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1.
Ann Clin Transl Neurol ; 11(8): 1999-2007, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38968332

RESUMEN

OBJECTIVE: Radiofrequency thermocoagulation (RFTC) has emerged as an effective and safe treatment method for patients with refractory focal epilepsy, when stereo-electroencephalography (SEEG) is implanted. Although real-world research results are still limited, a considerable number of patients have shown favorable outcomes with this less invasive method. This study aims to describe the outcomes and predictive factors of SEEG-RFTC in real-world research. METHODS: A retrospective observational study was conducted on patients in the authors' epilepsy center. In total, 121 patients who underwent RFTC were included in the study. Post-RFTC outcomes were evaluated using the seizure-free rate and response rate (seizure frequency reduction more than 50%). Predictive factors influencing post-RFTC outcome were considered by comparing different variables. RESULTS: The mean follow-up period was 18.3 months. Eighty-two patients (67.8%) were responders and 54 (44.6%) were seizure free. In 36 patients with malformation of cortical development, the seizure-free rate and the response rate were 69.44% and 83.33%, respectively. In 20 patients with hippocampal sclerosis, 19 patients were responders and 14 (70%) patients were seizure free at the last follow-up. The MRI feature and etiology of epilepsy are correlated with the outcome. MR-positive is a predictive factor for seizure freedom (p < 0.01) and responders (p < 0.01). Other factors have no predictive value for post-RFTC outcome. INTERPRETATION: SEEG-RFTC is a safe procedure and yields favorable outcomes in numerous cases of focal DRE. The MRI feature and etiology of epilepsy are correlated with the seizure-free rate and response rate. And MRI positivity is the predictor for good RFTC outcome.


Asunto(s)
Epilepsia Refractaria , Epilepsias Parciales , Humanos , Masculino , Femenino , Adulto , Epilepsias Parciales/fisiopatología , Epilepsia Refractaria/fisiopatología , Epilepsia Refractaria/diagnóstico , Adulto Joven , Estudios Retrospectivos , Adolescente , Persona de Mediana Edad , Niño , Electrocoagulación , Electroencefalografía , Estudios de Seguimiento , Electrocorticografía , Resultado del Tratamiento , Preescolar , Técnicas Estereotáxicas
2.
Dalton Trans ; 53(9): 4035-4040, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38332728

RESUMEN

Two carbonyl and o-NH2-NO2-containing energetic materials and their analogues were effectively designed, synthesized and fully characterized with multinuclear NMR, IR and elemental analyses. Their structures were also further confirmed via X-ray diffraction. Among them, compound 7 exhibits good potential for application as a secondary explosive with extremely high density (2.04 g cm-3), good sensitivity (IS > 40 J, FS > 360 N), and excellent calculated detonation performance (Dv = 8943 m s-1, P = 35.0 GPa). Furthermore, a detailed comparative study based on X-ray diffraction, Hirshfeld surfaces and 2D fingerprint plots among compounds 4, 7 and 9 has demonstrated that the density and detonation performance could be effectively improved via introducing a carbonyl group into fused-ring compounds. More importantly, the sensitivity of the resulting energetic materials did not deteriorate. Obviously, this strategy via introducing carbonyl, o-NH2-NO2 and nitroamino groups into fused-ring energetic compounds will help in the design of next-generation high-energy and insensitive fused-ring energetic materials.

3.
Chem Commun (Camb) ; 60(3): 296-299, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38054348

RESUMEN

We report a straightforward H/D exchange method for the synthesis of α-deuterated primary amines from a diverse set of primary amines with high levels of deuteration and chemo- and site selectivity and preparative utility. This cost-effective strategy enables the direct conversion of primary amines to α-deuterated counterparts using D2O as the deuterium source under mild reaction conditions without requiring additional functionality manipulation and with minimal byproduct production.

4.
World Neurosurg ; 181: e18-e28, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36791880

RESUMEN

OBJECTIVE: We assessed the feasibility of using compressed sensing accelerated, low-velocity encoded, isotropic resolution phase contrast (CLIP) magnetic resonance angiography (MRA) for avascular trajectory planning of stereoelectroencephalography. METHODS: Ten healthy subjects (1 woman and 9 men; age, 33.6 ± 9.0 years) and 20 consecutive patients (12 female patients; age, 22 ± 13.6 years) were enrolled in the present study. The healthy subjects underwent CLIP-MRA, and 3 other phase contrast MRA protocols with conventional parallel imaging (PI) acceleration, including low resolution with twofold PI (PI2), high resolution (HR) with fivefold PI (PI5), and HR-PI2. The patients underwent CLIP-MRA and computed tomography angiography (CTA). The image qualities were evaluated. The numbers and locations of trajectory-vessel conflict detected using CLIP-MRA were noted. RESULTS: With similar scan durations, CLIP-MRA achieved higher spatial resolution compared with low resolution with PI2 and detected significantly more branches compared with HR-PI5. With the same spatial resolution, the signal/noise and contrast/noise ratios of CLIP-MRA were higher than those with HR-PI2 with a shorter scan duration. For the 12 adult patients (10 female patients; 28.8 ± 12.7 years), CLIP-MRA had better signal/noise and contrast/noise ratios than CTA. The trajectory had required modification for 14 of the 20 patients (70%), with a proportion of trajectory modification of 10.7% (23 of 215 electrodes). The middle meningeal artery, cortical vessel, and skull vessel were the main vessels with conflict (n = 11, n = 7, and n = 5, respectively). CONCLUSIONS: In the present study, CLIP-MRA provided a clear cortical vascular display noninvasively without intravascular contrast and radiation. The middle meningeal artery and diploic and emissary veins were the main conflict vessels and could be clearly displayed using CLIP-MRA but not CTA.


Asunto(s)
Angiografía por Resonancia Magnética , Tomografía Computarizada por Rayos X , Adulto , Masculino , Humanos , Femenino , Adulto Joven , Niño , Adolescente , Angiografía por Resonancia Magnética/métodos , Angiografía por Tomografía Computarizada , Medios de Contraste
5.
PeerJ ; 11: e16241, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37849826

RESUMEN

Background: There remain controversies over the conclusion of different serum phosphate levels as prognostic predictors of sepsis patients. As such, this study investigated the association between different serum phosphate and the prognosis of sepsis. Methods: Data from PubMed, Embase, Cochrane Library, and Web of Science were systematically retrieved from the inception of databases to June 1, 2023 and independently screened and extracted by two authors. Binary variables in the study were estimated as relative risk ratio (RR) and 95% confidence interval (CI), and continuous variables were estimated as mean and standard deviation. The Newcastle-Ottawa Scale (NOS) was employed to evaluate the quality of the included studies, and subgroup analysis and sensitivity analysis were performed for all outcomes to explore the sources of heterogeneity. Results: Ten studies were included in this study including 38,320 patients with sepsis or septic shock. Against normal serum phosphate levels, a high serum phosphate level was associated with an elevated all-cause mortality risk (RR = 1.46; 95% CI [1.22-1.74]; P = 0.000) and prolonged Intensive Care Unit (ICU) length of stay (LOS) (WMD = 0.63; 95% CI [0.27-0.98]; P = 0.001). However, there was no significant difference in the in-hospital LOS (WMD = 0.22; 95% CI [-0.61-1.05]; P = 0.609). A low serum phosphate level was not significantly associated with the all-cause mortality risk (RR = 0.97; 95% CI [0.86-1.09]; P = 0.588), ICU LOS (WMD = -0.23; 95% CI [-0.75-0.29]; P = 0.394) and in-hospital LOS (WMD = -0.62; 95% CI [-1.72-0.49]; P = 0.274). Conclusion: Sepsis patients with high serum phosphate levels before therapeutic interventions were associated with a significant increase in the all-cause mortality risk, prolonged ICU LOS, and no significant difference in in-hospital LOS. Sepsis patients with low serum phosphate levels before interventions may have a reduced risk of all-cause mortality, shorter ICU LOS, and in-hospital LOS, but the results were not statistically significant.


Asunto(s)
Sepsis , Choque Séptico , Humanos , Pronóstico , Sepsis/diagnóstico , Unidades de Cuidados Intensivos , Fosfatos/uso terapéutico
6.
Hum Brain Mapp ; 44(17): 5953-5971, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37721369

RESUMEN

The evolution of magnetic susceptibility of the brain is mainly determined by myelin in white matter (WM) and iron deposition in deep gray matter (DGM). However, existing imaging techniques have limited abilities to simultaneously quantify the myelination and iron deposition within a voxel throughout brain development and aging. For instance, the temporal trajectories of iron in the brain WM and myelination in DGM have not been investigated during the aging process. This study aimed to map the age-related iron and myelin changes in the whole brain, encompassing myelin in DGM and iron deposition in WM, using a novel sub-voxel quantitative susceptibility mapping (QSM) method. To achieve this, a cohort of 494 healthy adults (18-80 years old) was studied. The sub-voxel QSM method was employed to obtain the paramagnetic and diamagnetic susceptibility based on the approximated R 2 ' map from acquired R 2 * map. The linear relationship between R 2 * and R 2 ' maps was established from the regression coefficients on a small cohort data acquired with both 3D gradient recalled echo data and R 2 mapping. Large cohort sub-voxel susceptibility maps were used to create longitudinal and age-specific atlases via group-wise registration. To explore the differential developmental trajectories in the DGM and WM, we employed nonlinear models including exponential and Poisson functions, along with generalized additive models. The constructed atlases reveal the iron accumulation in the posterior part of the putamen and the gradual myelination process in the globus pallidus with aging. Interestingly, the developmental trajectories show that the rate of myelination differs among various DGM regions. Furthermore, the process of myelin synthesis is paralleled by an associated pattern of iron accumulation in the primary WM fiber bundles. In summary, our study offers significant insights into the distinctive developmental trajectories of iron in the brain's WM and myelination/demyelination in the DGM in vivo. These findings highlight the potential of using sub-voxel QSM to uncover new perspectives in neuroscience and improve our understanding of whole-brain myelination and iron deposit processes across the lifespan.


Asunto(s)
Mapeo Encefálico , Imagen por Resonancia Magnética , Adulto , Humanos , Adolescente , Adulto Joven , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Mapeo Encefálico/métodos , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Hierro , Fenómenos Magnéticos , Sustancia Gris
7.
EMBO J ; 42(16): e113258, 2023 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-37409632

RESUMEN

Mitochondrial biogenesis is the process of generating new mitochondria to maintain cellular homeostasis. Here, we report that viruses exploit mitochondrial biogenesis to antagonize innate antiviral immunity. We found that nuclear respiratory factor-1 (NRF1), a vital transcriptional factor involved in nuclear-mitochondrial interactions, is essential for RNA (VSV) or DNA (HSV-1) virus-induced mitochondrial biogenesis. NRF1 deficiency resulted in enhanced innate immunity, a diminished viral load, and morbidity in mice. Mechanistically, the inhibition of NRF1-mediated mitochondrial biogenesis aggravated virus-induced mitochondrial damage, promoted the release of mitochondrial DNA (mtDNA), increased the production of mitochondrial reactive oxygen species (mtROS), and activated the innate immune response. Notably, virus-activated kinase TBK1 phosphorylated NRF1 at Ser318 and thereby triggered the inactivation of the NRF1-TFAM axis during HSV-1 infection. A knock-in (KI) strategy that mimicked TBK1-NRF1 signaling revealed that interrupting the TBK1-NRF1 connection ablated mtDNA release and thereby attenuated the HSV-1-induced innate antiviral response. Our study reveals a previously unidentified antiviral mechanism that utilizes a NRF1-mediated negative feedback loop to modulate mitochondrial biogenesis and antagonize innate immune response.


Asunto(s)
Antivirales , Biogénesis de Organelos , Animales , Ratones , ADN Mitocondrial/genética , Inmunidad Innata , Factor Nuclear 1 de Respiración/genética
8.
Neuroimage ; 274: 120148, 2023 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-37127191

RESUMEN

The brain tissue phase contrast in MRI sequences reflects the spatial distributions of multiple substances, such as iron, myelin, calcium, and proteins. These substances with paramagnetic and diamagnetic susceptibilities often colocalize in one voxel in brain regions. Both opposing susceptibilities play vital roles in brain development and neurodegenerative diseases. Conventional QSM methods only provide voxel-averaged susceptibility value and cannot disentangle intravoxel susceptibilities with opposite signs. Advanced susceptibility imaging methods have been recently developed to distinguish the contributions of opposing susceptibility sources for QSM. The basic concept of separating paramagnetic and diamagnetic susceptibility proportions is to include the relaxation rate R2* with R2' in QSM. The magnitude decay kernel, describing the proportionality coefficient between R2' and susceptibility, is an essential reconstruction coefficient for QSM separation methods. In this study, we proposed a more comprehensive complex signal model that describes the relationship between 3D GRE signal and the contributions of paramagnetic and diamagnetic susceptibility to the frequency shift and R2* relaxation. The algorithm is implemented as a constrained minimization problem in which the voxel-wise magnitude decay kernel and sub-voxel susceptibilities are determined alternately in each iteration until convergence. The calculated voxel-wise magnitude decay kernel could realistically model the relationship between the R2' relaxation and the volume susceptibility. Thus, the proposed method effectively prevents the errors of the magnitude decay kernel from propagating to the final susceptibility separation reconstruction. Phantom studies, ex vivo macaque brain experiments, and in vivo human brain imaging studies were conducted to evaluate the ability of the proposed method to distinguish paramagnetic and diamagnetic susceptibility sources. The results demonstrate that the proposed method provides state-of-the-art performances for quantifying brain iron and myelin compared to previous QSM separation methods. Our results show that the proposed method has the potential to simultaneously quantify whole brain iron and myelin during brain development and aging. The proposed model was also deployed with multiple-orientation complex GRE data input measurements, resulting in high-quality QSM separation maps with more faithful tissue delineation between brain structures compared to those reconstructed by single-orientation QSM separation methods.


Asunto(s)
Mapeo Encefálico , Encéfalo , Humanos , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Mapeo Encefálico/métodos , Envejecimiento , Imagen por Resonancia Magnética/métodos , Hierro/metabolismo
9.
Neurol Ther ; 12(3): 977-993, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36892782

RESUMEN

INTRODUCTION: This purpose of this work is to give a detailed description of a surgical technique for frameless robot-assisted asleep deep brain stimulation (DBS) of the centromedian thalamic nucleus (CMT) in drug-resistant epilepsy (DRE). METHODS: Ten consecutively enrolled patients who underwent CMT-DBS were included in the study. The FreeSurfer "Thalamic Kernel Segmentation" module and experience target coordinates were used for locating the CMT, and quantitative susceptibility mapping (QSM) images were used to check the target. The patient's head was secured with a head clip, and electrode implantation was performed with the assistance of the neurosurgical robot Sinovation®. After opening the dura, the burr hole was continuously flushed with physiological saline to stop air from entering the skull. All procedures were performed under general anesthesia without intraoperative microelectrode recording (MER). RESULTS: The mean age of the patients at surgery and onset of seizures was 22 years (range 11-41 years) and 11 years (range 1-21 years), respectively. The median duration of seizures before CMT-DBS surgery was 10 years (2-26 years). CMT was successfully segmented, and its position was verified by experience target coordinates and QSM images in all ten patients. The mean surgical time for bilateral CMT-DBS in this cohort was 165 ± 18 min. The mean pneumocephalus volume was 2 cm3. The median absolute errors in the x-, y-, and z-axes were 0.7 mm, 0.5 mm, and 0.9 mm, respectively. The median Euclidean distance (ED) and radial error (RE) was 1.3 ± 0.5 mm and 1.0 ± 0.3 mm, respectively. No significant difference was found between right- and left-sided electrodes regarding the RE nor the ED. After a mean 12-month follow-up, the average reduction in seizures was 61%, and six patients experienced a ≥ 50% reduction in seizures, including one patient who had no seizures after the operation. All patients tolerated the anesthesia operation, and no permanent or serious complications were reported. CONCLUSIONS: Frameless robot-assisted asleep surgery is a precise and safe approach for placing CMT electrodes in patients with DRE, shortening the surgery time. The segmentation of the thalamic nuclei enables the precise location of the CMT, and the flow of physiological saline to seal the burr holes is a good way to reduce the influx of air. CMT-DBS is an effective method to reduce seizures.

10.
EMBO Rep ; 24(4): e54731, 2023 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-36847607

RESUMEN

Ectopic lipid deposition and mitochondrial dysfunction are common etiologies of obesity and metabolic disorders. Excessive dietary uptake of saturated fatty acids (SFAs) causes mitochondrial dysfunction and metabolic disorders, while unsaturated fatty acids (UFAs) counterbalance these detrimental effects. It remains elusive how SFAs and UFAs differentially signal toward mitochondria for mitochondrial performance. We report here that saturated dietary fatty acids such as palmitic acid (PA), but not unsaturated oleic acid (OA), increase lysophosphatidylinositol (LPI) production to impact on the stability of the mitophagy receptor FUNDC1 and on mitochondrial quality. Mechanistically, PA shifts FUNDC1 from dimer to monomer via enhanced production of LPI. Monomeric FUNDC1 shows increased acetylation at K104 due to dissociation of HDAC3 and increased interaction with Tip60. Acetylated FUNDC1 can be further ubiquitinated by MARCH5 for proteasomal degradation. Conversely, OA antagonizes PA-induced accumulation of LPI, and FUNDC1 monomerization and degradation. A fructose-, palmitate-, and cholesterol-enriched (FPC) diet also affects FUNDC1 dimerization and promotes its degradation in a non-alcoholic steatohepatitis (NASH) mouse model. We thus uncover a signaling pathway that orchestrates lipid metabolism with mitochondrial quality.


Asunto(s)
Ácidos Grasos , Mitofagia , Ratones , Animales , Ácidos Grasos/metabolismo , Dimerización , Mitocondrias/metabolismo , Proteínas Mitocondriales/metabolismo , Proteínas de la Membrana/metabolismo
11.
Inflamm Res ; 72(4): 715-729, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36749385

RESUMEN

INTRODUCTION: Sepsis or endotoxemia can induce intestinal dysfunction in the epithelial and immune barrier. Th17 cells, a distinct subset of CD4+ T-helper cells, act as "border patrol" in the intestine under pathological condition and in the previous studies, Th17 cells exhibited an ambiguous function in intestinal inflammation. Our study will explore a specific role of Th17 cells and its relevant mechanism in endotoxemia-induced intestinal injury. MATERIALS AND METHODS: Lipopolysaccharide was used to establish mouse model of endotoxemia. miR-681 was analyzed by RT-PCR and northern blot analysis and its regulation by HIF-1α was determined by chromatin immunoprecipitation and luciferase reporter assay. Intestinal Th17 cells isolated from endotoxemic mice were quantitatively evaluated by flow cytometry and its recruitment to the intestine controlled by miR-681/CCR6 pathway was assessed by using anti-miRNA treatment and CCR6 knockout mice. Intestinal histopathology, villus length, intestinal inflammation, intestinal permeability, bacterial translocation and survival were investigated, by histology and TUNEL analysis, ELISA, measurement of diamine oxidase, bacterial culture, with or without anti-miR-681 treatment in endotoxemic wild-type and (or) CCR6 knockout mice. RESULTS: In this study, we found that miR-681 was significantly promoted in intestinal Th17 cells during endotoxemia, which was dependent on hypoxia-inducible factor-1α (HIF-1α). Interestingly, miR-681 could directly suppress CCR6, which was a critical modulator for Th17 cell recruitment to the intestines. In vivo, anti-miR-681 enhanced survival, increased number of intestinal Th17 cells, reduced crypt and villi apoptosis, decreased intestinal inflammation and bacterial translocation, resulting in protection against endotoxemia-induced intestinal injury in mice. However, CCR6 deficiency could neutralize the beneficial effect of anti-miR-681 on the intestine during endotoxemia, suggesting that the increment of intestinal Th17 cells caused by anti-miR-681 relies on CCR6 expression. CONCLUSION: The results of the study indicate that control of intestinal Th17 cells by regulating novel miR-681/CCR6 signaling attenuates endotoxemia-induced intestinal injury.


Asunto(s)
Endotoxemia , Células Th17 , Ratones , Animales , Endotoxemia/metabolismo , Antagomirs/metabolismo , Antagomirs/farmacología , Intestinos , Mucosa Intestinal , Receptores CCR6/genética
12.
IEEE Trans Vis Comput Graph ; 29(1): 701-711, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36155453

RESUMEN

Projection and ranking are frequently used analysis techniques in multi-attribute data exploration. Both families of techniques help analysts with tasks such as identifying similarities between observations and determining ordered subgroups, and have shown good performances in multi-attribute data exploration. However, they often exhibit problems such as distorted projection layouts, obscure semantic interpretations, and non-intuitive effects produced by selecting a subset of (weighted) attributes. Moreover, few studies have attempted to combine projection and ranking into the same exploration space to complement each other's strengths and weaknesses. For this reason, we propose RankAxis, a visual analytics system that systematically combines projection and ranking to facilitate the mutual interpretation of these two techniques and jointly support multi-attribute data exploration. A real-world case study, expert feedback, and a user study demonstrate the efficacy of RankAxis.

13.
Int J Med Robot ; 19(2): e2479, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36346988

RESUMEN

BACKGROUND: We aimed to evaluate the accuracy and safety of a novel self-tapping bone fiducial as a registration technique for stereoelectroencephalography (SEEG) implantation. METHODS: Each patient was installed with five bone fiducial markers. All procedures were performed using the same Sinovation robot system. The accuracy was determined by calculating the target point error (TPE) and the entry point error (EPE) of electrodes. RESULTS: Fourteen patients underwent SEEG implantation surgery; and the average installation time of the markers per patient was 86.1 s. In the operating theatre, the average registration time was 206.6 s, and the average registration error was 0.18 mm. The average TPE of 174 electrodes was 1.98 mm and the average EPE was 0.88 mm. CONCLUSION: Our study provided a bone fiducial marker installation and registration technique that was convenient and fast, highly accurate in registration, and highly tolerated by patients.


Asunto(s)
Robótica , Humanos , Marcadores Fiduciales , Electroencefalografía/métodos , Técnicas Estereotáxicas , Electrodos Implantados
14.
Elife ; 112022 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-35913115

RESUMEN

DBC1 has been characterized as a key regulator of physiological and pathophysiological activities, such as DNA damage, senescence, and tumorigenesis. However, the mechanism by which the functional stability of DBC1 is regulated has yet to be elucidated. Here, we report that the ubiquitination-mediated degradation of DBC1 is regulated by the E3 ubiquitin ligase SIAH2 and deubiquitinase OTUD5 under hypoxic stress. Mechanistically, hypoxia promoted DBC1 to interact with SIAH2 but not OTUD5, resulting in the ubiquitination and subsequent degradation of DBC1 through the ubiquitin-proteasome pathway. SIAH2 knockout inhibited tumor cell proliferation and migration, which could be rescued by double knockout of SIAH2/CCAR2. Human tissue microarray analysis further revealed that the SIAH2/DBC1 axis was responsible for tumor progression under hypoxic stress. These findings define a key role of the hypoxia-mediated SIAH2-DBC1 pathway in the progression of human breast cancer and provide novel insights into the metastatic mechanism of breast cancer.


Asunto(s)
Neoplasias de la Mama , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Mama/metabolismo , Neoplasias de la Mama/patología , Femenino , Humanos , Hipoxia/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinación
15.
Cell Rep ; 40(7): 111195, 2022 08 16.
Artículo en Inglés | MEDLINE | ID: mdl-35977480

RESUMEN

ATG9A is a highly conserved membrane protein required for autophagy initiation. It is trafficked from the trans-Golgi network (TGN) to the phagophore to act as a membrane source for autophagosome expansion. Here, we show that ATG9A is not just a passenger protein in the TGN but rather works in concert with GRASP55, a stacking factor for Golgi structure, to organize Golgi dynamics and integrity. Upon heat stress, the E3 ubiquitin ligase MARCH9 is promoted to ubiquitinate ATG9A in the form of K63 conjugation, and the nondegradable ubiquitinated ATG9A disperses from the Golgi apparatus to the cytoplasm more intensely, accompanied by inhibiting GRASP55 oligomerization, further resulting in Golgi fragmentation. Knockout of ATG9A or MARCH9 largely prevents Golgi fragmentation and protects Golgi functions under heat and other Golgi stresses. Our results reveal a noncanonical function of ATG9A for Golgi dynamics and suggest the pathway for sensing Golgi stress via the MARCH9/ATG9A axis.


Asunto(s)
Autofagosomas , Aparato de Golgi , Autofagosomas/metabolismo , Autofagia , Proteínas Relacionadas con la Autofagia/metabolismo , Aparato de Golgi/metabolismo , Transporte de Proteínas , Ubiquitina/metabolismo , Red trans-Golgi/metabolismo
16.
Sci Total Environ ; 839: 155955, 2022 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-35588813

RESUMEN

To improve the performance of graphitic carbon nitride (g-C3N4), a hotly researched metal-free photocatalyst, for better application in the efficient removal of organic pollutants, adsorption synergistically enhanced photocatalysis mechanism was thoroughly explored. Based on KOH pore-forming activated biochar (ACB) and K+ doped g-C3N4 (K-gC3N4), the novel activated biochar-based K-gC3N4 composite (ACB-K-gC3N4) was synthesized via the innovative ultrasonic-milling method. Rhodamine B (RhB), tetracycline (TC), norfloxacin (NOR), and chloramphenicol (CAP) were selected as target pollutants, and the effects of environmental factors, recycling and actual wastewater tests, disinfection effects, and various enhancement strategies were investigated. The results showed that K-gC3N4 was successfully composited with ACB by various characterizations, where the loading mass ratio of 1:2 exhibited the best performance. ACB-K-gC3N4 possessed a larger specific surface area, richer functional groups, suitable band gap (2.29 eV), and broader visible light absorption (~716 nm) than K-gC3N4. ACB-K-gC3N4 presented effective removal efficiency over K-gC3N4 for four pollutants, in which the removal efficiency of RhB reached 93.26%, and the degradation rate constant of 0.0119 min-1 was four times higher than K-gC3N4 (0.0029 min-1). Moreover, ACB-K-gC3N4 was superior to K-gC3N4 in disinfecting S. aureus and E. coli, with a sterilization rate of exceeding 90% for 12 h. The photodegradation activity was dominated by ·O2-, h+, and ·OH, and the mechanisms involved in the three stages. This was attributed to the unique structure and surface properties (defects and persistent free radicals) of ACB, as evidenced by improved adsorption stage and transfer of degradation intermediates, facilitated the generation of active species, accelerated migration of photogenerated electrons, and inhibited photogenerated carriers recombination by the heterojunction. The good reusability and stability, enhancement strategies (blowing air and heating), and satisfactory feasibility for actual wastewater allow ACB-K-gC3N4 possible to promote high-concentration wastewater treatment and disinfection.


Asunto(s)
Contaminantes Ambientales , Purificación del Agua , Antibacterianos/farmacología , Catálisis , Carbón Orgánico , Desinfección , Escherichia coli , Luz , Staphylococcus aureus , Aguas Residuales/química , Purificación del Agua/métodos
17.
Front Neurol ; 13: 864070, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35444610

RESUMEN

Familial lateral temporal lobe epilepsy (FLTLE) is genetic focal epilepsy usually characterised by auditory symptoms. Most FLTLE cases can be controlled by anti-seizure medications, and to our best knowledge, there are no previous reports about stereoelectroencephalography (SEEG) used for patients with FLTLE. In this report, we present two patients with FLTLE in one family and their SEEG performances, together with 18F-fluorodeoxyglucose (18F-FDG) PET and MRI results. In case 1, fast activities originated from the right superior temporal gyrus and spread rapidly to the right anterior insular lobe and hippocampus. In case 2, there were two seizure patterns: (1) The fast activities or sharp slow waves were identified at the left superior temporal gyrus, then, sharp waves and spike waves spread in the left superior temporal gyrus; (2) There were fast activities and slow-wave oscillation originated in the left superior temporal gyrus, then, the fast activities spread in the left superior temporal gyrus and finally spread to the other sites. An SEEG-guided radiofrequency thermocoagulation was performed for both patients and one of them underwent resection surgery. Seizures are well-controlled and the patients are very satisfied with the therapeutic effects.

18.
Front Surg ; 9: 869223, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35372483

RESUMEN

Objective: Percutaneous balloon compression (PBC) is a minimally invasive treatment for trigeminal neuralgia (TG) with a favorable cost-effectiveness ratio, but this technique has a steep learning curve. This study presents our initial clinical experience of robot-assisted PBC using a neurosurgical robot on six consecutive patients with TG. Methods: We fixed the patient's head with a skull clamp and connected it with the linkage arms of a Sinovation® neurosurgical robot, which was then registered using four bone fiducials by the robotic pointer. The puncture needle was positioned at the entry point on the skin using a robotic arm and advanced to the target point after the skin had been incised with a pointed surgical blade. This procedure was repeated for a second trajectory. A balloon was then advanced and inflated using 0.3 ml of a contrast agent. Upon injection of 0.6 ml contrast agent, the ganglion was kept compressed for 120 s. After removal of the balloon and puncture needle, compression of the face was performed to achieve hemostasis. Results: All patients achieved immediate pain relief following PBC. No permanent or severe complications were registered, and there was no pain recurrence in any of the patients during the follow-up period. Conclusions: Despite requiring a longer time for preoperative preparation, robot-assisted PBC provided a high degree of accuracy and safety, and it can also shorten the learning curve for surgeons unfamiliar with PBC. Robot-assisted surgical approaches should be further developed and adopted for PBC.

19.
Front Neurorobot ; 16: 848746, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35295674

RESUMEN

Objective: Our study aimed to develop an approach to improve the speed and resolution of cerebral-hemisphere and lesion modeling and evaluate the advantages and disadvantages of robot-assisted surgical planning software. Methods: We applied both conventional robot planning software (method 1) and open-source auxiliary software (FreeSurfer and 3D Slicer; method 2) to model the brain and lesions in 19 patients with drug-resistant epilepsy. The patients' mean age at implantation was 21.4 years (range, 6-52 years). Each patient received an average of 12 electrodes (range, 9-16) between May and November 2021. The electrode-implantation plan was designed based on the models established using the two methods. We statistically analyzed and compared the duration of designing the models and planning the implantation using these two methods and performed the surgeries with the implantation plan designed using the auxiliary software. Results: A significantly longer time was needed to reconstruct a cerebral-hemisphere model using method 1 (mean, 206 s) than using method 2 (mean, 20 s) (p < 0.05). Both methods identified a mean of 1.4 lesions (range, 1-5) in each patient. Overall, using method 1 required longer (mean, 130 s; range, 48-436) than using method 2 (mean, 68.1 s; range, 50-104; p < 0.05). In addition, the clarity of the model based on method 1 was lower than that based on method 2. To devise an electrode-implantation plan, it took 9.1-25.5 min (mean, 16) and 6.6-14.8 min (mean, 10.2) based on methods 1 and 2, respectively (p < 0.05). The average target point error of 231 electrodes amounted to 1.90 mm ± 0.37 mm (range, 0.33-3.61 mm). The average entry point error was 0.89 ± 0.26 mm (range, 0.17-1.67 mm). None of the patients presented with intracranial hemorrhage or infection, and no other serious complications were observed. Conclusions: FreeSurfer and 3D Slicer-assisted SEEG implantation is an excellent approach to enhance modeling speed and resolution, shorten the electrode-implantation planning time, and boost the efficiency of clinical work. These well-known, trusted open-source programs do not have explicitly restricted licenses. These tools, therefore, seem well suited for clinical-research applications under the premise of approval by an ethics committee, informed consent of the patient, and clinical judgment of the surgeon.

20.
Int J Gen Med ; 15: 1185-1192, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35153509

RESUMEN

PURPOSE: There is a limited evidence of durable effect of parathyroidectomy (PTX) on the quality of life (QoL) in dialysis populations. We aimed to investigate this concern by comparing the QoL scores in the pre- and post-PTX periods in a cohort of dialysis patients. PATIENTS AND METHODS: A total of 212 dialysis patients were enrolled in a hospital-facilitated dialysis center in China between July 1, 2016 and June 30, 2021. The mean age was 46.4 years; the male:female ratio was 96:116; hemodialysis 191, peritoneal dialysis 21. Informative data relating to demographics and dialysis were recorded for comparison. QoL was measured using the Chinese version of the Kidney Disease Quality of Life-36 (KDQOL-36™) and compared subscale scores between the pre-and post-PTX period. Appropriate statistical methods and Pearson's correlation test were used for statistical analysis. RESULTS: Nutritional markers, including hemoglobin and albumin, significantly increased post-PTX than pre-PTX. KDQOL-36 domain scale scores, including Symptoms and Problems of Kidney Disease, Burden of Kidney Disease, Effects of Kidney Disease (EKD), Physical Component Summary (PCS) score, and Mental Component Summary score, significantly increased post-PTX than pre-PTX. All patients were further stratified into three groups based on the PTX duration-0-2 years, >2-<5 years, and ≥5 years-and all KDQOL-36 domain scale scores increased in individual PTX durations. The PTX duration showed a significant negative correlation between PCS subscale scores and a positive correlation between EKD subscale scores. CONCLUSION: PTX could improve QoL in dialysis patients with medically refractory secondary hyperparathyroidism. The durable effects should be studied using a larger sample.

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