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1.
J Immunol ; 210(4): 475-485, 2023 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-36602596

RESUMEN

Porcine epidemic diarrhea virus (PEDV) is a highly pathogenic porcine enteric coronavirus that causes severe watery diarrhea and even death in piglets. The neonatal Fc receptor (FcRn) is the only transport receptor for IgG. FcRn expressed by intestinal epithelial cells can transport IgG from breast milk to piglets to provide immune protection. Previous studies have shown that viral infection affects FcRn expression. In this study, we showed for the first time, to our knowledge, that FcRn expression can be influenced by methyltransferases. In addition, we found that PEDV inhibited FcRn protein synthesis in porcine small intestinal epithelial cells postinfection. Then, we found that PEDV interfered with the transcription of genes through aberrant methylation modification of the FcRn promoter. DNA methyltransferase 3b (DNMT3b) has been implicated in this process. Using a series of PEDV structural and nonstructural protein (nsp) expression plasmids, we showed that nsp13 plays an important role in this aberrant methylation modification. PEDV nsp13 can affect the NF-κB canonical pathway and promote DNMT3b protein expression by facilitating p65 protein binding to chromatin. PEDV caused aberrant methylation of the FcRn promoter via DNMT3b. The same phenomenon was found in animal experiments with large white piglets. IgG transcytosis demonstrated that PEDV nsp13 can inhibit bidirectional IgG transport by FcRn. In addition, the core region of nsp13 (230-597 aa) is critical for FcRn inhibition. Taken together, to our knowledge, our findings revealed a novel immune escape mechanism of PEDV and shed new light on the design and development of vaccines and drugs.


Asunto(s)
Infecciones por Coronavirus , Virus de la Diarrea Epidémica Porcina , Animales , Porcinos , FN-kappa B/metabolismo , Virus de la Diarrea Epidémica Porcina/genética , Transducción de Señal , Inmunoglobulina G
2.
Am J Respir Crit Care Med ; 209(4): 427-443, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-37971785

RESUMEN

Rationale: Microplastics are a pressing global concern, and inhalation of microplastic fibers has been associated with interstitial and bronchial inflammation in flock workers. However, how microplastic fibers affect the lungs is unknown. Objectives: Our aim was to assess the effects of 12 × 31 µm nylon 6,6 (nylon) and 15 × 52 µm polyethylene terephthalate (polyester) textile microplastic fibers on lung epithelial growth and differentiation. Methods: We used human and murine alveolar and airway-type organoids as well as air-liquid interface cultures derived from primary lung epithelial progenitor cells and incubated these with either nylon or polyester fibers or nylon leachate. In addition, mice received one dose of nylon fibers or nylon leachate, and, 7 days later, organoid-forming capacity of isolated epithelial cells was investigated. Measurements and Main Results: We observed that nylon microfibers, more than polyester, inhibited developing airway organoids and not established ones. This effect was mediated by components leaching from nylon. Epithelial cells isolated from mice exposed to nylon fibers or leachate also formed fewer airway organoids, suggesting long-lasting effects of nylon components on epithelial cells. Part of these effects was recapitulated in human air-liquid interface cultures. Transcriptomic analysis revealed upregulation of Hoxa5 after exposure to nylon fibers. Inhibiting Hoxa5 during nylon exposure restored airway organoid formation, confirming Hoxa5's pivotal role in the effects of nylon. Conclusions: These results suggest that components leaching from nylon 6,6 may especially harm developing airways and/or airways undergoing repair, and we strongly encourage characterization in more detail of both the hazard of and the exposure to microplastic fibers.


Asunto(s)
Caprolactama/análogos & derivados , Microplásticos , Plásticos , Polímeros , Ratones , Humanos , Animales , Nylons , Textiles , Poliésteres
3.
Circulation ; 148(7): 589-606, 2023 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-37203562

RESUMEN

BACKGROUND: Aortic dissection (AD) is a fatal cardiovascular disorder without effective medications due to unclear pathogenic mechanisms. Bestrophin3 (Best3), the predominant isoform of bestrophin family in vessels, has emerged as critical for vascular pathological processes. However, the contribution of Best3 to vascular diseases remains elusive. METHODS: Smooth muscle cell-specific and endothelial cell-specific Best3 knockout mice (Best3SMKO and Best3ECKO, respectively) were engineered to investigate the role of Best3 in vascular pathophysiology. Functional studies, single-cell RNA sequencing, proteomics analysis, and coimmunoprecipitation coupled with mass spectrometry were performed to evaluate the function of Best3 in vessels. RESULTS: Best3 expression in aortas of human AD samples and mouse AD models was decreased. Best3SMKO but not Best3ECKO mice spontaneously developed AD with age, and the incidence reached 48% at 72 weeks of age. Reanalysis of single-cell transcriptome data revealed that reduction of fibromyocytes, a fibroblast-like smooth muscle cell cluster, was a typical feature of human ascending AD and aneurysm. Consistently, Best3 deficiency in smooth muscle cells decreased the number of fibromyocytes. Mechanistically, Best3 interacted with both MEKK2 and MEKK3, and this interaction inhibited phosphorylation of MEKK2 at serine153 and MEKK3 at serine61. Best3 deficiency induced phosphorylation-dependent inhibition of ubiquitination and protein turnover of MEKK2/3, thereby activating the downstream mitogen-activated protein kinase signaling cascade. Furthermore, restoration of Best3 or inhibition of MEKK2/3 prevented AD progression in angiotensin II-infused Best3SMKO and ApoE-/- mice. CONCLUSIONS: These findings unveil a critical role of Best3 in regulating smooth muscle cell phenotypic switch and aortic structural integrity through controlling MEKK2/3 degradation. Best3-MEKK2/3 signaling represents a novel therapeutic target for AD.


Asunto(s)
Disección Aórtica , Músculo Liso Vascular , Animales , Humanos , Ratones , Disección Aórtica/genética , Sistema de Señalización de MAP Quinasas , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/patología , Fosforilación
4.
J Am Chem Soc ; 146(22): 15251-15263, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38780071

RESUMEN

Glioblastoma (GBM) poses a significant therapeutic challenge due to its invasive nature and limited drug penetration through the blood-brain barrier (BBB). In response, here we present an innovative biomimetic approach involving the development of genetically engineered exosome nanocatalysts (Mn@Bi2Se3@RGE-Exos) for efficient GBM therapy via improving the BBB penetration and enzyme-like catalytic activities. Interestingly, a photothermally activatable multiple enzyme-like reactivity is observed in such a nanosystem. Upon NIR-II light irradiation, Mn@Bi2Se3@RGE-Exos are capable of converting hydrogen peroxide into hydroxyl radicals, oxygen, and superoxide radicals, providing a peroxidase (POD), oxidase (OXD), and catalase (CAT)-like nanocatalytic cascade. This consequently leads to strong oxidative stresses to damage GBM cells. In vitro, in vivo, and proteomic analysis further reveal the potential of Mn@Bi2Se3@RGE-Exos for the disruption of cellular homeostasis, enhancement of immunological response, and the induction of cancer cell ferroptosis, showcasing a great promise in anticancer efficacy against GBM with a favorable biosafety profile. Overall, the success of this study provides a feasible strategy for future design and clinical study of stimuli-responsive nanocatalytic medicine, especially in the context of challenging brain cancers like GBM.


Asunto(s)
Exosomas , Glioblastoma , Rayos Infrarrojos , Fototerapia , Glioblastoma/tratamiento farmacológico , Glioblastoma/terapia , Humanos , Exosomas/química , Exosomas/metabolismo , Animales , Fototerapia/métodos , Ratones , Catálisis , Línea Celular Tumoral , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patología , Antineoplásicos/química , Antineoplásicos/farmacología , Manganeso/química , Manganeso/farmacología , Barrera Hematoencefálica/metabolismo
5.
Anal Chem ; 96(23): 9438-9446, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38804325

RESUMEN

A high-sensitivity fiber-optic photoacoustic (PA) gas microsensor is demonstrated with dual enhancement based on acoustics and detection. Due to the characteristic of small size, a Helmholtz resonator is integrated into a miniature PA sensor. The acoustically amplified PA signal is detected by a high-sensitivity fiber Fabry-Perot (F-P) interferometric cantilever. The first-order resonant frequencies of the interferometric cantilever and Helmholtz resonator are matched by subtle adjustments. The weak PA signal is significantly enhanced in a volume of only 0.35 mL, which breaks the volume limitation of the resonance modes in traditional PA sensing systems. To improve the resolution of the microsensor, a white light interferometry (WLI)-based spectral demodulation algorithm is utilized. The experimental results indicate that the minimum detection limit of acetylene (C2H2) drops to about 15 ppb with an averaging time of 100 s, corresponding to the normalized noise equivalent absorption (NNEA) coefficient of 2.7 × 10-9 W·cm-1·Hz-1/2. The dual resonance enhanced fiber-optic PA gas microsensor has the merits of high sensitivity, intrinsic safety, and compact structure.

6.
Anal Chem ; 96(11): 4562-4569, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38451124

RESUMEN

Aiming at the problem of the fiber-optic photoacoustic (PA) sensor being easily disturbed by external vibration and noise, a differential cantilever enhanced fiber-optic PA sensor is proposed for diffusion gas detection. The sensor comprises two PA tubes with the same structure and a pair of differential interferometric cantilevers. The two PA tubes are symmetrically distributed. The laser is incident on the PA tube as the signal channel to excite the PA pressure wave. Another tube without incident laser is used as the reference channel to suppress external disturbance. The external interference signals and PA signals superimposed with disturbance are detected by the differential cantilevers from the two channels. The signals are simultaneously restored by a single white-light interferometry demodulator, which multiplexed the spectral frequency domain of the superimposed interference spectrum. The experimental results show that the suppression effect of the differential cantilever enhanced PA sensor on ambient noise is improved by 80%, compared to the traditional single-cantilever sensor. The external cofrequency disturbance is suppressed by 20.9 dB. The minimum detection limit to acetylene (C2H2) downs to about 60 ppb with an integration time of 100 s. The sensor has excellent antivibration and electromagnetic interference ability.

7.
Anal Chem ; 96(13): 5298-5306, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38507227

RESUMEN

A fiber-optic photoacoustic CO sensor for gas insulation equipment is proposed, which relies on F-P interferometric cantilever-based differential lock-in amplification and optical multipass excitation enhancement. The sensor has excellent characteristics of high sensitivity, antielectromagnetic interference, fast response, and long-distance detection. The photoacoustic pressure waves in the two resonators of the differential photoacoustic cell (DPAC) are simultaneously detected by two fiber-optic interferometric cantilevers and processed differentially; thereby, the gas flow noise is effectively suppressed. Based on the comprehensive analysis of the superposition of photoacoustic excitation and multipass absorption, the diameter of the resonator is determined to be 6 mm. The optical power emitted by the 1566.6 nm distributed feedback laser is increased to 500 mW by an erbium-doped fiber amplifier. The near-infrared light is reflected 30 times in the multipass cell, which improves the order of magnitude of optical effective excitation. Due to the low sound velocity of SF6 gas, the resonant frequency of the DPAC with a resonator length of 80 mm is 760 Hz. The response time to CO/SF6 gas is 93 s with a flow rate of 500 sccm. The detection limit of the CO sensor is 53 ppb, which realizes the accurate and timely perception of the SF6 decomposition derivative CO and provides technical support for trouble-free operation of gas insulation equipment.

8.
Anal Chem ; 96(6): 2543-2549, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38302445

RESUMEN

A self-calibration fiber-optic photoacoustic (PA) gas analyzer based on 2f/1f wavelength modulation spectroscopy (WMS) is proposed, which utilizes gas and solid multipass absorption enhancement. The laser light is incident obliquely on the cell wall, and one end of the cell is equipped with a highly reflective mirror. The gas analyzer takes full advantage of the miniature multipass PA cell, which enhances the absorption of gas and solid simultaneously. As a result, the double absorption enhancement of 1f and 2f PA signals are realized. A dual-channel lock-in white-light interferometer based on fiber-optic PA demodulation is designed to simultaneously extract the 1f and 2f PA signals detected by the silicon cantilever. The experimental results of methane gas detection show that the minimum detection limit (MDL) of the PA gas analyzer is 20 ppb when the integration time is 60 s. Moreover, the detection error of gas concentration is within 3% when the laser power is reduced by half. The fiber-optic PA gas analyzer eliminates the influence of changes in the laser power and optical path loss, which can be used for the high-precision detection of trace gases.

9.
Anal Chem ; 96(3): 1046-1053, 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38196109

RESUMEN

An ultrahigh sensitive trace gas sensing system was presented with dual cantilever-based differential photoacoustic detection. By combining the double enhancement of multipass absorption and optical differential detection, the gas detection sensitivity was significantly improved. The dual-channel synchronous photoacoustic detection was realized by fiber-optic Fabry-Perot interference spectrum multiplexing. The photoacoustic signals detected by two fiber-optic cantilever microphones installed in a differential photoacoustic cell (DPAC) were out of phase, while the detected gas flow noises were in phase. The optical differential detection method achieved both highly sensitive optical interference measurement and differential noise suppression. In the multipass configuration, the interaction path between excitation light and target gas achieved 4.1 m, which improved the photoacoustic signal by an order of magnitude compared with a single reflection. The maximum gas flow allowed by the system based on the DPAC was 250 sccm, which realized the dynamic monitoring of H2S in the SF6 background. The detection limit for H2S in SF6 background was 5.1 ppb, which corresponds to the normalized noise equivalent absorption coefficient of 9 × 10-10 cm-1 W Hz-1/2.

10.
Hum Brain Mapp ; 45(3): e26614, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38375980

RESUMEN

Auditory verbal hallucinations (AVH) are distinctive clinical manifestations of schizophrenia. While low-frequency repetitive transcranial magnetic stimulation (rTMS) has demonstrated potential in mitigating AVH, the precise mechanisms by which it operates remain obscure. This study aimed to investigate alternations in structural connectivity and functional connectivity (SC-FC) coupling among schizophrenia patients with AVH prior to and following treatment with 1 Hz rTMS that specifically targets the left temporoparietal junction. Initially, patients exhibited significantly reduced macroscopic whole brain level SC-FC coupling compared to healthy controls. Notably, SC-FC coupling increased significantly across multiple networks, including the somatomotor, dorsal attention, ventral attention, frontoparietal control, and default mode networks, following rTMS treatment. Significant alternations in SC-FC coupling were noted in critical nodes comprising the somatomotor network and the default mode network, such as the precentral gyrus and the ventromedial prefrontal cortex, respectively. The alternations in SC-FC coupling exhibited a correlation with the amelioration of clinical symptom. The results of our study illuminate the intricate relationship between white matter structures and neuronal activity in patients who are receiving low-frequency rTMS. This advances our understanding of the foundational mechanisms underlying rTMS treatment for AVH.


Asunto(s)
Esquizofrenia , Humanos , Esquizofrenia/complicaciones , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/terapia , Estimulación Magnética Transcraneal/métodos , Imagen por Resonancia Magnética , Alucinaciones/diagnóstico por imagen , Alucinaciones/etiología , Alucinaciones/terapia , Encéfalo
11.
Cancer Immunol Immunother ; 73(7): 127, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38739169

RESUMEN

Lactate dehydrogenase B (LDHB) reversibly catalyzes the conversion of pyruvate to lactate or lactate to pyruvate and expressed in various malignancies. However, the role of LDHB in modulating immune responses against hepatocellular carcinoma (HCC) remains largely unknown. Here, we found that down-regulation of lactate dehydrogenase B (LDHB) was coupled with the promoter hypermethylation and knocking down the DNA methyltransferase 3A (DNMT 3A) restored LDHB expression levels in HCC cell lines. Bioinformatics analysis of the HCC cohort from The Cancer Genome Atlas revealed a significant positive correlation between LDHB expression and immune regulatory signaling pathways and immune cell infiltrations. Moreover, immune checkpoint inhibitors (ICIs) have shown considerable promise for HCC treatment and patients with higher LDHB expression responded better to ICIs. Finally, we found that overexpression of LDHB suppressed HCC growth in immunocompetent but not in immunodeficient mice, suggesting that the host immune system was involved in the LDHB-medicated tumor suppression. Our findings indicate that DNMT3A-mediated epigenetic silencing of LDHB may contribute to HCC progression through remodeling the tumor immune microenvironment, and LDHB may become a potential prognostic biomarker and therapeutic target for HCC immunotherapy.


Asunto(s)
Carcinoma Hepatocelular , ADN Metiltransferasa 3A , Epigénesis Genética , L-Lactato Deshidrogenasa , Neoplasias Hepáticas , Microambiente Tumoral , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/metabolismo , Microambiente Tumoral/inmunología , Humanos , Animales , Ratones , L-Lactato Deshidrogenasa/metabolismo , L-Lactato Deshidrogenasa/genética , ADN Metiltransferasa 3A/metabolismo , Regulación Neoplásica de la Expresión Génica , Metilación de ADN , Isoenzimas/genética , Isoenzimas/metabolismo , Línea Celular Tumoral , Silenciador del Gen , Pronóstico
12.
Small ; : e2401054, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38488748

RESUMEN

2D conjugated extension on central units of small molecular acceptors (SMAs) has gained great successes in reaching the state-of-the-art organic photovoltaics. Whereas the limit size of 2D central planes and their dominant role in constructing 3D intermolecular packing networks are still elusive. Thus, by exploring a series of SMAs with gradually enlarged central planes, it is demonstrated that, at both single molecular and aggerated levels, there is an unexpected blue-shift for their film absorption but preferable reorganization energies, exciton lifetimes and binding energies with central planes enlarging, especially when comparing to their Y6 counterpart. More importantly, the significance of well-balanced molecular packing modes involving both central and end units is first disclosed through a systematic single crystal analysis, indicating that when the ratio of central planes area/end terminals area is no more than 3 likely provides a preferred 3D intermolecular packing network of SMAs. By exploring the limit size of 2D central planes, This work indicates that the structural profiles of ideal SMAs may require suitable central unit size together with proper heteroatom replacement instead of directly overextending 2D central planes to the maximum. These results will likely provide some guidelines for future better molecular design.

13.
Small ; 20(24): e2311561, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38546001

RESUMEN

Balancing the rigid backbones and flexible side chains of light-harvesting materials is crucially important to reach optimized intermolecular packing, micromorphology, and thus photovoltaic performance of organic solar cells (OSCs). Herein, based on a distinctive CH-series acceptor platform with 2D conjugation extended backbones, a series of nonfullerene acceptors (CH-6F-Cn) are synthesized by delicately tuning the lengths of flexible side chains from n-octyl to n-amyl. A systemic investigation has revealed that the variation of the side chain's length can not only modulate intermolecular packing modes and crystallinity but also dramatically improve the micromorphology of the active layer and eventual photovoltaic parameters of OSCs. Consequently, the highest PCE of 18.73% can be achieved by OSCs employing D18:PM6:CH-6F-C8 as light-harvesting materials.

14.
J Virol ; 97(6): e0038223, 2023 06 29.
Artículo en Inglés | MEDLINE | ID: mdl-37289075

RESUMEN

Palmitoylation of viral proteins is crucial for host-virus interactions. In this study, we examined the palmitoylation of Japanese encephalitis virus (JEV) nonstructural protein 2A (NS2A) and observed that NS2A was palmitoylated at the C221 residue of NS2A. Blocking NS2A palmitoylation by introducing a cysteine-to-serine mutation at C221 (NS2A/C221S) impaired JEV replication in vitro and attenuated the virulence of JEV in mice. NS2A/C221S mutation had no effect on NS2A oligomerization and membrane-associated activities, but reduced protein stability and accelerated its degradation through the ubiquitin-proteasome pathway. These observations suggest that NS2A palmitoylation at C221 played a role in its protein stability, thereby contributing to JEV replication efficiency and virulence. Interestingly, the C221 residue undergoing palmitoylation was located at the C-terminal tail (amino acids 195 to 227) and is removed from the full-length NS2A following an internal cleavage processed by viral and/or host proteases during JEV infection. IMPORTANCE An internal cleavage site is present at the C terminus of JEV NS2A. Following occurrence of the internal cleavage, the C-terminal tail (amino acids 195 to 227) is removed from the full-length NS2A. Therefore, it was interesting to discover whether the C-terminal tail contributed to JEV infection. During analysis of viral palmitoylated protein, we observed that NS2A was palmitoylated at the C221 residue located at the C-terminal tail. Blocking NS2A palmitoylation by introducing a cysteine-to-serine mutation at C221 (NS2A/C221S) impaired JEV replication in vitro and attenuated JEV virulence in mice, suggesting that NS2A palmitoylation at C221 contributed to JEV replication and virulence. Based on these findings, we could infer that the C-terminal tail might play a role in the maintenance of JEV replication efficiency and virulence despite its removal from the full-length NS2A at a certain stage of JEV infection.


Asunto(s)
Virus de la Encefalitis Japonesa (Especie) , Encefalitis Japonesa , Proteínas no Estructurales Virales , Replicación Viral , Animales , Ratones , Línea Celular , Cisteína/metabolismo , Virus de la Encefalitis Japonesa (Especie)/fisiología , Lipoilación , Serina/metabolismo , Proteínas no Estructurales Virales/metabolismo , Virulencia
15.
Opt Lett ; 49(3): 714-717, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38300097

RESUMEN

An ultrahigh-speed phase demodulation system was designed for the Fabry-Perot (F-P) interferometric sensor based on fiber array parallel spectral detection. A high-power amplified spontaneous emission (ASE) source served as the broadband detection light. The spectrum generated by the dispersion of the F-P interference light through an arrayed waveguide grating (AWG) was incident into the fiber array and was detected in parallel by 48 photodiodes. The 48-channel signals were acquired synchronously and processed in real time to achieve a phase demodulation for the F-P cavity at 200 kHz. As a result, a low-resolution spectral detection and demodulation system was constructed with high speed. The length demodulation range of the F-P cavity was 60-700 µm, and the demodulation resolution was as high as 0.22 nm. The designed high-sensitivity demodulator is expected to be used for ultrasonic and high-frequency vibration detection.

16.
BMC Cancer ; 24(1): 534, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38671413

RESUMEN

BACKGROUND: While there is an understanding of the association between the expression of Porphyromonas gingivalis (P. gingivalis) and prognosis of oral squamous cell carcinoma (OSCC), significance specially to address the relevance between different immunohistochemical intensities of P. gingivalis and tumor-associated macrophages (TAMs) in OSCC tissue and related clinicopathologic characteristics has not been well investigated. The present study aimed to investigate the pathological features related to M2-TAM in P. gingivalis-infected OSCC and ascertain its clinical relevance with patients' prognosis. METHODS: A prospective cohort study was designed to comparatively analyze 200 patients from June 2008 to June 2020. Bioinformatics analyses were implemented to identify DOK3 as a key molecule and to appraise immunocyte infiltration using Gene Expression Omnibus and The Cancer Genome Atlas databases. Immunohistochemical evaluation was performed to analyze the association between the expression levels of P. gingivalis, DOK3, and M2-TAM and clinicopathological variables using Fisher's exact test or Pearson's chi-square test. Cox analysis was used to calculate hazard ratios (HR) with corresponding 95% confidence interval (CI) for various clinicopathological features. The Kaplan-Meier approach and log-rank test were used to plot the survival curves. RESULTS: The expression level of P. gingivalis was positively associated with DOK3 and M2-TAMs expression level (P < 0.001). Parameters, including body mass index, clinical stage, recurrence, tumor differentiation, and P. gingivalis, DOK3, and M2-TAM immunoexpression levels, affected the prognosis of patients with OSCC (all P < 0.05). In addition, P. gingivalis (HR = 1.674, 95%CI 1.216-4.142, P = 0.012), DOK3 (HR = 1.881, 95%CI 1.433-3.457, P = 0.042), and M2-TAM (HR = 1.649, 95%CI 0.824-3.082, P = 0.034) were significantly associated with the 10-year cumulative survival rate. CONCLUSIONS: Elevated expression of P. gingivalis and DOK3 indicates M2-TAM infiltration and unfavorable prognosis of OSCC, and could be considered as three novel independent risk factors for predicting the prognosis of OSCC.


Asunto(s)
Infecciones por Bacteroidaceae , Neoplasias de la Boca , Porphyromonas gingivalis , Macrófagos Asociados a Tumores , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Infecciones por Bacteroidaceae/microbiología , Infecciones por Bacteroidaceae/inmunología , Biomarcadores de Tumor/metabolismo , China/epidemiología , Neoplasias de la Boca/microbiología , Neoplasias de la Boca/patología , Neoplasias de la Boca/mortalidad , Neoplasias de la Boca/inmunología , Pronóstico , Estudios Prospectivos , Macrófagos Asociados a Tumores/inmunología
17.
J Magn Reson Imaging ; 59(4): 1358-1370, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37491872

RESUMEN

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy has been implemented as a therapeutic alternative for the treatment of drug-refractory essential tremor (ET). However, its impact on the brain structural network is still unclear. PURPOSE: To investigate both global and local alterations of the white matter (WM) connectivity network in ET after MRgFUS thalamotomy. STUDY TYPE: Retrospective. SUBJECTS: Twenty-seven ET patients (61 ± 11 years, 19 males) with MRgFUS thalamotomy and 28 healthy controls (HC) (61 ± 11 years, 20 males) were recruited for comparison. FIELD STRENGTH/SEQUENCE: A 3 T/single shell diffusion tensor imaging by using spin-echo-based echo-planar imaging, three-dimensional T1 weighted imaging by using gradient-echo-based sequence. ASSESSMENT: Patients were undergoing MRgFUS thalamotomy and their clinical data were collected from pre-operation to 6-month post-operation. Network topological metrics, including rich-club organization, small-world, and efficiency properties were calculated. Correlation between the topological metrics and tremor scores in ET groups was also calculated to assess the role of neural remodeling in the brain. STATISTICAL TESTS: Two-sample independent t-tests, chi-squared test, ANOVA, Bonferroni test, and Spearman's correlation. Statistical significance was set at P < 0.05. RESULTS: For ET patients, the strength of rich-club connection and clustering coefficient significantly increased vs. characteristic path length decreased at 6-month post-operation compared with pre-operation. The distribution pattern of rich-club regions was different in ET groups. Specifically, the order of the rich-club regions was changed according to the network degree value after MRgFUS thalamotomy. Moreover, the altered nodal efficiency in the right temporal pole of the superior temporal gyrus (R = 0.434-0.596) and right putamen (R = 0.413-0.436) was positively correlated with different tremor improvement. DATA CONCLUSION: These findings might improve understanding of treatment-induced modulation from a network perspective and may work as an objective marker in the assessment of ET tremor control with MRgFUS thalamotomy. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 4.


Asunto(s)
Temblor Esencial , Sustancia Blanca , Masculino , Humanos , Imagen de Difusión Tensora , Temblor Esencial/diagnóstico por imagen , Temblor Esencial/cirugía , Estudios Retrospectivos , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/cirugía , Temblor , Tálamo/diagnóstico por imagen , Tálamo/cirugía , Imagen por Resonancia Magnética/métodos , Resultado del Tratamiento
18.
J Magn Reson Imaging ; 59(5): 1620-1629, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-37559435

RESUMEN

BACKGROUND: Ultra-high field 7T MRI can provide excellent tissue contrast and anatomical details, but is often cost prohibitive, and is not widely accessible in clinical practice. PURPOSE: To generate synthetic 7T images from widely acquired 3T images with deep learning and to evaluate the feasibility of this approach for brain imaging. STUDY TYPE: Prospective. POPULATION: 33 healthy volunteers and 89 patients with brain diseases, divided into training, and evaluation datasets in the ratio 4:1. SEQUENCE AND FIELD STRENGTH: T1-weighted nonenhanced or contrast-enhanced magnetization-prepared rapid acquisition gradient-echo sequence at both 3T and 7T. ASSESSMENT: A generative adversarial network (SynGAN) was developed to produce synthetic 7T images from 3T images as input. SynGAN training and evaluation were performed separately for nonenhanced and contrast-enhanced paired acquisitions. Qualitative image quality of acquired 3T and 7T images and of synthesized 7T images was evaluated by three radiologists in terms of overall image quality, artifacts, sharpness, contrast, and visualization of vessel using 5-point Likert scales. STATISTICAL TESTS: Wilcoxon signed rank tests to compare synthetic 7T images with acquired 7T and 3T images and intraclass correlation coefficients to evaluate interobserver variability. P < 0.05 was considered significant. RESULTS: Of the 122 paired 3T and 7T MRI scans, 66 were acquired without contrast agent and 56 with contrast agent. The average time to generate synthetic images was ~11.4 msec per slice (2.95 sec per participant). The synthetic 7T images achieved significantly improved tissue contrast and sharpness in comparison to 3T images in both nonenhanced and contrast-enhanced subgroups. Meanwhile, there was no significant difference between acquired 7T and synthetic 7T images in terms of all the evaluation criteria for both nonenhanced and contrast-enhanced subgroups (P ≥ 0.180). DATA CONCLUSION: The deep learning model has potential to generate synthetic 7T images with similar image quality to acquired 7T images. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.


Asunto(s)
Medios de Contraste , Imagen por Resonancia Magnética , Humanos , Estudios de Factibilidad , Estudios Prospectivos , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen
19.
Langmuir ; 40(12): 6571-6581, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38466081

RESUMEN

Graphene is a two-dimensional honeycomb-like nanomaterial generated by carbon atoms in sp2 hybridized orbitals to form a hexagonal lattice structure with excellent electrical, optical, and mechanical properties. The solution process method has been widely used to realize large-area patterned graphene structures for high-performance devices. In the method, graphene usually needs to be dispersed in solution, and the π-π bonding gravitational interactions between graphene sheets would lead to uncontrollable structures in solution and difficulty in obtaining high performance. In this work, a patterned graphene oxide (GO) structure with controllable thickness and layer spacing was realized by a direct-write printed slippery surface, which was used as a slippery limited template. After reducing GO into reduced graphene oxide (rGO), a flexible electric pattern with a conductivity of up to 6.425 × 103 S/m was realized. Furthermore, the patterned rGO structure was transferred on polydimethylsiloxane (PDMS), which could generate less than a 5% change in resistance after 10,000 consecutive bends, and an anisotropic expansion based on rGO and PDMS materials under electro-thermal coupling. The patterned rGO structures could meet the performance requirements of highly sensitive and complex deformation applications as flexible electric actuators. This study provides great research significance and application value for patterning high-quality graphene structures and realizing high-performance flexible electronic devices.

20.
Artículo en Inglés | MEDLINE | ID: mdl-38913036

RESUMEN

A novel chemoheterotrophic iron-reducing micro-organism, designated as strain LSZ-M11000T, was isolated from sediment of the Marianas Trench. Phylogenetic analysis based on the 16S rRNA gene revealed that strain LSZ-M11000T belonged to genus Tepidibacillus, with 97 % identity to that of Tepidibacillus fermentans STGHT, a mesophilic bacterium isolated from the Severo-Stavropolskoye underground gas storage facility in Russia. The polar lipid profile of strain LSZ-M11000T consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, as well as other unidentified phospholipids and lipids. The major fatty acids were C16 : 0 (28.4 %), C18 : 0 (15.8 %), iso-C15 : 0 (12.9 %), and anteiso-C15 : 0 (12.0 %). Strain LSZ-M11000T had no menaquinone. Genome sequencing revealed that the genome size of strain LSZ-M11000T was 2.97 Mb and the DNA G+C content was 37.9 mol%. The average nucleotide identity values between strain LSZ-M11000T and its close phylogenetic relatives, Tepidibacillus fermentans STGHT and Tepidibacillus decaturensis Z9T, were 76.4 and 72.6 %, respectively. The corresponding DNA-DNA hybridization estimates were 20.9 and 23.4 %, respectively. Cells of strain LSZ-M11000T were rod-shaped (1.0-1.5×0.3-0.5 µm). Using pyruvate as an electron donor, it was capable of reducing KMnO4, MnO2, As(V), NaNO3, NaNO2, Na2SO4, Na2S2O3, and K2Cr2O7. Based on phenotypic, genotypic, and phylogenetic evidence, strain LSZ-M11000T is proposed to be a novel strain of the genus Tepidibacillus, for which the name Tepdibacillus marianensis is proposed. The type strain is LSZ-M11000T (=CCAM 1008T=JCM 39431T).


Asunto(s)
Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano , Ácidos Grasos , Sedimentos Geológicos , Hierro , Fosfolípidos , Filogenia , ARN Ribosómico 16S , Análisis de Secuencia de ADN , ARN Ribosómico 16S/genética , Sedimentos Geológicos/microbiología , ADN Bacteriano/genética , Federación de Rusia , Hierro/metabolismo , Procesos Heterotróficos , Hibridación de Ácido Nucleico , Bacillaceae/clasificación , Bacillaceae/genética , Bacillaceae/aislamiento & purificación , Secuenciación Completa del Genoma , Oxidación-Reducción
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