation by promoting cell cycle progression and enhancing cell migration by inducing epithelial mesenchymal transition (EMT). Furthermore, depletion of facilitated PCa xenograft growth and lung metastasis in murine models. Mechanistically, the loss of activated the pathway in PCa cells.

Conclusion: suppresses PCa cell proliferation and metastasis the signaling pathway and is a novel therapeutic target.
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http://dx.doi.org/10.3389/fcell.2021.678967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267926PMC
June 2021

Syntheses, Biological Evaluations, and Mechanistic Studies of Benzo[][1,2,5]oxadiazole Derivatives as Potent PD-L1 Inhibitors with Antitumor Activity.

J Med Chem 2021 06 11;64(12):8391-8409. Epub 2021 Jun 11.

Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.

A series of novel benzo[][1,2,5]oxadiazole derivatives were designed, synthesized, and biologically evaluated as inhibitors of PD-L1. Among them, compound exhibited 1.8 nM IC value in a homogeneous time-resolved fluorescence (HTRF) assay, which was 20-fold more potent than the lead compound . In the surface plasmon resonance (SPR) assay, bound to human PD-L1 (hPD-L1) with a value of 3.34 nM, without showing any binding to hPD-1. In the cell-based coculture assay, blocked PD-1/PD-L1 interaction with an EC value of 375 nM, while had an EC value of 2075 nM. Moreover, compound , an ester prodrug of , was orally bioavailable and displayed significant antitumor effects in tumor models of syngeneic and PD-L1 humanized mice. Mechanistically, exhibited significant antitumor effects probably through promoting antitumor immunity. Together, this series of benzoxadiazole PD-L1 inhibitors holds promise for tumor immunotherapy. Preclinical trials with selected compounds are ongoing in our laboratory.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00392DOI Listing
June 2021

Production of SARS-CoV-2 Virus-Like Particles in Insect Cells.

Vaccines (Basel) 2021 May 26;9(6). Epub 2021 May 26.

Lanzhou Center for Tuberculosis Research and Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730070, China.

Coronavirus disease (COVID-19) causes a serious threat to human health. Virus-like particles (VLPs) constitute a promising platform in SARS-CoV-2 vaccine development. In this study, the E, M, and S genes were cloned into multiple cloning sites of a new triple expression plasmid with one p10 promoter, two pPH promoters, and three multiple cloning sites. The plasmid was transformed into DH10 Bac competent cells to obtain recombinant bacmid. Then the recombinant bacmid was transfected in ExpiSf9 insect cells to generate recombinant baculovirus. After ExpiSf9 cells infection with the recombinant baculovirus, the E, M, and S proteins were expressed in insect cells. Finally, SARS-CoV-2 VLPs were self-assembled in insect cells after infection. The morphology and the size of SARS-CoV-2 VLPs are similar to the native virions.
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http://dx.doi.org/10.3390/vaccines9060554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227081PMC
May 2021

Quantitative proteomics revealed the molecular characteristics of distinct types of granulated somatotroph adenomas.

Endocrine 2021 11 27;74(2):375-386. Epub 2021 May 27.

Department of Neurosurgery, Zhongshan Hospital, Fudan University, Shanghai, China.

Purpose: Somatotroph adenomas are obviously heterogeneous in clinical characteristics, imaging performance, pathological diagnosis and therapeutic effect. The heterogeneity of the tumors, especially for SG and DG type adenomas, have attracted great interest in identifying the specific pathological markers and therapeutic targets of them. However, previous analyses of the molecular characteristics of the subtypes of somatotroph adenomas were performed at genomic and transcriptome level. The proteomic differences between the two subtypes of somatotroph adenomas are still unknown.

Methods: Tumor samples were surgically removed from 10 sporadic pituitary somatotroph adenoma patients and grouped according to the pathological type. Tandem mass tag (TMT)-based quantitative proteomic analysis was employed to analyze the proteomic differences between SG and DG tumors.

Results: In total, 228 differentially expressed proteins were identified between SG adenomas and DG adenomas. They were enriched mainly in extracellular matrix (ECM)-receptor interaction, leukocyte transendothelial migration, arrhythmogenic right ventricular cardiomyopathy and DNA replication pathways. Protein-protein interaction (PPI) network analysis indicated that Cadherin-1 and Catenin beta-1 were the most important key proteins in the differences between SG and DG adenomas. Immunohistochemistry (IHC) confirmed the expression levels of the key proteins.

Conclusions: This study provides large-scale proteome molecular characteristics of distinct granulation subtypes of somatotroph adenomas. Compared with DG adenomas, The differential protein of SG adenomas mostly enrich in invasive and proliferative functions and pathways at the proteomic level. Cadherin-1 and Catenin beta-1 play key roles in the different biological characteristics of the two tumor subtypes.
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http://dx.doi.org/10.1007/s12020-021-02767-1DOI Listing
November 2021

Influence of Perceptual and Conceptual Information on Fear Generalization: A Behavioral and Event-Related Potential Study.

Cogn Affect Behav Neurosci 2021 Oct 21;21(5):1054-1065. Epub 2021 May 21.

Institute of Brain and Psychological Sciences, Sichuan Normal University, Chengdu, 610066, China.

Learned fear can be generalized through both perceptual and conceptual information. This study investigated how perceptual and conceptual similarities influence this generalization process. Twenty-three healthy volunteers completed a fear-generalization test as brain activity was recorded in the form of event-related potentials (ERPs). Participants were exposed to a de novo fear acquisition paradigm with four categories of conditioned stimuli (CS): two conceptual cues (animals and furniture); and two perceptual cues (blue and purple shapes). Animals (C+) and purple shapes (P+) were paired with the unconditioned stimulus (US), whereas furniture (C-) and blue shapes (P-) never were. The generalized stimuli were thus blue animals (C+P+, determined danger), blue furniture (C-P+, perceptual danger), purple animals (C+P-, conceptual danger), and purple furniture (C-P-, determined safe). We found that perceptual cues elicited larger fear responses and shorter reaction times than did conceptual cues during fear acquisition. This suggests that a perceptually related pathway might evoke greater fear than a conceptually based route. During generalization, participants were more afraid of C+ exemplars than of C- exemplars. Furthermore, C+ trials elicited greater N400 amplitudes. Thus, participants appear able to use conceptually based cues to infer the value of the current stimuli. Additionally, compared with C+ exemplars, we found an enhanced late positive potential effect in response to C- exemplars, which seems to reflect a late inhibitory process and might index safety learning. These findings may offer new insights into the pathological mechanism of anxiety disorders.
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http://dx.doi.org/10.3758/s13415-021-00912-xDOI Listing
October 2021

Efficient 3D printing via photooxidation of ketocoumarin based photopolymerization.

Nat Commun 2021 May 17;12(1):2873. Epub 2021 May 17.

Key Lab for Material Chemistry of Energy Conversion and Storage, Ministry of Education, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology (HUST), Wuhan, China.

Photopolymerization-based three-dimensional (3D) printing can enable customized manufacturing that is difficult to achieve through other traditional means. Nevertheless, it remains challenging to achieve efficient 3D printing due to the compromise between print speed and resolution. Herein, we report an efficient 3D printing approach based on the photooxidation of ketocoumarin that functions as the photosensitizer during photopolymerization, which can simultaneously deliver high print speed (5.1 cm h) and high print resolution (23 μm) on a common 3D printer. Mechanistically, the initiating radical and deethylated ketocoumarin are both generated upon visible light exposure, with the former giving rise to rapid photopolymerization and high print speed while the latter ensuring high print resolution by confining the light penetration. By comparison, the printed feature is hard to identify when the ketocoumarin encounters photoreduction due to the increased lateral photopolymerization. The proposed approach here provides a viable solution towards efficient additive manufacturing by controlling the photoreaction of photosensitizers during photopolymerization.
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http://dx.doi.org/10.1038/s41467-021-23170-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129151PMC
May 2021

Bioinspired Dual-Mode Temporal Communication via Digitally Programmable Phase-Change Materials.

Adv Mater 2021 Jun 7;33(24):e2008119. Epub 2021 May 7.

State Key Laboratory of Chemical Engineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, China.

Switchable optical properties are essential for numerous technologies including communication, anticounterfeiting, camouflage, and imaging/sensing. Typically, the switching is enabled by applying external stimulation such as UV light for fluorescence detection. In contrast, ground squirrels utilize spontaneous live infrared emission for fencing off predators as a unique way of communication. Inspired by this, live evolution of both optical and thermal images for temporal communication in which time is the encoded information is demonstrated. This system is based on a digitally light-cured polymeric phase-change material for which the crystallization kinetics can be controlled in a pixelated manner. Consequently, live evolution in optical transparency during the crystallization process enables temporal optical communication. Additionally, by harnessing the dynamic evolution of the thermal enthalpy, multiple sets of time-specific information can be reversibly retrieved as self-evolving infrared thermal images. The versatility of this dual-mode temporal system expands the scope for secured communication, with potential implications for various other areas including optics, thermal regulation, and 3D/4D printing.
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http://dx.doi.org/10.1002/adma.202008119DOI Listing
June 2021

Disparities in diagnosis, treatment and survival between Black and White Parkinson patients.

Parkinsonism Relat Disord 2021 06 21;87:7-12. Epub 2021 Apr 21.

Department of Public Health Sciences, University of Chicago, IL, 60637, USA.

Introduction: Racial disparities in diagnosis, treatment and survival in Black patients with Parkinson's disease (PD) compared to White patients have not been well studied, largely due to limited number of studies and information on Black patients in healthcare systems. Studying racial disparities and identifying underlying factors in large populations are important to understand PD and improve care.

Methods: We retrospectively identified PD patients on both races from 1/1/2006 to 10/31/2017 and compared demographics, socioeconomic status (educations, incomes and insurances), comorbidities (all categories, including mood, cognition and psychosis), treatment (medications for parkinsonism and major non-motor symptoms, and frequency and locations of healthcare) and survival, and identified factors associated with medication usage and survival.

Results: We retrospectively studied 2033 PD patients, of whom 725 were Black. Black patients lacked male predominance, were 4 years older at first diagnosis here, more likely to smoke and live in a low education and income community, and possessed limited insurances compared to White patients. Black patients also had more comorbidities and were more likely to receive care through emergency or inpatient service, but less likely to be on medications for parkinsonism and mood disorders. Race, age, smoking status, insurance type, frequency and locations of healthcare and comorbidities were associated with medication usage. Black race, older age, inpatient admission and malignancy were associated with increased risk of death.

Conclusion: We revealed racial disparities in diagnosis, treatment and survival, and factors associated with medication usage and survival in the largest reported Black PD cohort from a single center.
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http://dx.doi.org/10.1016/j.parkreldis.2021.04.013DOI Listing
June 2021

A case report of multi-ligaments injury of the ACL-MCL-PT combined with an occult fracture of the posterolateral tibial plateau.

Trauma Case Rep 2021 Jun 17;33:100457. Epub 2021 Mar 17.

Department of Orthopaedic Surgery, Affiliated Hangzhou First People's Hospital of Zhejiang University School of Medicine, 261 Huansha Road, Hangzhou 310006, China.

The anterior cruciate ligament and medial collateral ligament are important static stabilizers of the knee. The patellar tendon is part of the knee extensor mechanism. The injury simultaneously involving these three structures is very rare. This paper reports a case with simultaneous ipsilateral rupture of the anterior cruciate ligament, medial collateral ligament, patellar tendon, and an occult compression fracture of the posterolateral tibial plateau. This injury pattern has not been reported in literature yet. The injury mechanism was hypothesized as a sudden anterior translation and valgus of the proximal tibia when the knee was in high flexion, followed by an eccentric quadriceps' contracture. In the followed management, ruptured medial collateral ligament and patellar tendon were sutured with augment, while the torn anterior cruciate ligament and fracture were treated conservatively. The outcome of the treatment was satisfactory, and no complication was observed. To this combined injury, a comprehensive consideration, including physical examination, multiple imaging examinations, and analysis of injury mechanism, is essential for a full diagnosis and treatment decision. Especially, computed tomography may help to identify an occult or non-displaced fracture, which would be easily misdiagnosed when nothing unusual was found in routine X-rays. In the treatment, it is suggested to perform a selective or step-by-step repair to the damaged structures, rather than an immediate total repair after injury.
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http://dx.doi.org/10.1016/j.tcr.2021.100457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025053PMC
June 2021

Archaeobotanical evidence of the use of medicinal cannabis in a secular context unearthed from south China.

J Ethnopharmacol 2021 Jul 20;275:114114. Epub 2021 Apr 20.

National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China. Electronic address:

Ethnopharmacological Relevance: As one of the first plants used by ancient people, cannabis has been used for medicinal purposes for thousands of years. The long history of medicinal cannabis use contrasts with the paucity of archaeobotanical records. Moreover, physical evidence of medicinal cannabis use in a secular context is much rarer than evidence of medicinal cannabis use in religious or ritual activities, which impedes our understanding of the history of medicinal cannabis use.

Aim Of The Study: This study aims to provide archaeobotanical evidence of medicinal cannabis use and analyse the specific medicinal usage of cannabis in a secular context in ancient times.

Materials And Methods: Plant remains were collected from the Laoguanshan Cemetery of the Han Dynasty in Chengdu, South China, with the archaeological flotation process and were identified based on morphological and anatomical characteristics. The examination of the medicinal significance of the remains relied on the investigation of the documentation on unearthed medical bamboo slips, the diseases of the tomb occupants, the cemetery's cultural background and Chinese historical records.

Results: The botanical remains were accurately identified as cannabis. More than 120 thousand fruits were found, which represents the largest amount of cannabis fruit remains that have been statistically analysed from any cemetery in the world thus far. The cannabis fruits are suspected to have been used for medical purposes in a secular context and were most likely used to stop severe bleeding of the uterus and treat lumbago and/or arthralgia.

Conclusions: The cannabis fruit remains reported here likely represent the first physical evidence of medicinal cannabis use for the treatment of metrorrhagia, severe lumbago, and/or arthralgia. This study emphasizes the importance of the evidence of the diseases suffered by the occupants of the tomb in determining the medicinal use of cannabis in a secular context and contributes to a comprehensive understanding of the ancient history of medicinal cannabis.
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http://dx.doi.org/10.1016/j.jep.2021.114114DOI Listing
July 2021
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