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1.
Tissue Eng Part A ; 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35019728

RESUMO

Renal fibrosis predisposes patients to an increased risk of progressive chronic kidney disease (CKD), and effective treatments remain elusive. Mesenchymal stem cell (MSC) derived exosomes are considered a new treatment for tissue damage. Our study aimed to investigate the in vitro effects of bone marrow MSC-derived exosomes (BM-MSC-Ex) on transforming growth factor-ß1 (TGF-ß1)-induced fibrosis in renal tubular epithelial cells (HK-2 cells) and the associated mechanisms. Herein, we found exosomes derived from bone marrow mesenchymal stem cells (BM-MSC-Ex) could inhibit TGF-ß1-induced epithelial-mesenchymal transition (EMT) in HK-2 cells, and may involve autophagy activation of BM-MSC-Ex. Moreover, we first reported that after CeNPs treatment, the improvements induced by BM-MSC-Ex on EMT were significantly enhanced by up-regulating the expression of Nedd4Lof MSCs and promoting the secretion of exosomes, which contained Nedd4L. In addition, Nedd4L could activate autophagy in HK-2 cells. In conclusion, BM-MSC-Ex prevents the TGF-ß1-induced EMT of renal tubular epithelial cells by transporting Nedd4L, which activates autophagy. The results of this in vitro experiment may extend to renal fibrosis, whereby BM-MSC-Ex may also be used as a novel treatment for improving renal fibrosis.

2.
Anal Chim Acta ; 1191: 339251, 2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35033275

RESUMO

Owing to the high risk to human and environmental health, heavy metal pollution has become a global problem. Rapid, accurate and multiplexed determination of heavy metal ions is critical. In this work, we reported a promising approach to designing ratiometric fluorescent nanoprobes for multiplexed determination of Hg2+, Cu2+, and Ag+ ions. The nanoprobes (CDs-QDx) were designed by mixing the CDs and multicolor CdTe QDs without the involvement of recognition elements. The CDs were insensitive to heavy metal ions while CdTe QDs showed the size-dependent fluorescence response to different heavy metal ions, thereby establishing a ratiometric detection scheme by measuring the fluorescence intensity ratios of CDs-QDx systems. By evaluating the detection performance, the CDs-QDx (x = 570, 650, and 702) were successfully used for differentiation and quantification of Hg2+, Cu2+, and Ag+ ions. In addition, we also carried out the detection of heavy metal ions in actual samples with acceptable results. We believed that this work offers new insight into the design of ratiometric fluorescent nanoprobe for multiplexed determination of not only heavy metals but also some other analytes by combining the CDs with CdTe QDs with fine-tuned sizes.


Assuntos
Compostos de Cádmio , Metais Pesados , Pontos Quânticos , Carbono , Humanos , Íons , Telúrio
3.
Orphanet J Rare Dis ; 17(1): 3, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983612

RESUMO

BACKGROUND: Information about the specific regulatory environment of orphan drugs is scarce and inconsistent. Uncertainties surrounding the postmarketing long-term safety of orphan drugs remain. This study aimed to evaluate the labelling changes of orphan drugs and to identify postmarketing safety-associated approval factors. METHODS: This retrospective cohort study includes all drugs with orphan drug designation approved by the Center for Drug Evaluation and Research of the US Food and Drug Administration between 1999 and 2018. Main outcomes are safety-related labelling changes up to 31 December 2019. We defined any safety-related labelling changes as postmarketing safety events (PMSE). Safety-related withdrawals, suspensions, and boxed warnings were further categorised as severe postmarketing safety events (SPSE). Outcome measurements include frequencies of PMSE, SPSE, and association between approval factors and the occurrence of safety events. RESULTS: Amongst the 214 drugs identified with orphan drug designation (25.7% biologics), 83.6% were approved through at least one expedited programme, and 29.4% were approved with boxed warnings. During a median follow-up of 6.74 years since approval, 69.2% and 14.5% of the analysed orphan drugs had PMSE and SPSE, respectively. Safety-related withdrawal (0%, 0/214), suspended marketing (0.46%, 1/214) and new boxed warnings are uncommon (3.7%, 8/214). The safety-related labelling changes were more frequent in the drugs approved with boxed warnings [Incidence rate ratio (IRR): 1.95 (1.02-3.73)] and approved for long-term use [IRR: 2.76 (1.52-5.00)]. CONCLUSIONS AND RELEVANCE: In this long-term postmarketing analysis, approximately 70% of FDA-approved orphan drugs had safety-related labelling changes although severe safety events were rare. While maintaining early access to orphan drugs, the drug regulatory body has taken timely regulatory action with postmarketing surveillance to ensure patient safety.

4.
Adv Mater ; : e2108947, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34994990

RESUMO

High-nickel (Ni≥90%) cathodes with high specific capacity hold great potential for next-generation lithium-ion batteries (LIBs). However, their practical application is restricted by the high interfacial reactivity under continuous air erosion and electrolyte assaults. Herein, a stable high-nickel cathode was rationally designed via in-situ induction of a dense amorphous Li2 CO3 on the particle surface by a preemptive atmosphere control. Among the residual lithium compounds, Li2 CO3 is the most thermodynamically stable one so that the dense Li2 CO3 coating layer can serve as a physical protection layer to isolate the cathodes from contact with moist air. Furthermore, amorphous Li2 CO3 can be transformed into a robust F-rich cathode electrolyte interphase (CEI) during cycling, which reinforces the cathodes interfacial stability and improves electrochemical performance. The assembled coin cell with this modified cathode delivers a high discharge capacity of 232.4 mAh g-1 with a superior initial coulombic efficiency of 95.1%, and a considerable capacity retention of 90.4% after 100 cycles. Furthermore, no slurry gelation occurred during large-scale electrode fabrication process. This work opens a valuable perspective on the evolution of amorphous Li2 CO3 in LIBs and provides guidance on protecting unstable high-capacity cathodes for energy storage devices. This article is protected by copyright. All rights reserved.

5.
ACS Appl Mater Interfaces ; 14(1): 677-683, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-34939409

RESUMO

Sodium-ion batteries (SIBs) are currently the most promising candidates for large-scale energy storage devices owing to their low cost and abundant resources. Titanium-based layered oxides have attracted widespread attention as promising anode materials due to delivering a safe potential of about 0.7 V (vs Na+/Na) and a small volume contraction during cycles; P2-type Ti-based layered oxides are typically reported, due to the challenging synthesis of the O3-type counterpart resulting from the high percentage of unstable Ti3+. Herein, we report an anomalous O3-Na2/3Ni1/3Ti2/3O2 layered oxide as an ultrastable and high-rate anode material for SIBs. The anode material delivers a reversible capacity of 112 mA h g-1 after 300 cycles at 0.1 C, a good capacity retention rate of 91% after 1400 cycles at 2 C, and, in particular, a capacity of 52 mA h g-1 even at a high rate of 20 C (1780 mA g-1). Furthermore, the in situ X-ray diffraction monitoring reveals no phase transitions and almost zero strain both underlie the good long-cycle stability. The measured high apparent Na+ diffusion coefficient (2.06 × 10-10 cm2 s-1) and the low migration energy barrier (0.59 eV) from density functional theory calculations are responsible for the superior rate capability. Our results promise advanced high-performance O3-type Ti-based layered oxides as promising anode materials toward application for SIBs.

6.
Exp Brain Res ; 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34854933

RESUMO

Empathy for pain, the ability to share and understand the pain of others, plays an important role in the survival and development of individuals. Previous studies have found that social pain experience affects empathy for pain, but potential gender differences have not been considered. The stage of information processing during which gender is most likely to play a moderating role has yet to be clarified. In the current study, we set up two groups (social pain experience priming: social exclusion group; positive social interaction experience priming: social inclusion group) with a Cyberball game paradigm. We recorded the electrophysiological responses when participants were completing an empathy task. An early frontal P2 and N2 differentiation between painful stimuli and neutral stimuli was observed and females showed larger P2 amplitudes than males. At the P3 stage, in the social exclusion group, males showed similar parietal P3 amplitudes for painful and neutral stimuli, while females showed smaller P3 amplitudes for painful stimuli. At the central-parietal late positive potential (LPP) stage, females in the social inclusion group showed larger LPP amplitudes for painful stimuli than males. Our results suggest that gender plays a significant moderating role in how social pain experience affects empathy for pain during the late cognitive processing stage. Experiment 2 was designed to investigate the cognitive mechanism behind the results for the P3 component in females and the results partially confirmed our speculation. This study provides a neurophysiological basis for the dynamic gender differences in the effects of social pain experience on empathy for pain.

7.
Plant Cell ; 2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34919720

RESUMO

Starch is the main energy storage carbohydrate in plants and serves as an essential carbon storage molecule for plant metabolism and growth under changing environmental conditions. The TARGET of RAPAMYCIN (TOR) kinase is an evolutionarily conserved master regulator that integrates energy, nutrient, hormone, and stress signaling to regulate growth in all eukaryotes. Here, we demonstrate that TOR promotes guard cell starch degradation and induces stomatal opening in Arabidopsis thaliana. Starvation, caused by plants growing under short photoperiod or low light photon irradiance, as well as inactivation of TOR, impaired guard cell starch degradation and stomatal opening. Sugar and TOR induce the accumulation of ß-AMYLASE1 (BAM1), which is responsible for starch degradation in guard cells. The plant steroid hormone brassinosteroid (BR) and transcription factor BZR1 play crucial roles in sugar-promoted expression of BAM1. Furthermore, sugar supply induced BAM1 accumulation, but TOR inactivation led to BAM1 degradation, and the effects of TOR inactivation on BAM1 degradation were abolished by the inhibition of autophagy and proteasome pathways or by phospho-mimicking mutation of BAM1 at serine-31. Such regulation of BAM1 activity by sugar-TOR signaling allows carbon availability to regulate guard cell starch metabolism and stomatal movement, ensuring optimal photosynthesis efficiency of plants.

8.
Ann Transl Med ; 9(18): 1430, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34733982

RESUMO

Background: Adjuvant chemotherapy (ACT) is routinely the recommended treatment for patients with advanced non-small cell lung cancer (NSCLC) but remains a controversial option in stage IB patients. We therefore pooled the current evidence to determine the prognostic impact of ACT in stage IB NSCLC patients in the context of the eighth tumor, node, metastasis (TNM) staging system. Methods: Five electronic databases were searched for eligible studies up to December 2020 without language restrictions. The primary and secondary outcomes were overall survival (OS) and disease-free survival (DFS). Search results were filtered by a set of eligibility criteria and analyzed in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The risk of bias was assessed independently using a modified set. Stata 16.0 was used for general data analysis and meta-analysis, and subgroup analyses were performed to investigate the source of interstudy heterogeneity. Results: In all, 12 eligible studies were identified and 15,678 patients included. Our results demonstrated that ACT was associated with improved OS [n=11; hazard ratio (HR) =0.65; 95% confidence interval (CI): 0.60-0.70; P<0.001; I2=33.4%, P=0.131] and DFS (n=9; HR =0.73; 95% CI: 0.63-0.83; P<0.001; I2=66.7%, P=0.002) in stage IB NSCLC patients. Subgroup analysis by histology indicated that administration of ACT conferred more favorable survival to both stage IB squamous cell carcinoma (n=1; HR =0.56; 95% CI: 0.28-0.84; P<0.001) and adenocarcinoma (n=6; HR =0.59; 95% CI: 0.47-0.71; P<0.001; I2=31.0%, P=0.203). Meanwhile, both platinum-based ACT (n=7; HR =0.62; 95% CI: 0.51-0.74; P<0.001; I2=44.8%, P=0.093) and other regimens (n=2; HR =0.66; 95% CI: 0.61-0.72; P<0.001; I2=0.7%, P=0.316) could benefit patients with stage IB disease. Discussion: ACT might provide survival benefits to patients with stage IB NSCLC irrespective of histology or regimens. Patient selection and time trend biases were inevitable due to the limitation of retrospective studies. More prospective studies should be initiated to investigate the optimal ACT regimens in different histologic types in stage IB NSCLC patients.

9.
Genome ; : 1-7, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34756106

RESUMO

Chrysanthemums (Chrysanthemum morifolium Ramat.) are ornamental flowers, which are famous worldwide. The mode of inheritance has great implications for the genetic analysis of polyploid species. However, genetic analysis of chrysanthemum has been hampered because of its controversial inheritance mode (disomic or hexasomic). To classify the inheritance mode of chrysanthemums, an analysis of three approaches was carried out in an F1 progeny of 192 offspring using 223 expressed sequence tag-simple sequence repeat (EST-SSR) markers. The analysis included segregation analysis, the ratio of simplex marker alleles linked in coupling to repulsion, as well as the transmission and segregation patterns of EST-SSR marker alleles. After segregation analysis, 204 marker alleles fit hexasomic inheritance and 150 marker alleles fit disomic inheritance, showing that marker alleles were inherited predominantly in a hexasomic manner. Furthermore, the results of the analysis of allele configuration and segregation behavior of five EST-SSR markers also suggested random pairing of chromosomes. Additionally, the ratio of simplex marker alleles linked in coupling to repulsion was 1:0, further supporting hexasomic inheritance. Therefore, it could be inferred that chrysanthemum is a complete or near-complete hexasome.

10.
Ther Adv Med Oncol ; 13: 17588359211054895, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777583

RESUMO

Background: We aim to assess the prognostic ability of three common lymph node-based staging algorithms, namely, the number of positive lymph nodes (pN), the lymph node ratio (LNR), and log odds of positive lymph nodes (LODDS) in patients with esophageal squamous cell carcinoma (ESCC). Methods: A total of 3902 ESCC patients treated at 10 Chinese institutions between 2003 and 2013 were included, along with 2465 patients from the Surveillance, Epidemiology, and End Results (SEER) database. The prognostic ability of the aforementioned algorithms was evaluated using time-dependent receiver operating characteristic (tdROC) curves, R 2, Harrell's concordance index (C-index), and the likelihood ratio chi-square score. The primary outcomes included cancer-specific survival (CSS), overall survival (OS), and CSS with a competing risk of death by non-ESCC causes. Results: LODDS had better prognostic performance than pN or LNR in both continuous and stratified patterns. In the multicenter cohort, the multivariate analysis showed that the model based on LODDS classification was superior to the others in predictive accuracy and discriminatory capacity. Two nomograms integrating LODDS classification and other clinicopathological risk factors associated with OS as well as cancer-specific mortality were constructed and validated in the SEER database. Finally, a novel TNLODDS classification which incorporates the LODDS classification was built and categorized patients in to three new stages. Conclusion: Among the three lymph node-based staging algorithms, LODDS demonstrated the highest discriminative capacity and prognostic accuracy for ESCC patients. The nomograms and novel TNLODDS classification based on LODDS classification could serve as precise evaluation tools to assist clinicians in estimating the survival time of individual patients and improving clinical outcomes postoperatively in the future.

11.
BMC Plant Biol ; 21(1): 516, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34749644

RESUMO

BACKGROUND: Cucumber green mottle mosaic virus (CGMMV) causes substantial global losses in cucurbit crops, especially watermelon. N6-methyladenosine (m6A) methylation in RNA is one of the most important post-transcriptional modification mechanisms in eukaryotes. It has been shown to have important regulatory functions in some model plants, but there has been no research regarding m6A modifications in watermelon. RESULTS: We measured the global m6A level in resistant watermelon after CGMMV infection using a colorimetric method. And the results found that the global m6A level significantly decreased in resistant watermelon after CGMMV infection. Specifically, m6A libraries were constructed for the resistant watermelon leaves collected 48 h after CGMMV infection and the whole-genome m6A-seq were carried out. Numerous m6A modified peaks were identified from CGMMV-infected and control (uninfected) samples. The modification distributions and motifs of these m6A peaks were highly conserved in watermelon transcripts but the modification was more abundant than in other reported crop plants. In early response to CGMMV infection, 422 differentially methylated genes (DMGs) were identified, most of which were hypomethylated, and probably associated with the increased expression of watermelon m6A demethylase gene ClALKBH4B. Gene Ontology (GO) analysis indicated quite a few DMGs were involved in RNA biology and stress responsive pathways. Combined with RNA-seq analysis, there was generally a negative correlation between m6A RNA methylation and transcript level in the watermelon transcriptome. Both the m6A methylation and transcript levels of 59 modified genes significantly changed in response to CGMMV infection and some were involved in plant immunity. CONCLUSIONS: Our study represents the first comprehensive characterization of m6A patterns in the watermelon transcriptome and helps to clarify the roles and regulatory mechanisms of m6A modification in watermelon in early responses to CGMMV.

12.
J Glob Health ; 11: 08009, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34737869

RESUMO

Background: To evaluate the disease burden of age-related macular degeneration (AMD) in terms of disability-adjusted life years (DALY) in China from 1990 to 2019. Methods: Prevalence of blindness and vision loss due to AMD and DALY number, rate, and age-standardized rates of AMD were collected from the Global Burden of Disease Study 2019 database. The characters of variables were analyzed between China and its neighboring countries. Results: From 1990 to 2019, the all-age number and rate for AMD prevalence and DALYs increased significantly in China, while the age standardized DALYs rate in 2019 showed a decrease of 3.63% compared with that in 1990. Females were found to have a higher prevalence and DALYs than males. The 65-69 age group had the highest AMD DALYs number, while the DALYs rate showed a positive association with age. In 2019, when compared to neighboring countries, the age standardized prevalence rate of AMD in China was ranked second after Pakistan, while the age standardized DALYs rate ranked second after Pakistan and India. Conclusions: Despite a small decrease in age standardized DALYs rate in China in the past three decades, the disease burden of AMD is still considerable and much higher compared to neighboring developed countries. Optimizing health services allocation is needed to further reduce this burden.


Assuntos
Carga Global da Doença , Degeneração Macular , China/epidemiologia , Efeitos Psicossociais da Doença , Feminino , Saúde Global , Humanos , Degeneração Macular/epidemiologia , Masculino
13.
Int J Mol Sci ; 22(19)2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34638756

RESUMO

As sessile organisms, the precise development phase transitions are very important for the success of plant adaptability, survival and reproduction. The transition from juvenile to the adult phase-referred to as the vegetative phase change-is significantly influenced by numbers of endogenous and environmental signals. Here, we showed that brassinosteroid (BR), a major growth-promoting steroid hormone, positively regulates the vegetative phase change in Arabidopsis thaliana. The BR-deficient mutant det2-1 and BR-insensitive mutant bri1-301 displayed the increased ratio of leaf width to length and reduced blade base angle. The plant specific transcription factors SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) are key masters for the vegetative phase transition in plants. The expression levels of SPL9, SPL10 and SPL15 were significantly induced by BR treatment, but reduced in bri1-116 mutant compared to wild-type plants. The gain-of-function pSPL9:rSPL9 transgenic plants displayed the BR hypersensitivity on hypocotyl elongation and partially suppressed the delayed vegetative phase change of det2-1 and bri1-301. Furthermore, we showed that BRASSINAZOLE-RESISTANT 1 (BZR1), the master transcription factor of BR signaling pathway, interacted with SPL9 to cooperatively regulate the expression of downstream genes. Our findings reveal an important role for BRs in promoting vegetative phase transition through regulating the activity of SPL9 at transcriptional and post-transcriptional levels.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica de Plantas , Mutação , Transdução de Sinais , Transativadores/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Ligação a DNA/genética , Transativadores/genética
14.
New Phytol ; 2021 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-34693527

RESUMO

The timing and extent of cell division are crucial for the correct patterning of multicellular organism. In Arabidopsis, root ground tissue maturation involves the periclinal cell division of the endodermis to generate two cell layers: endodermis and middle cortex. However, the molecular mechanism underlying this pattern formation remains unclear. Here, we report that phytohormone brassinosteroid (BR) and redox signal hydrogen peroxide (H2 O2 ) interdependently promote periclinal division during root ground tissue maturation by regulating the activity of SHORT-ROOT (SHR), a master regulator of root growth and development. BR-activated transcription factor BRASSINAZOLE RESISTANT1 (BZR1) directly binds to the promoter of SHR to induce its expression, and physically interacts with SHR to increase the transcripts of RESPIRATORY BURST OXIDASE HOMOLOGs (RBOHs) and elevate the levels of H2 O2 , which feedback enhances the interaction between BZR1 and SHR. Additionally, genetic analysis shows that SHR is required for BZR1-promoted periclinal division, and BZR1 enhances the promoting effects of SHR on periclinal division. Together, our finding reveals that the transcriptional module of BZR1-SHR fine-tunes periclinal division during root ground tissue maturation in response to hormone and redox signals.

15.
Plant Physiol Biochem ; 168: 340-352, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34688195

RESUMO

N6-methyladenosine (m6A) in RNA is a very important post-transcriptional modification mechanism in eukaryotes. It has been reported to have important regulatory roles in some stress responses in model plants, but there has been no research regarding m6A modifications in watermelon. In this study, we cloned and characterized m6A methyltransferase, ClMTB (mRNA adenosine methylase B, METTL14 human homolog protein) in watermelon. ClMTB expression could be weakly induced by drought stress as determined by the quantitative real-time PCR (qRT-PCR) and Promoter::GUS analyses. ClMTB over-expressed in tobacco plants increased drought tolerance via enhancing reactive oxygen species (ROS) scavenging system and alleviating photosynthesis inhibition under drought. Transcriptome profiles indicated the multiple hormone and stress-responsive genes were specifically induced in over-expressed ClMTB plants under drought conditions. These results suggest that ClMTB-mediated m6A modification serves as a positive regulatory factor of drought tolerance. This study is the first one to provide an understanding of the specific roles of ClMTB in watermelon adaptation to drought stress, and may also provide important insights into the signaling pathway mediated by m6A modification in response to stress conditions.

16.
Ann Transl Med ; 9(16): 1344, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34532481

RESUMO

Background: A nomogram was developed for the estimation of individualized overall survival (OS) of patients diagnosed with small cell esophageal carcinoma (SCEC). Methods: From the SEER dataset, 427 patients diagnosed with SCEC during the period from 2004 to 2015 were selected as training sets. For the establishment of a nomogram capable of estimating the OS possibility of patients diagnosed with SCEC, a group of independent prognostic factors were identified and incorporated. The effectiveness of the nomogram was then both externally and internally verified among 159 patients from Fudan University Shanghai Cancer Center (FUSCC) who were diagnosed with SCEC between 2006 and 2015. The predictive accuracy and discriminative ability of the nomogram were measured by concordance index (C-index). Comparisons between nomogram and the AJCC staging systems (6th and 7th) were performed with calibration plots and area under the curves (AUC) values. Results: We identified age, gender, primary site, SEER stage, surgery, radiotherapy, and chemotherapy as seven independent risk factors which were then used to set up the nomogram. Calibration curves indicated that the prediction of the nomogram was consistent with real observations for the possibilities of 1-, 3-, and 5-year OS, and applying the nomogram to the cohort for validation led to reproducible results. Moreover, the C-indices and AUC values were higher in the nomogram than those in the AJCC staging system AJCC which is also aimed at the prediction of OS. Conclusions: This study resulted in the establishment of the first nomogram for the prediction of individualized OS of patients diagnosed with SCEC. The accuracy rate of prediction of this model may be higher than previously established staging systems.

17.
Nat Commun ; 12(1): 5267, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34489437

RESUMO

Na-ion cathode materials operating at high voltage with a stable cycling behavior are needed to develop future high-energy Na-ion cells. However, the irreversible oxygen redox reaction at the high-voltage region in sodium layered cathode materials generates structural instability and poor capacity retention upon cycling. Here, we report a doping strategy by incorporating light-weight boron into the cathode active material lattice to decrease the irreversible oxygen oxidation at high voltages (i.e., >4.0 V vs. Na+/Na). The presence of covalent B-O bonds and the negative charges of the oxygen atoms ensures a robust ligand framework for the NaLi1/9Ni2/9Fe2/9Mn4/9O2 cathode material while mitigating the excessive oxidation of oxygen for charge compensation and avoiding irreversible structural changes during cell operation. The B-doped cathode material promotes reversible transition metal redox reaction enabling a room-temperature capacity of 160.5 mAh g-1 at 25 mA g-1 and capacity retention of 82.8% after 200 cycles at 250 mA g-1. A 71.28 mAh single-coated lab-scale Na-ion pouch cell comprising a pre-sodiated hard carbon-based anode and B-doped cathode material is also reported as proof of concept.

18.
Lung Cancer ; 160: 32-35, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34391065

RESUMO

Alectinib, a highly selective inhibitor of anaplastic lymphoma kinase (ALK), has shown a high response rate and long progression-free survival in primary treatment of ALK-positive non-small-cell lung cancer (NSCLC). De novo resistance or refractory subtype is rare event. Herein, we identify the first case with serial next-generation sequencing (NGS) results that harboured a rare echinoderm microtubule associated protein like 4 gene (EML4) -ALK (breaking site at exon 19) fusion in a lung adenocarcinoma (LUAD) patient who acquired alectinib resistance rapidly (less than 3 months), followed by multi-drug resistance and short survival time.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Quinase do Linfoma Anaplásico/genética , Carbazóis , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Éxons/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Proteínas de Fusão Oncogênica/genética , Piperidinas , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico
19.
Front Surg ; 8: 655159, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395507

RESUMO

Purpose/objectives: Primary small cell esophageal carcinoma (SCEC) is a rare malignancy without an established treatment strategy. This study investigated the gene expression profile of SCEC and compared it with the expression profiles of small cell lung cancer (SCLC) and esophageal adeno/squamous carcinoma (EAC/ESCC). Materials/methods: All patients with SCEC, SCLC, and EAC/ESCC in the Surveillance, Epidemiology, and End Results (SEER) database 1973-2014 were included. Overall survival (OS) and prognostic analysis were conducted. De novo expression array analysis was performed on three pairs of frozen primary SCEC tissues and the corresponding normal samples from the institutional tissue bank using the Affymetrix HG U133 plus 2.0 Array. These data were complemented with public domain expression data sets from the Gene Expression Omnibus (GEO) repository using the same working platforms, which included primary SCLC, EAC/ESCC, and normal lung/esophagus specimens (series GSE30219 and GSE26886). After individual normalization, the primary tumors were submitted to statistical analysis (GeneSpring GX 13.0) to identify the differentially expressed genes (DEGs) relative to their paired normal tissues. Enrichments of genes categorized by function and gene interactions were analyzed by DAVID 6.8 and STRING 11.0, respectively. Results: The clinical outcomes of the patients with SCEC were significantly more worse than those with EAC/ESCC and SCLC in the SEER database. SCEC had more DEGs in common with SCLC than EAC/ESCC [829 vs. 450; false discovery rate (FDR) < 0.01; and fold change ≥2], leading to a stronger correlation between SCEC and SCLC (Pearson's correlation coefficient was 0.60 for SCEC vs. SCLC, 0.51 or 0.45 for SCEC vs. ESCC or EAC, and the coefficient was 0.73 for ESCC vs. EAC). Similar findings were obtained by principal component analysis (PCA) using all DEGs retrieved from these four groups. Functional annotation showed that a higher proportion of pathways and biological processes were common between SCEC and SCLC and were associated with the cell cycle (mitosis), DNA replication, telomere maintenance, DNA repair, and P53 and RB pathways (Benjamini p < 0.05). Compared with EAC/ESCC, SCEC shared more co-upregulated DEGs coding for the aforementioned common pathways with SCLC (584 vs. 155). In addition, SCEC and SCLC were found to have possessed overlapping gene-interactive networks, with centromere protein F (CENPF), never in mitosis gene A-related kinase 2 ( NEK2), kinesin family member 11 (KIF11), thymopoietin (TMPO), and forkhead box protein M1 (FOXM1) as common skeletons centered by gene regulatory network (NUF2). Conclusions: This study is the first attempt to examine the genomic signatures of SCEC at the transcriptomic level and compare the expression profiles between SCEC, SCLC, and EAC/ESCC. Our preliminary data indicate that SCEC and SCLC display notably similar patterns of gene expression for mitosis and DNA repair. Further validation studies are warranted.

20.
Artigo em Inglês | MEDLINE | ID: mdl-34415030

RESUMO

Counter-empathy significantly affects people's social lives. Previous evidence indicates that the degree of counter-empathy can be either strong or weak. Strong counter-empathy easily occurs when empathizers are prejudiced against the targets of empathy (e.g., prejudice against outgroup members) and activates brain regions that are opposite to those activated by empathy. Weak counter-empathy may have different neural processing paths from strong one, but its underlying neural mechanisms remain unclear. In this work, we used an unfair distribution paradigm, which can reduce participants' prejudice against persons empathized with, and functional magnetic resonance imaging (fMRI) to explore the neural mechanisms underlying counter-empathy. Here, empathy and counter-empathy shared a common neural mechanism, induced by unfair distribution, in the right middle temporal gyrus. Counter-empathy activated distinct brain regions that differed from those of empathic responses in different situations. The functions of these brain regions, which included the middle frontal, middle temporal and left medial superior gyri, were similar and mostly related to emotional regulation and cognitive processing. Here, we propose a process model of counter-empathy, involving two processing paths according to whether or not prejudice exists. This study has theoretical significance and broadens our understanding of the cognitive neural mechanisms underlying empathy and counter-empathy.

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