Publications by authors named "Tian Zhang"

722 Publications

Immunotherapy and targeted-therapy combinations mark a new era of kidney cancer treatment.

Nat Med 2021 Apr 5. Epub 2021 Apr 5.

Division of Medical Oncology, Department of Medicine, Durham, NC, USA.

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http://dx.doi.org/10.1038/s41591-021-01320-xDOI Listing
April 2021

Generation of a homozygous ALX1 knockout human embryonic stem cell line (WAe001-A-060) by a CRISPR/Cas9 system.

Stem Cell Res 2021 Mar 24;53:102309. Epub 2021 Mar 24.

Medical Research Center, People's Hospital of Longhua, Shenzhen 518109, China. Electronic address:

Human ALX1 gene (ALX Homeobox 1) is a protein coding gene and gene ontology annotations related to this gene include DNA-binding transcription factor activity and protein heterdimerization activity. It is necessary for survival of forebrain mesenchyme and may be involved in development of cervix. However, the function of the gene has yet to be determined in humans. Here we generated an ALX1 homozygous human embryonic stem cell line (WAe001-A-060) by a CRISPR/Cas9 system. The WAe001-A-060 has a normal undifferentiated morphology and karyotype, pluripotency and three germ layers differentiation potential in vivo.
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http://dx.doi.org/10.1016/j.scr.2021.102309DOI Listing
March 2021

Recycling of shrub landscaping waste: Exploration of bio-hydrogen production potential and optimization of photo-fermentation bio-hydrogen production process.

Bioresour Technol 2021 Mar 24;331:125048. Epub 2021 Mar 24.

Key Laboratory of New Materials and Facilities for Rural Renewable Energy (MOA of China), Henan Agricultural University, Zhengzhou 450002, China; Institute of Agricultural Engineering, Huanghe S & T University, Zhengzhou 450006, China. Electronic address:

Shrub landscaping waste, derived from afforestation of city, has increased annually, making it a promising feedstock for energy production. In this work, the photo-fermentation bio-hydrogen production potential from shrub landscaping waste was evaluated. Eight kinds of shrub landscaping wastes (Photinia fraseri, Buxus megistophylla, Buxus sinica, Pittosporum tobira, Sabina Chinensis, Berberis thunbergii, Ligustrum vicaryi and Ligustrum quihoui) were selected as substrate and the photo-fermentation bio-hydrogen production process of which was optimized. Buxus megistophylla was found to be the most suitable substrate for photo-fermentation bio-hydrogen production. Moreover, the initial pH value, temperature and substrate concentration had significant influence on photo-fermentation bio-hydrogen production. The maximum cumulated hydrogen yield of Buxus megistophylla was 73.82 ± 0.06 mL/g TS under the optimal conditions of light intensity of 3000 Lux, substrate mass concentration of 21.49 g/L, temperature of 29.78 °C, inoculant amount of 25% and initial pH value of 6.78.
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http://dx.doi.org/10.1016/j.biortech.2021.125048DOI Listing
March 2021

N-doped Porous Carbon Derived from Solvent-Free Synthesis of Cross-Linked Triazine Polymers for Simultaneously Achieving CO2 Capture and Supercapacitors.

Chemistry 2021 Mar 28. Epub 2021 Mar 28.

Sichuan University - Wangjiang Campus: Sichuan University, college of chemical engineering, Collge of Chemical Engeering, Sichuan University, 610065, Chengdu, CHINA.

It is highly attractive to design advanced heteroatomic doped porous carbon for widely application. Herein, N-doped porous carbon (NPC) was developed via the fabrication of high nitrogen cross-linked triazine polymers followed by pyrolysis and activation with controllable porous structure. The as-synthesized NPC at the pyrolysis temperature of 700 °C possessed rich nitrogen content (up to 11.51%) and high specific surface area (1353 m 2 g -1 ), which led to a high CO2 adsorption capability at 5.67 mmol·g -1 at 298.15K and 5 bar pressure and excellent stability. When the activation temperature at 600 °C, such NPC exhibited a superior electrochemical performance as anode for supercapacitors with a specific capacitance of 158.8 and 113 F g -1 in 6 M KOH at a current density of 1 and 10 A g -1 , respectively. Notably, it delivered an excellent stability with capacity retention of 97.4% at 20 A g -1 after 6000 cycles.
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http://dx.doi.org/10.1002/chem.202100414DOI Listing
March 2021

Epstein-Barr virus-positive lymphoproliferative disorder manifesting as pulmonary disease in a patient with acute myeloid leukemia: a case report.

J Med Case Rep 2021 Mar 28;15(1):170. Epub 2021 Mar 28.

Department of Medicine, Division of Hematology, Cancer Institute, and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA.

Background:  Patients with lymphoproliferative disorders following hematopoietic stem cell transplant (HSCT) most commonly present with fever and lymphadenopathy within the first 5 months of transplant. Pulmonary post-transplant lymphoproliferative disorder (PTLD) is a particularly aggressive and rapidly progressive disease, with high morbidity and mortality. There are a very limited number of reported pulmonary PTLD cases following HSCT in patients with acute myeloid leukemia (AML). Early diagnosis and detection of pulmonary PTLD is critical given its high lethality. However, variable clinical presentations and nonspecific radiographic findings make pulmonary PTLD difficult to distinguish from other more common causes of pulmonary disease in AML patients.

Case Presentation: Here, we describe a 68-year-old Caucasian man who presented for salvage induction therapy following relapse of his AML after a haploidentical allogeneic HSCT 10 months earlier. He developed recurrent fevers, dry cough, and hypoxemia, with chest computed tomography (CT) showing bibasilar consolidations and increased nodularity without increased lymphadenopathy. His symptoms initially improved with antibiotic and antifungal therapy, but his follow-up chest CT showed progression of disease despite symptomatic improvement. Epstein-Barr virus (EBV) was detected in his blood by polymerase chain reaction (PCR), and a lung biopsy revealed monomorphic PTLD with B cells positive for EBV. Unfortunately, the patient's condition rapidly deteriorated, and he passed away prior to treatment initiation.

Conclusions:  To our knowledge, this is the first reported case of an AML patient developing pulmonary PTLD relatively late in his post-transplant course in the setting of relapsed disease and salvage therapy. Pulmonary PTLD, a rare but highly lethal disorder, can imitate the symptoms and radiographic findings of pneumonia, a common diagnosis in immunocompromised AML patients. This case illustrates the importance of considering pulmonary PTLD in the differential diagnosis for pulmonary disease in AML patients with a history of HSCT, especially in the setting of progressive radiographic findings despite broad antibacterial and antifungal therapy. Further, our case demonstrates the importance of biopsy and uninterrupted EBV DNA monitoring in the definitive diagnosis of PTLD, given nonspecific symptomatology and radiographic findings.
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http://dx.doi.org/10.1186/s13256-021-02744-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005240PMC
March 2021

Discordant results between conventional newborn screening and genomic sequencing in the BabySeq Project.

Genet Med 2021 Mar 26. Epub 2021 Mar 26.

Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA, USA.

Purpose: Newborn screening (NBS) is performed to identify neonates at risk for actionable, severe, early-onset disorders, many of which are genetic. The BabySeq Project randomized neonates to receive conventional NBS or NBS plus exome sequencing (ES) capable of detecting sequence variants that may also diagnose monogenic disease or indicate genetic disease risk. We therefore evaluated how ES and conventional NBS results differ in this population.

Methods: We compared results of NBS (including hearing screens) and ES for 159 infants in the BabySeq Project. Infants were considered "NBS positive" if any abnormal result was found indicating disease risk and "ES positive" if ES identified a monogenic disease risk or a genetic diagnosis.

Results: Most infants (132/159, 84%) were NBS and ES negative. Only one infant was positive for the same disorder by both modalities. Nine infants were NBS positive/ES negative, though seven of these were subsequently determined to be false positives. Fifteen infants were ES positive/NBS negative, all of which represented risk of genetic conditions that are not included in NBS programs. No genetic explanation was identified for eight infants referred on the hearing screen.

Conclusion: These differences highlight the complementarity of information that may be gleaned from NBS and ES in the newborn period.
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http://dx.doi.org/10.1038/s41436-021-01146-5DOI Listing
March 2021

A New Method (Ball Milling and Sodium Sulfide) for Mechanochemical Treatment of Soda Ash Chromite Ore Processing Residue.

J Hazard Mater 2021 Mar 5;415:125601. Epub 2021 Mar 5.

Civil and Environmental Engineering Department, College of Engineering, University of Nebraska-Lincoln, Omaha, NE 68182, USA.

Hexavalent chromium in soda ash Chromite Ore Processing Residue (COPR) is harmful to the environment, it is imperative to develop a low cost, efficient, and effective treatment. Herein, a new method (ball milling+sodium sulfide) was developed for mechanochemical treatment of water-leached COPR (W-COPR, about 900 mg/kg non-exchangeble Cr(VI) and mostly chromite bounded). Under a stoichiometric ratio of S to Cr(VI) of 5, milling speed of 200 rpm, milling time of 30 min, ball-to-powder weight ratios of 8.5, and, a total Cr(VI) of 76.88 mg/kg and a Toxicity Characteristic Leaching Procedure (TCLP) total Cr value of 1.15 mg/L were achieved after treatment. Results of the mineral liberation analyser (MLA) analyses showed 10% increase of chromite grains liberation and grain size reduction were beneficial to the chromite-bound Cr(VI) reduction. Similar effects were also observed on magnesioferrite encapsulated Cr(VI). Particle aggregation and formation of glass phase colloid precipitation could potentially impede Cr(VI) reduction. Results of X-ray absorption near edge structure (XANES) analyses indicated that the treatment method reduced the actual Cr(VI) concentration to 312 mg/kg with Cr(VI) reduction efficiency of 98% being achieved. Overall, the new method is simple and efficient, and provides a guidance for future industrial application.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125601DOI Listing
March 2021

Strain-Specific Peptide (SSP) Interference Reference Sample: A Genetically Encoded Quality Control for Isobaric Tagging Strategies.

Anal Chem 2021 03 18;93(12):5241-5247. Epub 2021 Mar 18.

Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, United States.

Isobaric tag-based sample multiplexing strategies are extensively used for global protein abundance profiling. However, such analyses are often confounded by ratio compression resulting from the co-isolation, co-fragmentation, and co-quantification of co-eluting peptides, termed "interference." Recent analytical strategies incorporating ion mobility and real-time database searching have helped to alleviate interference, yet further assessment is needed. Here, we present the strain-specific peptide (SSP) interference reference sample, a tandem mass tag (TMT)pro-labeled quality control that leverages the genetic variation in the proteomes of eight phylogenetically divergent mouse strains. Typically, a peptide with a missense mutation has a different mass and retention time than the reference or native peptide. TMT reporter ion signal for the native peptide in strains that encode the mutant peptide suggests interference which can be quantified and assessed using the interference-free index (IFI). We introduce the SSP by investigating interference in three common data acquisition methods and by showcasing improvements in the IFI when using ion mobility-based gas-phase fractionation. In addition, we provide a user-friendly, online viewer to visualize the data and streamline the calculation of the IFI. The SSP will aid in developing and optimizing isobaric tag-based experiments.
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http://dx.doi.org/10.1021/acs.analchem.0c05483DOI Listing
March 2021

Puerarin Attenuates LPS-Induced Inflammatory Responses and Oxidative Stress Injury in Human Umbilical Vein Endothelial Cells through Mitochondrial Quality Control.

Oxid Med Cell Longev 2021 27;2021:6659240. Epub 2021 Feb 27.

State Key Laboratory of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.

Atherosclerosis is closely associated with the inflammatory reaction of vascular endothelial cells. Puerarin (Pue), the main active component isolated from the rhizome of , is an isoflavone compound with potent antioxidant properties. Although Pue exhibits promising antiatherosclerotic pharmacological effects, only a few studies have reported its protective effect on endothelial cells. This study found that Pue could partly regulate mitochondrial function in human umbilical vein endothelial cells (HUVECs) and reduce or inhibit lipopolysaccharide-induced inflammatory reactions and oxidative stress injury in HUVECs, likely via mitochondrial quality control. Furthermore, the protective effect of Pue on HUVECs was closely related to the SIRT-1 signaling pathway. Pue increased autophagy and mitochondrial antioxidant potential via increased SIRT-1 expression, reducing excessive production of ROS and inhibiting the expression of inflammatory factors and oxidative stress injury. Therefore, Pue may improve mitochondrial respiratory function and energy metabolism, increasing the vulnerability of HUVECs to an inflammatory state.
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http://dx.doi.org/10.1155/2021/6659240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937474PMC
February 2021

Musculoskeletal ultrasound diagnosis of quadrilateral space syndrome: A case report.

Medicine (Baltimore) 2021 Mar;100(10):e24976

Department of Ultrasound, Baoji High-tech Hospital, Baoji, Shaanxi, China.

Introduction: Quadrilateral space syndrome (QSS) is a peripheral nerve entrapment disease, which can be misdiagnosed in clinic. In the past, QSS was mainly diagnosed by clinical symptoms combined with magnetic resonance imaging (MRI), electromyography (EMG), and arterial angiography. There are few reports on the diagnosis of QSS by musculoskeletal ultrasound (MSKUS) combined with clinical symptoms.

Patient Concerns: A middle-aged female patient had posterolateral pain and numbness in her right shoulder for 2 months.

Diagnoses: At first, she was diagnosed as suprascapular nerve entrapment, while EMG of suprascapular nerve and axillary nerve indicated that nerve conduction was normal. Then, MRI was performed, showing the shoulder had no abnormalities, and EMG and arterial angiography of upper limb showed no abnormalities too. Finally, she was diagnosed as QSS according to MSKUS and lidocaine block test.

Interventions: Two sealing treatments of axillary nerve block in quadrilateral space under the guidance of MSKUS were performed.

Outcomes: After 2 treatments, the pain and numbness in her shoulder disappeared, and her shoulder could move normally. There was no recurrence after 3 months of follow-up.

Conclusion: MSKUS is an effective method to diagnose QSS. It is fast, convenient and inexpensive, and is worth popularizing in clinic.
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http://dx.doi.org/10.1097/MD.0000000000024976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969238PMC
March 2021

Repurposing CFDA-approved drug carrimycin as an antiviral agent against human coronaviruses, including the currently pandemic SARS-CoV-2.

Acta Pharm Sin B 2021 Mar 11. Epub 2021 Mar 11.

Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing 100050, China.

COVID-19 pandemic caused by SARS-CoV-2 infection severely threatens global health and economic development. No effective antiviral drug is currently available to treat COVID-19 and any other human coronavirus infections. We report herein that a CFDA-approved macrolide antibiotic, carrimycin, potently inhibited the cytopathic effects (CPE) and reduced the levels of viral protein and RNA in multiple cell types infected by human coronavirus 229E, OC43, and SARS-CoV-2. Time-of-addition and pseudotype virus infection studies indicated that carrimycin inhibited one or multiple post-entry replication events of human coronavirus infection. In support of this notion, metabolic labelling studies showed that carrimycin significantly inhibited the synthesis of viral RNA. Our studies thus strongly suggest that carrimycin is an antiviral agent against a broad-spectrum of human coronaviruses and its therapeutic efficacy to COVID-19 is currently under clinical investigation.
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http://dx.doi.org/10.1016/j.apsb.2021.02.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946546PMC
March 2021

A nomogram for predicting brain metastases of EGFR-mutated lung adenocarcinoma patients and estimating the efficacy of therapeutic strategies.

J Thorac Dis 2021 Feb;13(2):883-892

Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Centre for Cancer, Tianjin, China.

Background: To establish a nomogram for predicting the outcome of EGFR-mutated lung adenocarcinoma patients with brain metastases (BMs) and to estimate the efficacy of different therapeutic strategies.

Methods: The data of 129 cases with BM from the period between January 1st 2011 and December 31st 2014 were collected, and all of the cases were pathologically confirmed to be lung adenocarcinoma, stages I-IV and with 19 and/or 21 exon mutations of EGFR. Cox regression analysis and log-rank test were used for data analysis. The nomogram was used to establish the progression models.

Results: In the univariate analysis, the stage, ECOG score, interval between the diagnosis of lung cancer and BM, the number of brain metastatic lesions, and the diameter of the maximal brain metastatic lesion correlated well with overall survival (OS). In multivariate Cox proportional hazard analysis, the ECOG score, interval between the diagnosis of lung cancer and BM, and the number of brain metastatic lesions correlated well with the OS. Patients were divided into the poor prognostic group and the good prognostic group based on the nomogram prognostic model score. Subgroup analysis showed that in the poor prognostic group, the OS of patients who received radiotherapy was better than that of the patients who did not receive radiotherapy as the first-line treatment (30 19 months, P<0.05). The OS was 30 months in the TKI subgroup and 21 months in the no TKI subgroup, but no statistical difference was found (P>0.05). Patients in the good prognostic group who received radiotherapy had a better 3-y OS rate than the patients who received no radiotherapy as the first-line treatment (91.2% 58.1%, P<0.05). The 3-y OS rate was 87.6% in the TKI subgroup and 67.8% in the no TKI group (P<0.05).

Conclusions: We established an effective nomogram model to predict the progression of EGFR-mutated lung adenocarcinoma patients with BM and the therapeutic effect of the individual treatments. Radiotherapy was beneficial for the patients of both the poor and good prognostic groups, but TKI may be better suited for treating the patients with good prognosis.
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http://dx.doi.org/10.21037/jtd-20-1587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947515PMC
February 2021

Aberrant multimodal brain networks in patients with anti-NMDA receptor encephalitis.

CNS Neurosci Ther 2021 Mar 13. Epub 2021 Mar 13.

Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Aims: To explore large-scale brain network alterations and examine their clinical and neuropsychological relevance in patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis.

Methods: Twenty-four patients with anti-NMDAR encephalitis and 26 matched healthy controls (HCs) were enrolled in our study. Based on the multimodal MRI dataset, individual morphological, structural, and functional brain networks were constructed and compared between the two groups at multiple levels. The associations with clinical/neuropsychological variables and the discriminant ability of significant alterations were further studied.

Results: Multimodal network analysis revealed that anti-NMDAR encephalitis mainly affected morphological and structural networks, but subtle alterations were observed in functional networks. Intriguingly, decreased network local efficiency was observed for both morphological and structural networks and increased nodal centrality in the lateral orbital gyrus was convergently observed among the three types of networks in the patients. Moreover, the alterations, particularly those from structural networks, accounted largely for cognitive deficits of the patients and could distinguish the diseased individuals from the HCs with excellent performance (area under the curve =0.933).

Conclusions: The current study provides a comprehensive view of characteristic multimodal network dysfunction in anti-NMDAR encephalitis, which is crucial to establish new diagnostic biomarkers and promising therapeutic targets for the disease.
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http://dx.doi.org/10.1111/cns.13632DOI Listing
March 2021

Microbial community associated with ectomycorrhizal Russula symbiosis and dominated nature areas in southern China.

FEMS Microbiol Lett 2021 Mar 9. Epub 2021 Mar 9.

State Key Laboratory of Ecological Pest Control for Fujian and Taiwan Crops, and Fujian Universities Key Laboratory of Plant- Microbe Interaction, College of Life Sciences and College of Plant Protection, Fujian Agriculture and Forestry University, Fuzhou, China.

Russula griseocarnosa is one of the uncultivable important mycorrhizal edible fungi. Currently, there is a limited insight into the dynamic composition of the microbial communities associated with Russula. Here, the microbiota in the root and mycorrhizosphere from Russula-Fagaceae nature areas of Fujian province were identified by Illumina MiSeq high-throughput sequencing. First, we compared three types of fungal communities associated with Russula-Fagaceae root mycelia-running stage (stage-1), Russula sporocarping stage-2 (stage-2), and Russula -free Fagaceae root (stage-3). Fungal diversity negatively correlated with Russula. Russula, Tomentella, and Lactarius were core EcM in Fagaceae roots. Eight genera, including Boletus, are likely a positive indicator of Russula sporocarp production in Russula-Fagaceae roots, while Tomentella and Elaphomyces for Russula symbiosis. Secondly, analysis of fungal and bacterial communities within rhizosphere soils from the three stages revealed six genera, including Dacryobolus and Acidocella, as possible indicator species associated with sporocarping in Russula. Elaphomyces, Tomentella, Sorangium, Acidicaldus, Acidobacterium, and Haliangium occurred more frequently in the Russula rhizosphere. Furthermore, operational taxonomic unit (OTU) network analysis showed a positive correlation between Russula, Tomentella, Elaphomyces, and Sorangium. Overall, our results revealed a relationship between micro-community and Russula, which may provide a new strategy for improving Russula symbiosis and sporocarp production.
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http://dx.doi.org/10.1093/femsle/fnab028DOI Listing
March 2021

Brain structural alterations in MOG antibody diseases: a comparative study with AQP4 seropositive NMOSD and MS.

J Neurol Neurosurg Psychiatry 2021 Mar 9. Epub 2021 Mar 9.

Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

Background: Brain structural alterations and their clinical significance of myelin oligodendrocyte glycoprotein antibody disease (MOGAD) have not been determined.

Methods: We recruited 35 MOGAD, 38 aquaporin 4 antibody positive neuromyelitis optica spectrum diseases (AQP4+ NMOSD), 37 multiple sclerosis (MS) and 60 healthy controls (HC) who underwent multimodal brain MRI from two centres. Brain lesions, volumes of the whole brain parenchyma, cortical and subcortical grey matter (GM), brainstem, cerebellum and cerebral white matter (WM) and diffusion measures (fractional anisotropy, FA and mean diffusivity, MD) were compared among the groups. Associations between the MRI measurements and the clinical variables were assessed by partial correlations. Logistic regression was performed to differentiate MOGAD from AQP4+ NMOSD and MS.

Results: In MOGAD, 19 (54%) patients had lesions on MRI, with cortical/juxtacortical (68%) as the most common location. MOGAD and MS showed lower cortical and subcortical GM volumes than HC, while AQP4+ NMOSD only demonstrated a decreased cortical GM volume. MS demonstrated a lower cerebellar volume, a lower FA and an increased MD than MOGAD and HC. The subcortical GM volume was negatively correlated with Expanded Disability Status Scale in MOGAD (R=-0.51; p=0.004). A combination of MRI and clinical measures could achieve an accuracy of 85% and 93% for the classification of MOGAD versus AQP4+ NMOSD and MOGAD versus MS, respectively.

Conclusion: MOGAD demonstrated cortical and subcortical atrophy without severe WM rarefaction. The subcortical GM volume correlated with clinical disability and a combination of MRI and clinical measures could separate MOGAD from AQP4+ NMOSD and MS.
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http://dx.doi.org/10.1136/jnnp-2020-324826DOI Listing
March 2021

Mechanochemical activation on selective leaching of arsenic from copper smelting flue dusts.

J Hazard Mater 2021 Feb 18;414:125436. Epub 2021 Feb 18.

Key Laboratory of Catalysis Conversion and Energy Materials, Ministry of Education, China; Engineering Research Center for Heavy Metal Pollution Control of Hubei Province, College of Resources and Environmental Science, South-Central University for Nationalities, Wuhan 430074, China. Electronic address:

A novel application, including mechanochemical pre-treating and alkali leaching, for arsenic selective leaching from copper smelter flue dusts (CSFUs) was developed to overcome the disadvantages of hydrometallurgical methods. Compared with raw CSFU powders, the mechanical-activated ones showed higher maximum arsenic leaching efficiency (increased by ~20%), and lower apparent activation energy (decreased by ~7 kJ·mol). Furthermore, this novel process only consumed half of alkali and sulfides and needed one-third of the leaching time to compare with the ones used in the traditional alkali leaching process. The promoting effect of mechanical force on arsenic leaching firstly relied on the physical property changes of CSFU powders, including a decrease of particle sizes and an increase of the specific surface. Secondly, mechanochemical force converted As species into reduced phases (e.g. AsO, NaAsO), and thio-arsenates (e.g. AsOS, AsOS), which could spur its leaching due to their stronger mobilities in the alkali solution within sulfides. Finally, mechanochemical activation could be facilitated to separate discrete soluble arsenic species or incorporated ones from sulfate minerals in the CSFUs. This work may have important implications for the development of new eco-friendly technologies for purifying arsenic-bearing materials.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125436DOI Listing
February 2021

mutations are associated with favorable outcomes to immune checkpoint inhibitors across multiple cancer types.

J Immunother Cancer 2021 Mar;9(3)

Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, North Carolina, USA

Background: Low-density lipoprotein receptor-related protein 1b (encoded by ) is a putative tumor suppressor, and preliminary evidence suggests mutated cancers may have improved outcomes with immune checkpoint inhibitors (ICI).

Methods: We conducted a multicenter, retrospective pan-cancer analysis of patients with alterations treated with ICI at Duke University, Johns Hopkins University (JHU) and University of Michigan (UM). The primary objective was to assess the association between overall response rate (ORR) to ICI and pathogenic or likely pathogenic (P/LP) alterations compared with variants of unknown significance (VUS). Secondary outcomes were the associations with progression-free survival (PFS) and overall survival (OS) by status.

Results: We identified 101 patients (44 Duke, 35 JHU, 22 UM) with alterations who were treated with ICI. The most common tumor types by alteration (P/LP vs VUS%) were lung (36% vs 49%), prostate (9% vs 7%), sarcoma (5% vs 7%), melanoma (9% vs 0%) and breast cancer (3% vs 7%). The ORR for patients with P/LP versus VUS alterations was 54% and 13%, respectively (OR 7.5, 95% CI 2.9 to 22.3, p=0.0009). P/LP alterations were associated with longer PFS (HR 0.42, 95% CI 0.26 to 0.68, p=0.0003) and OS (HR 0.62, 95% CI 0.39 to 1.01, p=0.053). These results remained consistent when excluding patients harboring microsatellite instability (MSI) and controlling for tumor mutational burden (TMB).

Conclusions: This multicenter study shows significantly better outcomes with ICI therapy in patients harboring P/LP versus VUS alterations, independently of TMB/MSI status. Further mechanistic and prospective validation studies are warranted.
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http://dx.doi.org/10.1136/jitc-2020-001792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929846PMC
March 2021

Light absorption properties and molecular profiles of HULIS in PM emitted from biomass burning in traditional "Heated Kang" in Northwest China.

Sci Total Environ 2021 Feb 23;776:146014. Epub 2021 Feb 23.

State Key laboratory of Loess and Quaternary Geology, Institute of Earth Environment, Chinese Academy of Sciences, Xi'an 710049, China.

Humic-like substances (HULIS) in PM emitted from biomass burning (BB), including maize cob, wheat straw, maize straw, wood branch, and wood, in a traditional "Heated Kang" were investigated. The relative abundances, optical properties, chemical functional groups, and molecular components in HULIS were characterized using total organic carbon (TOC) analyzer, ultraviolet-visible spectroscopy (UV-vis), Fourier-transform infrared spectroscopy (FT-IR), and Fourier-transform ion cyclotron resonance mass spectrometer (FT-ICR/MS), respectively. The emission factors (EF) of HULIS-C (in term of carbon weight, EF) from BB were in the range of 0.83 to 5.17 g/kg fuel, with a mean value of 1.93 ± 1.31 g/kg fuel. The HULIS-C accounted for 15.0-37.8% and 9.1-12.6% of fractions in organic carbon (OC) and PM, respectively, suggesting that BB is an important emission source of atmospheric HULIS. The FT-IR spectra showed BB HULIS mainly contain O-containing, aliphatic CH, and aromatic CC functional groups. The presences of carboxyl group and OH band demonstrated the uniqueness of maize straw and wood burning. Moreover, the higher ratio of CH and -CH groups could be used to distinguish the wood branches from the maize cob. CHO and CHON were much dominant in BB HULIS, which accounted for 44.6-47.6% and 50.1-54.2%, respectively, to the total molecular mass. The positive correlation between MAE and AAE in term of number concentration of CHNO implied that the CHNO species could greatly influence on the light absorption properties of the BB HULIS. The CHO and S-containing compounds (i.e., CHNOS and CHOS, that is CHNOS+CHOS) showed weak light absorbances of the BB HULIS. The BB HULIS from maize straw had relatively high molecular weight in comparison to that in other BB emissions. The highest and lowest aromaticity were seen on the wood burning and maize cob, respectively.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146014DOI Listing
February 2021

Combination antiangiogenic tyrosine kinase inhibition and anti-PD1 immunotherapy in metastatic renal cell carcinoma: A retrospective analysis of safety, tolerance, and clinical outcomes.

Cancer Med 2021 Apr 1;10(7):2341-2349. Epub 2021 Mar 1.

Department of Genitourinary Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.

Introduction: Two separate antiangiogenic tyrosine kinase inhibitors (TKIs) and immunotherapy (IO) combinations are FDA-approved as front-line treatment for metastatic renal cell carcinoma (mRCC). Little is known about off-protocol and post-front-line experience with combination TKI-IO approaches.

Methods: We conducted a retrospective analysis of mRCC patients who received combination TKI-IO post-first-line therapy between November 2015 and January 2019 at MD Anderson Cancer Center and Duke Cancer Institute. Chart review detailed patient characteristics, treatments, toxicity, and survival. Independent radiologists, blinded to clinical data, assessed best radiographic response using RECIST v1.1.

Results: We identified 48 mRCC patients for inclusion: median age 65 years, 75.0% clear cell histology, 68.8% IMDC intermediate risk, and median two prior systemic therapies. TKI-IO combinations included nivolumab-cabozantinib (N +C; 24 patients), nivolumab-pazopanib (N+P; 13), nivolumab-axitinib (6), nivolumab-lenvatinib (2), and nivolumab-ipilimumab-cabozantinib (3). The median progression-free survival was 11.6 months and the median overall survival was not reached. Response data were available in 45 patients: complete response (CR; n = 3, 6.7%), partial response (PR; 20, 44.4%), stable disease (SD; 19, 42.2%), and progressive disease (3, 6.7%). Overall response rate was 51% and disease control rate (CR+PR+SD) was 93%. Only one patient had a grade ≥3 adverse event.

Conclusion: To our knowledge, this is the first case series reporting off-label use of combination TKI-IO for mRCC. TKI-IO combinations, particularly N+P and N+C, are well tolerated and efficacious. Although further prospective research is essential, slow disease progression on IO or TKI monotherapy may be safely controlled with addition of either TKI or IO.
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http://dx.doi.org/10.1002/cam4.3812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982609PMC
April 2021

COVID-19 vaccines for patients with cancer: benefits likely outweigh risks.

J Hematol Oncol 2021 02 27;14(1):38. Epub 2021 Feb 27.

Pelotonia Institute for Immuno-Oncology, The OH State University Comprehensive Cancer Center - James, Columbus, OH, USA.

Less than a year since the start of the COVID-19 pandemic, ten vaccines against SARS-CoV-2 have been approved for at least limited use, with over sixty others in clinical trials. This swift achievement has generated excitement and arrives at a time of great need, as the number of COVID-19 cases worldwide continues to rapidly increase. Two vaccines are currently approved for full use, both built on mRNA and lipid nanotechnology platforms, a success story of mRNA technology 20 years in the making. For patients with cancer, questions arise around the safety and efficacy of these vaccines in the setting of immune alterations engendered by their malignancy and/or therapies. We summarize the current data on leading COVID-19 vaccine candidates and vaccination of patients undergoing immunomodulatory cancer treatments. Most current cancer therapeutics should not prevent the generation of protective immunity. We call for more research in this area and recommend that the majority of patients with cancer receive COVID vaccinations when possible.
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http://dx.doi.org/10.1186/s13045-021-01046-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910769PMC
February 2021

Recent progress in g-CN, TiO and ZnO based photocatalysts for dye degradation: Strategies to improve photocatalytic activity.

Sci Total Environ 2021 May 29;767:144896. Epub 2021 Jan 29.

School of Chemical Sciences, Central University of Gujarat, Gandhinagar 382030, India. Electronic address:

Water contamination by dyes is a matter of concern for human health and the environment. Various methods (membrane separation, coagulation and adsorption) have been explored to remove/degrade dyes. However, now the exploitation of semiconductor assisted materials using renewable solar energy has emerged as a potential candidate to resolve the issue. Although, single component photocatalysts (ZnO, TiO, ZrO) were experimented, due to their low efficiency and stability due to the high recombination rate electron-hole pair and inefficient visible light absorption, composites of semiconductor materials are being used. Semiconductor heterojunction systems are developed by coupling two or more semiconductor components. The synergistic effect of their properties, such as adsorption and improved charge carrier migration, is observed to increase overall stability. This review covers recent progress in advanced nanocomposite materials based on g-CN, TiO and ZnO used as photocatalysts with details of enhancing the photocatalytic properties by heterojunctions, crystallinity and doping. The conclusion at the end displays a summary, research gaps and future outlook. A holistic analysis of recent progress to demonstrate the efficient heterojunctions for photodegradation with optimal conditions, this review will be helpful for the development of efficient heterostructured systems for photodegradation. This review covers references from the year 2017-2020.
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http://dx.doi.org/10.1016/j.scitotenv.2020.144896DOI Listing
May 2021

Matrine, as a CaSR agonist promotes intestinal GLP-1 secretion and improves insulin resistance in diabetes mellitus.

Phytomedicine 2021 Apr 14;84:153507. Epub 2021 Feb 14.

Department of Pharmacy, The Second Affiliated Hospital of Air Force Medical University, Xi'an, 710038, PR China.. Electronic address:

Background: Matrine (Mat), a bitter tastes compounds of derived from leguminosae such as Sophora flavescens and S. subprostrata, commonly used to improve obesity and diabetes.

Purpose: Our study to demonstrate bitter substances can stimulate the Bitter taste receptors (TAS2Rs) or Calcium-sensing receptor (CaSR) to stimulate the secretion of GLP-1 to promote blood glucose regulation.

Methods: The diabetic mice and intestinal secretory cell model were established to evaluate the Mat on glucose metabolism, intestinal insulin secretion and GLP-1 secretion related substances. To clarify the mechanism of Mat in regulating GLP-1 secretion by immunofluorescence, calcium labeling, siRNA, and molecular docking.

Results: The results showed that Mat could significantly improve glucose metabolism and increased insulin and GLP-1 secretion in diabetic mice and increased trisphosphate inositol (IP3) levels by affecting the expression of phospholipase C β2 (PLCβ2) and promote an increase in intracellular Ca2 levels in STC-1 cells to subsequently stimulate the secretion of GLP-1. Knockdown of the bitter taste receptors mTas2r108, mTas2r137, and mTas2r138 in STC-1 cells by siRNA did could not affect the role of Mat in regulating GLP-1. However, the secretion of GLP-1 by Mat could be significantly inhibited by administration of a CaSR inhibitor or siRNA CaSR. Molecular docking analysis showed that Mat could embed CaSR protein and bind to the original ligand of the egg white at the same amino acid site to play the role of an agonist.

Conclusion: Matrine is a typical bitter alkaloid could be used as an agonist of CaSR to stimulate the secretion of GLP-1 in the intestine, and it may be used as a potential drug for diabetes treatment.
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http://dx.doi.org/10.1016/j.phymed.2021.153507DOI Listing
April 2021

Association Between Hemoglobin and Growth Hormone Peak in Chinese Children and Adolescents with Short Stature: A Cross-Sectional Study.

Int J Gen Med 2021 16;14:497-504. Epub 2021 Feb 16.

Department of Clinical Medicine, Jining Medical University, Jining, Shandong, People's Republic of China.

Objective: This research aimed to investigate the relationship between hemoglobin (Hb) and growth hormone (GH) peak in children and adolescents with short stature.

Design: This cross-sectional study included a total of 787 children and adolescents with short stature. Anthropometric and biochemical indicators were measured at baseline. All patients underwent GH provocation tests with L-dopa and insulin to assess GH peak levels.

Results: The univariate analysis results showed that Hb was positively associated with GH peak (β 0.07, P=0.001). Furthermore, a non-linear relationship was detected between Hb and GH peaks through smooth curve fitting, and the inflection point was 123 g/L after multivariate piecewise linear regression analysis. GH peak increased with Hb elevation when the Hb level was greater than 123 g/L (β 0.08, 95% CI 0.01, 0.14; P=0.0207).

Conclusion: In children and adolescents with short stature, we found GH peak was positively associated with the Hb level when the Hb level reached the inflection point.
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http://dx.doi.org/10.2147/IJGM.S292920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896770PMC
February 2021

Expression of immune checkpoints on circulating tumor cells in men with metastatic prostate cancer.

Biomark Res 2021 Feb 18;9(1):14. Epub 2021 Feb 18.

Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, DUMC 103861, Durham, NC, 27710, UK.

Background: A subset of men with metastatic prostate cancer (mPC) responds to immune checkpoint inhibitors, and there is an unmet need to predict those most likely to benefit. We characterized circulating tumor cells (CTCs) for expression of immune checkpoint ligands in men with mPC as a non-invasive biomarker of immune evasion and immunotherapy benefit.

Methods: Three cohorts of patients were enrolled: 1) men with mCRPC starting abiraterone acetate/prednisone or enzalutamide (pre-ARSI), 2) men with mCRPC who were progressing on enzalutamide or abiraterone acetate/prednisone (post-ARSI), and 3) men with newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC) starting androgen deprivation therapy. CTCs were captured using the CellSearch® system and stained for PD-L1, PD-L2, B7-H3, and CTLA-4 at baseline, on treatment, and disease progression. Summary statistics on mean CTCs per cohort, as well as rates of ligand positivity were used to analyze CTCs by cohort and by timepoint.

Results: Men in all cohorts and timepoints had prevalent CTC B7-H3 expression (> 80%). We found evidence for CTC PD-L1 expression across disease states, in which > 1 positive CTC or > 50% of CTCs were positive for PD-L1 in 40 and 30% of men with mHSPC, respectively, 60 and 20% of men with mCRPC pre-ARSI, and 70 and 30% of men with mCRPC post-ARSI. CTC PD-L2 expression was present in 20-40% of men in each disease state, while CTC CTLA-4 expression was rare, present in 20% of men with mCRPC pre-ARSI and 10% of men with mCRPC post-ARSI or with mHSPC. CTC immune checkpoint expression was heterogeneous within/between men and across disease states.

Conclusions: We have identified that CTCs from men with mPC heterogeneously express immune checkpoints B7-H3, PD-L1, PD-L2, and CTLA-4, and the detection of these immune checkpoints may enable monitoring on immunotherapy.
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http://dx.doi.org/10.1186/s40364-021-00267-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890610PMC
February 2021

A long-term chemical characteristics and source apportionment of atmospheric rainfall in a northwest megacity of Xi'an, China.

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

School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, USA.

A long-term measurement on rainfall was conducted in urban Xi'an, China, from 2009 to 2016. The seasonal and annual variations of major inorganic components and their chemical properties in the rainfall were studied. The annual rainfall ranged from 165.3 to 916.3 mm. The pH value of the rainfall ranged from 6.36 to 7.19, with an average value of 6.70. The electric conductivity (EC) in the rainfall was in a range of 55.91 to 227.44 μS·cm. Ammonium (NH), calcium (Ca), nitrate (NO), and sulfate (SO) were the four major components, accounting for 88.5% of the total quantified inorganic ion concentration. Neutralization factors were determined for Ca (1.03), NH (0.57), Mg (0.10), Na (0.06), and K (0.04). The high abundance of NH that formed from its precursor of ammonia gas (NH) suggested the contribution of agricultural fertilization. Ca in the rainfall was mainly from natural sources such as soil dust, while anions of NO and SO originated from fossil fuel combustion. Source apportionment was conducted with positive matrix factorization (PMF) which identified that secondary inorganic formation, crustal dust, coal combustion, and biomass burning are the contributors to the rainfall. In between, secondary inorganic formation was the largest contributor, which accounted for 27.8-58.1% of the total sources, followed by crustal dust of 0.4-42.6%. The results of this long-term study demonstrated the decreasing trends of contributions from coal combustion and biomass burning under a series of air pollution control measures implemented by the government. However, continuous urbanization and development of the city caused substantial increases of the construction activities, inducing more crustal dusts to the environment in urban Xi'an.
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http://dx.doi.org/10.1007/s11356-021-13015-4DOI Listing
February 2021

A comparison of sunitinib with cabozantinib, crizotinib, and savolitinib for treatment of advanced papillary renal cell carcinoma: a randomised, open-label, phase 2 trial.

Lancet 2021 Feb 13;397(10275):695-703. Epub 2021 Feb 13.

University of California Davis Comprehensive Cancer Center, Sacramento, CA, USA.

Background: MET (also known as hepatocyte growth factor receptor) signalling is a key driver of papillary renal cell carcinoma (PRCC). Given that no optimal therapy for metastatic PRCC exists, we aimed to compare an existing standard of care, sunitinib, with the MET kinase inhibitors cabozantinib, crizotinib, and savolitinib for treatment of patients with PRCC.

Methods: We did a randomised, open-label, phase 2 trial done in 65 centres in the USA and Canada. Eligible patients were aged 18 years or older with metastatic PRCC who had received up to one previous therapy (excluding vascular endothelial growth factor-directed and MET-directed agents). Patients were randomly assigned to receive sunitinib, cabozantinib, crizotinib, or savolitinib, with stratification by receipt of previous therapy and PRCC subtype. All drug doses were administered orally: sunitinib 50 mg, 4 weeks on and 2 weeks off (dose reductions to 37·5 mg and 25 mg allowed); cabozantinib 60 mg daily (reductions to 40 mg and 20 mg allowed); crizotinib 250 mg twice daily (reductions to 200 mg twice daily and 250 mg once daily allowed); and savolitinib 600 mg daily (reductions to 400 mg and 200 mg allowed). Progression-free survival (PFS) was the primary endpoint. Analyses were done in an intention-to-treat population, with patients who did not receive protocol therapy excluded from safety analyses. This trial is registered with ClinicalTrials.gov, NCT02761057.

Findings: Between April 5, 2016, and Dec 15, 2019, 152 patients were randomly assigned to one of four study groups. Five patients were identified as ineligible post-randomisation and were excluded from these analyses, resulting in 147 eligible patients. Assignment to the savolitinib (29 patients) and crizotinib (28 patients) groups was halted after a prespecified futility analysis; planned accrual was completed for both sunitinib (46 patients) and cabozantinib (44 patients) groups. PFS was longer in patients in the cabozantinib group (median 9·0 months, 95% CI 6-12) than in the sunitinib group (5·6 months, 3-7; hazard ratio for progression or death 0·60, 0·37-0·97, one-sided p=0·019). Response rate for cabozantinib was 23% versus 4% for sunitinib (two-sided p=0·010). Savolitinib and crizotinib did not improve PFS compared with sunitinib. Grade 3 or 4 adverse events occurred in 31 (69%) of 45 patients receiving sunitinib, 32 (74%) of 43 receiving cabozantinib, ten (37%) of 27 receiving crizotinib, and 11 (39%) of 28 receiving savolitinib; one grade 5 thromboembolic event was recorded in the cabozantinib group.

Interpretation: Cabozantinib treatment resulted in significantly longer PFS compared with sunitinib in patients with metastatic PRCC.

Funding: National Institutes of Health and National Cancer Institute.
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http://dx.doi.org/10.1016/S0140-6736(21)00152-5DOI Listing
February 2021

Author Correction: Antigen-capturing nanoparticles improve the abscopal effect and cancer immunotherapy.

Nat Nanotechnol 2021 Feb 12. Epub 2021 Feb 12.

Laboratory of Nano- and Translational Medicine, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, USA.

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http://dx.doi.org/10.1038/s41565-021-00864-wDOI Listing
February 2021