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1.
Sci Total Environ ; 753: 142028, 2020 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-32906049

RESUMO

Although some persistent organic pollutants (POPs) were prohibited or limited in use several decades ago, they are still frequently detected in the human body. The purpose of this study was to understand the levels and profiles of POPs in breast milk in China and assess their potential health risks among breastfed infants under six months of age. A literature review focused on China was performed for studies published from 2001 to 2020. The POP levels in breast milk along with other important variables were extracted, and then the average individual POP levels in breast milk were estimated. This review summarises the distribution of traditional and new POPs, including polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), legacy brominated flame retardants (BFRs), perfluorinated compounds (PFCs), and chlorinated paraffins (CPs) and reported notably high levels of short-chain chlorinated paraffins and 1,1-dichloro-2,2-bis (p-chlorophenyl) ethylene (p,p'-DDE) in breast milk. Although the levels of traditional POPs generally declined over time, especially p,p'-DDE and beta-hexachlorocyclohexane (ß-HCH), women living in coastal areas, urban areas, and southern China still have a high body burden of certain POPs. In the present study, the estimated daily intake (EDI) of POPs through breastfeeding was used to evaluate the health risk for infants by comparing with acceptable levels. The findings suggested that infants born in coastal areas most likely suffered potential health risk from exposure to DDT, and the health risk of hexachlorobenzene (HCB) in infants in most nationwide regions remains a concern. More importantly, the EDI of PCBs for infants exceeds the safe limit on a national scale. Continuous surveillance of PCBs in breast milk is critical to evaluate the potential health effects on humans.

3.
Acta Biomater ; 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32920175

RESUMO

Current bioactive modifications of Ti-based materials for promoting osteogenesis often decrease corrosion fatigue strength (σcf) of the resultant implants, thereby shortening their service lifespan. To solve this issue and accelerate the osteogenesis process, in the present study, a TiO2 nanorods (TNR)-arrayed coating was hydrothermally grown on optimal surface mechanical attrition treated (SMATed) titanium (S-Ti). The microstructure, bond integrity, residual stress distribution, and corrosion fatigue of TNR-coated S-Ti (TNR/S-Ti) and the response of macrophages and bone marrow-derived mesenchymal stem cells (BMSCs) to TNR/S-Ti were investigated and compared with those of mechanically polished Ti (P-Ti), S-Ti, and TNR-coated P-Ti (TNR/P-Ti). S-Ti showed a nanograined layer and an underlying grain-deformed region with residual compressive stress, which was sustained even when it was hydrothermally coated with TNR. TNR on S-Ti showed nanotopography, composition, and bond strength almost identical to those of P-Ti. While TNR/P-Ti showed a considerable decrease in σcf compared to P-Ti, TNR/S-Ti exhibited an improved σcf which was even higher than that of P-Ti. Biologically, TNR/S-Ti enhanced adhesion, differentiation, and mineralization of BMSCs, and it also promoted adhesion and M1-to-M2 transition of macrophages as compared to S-Ti and P-Ti. With rapid phenotype switch of macrophages, the level of proinflammatory cytokines decreased, while anti-inflammatory cytokines were upregulated. In co-culture conditions, the migration, differentiation, and mineralization of BMSCs were enhanced by increased level of secretion factors of macrophages on TNR/S-Ti. The modified structure accelerated bone apposition in rabbit femur and is expected to induce a favorable immune microenvironment to facilitate osseointegration earlier; it can also simultaneously improve corrosion fatigue resistance of Ti-based implants and thereby enhance their service life.

4.
ACS Nano ; 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32924505

RESUMO

Killing the tumor cells by a visualized system is a promising strategy in tumor therapy to achieve low side effects and high efficiency. Herein, a theranostic nanomedicine (AuNCs-Pt) is developed based on nanocarrier AuNCs with bifunctions of both NIR-I/NIR-II imaging and glutathione-scavenging abilities. AuNCs-Pt possesses NIR-II imaging capability on a fatal high-grade serous ovarian cancer (HGSOC) model in the deep abdomen, thus facilitating it to be a promising tool for monitoring platinum transportation. Meanwhile, AuNCs-Pt depletes intracellular glutathione to minimize platinum detoxification, effectively maximizing chemotherapeutic efficacy of platinum. AuNCs-Pt is used to eradicate the tumor burden in this study on a HGSOC model and a patient-derived tumor xenograft model of hepatocellular carcinoma (PDHC), performing a great potential on clinical visualized therapy and platinum drugs sensitization.

5.
Eur Radiol ; 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32929641

RESUMO

OBJECTIVE: To investigate the effect of coronary calcification morphology and severity on the diagnostic performance of machine learning (ML)-based coronary CT angiography (CCTA)-derived fractional flow reserve (CT-FFR) with FFR as a reference standard. METHODS: A total of 442 patients (61.2 ± 9.1 years, 70% men) with 544 vessels who underwent CCTA, ML-based CT-FFR, and invasive FFR from China multicenter CT-FFR study were enrolled. The effect of calcification arc, calcification remodeling index (CRI), and Agatston score (AS) on the diagnostic performance of CT-FFR was investigated. CT-FFR ≤ 0.80 and lumen reduction ≥ 50% determined by CCTA were identified as vessel-specific ischemia with invasive FFR as a reference standard. RESULTS: Compared with invasive FFR, ML-based CT-FFR yielded an overall sensitivity of 0.84, specificity of 0.94, and accuracy of 0.90 in a total of 344 calcification lesions. There was no statistical difference in diagnostic accuracy, sensitivity, or specificity of CT-FFR across different calcification arc, CRI, or AS levels. CT-FFR exhibited improved discrimination of ischemia compared with CCTA alone in lesions with mild-to-moderate calcification (AUC, 0.89 vs. 0.69, p < 0.001) and lesions with CRI ≥ 1 (AUC, 0.89 vs. 0.71, p < 0.001). The diagnostic accuracy and specificity of CT-FFR were higher than CCTA alone in patients and vessels with mid (100 to 299) or high (≥ 300) AS. CONCLUSION: Coronary calcification morphology and severity did not influence diagnostic performance of CT-FFR in ischemia detection, and CT-FFR showed marked improved discrimination of ischemia compared with CCTA alone in the setting of calcification. KEY POINTS: • CT-FFR provides superior diagnostic performance than CCTA alone regardless of coronary calcification. • No significant differences in the diagnostic performance of CT-FFR were observed in coronary arteries with different coronary calcification arcs and calcified remodeling indexes. • No significant differences in the diagnostic accuracy of CT-FFR were observed in coronary arteries with different coronary calcification score levels.

6.
Phytomedicine ; 78: 153314, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32882582

RESUMO

BACKGROUND: Sarsasapogenin (Sar) shows good effects on diabetic nephropathy (DN) through inhibition of the NLRP3 inflammasome, yet the potential mechanism is not well known. PURPOSE: This study was designed to explore the regulation of thrombin and/or its receptor protease-activated receptor 1 (PAR-1) on the NLRP3 inflammasome and NF-κB signaling in DN condition, and further expounded the molecular mechanism of Sar on DN. METHODS: Streptozotocin-induced diabetic rats were treated by gavage with Sar (0, 20 and 60 mg/kg) for consecutive 10 weeks. Then urine and serum were collected for protein excretion, creatinine, urea nitrogen, and uric acid assay reflecting renal functions, renal tissue sections for periodic acid-Schiff staining and ki67 expression reflecting cell proliferation, and renal cortex for the NLRP3 inflammasome and NF-κB signaling as well as thrombin/PAR-1 signaling. High glucose-cultured human mesangial cells (HMCs) were used to further investigate the effects and mechanisms of Sar. RESULTS: Sar markedly ameliorated the renal functions and mesangial cell proliferation in diabetic rats, and suppressed activation of the NLRP3 inflammasome and NF-κB in renal cortex. Moreover, Sar remarkably down-regulated PAR-1 in protein and mRNA levels but didn't affect thrombin activity in kidney, although thrombin activity was significantly decreased in the renal cortex of diabetic rats. Meanwhile, high glucose induced activation of the NLRP3 inflammasome and NF-κB, and increased PAR-1 expression while didn't change thrombin activity in HMCs; however, Sar co-treatment ameliorated all the above indices. Further studies demonstrated that PAR-1 knockdown attenuated activation of the NLRP3 inflammasome and NF-κB, and Sar addition strengthened these effects in high glucose-cultured HMCs. CONCLUSION: Sar relieved DN in rat through inhibition of the NLRP3 inflammasome and NF-κB by down-regulating PAR-1 in kidney.

7.
Sci Rep ; 10(1): 14424, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32879364

RESUMO

Fungal keratitis (FK) is the most devastating and vision-threatening microbial keratitis, but clinical diagnosis a great challenge. This study aimed to develop and verify a deep learning (DL)-based corneal photograph model for diagnosing FK. Corneal photos of laboratory-confirmed microbial keratitis were consecutively collected from a single referral center. A DL framework with DenseNet architecture was used to automatically recognize FK from the photo. The diagnoses of FK via corneal photograph for comparing DL-based models were made in the Expert and NCS-Oph group through a majority decision of three non-corneal specialty ophthalmologist and three corneal specialists, respectively. The average percentage of sensitivity, specificity, positive predictive value, and negative predictive value was approximately 71, 68, 60, and 78. The sensitivity was higher than that of the NCS-Oph (52%, P < .01), whereas the specificity was lower than that of the NCS-Oph (83%, P < .01). The average accuracy of around 70% was comparable with that of the NCS-Oph. Therefore, the sensitive DL-based diagnostic model is a promising tool for improving first-line medical care at rural area in early identification of FK.

8.
Nanoscale ; 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32895690

RESUMO

The misfolding and abnormal amyloid fibrillation of proteins/peptides are associated with more than 20 human diseases. Although dozens of nanoparticles have been investigated for the inhibition effect on the misfolding and fibrillation of pathogenesis-related proteins/peptides, there are few reports on charge effects of nano inhibitors on amyloid fibrillation. Herein, same-sized gold nanoclusters modified with 2-aminoethanethiol hydrochloride (CSH-AuNCs, positively charged in pH 7.4) or 3-mercaptopropionic acid (MPA-AuNCs, negatively charged in pH 7.4) were synthesized and adopted as models to explore the charge effect of nano inhibitors on amylin fibrillation at the nano-bio interface. ThT fluorescence kinetics analysis, AFM images and circular dichroism (CD) spectra showed that electropositive CSH-AuNCs inhibited the misfolding and fibrillation of amylin in a dosage-dependent manner, but electronegative MPA-AuNCs accelerated the misfolding and fibrillation of amylin in a dosage-dependent manner. Moreover, the theoretical and experimental results revealed the interaction mechanism between amylin and ligands of AuNCs at the nano-bio interfaces. Electropositive CSH-AuNCs could be bound to the main nucleating region of amylin via hydrogen bonding and endowed the nanocomplex with more positive net charges (amylin monomer with a positive +26.23 ± 0.80 mV zeta potential), which would inhibit the misfolding and aggregation of amylin via electrostatic repulsion and steric hindrance. In contrast, electronegative MPA-AuNCs could absorb electropositive amylin via strong electrostatic attractions, which accelerated the fibrillation process of amylin via enhancing local concentrations. Moreover, cell experiments showed that both the charged AuNCs had good biocompatibility and electronegetive MPA-AuNCs showed a better protective effect in the amylin-induced cell model than electropositive CSH-AuNCs. These results provide an insight into structure-based nanodrug design for protein conformational diseases.

9.
BMC Pediatr ; 20(1): 418, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32878600

RESUMO

BACKGROUND: To explore the relationship between the pathological changes of the colon, terminal ileum, lung, liver and kidney, and the changes of Bax, PCNA and PAF in a rat model of NEC. METHODS: One hundred and forty neonatal SD rats were randomly divided into NEC group and control group (70 in each group). NEC group was given hypoxia, cold stimulation and artificial feeding twice a day for 3 consecutive days. The control group was only fed normally. After modeling, From the 1st day to the 7th day, 10 rats were sampled in each group for pathological examination of colon, terminal ileum, lung, liver and kidney tissue. The levels of Bax, PCNA and PAF were investigated by immunohistochemistry. RESULTS: Compared with the normal group, in the NEC group, on the 1st day, the colon, terminal ileum, lung, liver and kidney showed inflammatory damage. On the 5th day, the inflammatory injury was reduced. The inflammation disappeared on the 7th day. There were differences in the time of apoptosis in the intestine. In the intestine, the proliferation of PCNA was weak at first and then strong. Bax in liver and kidney showed marked apoptosis and apoptosis time increased in the lung. The expression of PCNA increased in lung, liver and kidney, and the expression of PAF increased in lung and liver. CONCLUSIONS: NEC can lead to secondary injury of different degrees in colon, terminal ileum, lung, liver and kidney, and the degree and time of injury and repair were different. In general, organ repair played a leading role on the 4th day after modeling.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32883521

RESUMO

Embryonic stem (ES) cells are unique in their ability to self-renew indefinitely while maintaining pluripotency. Krüppel-like factor (Klf) 4 is an important member of the Klf family that is known to play a key role in pluripotency and somatic cell reprogramming. However, the identification and functional comparison of Klf4 splicing isoforms in mouse ESCs (mESCs) remains to be elucidated. Here, we identified three novel alternative splicing variants of Klf4 in mESCs-mKlf4-108, mKlf4-375 and mKlf4-1482-that are distinct from the previously known mKlf4-1449. mKlf4-1449 and mKlf4-1482 may stimulate the growth of ESCs, while mKlf4-108 can only promote the growth of ESCs in LIFlow/serum conditions. In addition, both mKlf4-1449 and mKlf4-1482 can inhibit the differentiation of mESCs. However, the ability of mKlf4-1482 to promote self-renewal and inhibit differentiation is not as strong as that of mKlf4-1449. In contrast, both mKlf4-108 and mKlf4-375 may have the ability to induce endodermal differentiation. Taken together, we have identified for the first time the existence of alternative splicing variants of mKlf4 and have revealed their different roles, which provide new insights into the contribution of Klf4 to the self-renewal and pluripotency of mouse ESCs.

11.
Orthop Surg ; 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32851772

RESUMO

OBJECTIVE: Treatment of massive irreparable rotator cuff tears (RCT) has shown limited clinical success and a variety of subsequent complications. Superior capsule reconstruction (SCR) has been proved to reestablish superior stability but does not restore the dynamic force or shoulder kinematics. There are numerous reports of the short-term failure of SCR grafts at the glenoid side, which relate to the non-biological healing of grafts. To restore both dynamic and static stability and to provide biologic augmentation, an integrated procedure for massive irreparable RCT using an Achilles tendon-bone allograft (ATBA) was developed. METHOD: This was a retrospect study completed between October 2019 and April 2020. A 71-year-old woman with massive and irreparable rotator cuff tears was enrolled in our study. The ATBA was folded into a double-layer structure. The superior layer (proximal portion) served as a bridge patch to dynamic the glenohumeral joint, while the inferior layer (distal portion) served as the superior capsule to restore static stability of glenohumeral joint. To enhance biologic healing on the glenoid side, we fixed the calcaneus of the graft on the superior-posterior side of the superior glenoid rim. The recovery of shoulder function (including strength, range of motion, acromiohumeral interval, and fatty infiltration) was assessed at 6 months postoperation. RESULT: At 6-month follow-up, the patient's strength had improved significantly (from abduction of grade 3 preoperatively to grade 4 at 6 months). Radiographic analysis showed an increase in the acromiohumeral interval from 3 to 7 mm. Magnetic resonance imaging revealed an intact graft, with the thickness of the ligament part maintained (at 6-7 mm). Most importantly, recovery of atrophy and fatty infiltration of the supraspinatus were observed. No graft tears were observed on the glenoid side. CONCLUSION: This technique could provide a preferable treatment option by restoring shoulder kinematics and augmentating biological healing for patients with massive irreparable RCT.

12.
AAPS PharmSciTech ; 21(6): 227, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32767025

RESUMO

Streptococcus mutans (S. mutans) is the principal etiologic agent in the occurrence of human dental caries and the formation of biofilms on the surface of teeth. Tea tree oil (TTO) has been demonstrated to exhibit a wide range of pharmacological actions that can effectively inhibit the activity of bacteria. In this context, we evaluated the in vitro antimicrobial effects of TTO on S. mutans both during planktonic growth and in biofilms compared with 0.2% CHX. We determined the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) using the microdilution method, the bacteriostatic rate using an MTT assay, and the antimicrobial time using a time-kill assay. Then, we explored the effects of TTO on acid production and cell integrity. Furthermore, the effects of TTO on the biomass and bacterial activity of S. mutans biofilms were studied. Finally, scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) were used to investigate the structure and activity of biofilms. The MIC and MBC values were 0.125% and 0.25%, and the bacterial inhibition rate was concentration dependent. TTO can effectively inhibit bacterial acid production and destroy the integrity of the cell membrane. Electron micrographs revealed a reduction in bacterial aggregation, inhibited biofilm formation, and reduced biofilm thickness. The effect of TTO was the same as that of 0.2% CHX at a specific concentration. In summary, we suggest that TTO is a potential anticariogenic agent that can be used against S. mutans.

13.
Can J Microbiol ; 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32841574

RESUMO

Ochrobactrum intermedium strain SCUEC4 is a newly isolated nicotine-degrading bacterium and can use the nicotine as the sole carbon source via a series of enzymatic catalytic processes. Mechanisms underlying nicotine degradation in this bacterium and the corresponding functional genes remain unclear. Here, we analyzed the function and biological properties of the ocnE gene involved in nicotine degradation pathways in strain SCUEC4. The ocnE gene was cloned by PCR with total DNA of strain SCUEC4, and used to construct the recombinant plasmid pET28a-ocnE. The overexpression of OcnE protein was detected by SDS-PAGE analysis, and functional insight of this protein was spectrophotometrically carried out with monitoring the changes of 2, 5-dihydroxypyridine. Moreover, effects of temperature, pH and metal ions on the biological activities of OcnE protein were analyzed. The results demonstrated that optimal conditions for the biological activities of OcnE, approximate 37.6 kDa, was determined as 25°C, pH 7.0 and 25 µM Fe2+, and the suitable storage conditions for OcnE protein was determined as 0°C and pH 7.0. Conclusively, the ocnE gene owns the ability of 2, 5-dihydroxypyridine dioxygenase. These findings will be beneficial in clarifying the mechanisms of nicotine degradation in Ochrobactrum intermedium strain SCUEC4.

14.
Inorg Chem ; 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32856902

RESUMO

Metal-organic frameworks (MOFs) have been explored as crystal sponges (CSs) to organic substrates, but attention had rarely been paid to inorganic substrates. Herein, hierarchical zirconium-based MOFs exhibiting different topological structures had been fabricated by modulating the functional groups of the V-shaped linkers, including a new 4-fold-interpenetrating one, which displays a great performance as a CS applicable to inorganic matter (I2 and ReO4-) even in the extreme conditions.

15.
Abdom Radiol (NY) ; 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32761406

RESUMO

OBJECTIVES: The purpose of the present study is to develop a predictive model for incomplete response (IR) after conventional transarterial chemoembolization (cTACE) for hepatocellular carcinoma (HCC) based on hepatic angiographic and cross-sectional imaging. METHODS: Sixty patients with 139 target HCC lesions who underwent cTACE from February 2013 to March 2019 were included in this retrospective study. Hepatic angiographic features were identified: the number of feeding arteries, vascularity of the tumor, tumor staining on angiography, vascular lake phenomenon, and hepatic arterio-portal shunt. Cross-sectional imaging features were also identified: tumor extent, location, size, and enhancement pattern. Treatment response was assessed by the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. Logistic regression analysis was performed to determine the potential predictive factors for treatment response. To validate the predictive value of potential factors, the means of a decision tree were also calculated by Classification and Regression Tree (CART). P < 0.05 was considered statistically significant. RESULTS: The IR rate was 43.2% (60/139) in the entire study population. Logistic regression analysis showed that a tumor size > 50 mm (P = 0.005; odds ratio, 7.25; 95% CI 1.79-29.33), central location (P = 0.007; odds ratio, 0.14; 95% CI 0.03-0.59), and nondense tumor staining (P < 0.001; odds ratio, 0.08; 95% CI 0.02-0.28) were predictors of IR after cTACE. Decision tree analysis showed a good ability to classify treatment response with an accuracy of 78.4%. CONCLUSION: Tumor size > 50 mm, central tumor location, and nondense tumor staining were predictors of IR after cTACE. These factors should be taken into consideration when performing cTACE.

16.
J Hematol Oncol ; 13(1): 109, 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32778133

RESUMO

Noncoding RNAs (ncRNAs) are a large segment of the transcriptome that do not have apparent protein-coding roles, but they have been verified to play important roles in diverse biological processes, including disease pathogenesis. With the development of innovative technologies, an increasing number of novel ncRNAs have been uncovered; information about their prominent tissue-specific expression patterns, various interaction networks, and subcellular locations will undoubtedly enhance our understanding of their potential functions. Here, we summarized the principles and innovative methods for identifications of novel ncRNAs that have potential functional roles in cancer biology. Moreover, this review also provides alternative ncRNA databases based on high-throughput sequencing or experimental validation, and it briefly describes the current strategy for the clinical translation of cancer-associated ncRNAs to be used in diagnosis.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32790890

RESUMO

19 F magnetic resonance-based detection coupled with well-designed inorganic systems shows great promise in biological investigations including metabolic tracking, studies of protein structure and function, molecular imaging, and medical diagnostics, providing low biological background and high specificity of the modality. Two proof-of-concept inorganic probes are reported that exploit a novel mechanism for 19 F MR sensing based on converting from low-spin (S=0) to high-spin (S=1) Ni 2+ . Activation of diamagnetic NiL 1 and NiL 2 via light or ß-galactosidase respectively converts them into paramagnetic NiL 0 that displays a single 19 F NMR peak shifted by >35 ppm with accelerated relaxation rates. This large chemical shift change is facilitated by contact and pseudo-contact interactions between the 19 F reporter and the 5-coordinate Ni 2+ . This spin-state switch is effective for sensing light or enzyme expression in live cells using 19 F MR spectroscopy and imaging that differentiate signals based on chemical shift and relaxation times. This general inorganic scaffold has potential for developing agents that can sense analytes ranging from ions to enzymes, opening up diverse possibilities for 19 F MR-based biosensing.

18.
Sci Immunol ; 5(49)2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32620560

RESUMO

CD8+ T cell exhaustion is a hallmark of many cancers and chronic infections. In mice, T cell factor 1 (TCF-1) maintains exhausted CD8+ T cell responses, whereas thymocyte selection-associated HMG box (TOX) is required for the epigenetic remodeling and survival of exhausted CD8+ T cells. However, it has remained unclear to what extent these transcription factors play analogous roles in humans. In this study, we mapped the expression of TOX and TCF-1 as a function of differentiation and specificity in the human CD8+ T cell landscape. Here, we demonstrate that circulating TOX+ CD8+ T cells exist in most humans, but that TOX is not exclusively associated with exhaustion. Effector memory CD8+ T cells generally expressed TOX, whereas naive and early-differentiated memory CD8+ T cells generally expressed TCF-1. Cytolytic gene and protein expression signatures were also defined by the expression of TOX. In the context of a relentless immune challenge, exhausted HIV-specific CD8+ T cells commonly expressed TOX, often in clusters with various activation markers and inhibitory receptors, and expressed less TCF-1. However, polyfunctional memory CD8+ T cells specific for cytomegalovirus (CMV) or Epstein-Barr virus (EBV) also expressed TOX, either with or without TCF-1. A similar phenotype was observed among HIV-specific CD8+ T cells from individuals who maintained exceptional immune control of viral replication. Collectively, these data demonstrate that TOX is expressed by most circulating effector memory CD8+ T cell subsets and not exclusively linked to exhaustion.

19.
Huan Jing Ke Xue ; 41(3): 1085-1092, 2020 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-32608608

RESUMO

From March 2018 to February 2019, quantitative detection was made of 102 kinds of atmospheric volatile organic compounds (VOCs) using online gas chromatography in Ezhou City. We compared and analyzed the composition, seasonal variation, and diurnal variation of VOCs. Using maximum incremental reactivity (MIR), we estimated the ozone generation potential (OFP) of VOCs. The results show that the annual average volume fraction of atmospheric VOCs in Ezhou is (30.78±15.89)×10-9, and is overall higher in winter than summer, represented by alkane > oxygen > halogenated hydrocarbon > olefin > aromatic hydrocarbon > alkyne. The night volume fraction is higher than in the daytime, and overall the distribution is "double peak". The aromatic hydrocarbons, halogenated hydrocarbons, and OVOCs appear as a "third peak" at 00:00-02:00. Aromatic hydrocarbons and olefins contribute more to the OFP potential of VOCs, with contribution rates of 35.45% and 29.5%, respectively. The highest contribution rate to OFP is ethylene, reaching 24.217%. Analysis of VOC characteristic species found that vehicle exhaust fumes and solvent volatilization are the main sources of VOCs in Ezhou. Of these, motor vehicle emissions are the most important source. Controlling Ezhou's motor vehicle emissions helps to reduce the composition of atmospheric VOCs, thereby reducing ozone production.

20.
Cell Death Dis ; 11(7): 566, 2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32703936

RESUMO

Aberrant chromosomal translocations leading to tumorigenesis have been ascribed to the heterogeneously oncogenic functions. However, how fusion transcripts exporting remains to be declared. Here, we showed that the nuclear speckle-specific long noncoding RNA MALAT1 controls chimeric mRNA export processes and regulates myeloid progenitor cell differentiation in malignant hematopoiesis. We demonstrated that MALAT1 regulates chimeric mRNAs export in an m6A-dependent manner and thus controls hematopoietic cell differentiation. Specifically, reducing MALAT1 or m6A methyltransferases and the 'reader' YTHDC1 result in the universal retention of distinct oncogenic gene mRNAs in nucleus. Mechanically, MALAT1 hijacks both the chimeric mRNAs and fusion proteins in nuclear speckles during chromosomal translocations and mediates the colocalization of oncogenic fusion proteins with METTL14. MALAT1 and fusion protein complexes serve as a functional loading bridge for the interaction of chimeric mRNA and METTL14. This study demonstrated a universal mechanism of chimeric mRNA transport that involves lncRNA-fusion protein-m6A autoregulatory loop for controlling myeloid cell differentiation. Targeting the lncRNA-triggered autoregulatory loop to disrupt chimeric mRNA transport might represent a new common paradigm for treating blood malignancies.

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