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1.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35554568

RESUMO

Neuropathic pain is a debilitating chronic condition that remains difficult to treat. There is a high priority to identify novel non-opioid-based therapeutic targets as long-term use of opioids is problematic due to its severe side effects and strong abuse potential. Our lab recently discovered G-protein coupled receptor 160 (GPR160) has a role in neuropathic pain. Gpr160 was upregulated in the dorsal horn of the spinal cord (DH-SC) on the side of nerve injury relative to the uninjured side in mice. Blocking GPR160 using siRNA or a neutralizing antibody (Ab) reversed and prevented pain hypersensitivity. In addition, our lab deorphanized GPR160 as the receptor for cocaine- and amphetamine-regulated transcript peptide (CARTp). We showed that an intrathecal (i.th.) injection of CARTp in naive mice caused mechano-hypersensitivity that was dependent on GPR160. CARTp-induced gene expression is relatively unexplored and the mechanism by which CARTp/GPR160 signaling promotes chronic pain is not well known. Therefore, our objective was to perform an unbiased RNA transcriptomics analysis to identify which genes were altered at the time of CARTp-mediated peak pain in the DH-SC. We found that Nucleotide-binding oligomerization domain-containing protein 2 (Nod2) expression was increased upon i.th. injection of CARTp and its expression decreased after CARTp was co-administered with GPR160 Ab, pointing to a potential interaction between CARTp/GPR160 and NOD2. NOD2 is a cytosolic pattern recognition receptor that is involved in activating the immune system in response to pathogens. Moreover, a recent study linked NOD2 to the development of neuropathic pain. This led to our hypothesis that CARTp/GPR160 causes mechano-hypersensitivity through NOD2 and NOD2 has a functional role in neuropathic pain. C57BL/6 (WT) and NOD2-/- mice received an i.th. injection of CARTp and mechano-allodynia was assessed. The WT mice developed mechano-allodynia by 30min and persisted for 5hrs. In contrast, mechano-allodynia was attenuated for 4hrs in NOD2-/- mice, suggesting CARTp/GPR160 induces mechano-hypersensitivity through NOD2. Furthermore, we found that NOD2 has a functional role in a chronic constriction injury (CCI) model of neuropathic pain. WT mice started developing mechano-allodynia on day 3 (D3) after CCI, reached a maximum by D7, and persisted until D14. However, NOD2-/- mice did not develop mechano-allodynia until D10, indicating that NOD2 is involved in the development of CCI neuropathic pain. Overall, our results provide a potential mechanistic insight on how CARTp causes mechano-sensitivity and NOD2 has a functional role in CCI-mediated neuropathic pain.

2.
Am J Transl Res ; 14(4): 2436-2442, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35559368

RESUMO

OBJECTIVE: To explore the clinical value of extracorporeal cardiopulmonary resuscitation (ECPR) combined with different targeted temperature management (TTM) for the treatment of cardiac arrest. METHODS: From January 2018 to September 2020, ECPR was initiated in patients with cardiac arrest who did not have their spontaneous circulation restored after 20 minutes of traditional cardiopulmonary resuscitation (CPR). A total of 22 patients (observation group) given TTM were treated with Hico-variotherm 550 (HU 550) and 30 patients (control group) not given TTM were treated with a medical water circulation cooling blanket. The Glasgow Coma scale (GCS) score, serum neuron-specific enolase (NSE), survival rate and neurological prognosis after ECMO weaning were compared between the two groups. RESULTS: There was no significant difference between the two groups in GCS score on the third and seventh days after resuscitation and serum NSE on the first and third day after treatment (P>0.05). Compared with the control group, the survival rate (40.91% vs 33.33%) and favorable neurological outcome (36.36% vs 26.67%) of patients in the observation group were slightly higher, but the differences were not statistically significant (all P>0.05). The incidence of shivering and body temperature fluctuation during rewarming in the observation group was lower than that in the control group (P<0.05). CONCLUSION: HU550 poikilothermia water cabinet combined with ECMO can better control the targeted temperature of patients in a more accurate range and improve the survival rate; however, it exerts no statistical improvement in the incidence of complications.

3.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35560379

RESUMO

Neuropathic pain is a debilitating health concern and there is an urgent need for non-opioid analgesic targets. Our group has identified GPR183 as a novel potential therapeutic target for neuropathic pain. GPR183 is a G-protein coupled receptor that promotes the migration of immune cells in response to its ligand, 7α,25-dihydroxycholesterol (7α,25-OHC). We have shown that GPR183 is upregulated in the dorsal horn spinal cord during neuropathic pain states in rodents and intrathecal injections of 7α,25-OHC is able to induce allodynia in mice in a GPR183-dependent manner. However, the mechanism by which GPR183 activation leads to pain is unknown. These studies aim to elucidate the molecular signaling pathways that contribute to 7α,25-OHC-induced hypersensitivity. Based on previous literature, we hypothesized that GPR183 activation in the spinal cord would activate mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK) and p38, leading to the production of neuroexcitatory cytokines contributing to hypersensitivity. METHODS: To investigate the signaling pathways downstream of GPR183 activation in the spinal cord, we performed unbiased RNA-Sequencing following intrathecal injections of 7α,25-OHC with or without the GPR183 antagonist, SAE-14, in male and female ICR mice. We then performed follow-up studies giving pharmacological inhibitors of the identified pathways prior to intrathecal 7α,25-OHC to confirm functional relevance. We also took spinal cord tissue for western blot and enzyme-linked immunoassay (ELISA) analysis following intrathecal injections. RESULTS: Through our unbiased RNA-sequencing we found that many of the genes that were differentially regulated by GPR183 activation contain binding sites for NF-κB or transcription factors that are regulated by the MAPK's, ERK or p38. Additionally, we found that small molecule inhibitors of these pathways delayed 7α,25-OHC-induced mechanical allodynia. Importantly, the GPR183 antagonist, SAE-14, blocked the 7α,25-OHC-induced upregulation of these pathways, including the upregulation of neuroexcitatory cytokines interleukin-1ß and tumor necrosis factor α. CONCLUSION: These findings provide novel insight into how spinal GPR183 signaling produces hypersensitivity and can contribute to neuropathic pain states.

4.
Front Oncol ; 12: 802437, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35530360

RESUMO

Objective: To discuss the differences in the effectiveness and security for T1 renal tumors by radiofrequency ablation (RFA) and cryoablation (CA). Methods: We systematically searched the Cochrane Library, PubMed, Embase, CNKI databases, and Science databases, and the date was from the above database establishment to August 2021. Controlled trials on RFA and CA for T1 renal tumors were included. The meta-analysis was conducted with the Review Manager 5.4 software. Results: A total of ten studies with 2,367 patients were included in the analysis. There were no significant differences in complications (odds ratio [OR], 1.23; 95% CI, 0.80 to 1.90; p=0.35), primary technique efficacy rate (OR, 1.01; 95% CI, 0.33 to 3.14; p=0.98), changes in serum creatinine (weighted mean difference [WMD], 0.53; 95% CI, -0.50 to 1.57; p=0.31), or 5-year survival rate (hazard ratio [HR], 1.11; 95% CI, 0.41 to 3.00; p=0.84) among patients undergoing RFA and CA. However, compared with patients who underwent RFA, patients who underwent CA had a lower Local recurrence (OR: 2.25; 95% CI: 1.38 to 3.67; p = 0.001). Conclusion: The analysis demonstrated that in the treatment of T1 renal tumors, CA may be associated with lower local recurrence rates. However, no differences were observed in terms of primary technique efficacy rate, 5-year survival rate, changes in serum creatinine, and complication rate between groups. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier PROSPERO (CRD42021295160).

5.
Water Res ; 219: 118540, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35550966

RESUMO

Spore forming bacteria (SFB) are strongly chlorine resistant. Their presence in drinking water may cause diseases and pose threat to public health. Three SFB strains, i.e. Bacillus alvei, Bacillus cereus, and Lysinibacillus fusiformis, were isolated and identified from the finished water of a drinking water treatment plant where bacteria colonies occasionally reached the limit value. Due to their chlorine resistance, a SFB control strategy coupling pre-oxidation, coagulation sedimentation, and UV-AOPs inactivation in water treatment process was studied in lab scale. Five minutes pre-oxidation treatment by applying Cl2 and ClO2 induced remarkable spore transformation. Longer pre-oxidation exposure time didn't have apparent improvement. Cl2 and ClO2 dosages of 0.9 mg/L and 0.5 mg/L were suggested, respectively. The formed spores can be efficiently removed by the following coagulation sedimentation treatment. At a suggested dosage combination of 20 mg/L PAC and 0.08 mg/L PAM, spore removal efficiency reached about 3.15-lg. Comparing to applying sole UV irradiation, enhanced UV inactivation by adding 0.1 mM H2O2, or Cl2, or peroxymonosulfate (PMS) substantially improved the inactivation of the most chlorine resistant SFB strain, Lysinibacillus fusiformis. UV-AOPs stably achieved 2-lg inactivation rate at UV dosage of 40 mJ/cm2. UV/H2O2, UV/Cl2 and UV/PMS inactivation kinetically enhanced 1.20 times, 1.36 times and 1.91 times over sole UV irradiation. Intracellular DNA and ATP leakages were detected, and remarkable damages of Lysinibacillus fusiformis cells' surface and ultrastructure were observed. These findings evidenced cell wall and cell membrane destructions, guaranteeing substantial SFB cells inactivation. This study was carried out based on three SFB strains isolated from a finished water, and common engineering practical operations. By providing engineeringly relevant references, the outcomes obtained would be helpful for dealing with SFB outbreak risk in drinking water treatment.

6.
Plant Biotechnol J ; 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35403801

RESUMO

Grain size is one of the essential determinants of rice yield. Our previous studies revealed that ethylene plays an important role in grain-size control; however, the precise mechanism remains to be determined. Here, we report that the ethylene response factor OsERF115 functions as a key downstream regulator for ethylene-mediated grain development. OsERF115 encodes an AP2/ERF-type transcriptional factor that is specifically expressed in young spikelets and developing caryopses. Overexpression of OsERF115 significantly increases grain length, width, thickness and weight by promoting longitudinal elongation and transverse division of spikelet hull cells, as well as enhancing grain-filling activity, whereas its knockout mutations lead to the opposite effects, suggesting that OsERF115 positively regulates grain size and weight. OsERF115 transcription is strongly induced by ethylene, and OsEIL1 directly binds to the promoter to activate its expression. OsERF115 acts as a transcriptional repressor to directly or indirectly modulate a set of grain-size genes during spikelet growth and endosperm development. Importantly, haplotype analysis reveals that the SNP variations in the EIN3-binding sites of OsERF115 promoter are significantly associated with the OsERF115 expression levels and grain weight, suggesting that natural variations in the OsERF115 promoter contribute to grain-size diversity. In addition, the OsERF115 orthologues are identified only in grass species, implying a conserved and unique role in the grain development of cereal crops. Our results provide insights into the molecular mechanism of ethylene-mediated grain-size control and a potential strategy based on the OsEIL1-OsERF115-target gene regulatory module for genetic improvement of rice yield.

7.
Artigo em Inglês | MEDLINE | ID: mdl-35420989

RESUMO

Knowledge distillation (KD) transfers discriminative knowledge from a large and complex model (known as teacher) to a smaller and faster one (known as student). Existing advanced KD methods, limited to fixed feature extraction paradigms that capture teacher's structure knowledge to guide the training of the student, often fail to obtain comprehensive knowledge to the student. Toward this end, in this article, we propose a new approach, synchronous teaching knowledge distillation (STKD), to integrate online teaching and offline teaching for transferring rich and comprehensive knowledge to the student. In the online learning stage, a blockwise unit is designed to distill the intermediate-level knowledge and high-level knowledge, which can achieve bidirectional guidance of the teacher and student networks. Intermediate-level information interaction provides more supervisory information to the student network and is useful to enhance the quality of final predictions. In the offline learning stage, the STKD approach applies a pretrained teacher to further improve the performance and accelerate the training process by providing prior knowledge. Trained simultaneously, the student learns multilevel and comprehensive knowledge by incorporating online teaching and offline teaching, which combines the advantages of different KD strategies through our STKD method. Experimental results on the SVHN, CIFAR-10, CIFAR-100, and ImageNet ILSVRC 2012 real-world datasets show that the proposed method achieves significant performance improvements compared with the state-of-the-art methods, especially with satisfying accuracy and model size. Code for STKD is provided at https://github.com/nanxiaotong/STKD.

8.
ACS Chem Biol ; 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35417135

RESUMO

Hyperlipidemia and increased circulating cholesterol levels are associated with increased cardiovascular disease risk. The liver X receptors (LXRs) are regulators of de novo lipogenesis and cholesterol transport and have been validated as potential therapeutic targets for the treatment of atherosclerosis. However, efforts to develop LXR agonists to reduce cardiovascular diseases have failed due to poor clinical outcomes-associated increased hepatic lipogenesis and elevated low-density lipoprotein (LDL) cholesterol (C). Here, we report that LXR inverse agonists are effective in lowering plasma LDL cholesterol and triglycerides in several models of hyperlipidemia, including the Ldlr null mouse model of atherosclerosis. Mechanistic studies demonstrate that LXR directly regulates the expression of Soat2 enzyme in the intestine, which is directly responsible for the re-uptake or excretion of circulating lipids. Oral administration of a gut-specific LXR inverse agonist leads to reduction of Soat2 expression in the intestine and effectively lowers circulating LDL cholesterol and triglyceride levels without modulating LXR target genes in the periphery. In summary, our studies highlight the therapeutic potential of the gut-restricted molecules to treat hyperlipidemia and atherosclerosis through the intestinal LXR-Soat2 axis.

9.
Food Chem ; 386: 132812, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-35364491

RESUMO

In the current study, the prooxidant activities of (-)-epigallocatechin-3-gallate (EGCG) and chlorogenic acid (CGA) were systematically compared both in multiple in vitro models and in mice. At equimolar concentrations in vitro and in vivo, EGCG displayed powerful prooxidant effects though CGA exhibited none. In vitro, though CGA and EGCG synergistically produced hydrogen peroxide, CGA was able to scavenge hydroxyl radicals generated by EGCG/copper. Consistent with the selective modulation of reactive oxygen species produced from EGCG, CGA lowered hepatotoxicity but did not perturb hepatic AMPK activation nor the increase of hepatic Nrf2-associated proteins induced by high-dose EGCG. CGA, along with low-dose EGCG, synergistically activated hepatic AMPK and increased hepatic Nrf2-associated proteins without causing toxicity in mice. This proof-of-principle study suggests that polyphenols with potent prooxidant activities (e.g., EGCG) together with antioxidant polyphenols with noticeably low prooxidant activities (e.g., CGA) may yield health benefits with a low risk of side effects.


Assuntos
Ácido Clorogênico , Fator 2 Relacionado a NF-E2 , Proteínas Quinases Ativadas por AMP , Animais , Catequina/análogos & derivados , Ácido Clorogênico/farmacologia , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Polifenóis , Espécies Reativas de Oxigênio/metabolismo
10.
J Biol Chem ; 298(5): 101895, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35378133

RESUMO

Long noncoding RNAs (lncRNAs) have gained widespread attention as a new layer of regulation in biological processes during development and disease. The lncRNA ELDR (EGFR long noncoding downstream RNA) was recently shown to be highly expressed in oral cancers as compared to adjacent nontumor tissue, and we previously reported that ELDR may be an oncogene as inhibition of ELDR reduces tumor growth in oral cancer models. Furthermore, overexpression of ELDR induces proliferation and colony formation in normal oral keratinocytes (NOKs). In this study, we examined in further detail how ELDR drives the neoplastic transformation of normal keratinocytes. We performed RNA-seq analysis on NOKs stably expressing ELDR (NOK-ELDR), which revealed that ELDR enhances the expression of cell cycle-related genes. Expression of Aurora kinase A and its downstream targets Polo-like kinase 1, cell division cycle 25C, cyclin-dependent kinase 1, and cyclin B1 (CCNB1) are significantly increased in NOK-ELDR cells, suggesting induction of G2/M progression. We further identified CCCTC-binding factor (CTCF) as a binding partner of ELDR in NOK-ELDR cells. We show that ELDR stabilizes CTCF and increases its expression. Finally, we demonstrate the ELDR-CTCF axis upregulates transcription factor Forkhead box M1, which induces Aurora kinase A expression and downstream G2/M transition. These findings provide mechanistic insights into the role of the lncRNA ELDR as a potential driver of oral cancer during neoplastic transformation of normal keratinocytes.

12.
J Control Release ; 346: 148-157, 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35429574

RESUMO

Despite the successful treatment of drug intoxications, little information is available to quantitively predict the effect of lipid emulsions on pharmacokinetic features of overdosed drug molecules. We defined two new parameters, drug accommodation capacity and drug capture kinetics, to characterize the drug capture capability of lipid emulsions. By precisely characterizing their drug capture capability, the effect of lipid emulsions on pharmacokinetic features of overdosed drug molecules was quantitively described. This quantitative description enabled an accurate prediction of the reducing extent on the half-life and area under drug concentration-time curve, which was verified by the successful treatment of overdosed propafenone. Moreover, the capture effect prediction using drug capture capability was more accurate than that of directly using logP. Overall, the developed capture capability accurately described the effect of lipid emulsions on drug pharmacokinetic features, which can guide the clinical application of lipid emulsions for the treatment of drug overdose.

14.
Biochem Biophys Res Commun ; 604: 37-42, 2022 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-35286868

RESUMO

Sepsis-associated acute renal injury (SA-AKI) is a common critical clinical disease. It is associated with increased mortality and increased risk of progression to chronic kidney disease. However, its pathogenesis is not fully known. We hypothesized that metabolic interactions mediate cell apoptosis and AKI. We found that phosphatidylcholine content in human renal tubular epithelial cells following lipopolysaccharide-induced injury was increased. The activity of lysophosphatidylcholine acyltransferase 3 (LPCAT3), a key enzyme in phospholipid metabolism, was increased, while the expression of miR-124-3p.1, which targets LPCAT3, was decreased. We also found that in the serum of SA-AKI patients, LPCAT3 activity was increased, and miR-124-3p.1 expression was decreased. Further experiments confirmed the specific binding of exocrine miR-124-3p.1 to LPCAT3. Our data reveal the molecular mechanisms of phospholipid metabolic disorder in early SA-AKI as well as the role of the miR-124-3p.1/LPCAT3 pathway in SA-AKI, which leads to ferroptosis. These results could provide the scientific basis for early diagnosis and renal replacement therapy in SA-AKI.


Assuntos
Injúria Renal Aguda , MicroRNAs , 1-Acilglicerofosfocolina O-Aciltransferase/metabolismo , Injúria Renal Aguda/metabolismo , Apoptose , Proliferação de Células , Células Epiteliais/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Fosfolipídeos/metabolismo
15.
Ying Yong Sheng Tai Xue Bao ; 33(2): 439-447, 2022 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-35229518

RESUMO

Negative air ion (NAI) is an essential indicator for measuring air cleanliness of a given area, with vital role in regulating psychological and physiological functions of human body. The photoelectric effect is an important source and influencing factor for the generation of NAI during photosynthesis, but the photoelectric effect is extremely weak and difficult to monitor. Plant electrical signal is an important indicator that indirectly reflects photoelectric effect. Previous studies mostly focused on the spatiotemporal variation of NAI in different forest communities and its relationship with meteorological factors. At present, there is little research on NAI and plant electrical signal. In this study, we explored the effect of different light intensities (0, 150, 300, 500, 700, 800, 1000 and 1200 µmol·m-2·s-1) on characteristics of the plant electrical signal and its relationship with negative air ion, with Pinus bungeana as the research object. The results showed that the intensity of plant electrical signal increased significantly with the increases of light intensity in the illumination range of 0-700 µmol·m-2·s-1. When light intensity reached 700 µmol·m-2·s-1, plant electrical signal activity reached the highest level, and plant was inhibited by light when light intensity increased further, with plant electrical signal activity decreased. The frequency-domain parameters (edge frequency, gravity frequency, power spectrum entropy and power spectrum peak) of plant electrical signals were significantly correlated with NAI. The correlation coefficient between edge frequency (E) and NAI was the highest, the relationship between them was NAI=30.981E+168.814 (R2=0.54), and the mean square error was 52.203. There was a significant correlation between plant electrical signals and NAI, which could characterize the change rule of NAI, and provide scientific evidence for further understanding the contribution potential and production mechanism of forest to NAI.


Assuntos
Eletricidade , Florestas , Plantas , Conceitos Meteorológicos , Fotossíntese
16.
Front Pharmacol ; 13: 763184, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35330833

RESUMO

Background: Lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) are common in middle-aged and elderly men. The current drugs for treating this disease include α1-adrenoceptor antagonists (ABs), muscarinic receptor antagonists (MRAs), phosphodiesterase five inhibitors (PDE5-Is), and ß3-adrenoceptor agonists (B3As). However, direct comparative studies analyzing different therapies are limited; therefore, we conducted a network meta-analysis (NMA) to evaluate the efficacy of different drug regimens for treating BPH/LUTS. Methods: The PubMed, EMbase, Web of Science, and Cochrane Library databases were searched to collect randomized controlled trials (RCTs) of different drug treatments for BPH/LUTS from January 2000 to April 2021. The NMA was performed using R 4.1 software. Results: Fifty-five RCTs were included among a total of 1639 trials. ① ABs + PDE5-Is, ABs + B3As, ABs + MRAs, ABs, and PDE5-IS were superior to the placebo in improving the total International Prostate Symptom Score (IPSS), IPSS-Voiding, and IPSS-storage. ② For increasing the maximum flow rate (Qmax), ABs + PDE5-Is, ABs + MRAs, and ABs were more effective than the placebo. ③ Regarding reducing post-void residual urine (PVR), none of the six treatment plans had significant effects. Conclusion: Combination therapy showed greater efficacy than monotherapy, and ABs + PDE5-Is was the most successful treatment for improving the overall IPSS score. ABs are a primary therapeutic measure to increase Qmax, and ABs + PDE5-I may be a more suitable choice for enhancing Qmax. The combination of MRA and AB+ MRA may lead to an increase in PVR. Systematic Review Registration: [website], identifier [registration number].

17.
Front Oncol ; 12: 842182, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35311085

RESUMO

Background: Bacillus Calmette-Guérin (BCG) is currently the most effective intravesical therapy for non-muscle-invasive bladder cancer (NMIBC) as it can prevent disease recurrence and progression and lower mortality. However, the response rates to BCG vary widely and are dependent on a multitude of factors. Methods: We performed a systematic discovery by analyzing the whole exome sequence, expression profile, and immune repertoire sequence of treatment-naive and 5-year time-serial relapsed tumors from 24 NMIBC patients. Results: BCG therapy showed bidirectional effects on tumor evolution and immune checkpoint landscape, along with a significant reduction of the percentage of neoantigen burden. In addition, a remarkable proportion of subclonal mutations were unique to the matched pre- or post-treatment tumors, suggesting the presence of BCG-induced and/or spatial heterogeneity. In the relapsed tumors, we identified and validated a shift in the mutational signatures in which mutations associated with aristolochic acid (AA) exposure were enriched, implying AA may be associated with tumor recurrence. Enhanced expressions of immune checkpoint regulation genes were found in the relapsed tumors, suggesting that the combination of immune checkpoint with BCG treatment may be an effective strategy to treat NMIBC. TCR sequencing revealed treatment-associated changes in the T-cell repertoire in the primary and relapsed tumors. Conclusion: Our results provide insight into the genomic and immune dynamics of tumor evolution with BCG treatment, suggest new mechanisms of BCG resistance, and inform the development of clinically relevant biomarkers and trials of potential immune checkpoint inhibitor combination therapies.

18.
Nature ; 602(7897): 431-436, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35173341

RESUMO

Marked evolution of properties with minute changes in the doping level is a hallmark of the complex chemistry that governs copper oxide superconductivity as manifested in the celebrated superconducting domes and quantum criticality taking place at precise compositions1-4. The strange-metal state, in which the resistivity varies linearly with temperature, has emerged as a central feature in the normal state of copper oxide superconductors5-9. The ubiquity of this behaviour signals an intimate link between the scattering mechanism and superconductivity10-12. However, a clear quantitative picture of the correlation has been lacking. Here we report the observation of precise quantitative scaling laws among the superconducting transition temperature (Tc), the linear-in-T scattering coefficient (A1) and the doping level (x) in electron-doped copper oxide La2-xCexCuO4 (LCCO). High-resolution characterization of epitaxial composition-spread films, which encompass the entire overdoped range of LCCO, has enabled us to systematically map its structural and transport properties with unprecedented accuracy and with increments of Δx = 0.0015. We have uncovered the relations Tc ~ (xc - x)0.5 ~ (A1□)0.5, where xc is the critical doping in which superconductivity disappears and A1□ is the coefficient of the linear resistivity per CuO2 plane. The striking similarity of the Tc versus A1□ relation among copper oxides, iron-based and organic superconductors may be an indication of a common mechanism of the strange-metal behaviour and unconventional superconductivity in these systems.


Assuntos
Cobre , Supercondutividade , Cobre/química , Elétrons , Metais , Óxidos/química
19.
World J Clin Cases ; 10(5): 1630-1638, 2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35211603

RESUMO

BACKGROUND: Small-cell carcinoma of the prostate (SCCP) is a clinically rare malignant tumor, accounting for < 1% of all prostate tumors. However, negativity for all SCCP neuroendocrine markers is rare. Herein, we report a case of SCCP with completely negative neuroendocrine markers and explore its clinicopathologic features, thus improving the understanding of its clinical diagnosis and management. CASE SUMMARY: We report the case of a 48-year-old patient with SCCP negative for common sensitive neuroendocrine-staining indicators. Dysuria was the first symptom, and rectal examination revealed a hard prostate, palpable nodules, diffuse prostate enlargement, no pressure pain, no blood staining in the finger sleeve, 1.33 ng/mL total prostate-specific antigen level, and a free-to-total prostate-specific antigen ratio of 0.21 ng/mL. Ultrasound suggested a prostate size of 5.3 cm × 5.8 cm × 5.6 cm, and magnetic resonance imaging suggested prostate cancer. The lower posterior bladder wall, rectal mesentery, and bilateral seminal vesicles were invaded, with multiple lymph node metastases in the pelvis. A whole-body bone scan suggested an abnormally active multiple bone metabolism and possible bone metastases. Head and lungs computed tomography revealed no significant nodal shadow. Following a pathological diagnosis of SCCP after a prostate puncture, with negative indicators of common sensitive neuroendocrine staining, chemotherapy was administered; the patient died 4-5 mo after SCCP diagnosis. CONCLUSION: SCCP is a rare disease characterized by atypical clinical symptoms, limited treatment options, a short survival period, and a poor prognosis.

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