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1.
Alzheimers Res Ther ; 13(1): 190, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34798903

RESUMO

BACKGROUND: Despite the known associations between zinc levels and Alzheimer's disease (AD) dementia and related cognitive impairment, the underlying neuropathological links remain poorly understood. We tested the hypothesis that serum zinc level is associated with cerebral beta-amyloid protein (Aß) deposition. Additionally, we explored associations between serum zinc levels and other AD pathologies [i.e., tau deposition and AD-signature cerebral glucose metabolism (AD-CM)] and white matter hyperintensities (WMHs), which are measures of cerebrovascular injury. METHODS: A total of 241 cognitively normal older adults between 55 and 90 years of age were enrolled. All the participants underwent comprehensive clinical assessments, serum zinc level measurement, and multimodal brain imaging, including Pittsburgh compound B-positron emission tomography (PET), AV-1451 PET, fluorodeoxyglucose (FDG)-PET, and magnetic resonance imaging. Zinc levels were stratified into three categories: < 80 µg/dL (low), 80 to 90 µg/dL (medium), and > 90 µg/dL (high). RESULTS: A low serum zinc level was significantly associated with increased Aß retention. In addition, apolipoprotein E ε4 allele (APOE4) status moderated the association: the relationship between low zinc level and Aß retention was significant only in APOE4 carriers. Although a low zinc level appeared to reduce AD-CM, the relationship became insignificant on sensitivity analysis including only individuals with no nutritional deficiency. The serum zinc level was associated with neither tau deposition nor the WMH volume. CONCLUSIONS: Our findings suggest that decreased serum zinc levels are associated with elevation of brain amyloid deposition. In terms of AD prevention, more attention needs to be paid to the role of zinc.

2.
Zootaxa ; 5052(1): 61-77, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34810888

RESUMO

Although the high level of species diversity within the Pholcus phungiformes-group (Araneae: Pholcidae) in the Korean Peninsula has been recognized recently, taxonomic studies, including new species discovery, have not been conducted in western regions of South Korea. In this study, five additional species belonging to the Pholcus phungiformes-group discovered from Seoul and surrounding areas are described as new, viz., Pholcus seoulensis Lee Lee, sp. nov. Pholcus suraksanensis Lee Lee, sp. nov., Pholcus incheonensis Lee Lee, sp. nov., Pholcus seokmodoensis Lee Lee, sp. nov. and Pholcus chilgapsanensis Lee Lee, sp. nov. Detailed descriptions and geographic distributions are provided with accompanying photographs.


Assuntos
Aranhas , Distribuição Animal , Animais , República da Coreia
3.
Int J Mol Sci ; 22(21)2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34769165

RESUMO

Our recent study demonstrated that the CC-chemokine ligand 2 (CCL2) present in primary afferent fibers (PAFs) plays an important role in the microglia-dependent neuronal activation associated with zymosan-induced inflammatory pain. The present study was aimed to evaluate whether BD1047 (a prototypical sigma-1 receptor (Sig-1R) antagonist) is capable of modifying elevated levels of inflammation-evoked CCL2 as a peripheral antinociceptive mechanism. In DRG primary culture, zymosan dose-dependently increased CCL2 release from isolectin B4 (IB4)-positive DRG neurons, a process that was inhibited by co-culture with BD1047. Single treatment of BD1047 before intraplantar injection of zymosan in rats significantly reduced thermal hyperalgesia and mechanical hyperalgesia, as well as CCL2 expression in DRG neurons and microglia activation in the spinal dorsal horn. In the Complete Freund's adjuvant (CFA)-induced inflammation model, repeated administration of BD1047 dramatically attenuated thermal hyperalgesia and mechanical hyperalgesia, and significantly diminished CCL2 immunoreactivity and microglia activation. Notably, CFA-induced inflammation significantly increased Sig-1R immunoreactivity in DRG neurons, which was co-localized with CCL2 and IB4, respectively. Taken together, our results suggest that BD1047's anti-nociceptive property was substantially mediated by the inhibition of CCL2 release in unmyelinated PAFs and that this may, in turn, have attenuated the spinal microglia activation that is associated with inflammatory pain.

4.
Ann Occup Environ Med ; 33: e22, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34754483

RESUMO

Background: Recently, lung cancer screenings based on age and smoking history using low-dose computed tomography (LDCT) have begun in Korea. This study aimed to evaluate the distribution of lung imaging reporting and data system (Lung-RADS) categories in shipyard workers exposed to lung carcinogens such as nickel, chromium, and welding fumes according to job type, to provide basic data regarding indications for LDCT in shipyard workers. Methods: This study included 6,326 workers from a single shipyard, who underwent health examinations with LDCT between January 2010 and December 2018. Data on age, smoking status and history, medical history, and job type were investigated. The participants were categorized into high-exposure, low-exposure, and non-exposure job groups based on the estimated exposure level of nickel, chromium, and welding fumes according to job type. Cox proportional hazard regression analysis was used to determine the difference between exposure groups in Lung-RADS category ≥ 3 (3, 4A, and 4B). Results: Out of all participants, 97 (1.5%) participants were classified into Lung-RADS category ≥ 3 and 7 (0.1%) participants were confirmed as lung cancer. The positive predictive value (ratio of diagnosed lung cancer cases to Lung-RADS category ≥ 3) was 7.2%. The hazard ratio (HR) of Lung-RADS category ≥ 3 was 1.451 (95% confidence interval [CI]: 0.911-2.309) in low-exposure and 1.692 (95% CI: 1.007-2.843) in high-exposure job group. Adjusting for age and pack-years, the HR was statistically significant only in the high-exposure job group (HR: 1.689; 95% CI: 1.004-2.841). Conclusions: Based on LDCT and Lung-RADS, among male shipyard workers, Lung-RADS category ≥ 3 were significantly higher in the high-exposure job group. Their HR tended to be > 1.0 and was statistically significant in the high-exposure job group. Additional studies should be conducted to establish more elaborate LDCT indications for occupational health examination.

6.
Opt Express ; 29(17): 27508-27520, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34615165

RESUMO

We propose a new method of through-focus scanning optical microscopy (TSOM) without a reference database, i.e., a model-less TSOM method. Building a TSOM reference database is time-consuming or even impractical in some TSOM applications that involve complex structures, such as 3D NAND, or irregular shapes such as defects. The proposed model-less TSOM method was used to determine just the height of defect particles, for the first time as far as we are aware. Defect height is the only relevant dimension for the display panel application. Specifically, we analyzed 40 organic light-emitting diode (OLED) surface defects using a lab-developed motion-free TSOM tool consisting of a 50× objective lens (numerical aperture (NA) 0.55), a 532-nm light source, an imaging detector with a 7.5-µm pitch, and a deformable mirror. The tool is in-line and capable of achieving high throughput non-destructively, both relevant features for industrial applications. We investigated linear regression relations between newly defined TSOM parameters (TSOM height, TSOM area and TSOM volume) and the defect heights, which were first measured by atomic force microscopy (AFM). Following defect classification based on in-focus images, we successfully found that the AFM height has a linear correlation with 50% TSOM height (H50%) within ± 20.3 nm (1σ) error over the range of 140 to 950 nm. The one-sigma error, i.e., 20.3 nm, was approximately λ/26 or 1/43 of the depth of focus (DOF) of the applied microscope.

8.
J Int Adv Otol ; 17(5): 380-386, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34617886

RESUMO

OBJECTIVES: Prediction of cochlear implantation (CI) outcome is often difficult because outcomes vary among patients. Though the brain plasticity across modalities during deafness is associated with individual CI outcomes, longitudinal observations in multiple patients are scarce. Therefore, we sought a prediction system based on cross-modal plasticity in a longitudinal study with multiple patients. METHODS: Classification of CI outcomes between excellent or poor was tested based on the features of brain cross-modal plasticity, measured using event-related responses and their corresponding electromagnetic sources. A machine learning estimation model was applied to 13 datasets from 3 patients based on linear supervised training. Classification efficiency was evaluated comparing prediction accuracy, sensitivity/specificity, total mis-classification cost, and training time among feature set conditions. RESULTS: Combined feature sets with the sensor and source levels dramatically improved classification accuracy between excellent and poor outcomes. Specifically, the tactile feature set best explained CI outcome (accuracy, 98.83 ± 2.57%; sensitivity, 98.00 ± 0.01%; specificity, 98.15 ± 4.26%; total misclassification cost, 0.17 ± 0.38; training time, 0.51 ± 0.09 sec), followed by the visual feature (accuracy, 93.50 ± 4.89%; sensitivity, 89.17 ± 8.16%; specificity, 98.00 ± 0.01%; total misclassification cost, 0.65 ± 0.49; training time, 0.38 ± 0.50 sec). CONCLUSION: Individual tactile and visual processing in the brain best classified the current status when classified by combined sensor-source level features. Our results suggest that cross-modal brain plasticity due to deafness may provide a basis for classifying the status. We expect this novel method to contribute to the evaluation and prediction of CI outcomes.


Assuntos
Córtex Auditivo , Implante Coclear , Implantes Cocleares , Surdez , Adulto , Encéfalo , Surdez/cirurgia , Humanos , Estudos Longitudinais , Aprendizado de Máquina
9.
Pain Physician ; 24(6): E839-E847, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34554704

RESUMO

BACKGROUND: There is paucity in the literature directly comparing the clinical results between the paramedian and the midline interlaminar cervical epidural injections. OBJECTIVE: To compare the proportion of ventral epidural spread of injectate and consequent clinical outcome between the paramedian and midline approach during interlaminar epidural injection in patients with axial neck and/or interscapular pain triggered from the underlying cervical spine pathologic condition. STUDY DESIGN: Retrospective study. SETTING: Primary pain clinic and spine hospital. METHODS: Two hundred and twenty-three patients with axial neck and/or interscapular pain due to cervical problem underwent interlaminar epidural injection through either a paramedian approach (PM group, n = 93) or a midline approach (ML group, n = 130). We compared the portion of ventral epidural filling, Numeric Rating Scale (NRS), and McNab criteria between both groups. The NRS and McNab criteria were also separately compared between the ventrally spread (VS) group and non-ventral spread (non-VS) group inside each PM and ML group, respectively, at 2 weeks and 10 weeks post-injection. RESULTS: The PM group showed a significantly higher proportion of ventral spread, successful NRS reduction, and satisfactory McNab criteria than the ML group at 10 weeks. In the PM group, the VS group showed the same results as above compared to the non-VS group. LIMITATIONS: A retrospective analysis based on the relatively short-term follow-up period clinical results. CONCLUSIONS: The paramedian approach showed the better direct injectate transfer over the ventral epidural space and subsequently superior clinical efficacy for the patients suffering from axial neck and/or interscapular pain secondary to cervical spine problems.


Assuntos
Espaço Epidural , Preparações Farmacêuticas , Vértebras Cervicais , Fluoroscopia , Humanos , Injeções Epidurais , Estudos Retrospectivos , Resultado do Tratamento
10.
Front Neurol ; 12: 710422, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34589046

RESUMO

Objective: We used volumetric three-dimensional (3D) analysis to quantitatively evaluate the extent of endolymphatic hydrops (EH) in the entire inner ear. We tested for correlations between the planimetric and volumetric measurements, to identify their advantages and disadvantages. Methods: HYDROPS2-Mi2 EH images were acquired for 32 ears (16 patients): 16 ipsilateral ears of MD patients (MD-ears) and 16 contralateral ears. Three-T MR unit with a 32-channel phased-array coil/the contrast agent to fill the perilymphatic space and the HYDROPS2-Mi2 sequence. We calculated the EH% [(endolymph)/(endolymph+perilymph)] ratio and analyzed the entire inner ear in terms of the volumetric EH% value, but only single cochlear and vestibular slices were subjected to planimetric EH% evaluation. The EH% values were compared between MD ears and non-MD ears, to evaluate the diagnostic accuracy of the two methods. Results: The volumetric EH% was significantly higher for MD vestibules (50.76 ± 13.78%) than non-MD vestibules (39.50 ± 8.99%). The planimetric EH% was also significantly higher for MD vestibules (61.98 ± 20.65%) than non-MD vestibules (37.22 ± 12.95%). The vestibular and cochlear volumetric EH% values correlated significantly with the planimetric EH% values of the MD ear. Conclusion: Volumetric and planimetric EH measurements facilitate diagnosis of MD ears compared to non-MD ears. Both methods seem to be reliable and consistent; the measurements were significantly correlated in this study. However, the planimetric EH% overestimates the extent of vestibular hydrops by 26.26%. Also, planimetric data may not correlate with volumetric data for non-MD cochleae with normal EH% values.

11.
Int Urol Nephrol ; 53(11): 2261-2266, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34546557

RESUMO

PURPOSE: We assessed the relationship between chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and erectile dysfunction (ED) using propensity score matching. METHODS: Data from 8727 middle-aged men who had undergone health checkups were analyzed. The National Institutes of Health Chronic Prostatitis Symptoms Index (NIH-CPSI), the International Index of Erectile Function-5 (IIEF), the Premature Ejaculation Diagnostic Tool (PEDT), testosterone measurement, basic blood chemistry, and metabolic syndrome (MetS) assessment were performed in this study. Of the 8727 men considered, 7181 formed the cohort for propensity score matching, including 597 men with moderate to severe prostatitis-like symptoms (case) and 6584 men with no prostatitis-like symptoms (control); ultimately, however, members of the case and control groups were matched at a 1:1 ratio by propensity score. RESULTS: After matching, the variables of age, testosterone, PEDT and MetS were evenly distributed between the groups. After matching, the mean IIEF score of the case group was significantly lower than that of the control group (17.2 ± 5.5 vs. 14.7 ± 5.3; P < 0.001). Additionally, the severity of ED was significantly greater in the case group (no, mild, mild to moderate, moderate, and severe, respectively: 27.5%, 30.2%, 24.6%, 13.1%, and 4.7% in the control group; 10.7%, 27.0%, 33.0%, 18.9%, and 10.4% in the case group; P < 0.001). Finally, the rate of moderate to severe ED was significantly higher in the case group than in the control group (17.8% vs. 29.3%; P < 0.001). CONCLUSION: Moderate to severe prostatitis-like symptoms were significantly and independently correlated with ED in middle-aged men.

12.
Pathol Oncol Res ; 27: 1609860, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512204

RESUMO

Collagen is a major component in the tumor microenvironment. This study reveals a novel biomarker candidate, type VII collagen (COL7A1), in patients with gastric cancer. To identify genes differentially expressed in gastric cancer tissue, we analyzed cancerous (n = 20) and noncancerous tissues (n = 13) using a DNA microarray. To perform immunohistochemistry and validate the upregulation of COL7A1 expression, we collected 200 more gastric cancer tissues and 100 normal gastric tissues from 200 randomly selected patients who underwent gastrectomy for gastric cancer between January 2010 and December 2013. The correlations between COL7A1 expression and clinicopathological parameters and patients' overall survival (OS) were analyzed. In the microarray, COL7A1 was upregulated in gastric cancer tissue compared with normal tissue. In the immunohistochemistry study, COL7A1 was more highly expressed in cancer tissue than in normal tissue (p = 0.001). Patients with intracellular COL7A1 expression had significantly poorer five-year OS than those with only extracellular expression (41.5 versus 69.7%, p = 0.001), and the site of expression was an independent prognostic factor of OS (hazard ratio 2.00, 95% CI 1.26-3.16, p = 0.003). Also, we found a significant association between the COL7A1 immunohistochemistry score and distant metastasis (high versus low, odds ratio 4.45, 95% CI 1.40-14.16, p = 0.011). The site and total immunohistochemistry score of COL7A1 expression in gastric cancer showed prognostic significance for OS and distant metastasis, respectively. COL7A1 could be a novel biomarker with diagnostic and therapeutic value.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34516935

RESUMO

Background: This study was conducted to assess the association of pulse pressure (PP) and visceral adiposity index (VAI) by gender in Korean adults. Methods: This study used the data of 4960 adults at age ≥20 years, from the 2015 Korean National Health and Nutrition Examination Survey. Results: In the overall population (n = 4960), after adjustment for related variables and with quartile 1 of VAI as a reference, the odds ratios of high PP (PP >60 mmHg) was significantly higher in quartile 3 [1.32 (95% confidence interval [CI], 1.02-1.71)] and quartile 4 of VAI [1.40 (95% CI, 1.07-1.83)]. In women (n = 2784), the OR of high PP, with quartile 1 of VAI as a reference, was significantly higher in quartile 3 [2.36 (95% CI, 1.55-3.61)] and quartile 4 of VAI [2.70 (95% CI, 1.77-4.12)]. In men (n = 2176), high PP was not associated with the quartiles of VAI. In addition, after adjustment for related variables, the PP level was positively associated with the quartiles of VAI in the overall population (P < 0.001) and women (P < 0.001), but not in men (P = 0.316). Conclusions: VAI was positively associated with PP in Korean women, but not in Korean men.

14.
J Korean Neurosurg Soc ; 64(5): 837-842, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34503315

RESUMO

An atlantoaxial subluxation from the unstable Os odontoideum by the failure of proper integrations between the embryological somites might be a commonly reported pathology. However, its suspicious origin or paralleled occurrence with other congenital anomalies of vertebral body might be a relatively rare phenomenon. The authors present two cases, who simply presented with clinical signs of prolonged, intractable cervicalgia without any neurological deficits, revealed this rare feature of C1-2 subluxation from the unstable, orthotropic type of Os odontoideum that coincide with congenitally fused cervical vertebral bodies between C2-3. Surprisingly, in one case, when traced from the lower cervical down to the thoracic-lumbar levels during the preoperative work-up process, was also compromised with multi-level butterfly vertebrae formations. Presented cases highlight the association of various congenital vertebrae anomalies and the rationale to fuse only affected joints.

15.
Prostate Int ; 9(2): 101-106, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34386453

RESUMO

Background: To compare the safety and efficacy of open simple prostatectomy (OSP) and robotic simple prostatectomy (RSP) for the treatment of large benign prostatic hyperplasia (BPH). Materials and methods: We retrospectively reviewed the medical records of 52 patients who underwent OSP (n = 23) and RSP (n = 29) between January 2005 and March 2019 at a single institution. The preoperative status of the patients, complications related to surgery, and the functional outcomes of the surgery were analyzed. Results: There were no significant differences in the preoperative total prostate volume, transitional volume, prostate-specific antigen value, and age between the two groups. Postoperative improvements in the International Prostate Symptom Score, maximum urinary flow rate, and postvoid residual were significant and similar for both groups. There were no significant differences between the two groups regarding surgery duration and resected prostate volume. The majority of patients in both groups had the urethral Foley catheter removed within the planned 10 day postoperative period, with the exception of two patients in the OSP group who had prolonged indwelling Foley catheter placement because of persistent hematuria. Postoperative hematocrit changes were significantly lower in the RSP group (RSP: 7.8 ± 4.1%, OSP: 14.2 ± 4.9%, P < 0.001). Seven patients (30.4%) who underwent OSP and two patients (6.9%) who underwent RSP were transfused because of significant intraoperative bleeding. Two patients from the RSP group who received transfusion comprised the first two cases that underwent RSP treatment. During the follow-up period, two patients (one patient in the OSP group and one patient in the RSP group) underwent transurethral incision of the bladder neck for bladder neck contracture. Conclusion: Both OSP and RSP can produce excellent outcomes after surgery. However, complications of bleeding are significantly less prevalent in RSP, suggesting that RSP can replace conventional OSP.

16.
Mar Drugs ; 19(8)2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34436282

RESUMO

One of the well-known causes of hearing loss is noise. Approximately 31.1% of Americans between the ages of 20 and 69 years (61.1 million people) have high-frequency hearing loss associated with noise exposure. In addition, recurrent noise exposure can accelerate age-related hearing loss. Phlorofucofuroeckol A (PFF-A) and dieckol, polyphenols extracted from the brown alga Ecklonia cava, are potent antioxidant agents. In this study, we investigated the effect of PFF-A and dieckol on the consequences of noise exposure in mice. In 1,1-diphenyl-2-picrylhydrazyl assay, dieckol and PFF-A both showed significant radical-scavenging activity. The mice were exposed to 115 dB SPL of noise one single time for 2 h. Auditory brainstem response(ABR) threshold shifts 4 h after 4 kHz noise exposure in mice that received dieckol were significantly lower than those in the saline with noise group. The high-PFF-A group showed a lower threshold shift at click and 16 kHz 1 day after noise exposure than the control group. The high-PFF-A group also showed higher hair cell survival than in the control at 3 days after exposure in the apical turn. These results suggest that noise-induced hair cell damage in cochlear and the ABR threshold shift can be alleviated by dieckol and PFF-A in the mouse. Derivatives of these compounds may be applied to individuals who are inevitably exposed to noise, contributing to the prevention of noise-induced hearing loss with a low probability of adverse effects.

17.
Brain Sci ; 11(7)2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34356126

RESUMO

Using behavioral evaluation of free recall performance, we investigated whether reverberation and/or noise affected memory performance in normal-hearing adults. Thirty-four participants performed a free-recall task in which they were instructed to repeat the initial word after each sentence and to remember the target words after each list of seven sentences, in a 2 (reverberation) × 2 (noise) factorial design. Pupil dilation responses (baseline and peak pupil dilation) were also recorded sentence-by-sentence while the participants were trying to remember the target words. In noise, speech was presented at an easily audible level using an individualized signal-to-noise ratio (95% speech intelligibility). As expected, recall performance was significantly lower in the noisy environment than in the quiet condition. Regardless of noise interference or reverberation, sentence- baseline values gradually increased with an increase in the number of words to be remembered for a subsequent free-recall task. Long reverberation time had no significant effect on memory retrieval of verbal stimuli or pupillary responses during encoding.

18.
Exp Ther Med ; 22(3): 1031, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34373717

RESUMO

The present study aimed to investigate the renoprotective effect of therapeutic hypothermia (TH) on renal ischemia-reperfusion injury (RI/RI) induced by asphyxial cardiac arrest (CA) in rats. A total of 48 male rats were randomly divided into five groups: i) Sham (n=6); ii) Normothermia + CA (Normo.) (n=14); iii) Normo. and 2 h of TH after return of spontaneous circulation (ROSC) (n=12); iv) Normo. and 4 h of TH after ROSC (n=9); and v) Normo. and 6 h of TH after ROSC (n=7). All rats except the Sham group underwent asphyxia CA and were sacrificed 1 day after ROSC. The survival rate increased from 42.8% in the Normo. group to 50, 66.6 and 85.7% in the groups with 2, 4 and 6 h of TH after CA, respectively. TH attenuated the histopathological changes of the renal tissues following ROSC and the levels of blood urea nitrogen, serum creatinine and malondialdehyde in renal tissues. On immunohistochemistry, the relative optical density of nuclear erythroid-related factor-2 (Nrf2) and heme oxygenase (HO-1) expression in renal tissues increased in the Normo. group compared with that in the Sham group and exhibited further significant increases at 6 h of TH after ROSC. In conclusion, TH attenuated renal injury and increased the expression of Nrf2 and HO-1 in a TH treatment time-dependent manner.

19.
Phys Chem Chem Phys ; 23(32): 17279-17286, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34369515

RESUMO

Using first-principles calculation methods, we reveal a series of phase transitions as a function of gating or electron doping in monolayered quantum spin Hall (QSH) insulators, 1T'-MoTe2 and 1T'-WTe2. With increasing electron doping, we show that a phonon mediated superconducting phase is realized first and is followed by a charge density wave (CDW) phase with a nonsymmorphic lattice symmetry. The newly found CDW phase exhibits Weyl energy bands with spin-orbit coupling with fractional band filling, and reforms into a topological nontrivial phase with fully filled bands. The robust resurgence of the QSH state coexisting with the CDW phase is shown to originate from band inversions induced by the nonsymmorphic lattice distortion through the strong electron-phonon interaction, thus suggesting the realization of various interfacial states between superconducting states, and various CDW and topological states on a two-dimensional crystal by inhomogeneous gating or doping.

20.
Int J Mol Sci ; 22(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34445415

RESUMO

Chimeric antigen receptor (CAR)-T cells are effective in the treatment of hematologic malignancies but have shown limited efficacy against solid tumors. Here, we demonstrated an approach to inhibit recurrence of B cell lymphoma by co-expressing both a human anti-CD19-specific single-chain variable fragment (scFv) CAR (CD19 CAR) and a TGF-ß/IL-7 chimeric switch receptor (tTRII-I7R) in T cells (CD19 CAR-tTRII-I7R-T cells). The tTRII-I7R was designed to convert immunosuppressive TGF-ß signaling into immune-activating IL-7 signaling. The effect of TGF-ß on CD19 CAR-tTRII-I7R-T cells was assessed by western blotting. Target-specific killing by CD19 CAR-tTRII-I7R-T cells was evaluated by Eu-TDA assay. Daudi tumor-bearing NSG (NOD/SCID/IL2Rγ-/-) mice were treated with CD19 CAR-tTRII-I7R-T cells to analyze the in vivo anti-tumor effect. In vitro, CD19 CAR-tTRII-I7R-T cells had a lower level of phosphorylated SMAD2 and a higher level of target-specific cytotoxicity than controls in the presence of rhTGF-ß1. In the animal model, the overall survival and recurrence-free survival of mice that received CD19 CAR-tTRII-I7R-T cells were significantly longer than in control mice. These findings strongly suggest that CD19 CAR-tTRII-I7R-T cell therapy provides a new strategy for long-lasting, TGF-ß-resistant anti-tumor effects against B cell lymphoma, which may lead ultimately to increased clinical efficacy.


Assuntos
Antígenos CD19/imunologia , Interleucina-7/genética , Linfoma de Células B/terapia , Recidiva Local de Neoplasia/terapia , Anticorpos de Cadeia Única/metabolismo , Fator de Crescimento Transformador beta/genética , Animais , Células Cultivadas , Feminino , Humanos , Imunoterapia Adotiva , Interleucina-7/metabolismo , Células K562 , Linfoma de Células B/imunologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Recidiva Local de Neoplasia/imunologia , Receptores de Antígenos Quiméricos/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
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