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1.
Nature ; 621(7978): 396-403, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37130545

RESUMO

Messenger RNA (mRNA) vaccines are being used to combat the spread of COVID-19 (refs. 1-3), but they still exhibit critical limitations caused by mRNA instability and degradation, which are major obstacles for the storage, distribution and efficacy of the vaccine products4. Increasing secondary structure lengthens mRNA half-life, which, together with optimal codons, improves protein expression5. Therefore, a principled mRNA design algorithm must optimize both structural stability and codon usage. However, owing to synonymous codons, the mRNA design space is prohibitively large-for example, there are around 2.4 × 10632 candidate mRNA sequences for the SARS-CoV-2 spike protein. This poses insurmountable computational challenges. Here we provide a simple and unexpected solution using the classical concept of lattice parsing in computational linguistics, where finding the optimal mRNA sequence is analogous to identifying the most likely sentence among similar-sounding alternatives6. Our algorithm LinearDesign finds an optimal mRNA design for the spike protein in just 11 minutes, and can concurrently optimize stability and codon usage. LinearDesign substantially improves mRNA half-life and protein expression, and profoundly increases antibody titre by up to 128 times in mice compared to the codon-optimization benchmark on mRNA vaccines for COVID-19 and varicella-zoster virus. This result reveals the great potential of principled mRNA design and enables the exploration of previously unreachable but highly stable and efficient designs. Our work is a timely tool for vaccines and other mRNA-based medicines encoding therapeutic proteins such as monoclonal antibodies and anti-cancer drugs7,8.


Assuntos
Algoritmos , Vacinas contra COVID-19 , COVID-19 , Estabilidade de RNA , RNA Mensageiro , SARS-CoV-2 , Vacinas de mRNA , Animais , Humanos , Camundongos , Códon/genética , COVID-19/genética , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/química , Vacinas contra COVID-19/genética , Vacinas contra COVID-19/imunologia , Meia-Vida , Herpesvirus Humano 3/genética , Herpesvirus Humano 3/imunologia , Vacinas de mRNA/química , Vacinas de mRNA/genética , Vacinas de mRNA/imunologia , Estabilidade de RNA/genética , Estabilidade de RNA/imunologia , RNA Mensageiro/química , RNA Mensageiro/genética , RNA Mensageiro/imunologia , RNA Mensageiro/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/imunologia
2.
Nat Chem Biol ; 20(2): 162-169, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37537379

RESUMO

Amylin receptors (AMYRs), heterodimers of the calcitonin receptor (CTR) and one of three receptor activity-modifying proteins, are promising obesity targets. A hallmark of AMYR activation by Amy is the formation of a 'bypass' secondary structural motif (residues S19-P25). This study explored potential tuning of peptide selectivity through modification to residues 19-22, resulting in a selective AMYR agonist, San385, as well as nonselective dual amylin and calcitonin receptor agonists (DACRAs), with San45 being an exemplar. We determined the structure and dynamics of San385-bound AMY3R, and San45 bound to AMY3R or CTR. San45, via its conjugated lipid at position 21, was anchored at the edge of the receptor bundle, enabling a stable, alternative binding mode when bound to the CTR, in addition to the bypass mode of binding to AMY3R. Targeted lipid modification may provide a single intervention strategy for design of long-acting, nonselective, Amy-based DACRAs with potential anti-obesity effects.


Assuntos
Polipeptídeo Amiloide das Ilhotas Pancreáticas , Receptores da Calcitonina , Humanos , Receptores da Calcitonina/agonistas , Receptores da Calcitonina/metabolismo , Polipeptídeo Amiloide das Ilhotas Pancreáticas/metabolismo , Obesidade , Lipídeos
3.
J Pathol ; 263(4-5): 454-465, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38845115

RESUMO

Gastric cancer (GC) is one of the most heterogeneous tumors. However, research on normal tissue adjacent to the tumor (NAT) is very limited. We performed multi-regional omics sequencing on 150 samples to assess the genetic basis and immune microenvironment in NAT and matched primary tumor or lymph node metastases. NATs demonstrated different mutated genes compared with GC, and NAT genomes underwent independent evolution with low variant allele frequency. Mutation profiles were predominated by aging and smoking-associated signatures in NAT instead of signatures associated with genetic instability. Although the immune microenvironment within NATs shows substantial intra-patient heterogeneity, the proportion of shared TCR clones among NATs is five times higher than that of tumor regions. These findings support the notion that subclonal expansion is not pronounced in NATs. We also demonstrated remarkable intra-patient heterogeneity of GCs and revealed heterogeneity of focal amplification of CD274 (encoding PD-L1) that leads to differential expression. Finally, we identified that monoclonal seeding is predominant in GC, which is followed by metastasis-to-metastasis dissemination in individual lymph nodes. These results provide novel insights into GC carcinogenesis. © 2024 The Pathological Society of Great Britain and Ireland.


Assuntos
Antígeno B7-H1 , Mutação , Neoplasias Gástricas , Microambiente Tumoral , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/imunologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Antígeno B7-H1/genética , Heterogeneidade Genética , Metástase Linfática , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética
4.
J Am Chem Soc ; 146(18): 12485-12495, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38651836

RESUMO

Understanding the mechanisms of C-H activation of alkanes is a very important research topic. The reactions of metal clusters with alkanes have been extensively studied to reveal the electronic features governing C-H activation, while the experimental cluster reactivity was qualitatively interpreted case by case in the literature. Herein, we prepared and mass-selected over 100 rhodium-based clusters (RhxVyOz- and RhxCoyOz-) to react with light alkanes, enabling the determination of reaction rate constants spanning six orders of magnitude. A satisfactory model being able to quantitatively describe the rate data in terms of multiple cluster electronic features (average electron occupancy of valence s orbitals, the minimum natural charge on the metal atom, cluster polarizability, and energy gap involved in the agostic interaction) has been constructed through a machine learning approach. This study demonstrates that the general mechanisms governing the very important process of C-H activation by diverse metal centers can be discovered by interpreting experimental data with artificial intelligence.

5.
J Neuroinflammation ; 21(1): 193, 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39095832

RESUMO

Lactate-derived histone lactylation is involved in multiple pathological processes through transcriptional regulation. The role of lactate-derived histone lactylation in the repair of spinal cord injury (SCI) remains unclear. Here we report that overall lactate levels and lactylation are upregulated in the spinal cord after SCI. Notably, H4K12la was significantly elevated in the microglia of the injured spinal cord, whereas exogenous lactate treatment further elevated H4K12la in microglia after SCI. Functionally, lactate treatment promoted microglial proliferation, scar formation, axon regeneration, and locomotor function recovery after SCI. Mechanically, lactate-mediated H4K12la elevation promoted PD-1 transcription in microglia, thereby facilitating SCI repair. Furthermore, a series of rescue experiments confirmed that a PD-1 inhibitor or microglia-specific AAV-sh-PD-1 significantly reversed the therapeutic effects of lactate following SCI. This study illustrates the function and mechanism of lactate/H4K12la/PD-1 signaling in microglia-mediated tissue repair and provides a novel target for SCI therapy.


Assuntos
Histonas , Ácido Láctico , Microglia , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Animais , Microglia/metabolismo , Microglia/efeitos dos fármacos , Histonas/metabolismo , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologia , Ácido Láctico/metabolismo , Ratos , Lisina/metabolismo , Lisina/análogos & derivados , Lisina/farmacologia , Camundongos , Cicatriz/metabolismo , Cicatriz/patologia , Feminino , Ratos Sprague-Dawley , Camundongos Endogâmicos C57BL , Masculino , Locomoção/efeitos dos fármacos , Locomoção/fisiologia
6.
Magn Reson Med ; 92(6): 2491-2505, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39155401

RESUMO

PURPOSE: To develop a novel framework to improve the visualization of distal arteries in arterial spin labeling (ASL) dynamic MRA. METHODS: The attenuation of ASL blood signal due to the repetitive application of excitation RF pulses was minimized by splitting the acquisition volume into multiple thin 2D (M2D) slices, thereby reducing the exposure of the arterial blood magnetization to RF pulses while it flows within the brain. To improve the degraded vessel visualization in the slice direction due to the limited minimum achievable 2D slice thickness, a super-resolution (SR) convolutional neural network (CNN) was trained by using 3D time-of-flight (TOF)-MRA images from a large public dataset. And then, we applied domain transfer from 3D TOF-MRA to M2D ASL-MRA, while avoiding acquiring a large number of ASL-MRA data required for CNN training. RESULTS: Compared to the conventional 3D ASL-MRA, far more distal arteries were visualized with higher signal intensity by using M2D ASL-MRA. In general, however, the vessel visualization with a conventional interpolation was prone to be blurry and unclear due to the limited spatial resolution in the slice direction, particularly in small vessels. Application of CNN-based SR transferred from 3D TOF-MRA to M2D ASL-MRA successfully addressed such a limitation and achieved clearer visualization of small vessels than conventional interpolation. CONCLUSION: This study demonstrated that the proposed framework provides improved visualization of distal arteries in later dynamic phases, which will particularly benefit the application of this approach in patients with cerebrovascular disease who have slow blood flow.


Assuntos
Imageamento Tridimensional , Angiografia por Ressonância Magnética , Redes Neurais de Computação , Marcadores de Spin , Humanos , Angiografia por Ressonância Magnética/métodos , Imageamento Tridimensional/métodos , Masculino , Adulto , Feminino , Encéfalo/diagnóstico por imagem , Encéfalo/irrigação sanguínea , Processamento de Imagem Assistida por Computador/métodos , Circulação Cerebrovascular/fisiologia , Artérias Cerebrais/diagnóstico por imagem , Pessoa de Meia-Idade , Algoritmos
7.
Cell Tissue Res ; 395(1): 63-79, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38040999

RESUMO

To investigate the effect and mechanism of Huogu injection (HG) on steroid-induced osteonecrosis of the femoral head (SONFH), we established a SONFH model in rabbits using horse serum and dexamethasone (DEX) and applied HG locally at the hip joint. We evaluated the therapeutic efficacy at 4 weeks using scanning electron microscopy (SEM), micro-CT, and qualitative histology including H&E, Masson's trichrome, ALP, and TUNEL staining. In vitro, we induced osteogenic differentiation of bone marrow stromal cells (BMSCs) and performed analysis on days 14 and 21 of cell differentiation. The findings, in vivo, including SEM, micro-CT, and H&E staining, showed that HG significantly maintained bone quality and trabecular number. ALP staining indicated that HG promoted the proliferation of bone cells. Moreover, the results of Masson's trichrome staining demonstrated the essential role of HG in collagen synthesis. Additionally, TUNEL staining revealed that HG reduced apoptosis. ALP and ARS staining in vitro confirmed that HG enhanced osteogenic differentiation and mineralization, consistent with the WB and qRT-PCR analysis. Furthermore, Annexin V-FITC/PI staining verified that HG inhibited osteoblast apoptosis, in agreement with the WB and qRT-PCR analyses. Furthermore, combined with the UPLC analysis, we found that naringin enhanced the osteogenic differentiation and accelerated the deposition of calcium phosphate. Salvianolic acid B protected osteoblasts derived from BMSCs against GCs-mediated apoptosis. Thus, this study not only reveals the mechanism of HG in promoting osteogenesis and anti-apoptosis of osteoblasts but also identifies the active-related components in HG, by which we provide the evidence for the application of HG in SONFH.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Animais , Coelhos , Diferenciação Celular , Osteoblastos , Apoptose , Células Cultivadas
8.
Ann Surg Oncol ; 31(2): 774-782, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37993745

RESUMO

BACKGROUND: Prognosis prediction of patients with gastric cancer after neoadjuvant chemotherapy is suboptimal. This study aims to develop and validate a dynamic radiomic model for prognosis prediction of patients with gastric cancer on the basis of baseline and posttreatment features. PATIENTS AND METHODS: This single-center cohort study included patients with gastric adenocarcinoma treated with neoadjuvant chemotherapy from June 2009 to July 2015 in the Gastrointestinal Cancer Center of Peking University Cancer Hospital. Their clinicopathological data, pre-treatment and post-treatment computed tomography (CT) images, and pathological reports were retrieved and analyzed. Four prediction models were developed and validated using tenfold cross-validation, with death within 3 years as the outcome. Model discrimination was compared by the area under the curve (AUC). The final radiomic model was evaluated for calibration and clinical utility using Hosmer-Lemeshow tests and decision curve analysis. RESULTS: The study included 205 patients with gastric adenocarcinoma [166 (81%) male; mean age 59.9 (SD 10.3) years], with 71 (34.6%) deaths occurring within 3 years. The radiomic model alone demonstrated better discrimination than the pathological T stage (ypT) stage model alone (cross-validated AUC 0.598 versus 0.516, P = 0.009). The final radiomic model, which incorporated both radiomic and clinicopathological characteristics, had a significantly higher cross-validated AUC (0.769) than the ypT stage model (0.516), the radiomics alone model (0.598), and the ypT plus other clinicopathological characteristics model (0.738; all P < 0.05). Decision curve analysis confirmed the clinical utility of the final radiomic model. CONCLUSIONS: The developed radiomic model had good accuracy and could be used as a decision aid tool in clinical practice to differentiate prognosis of patients with gastric cancer.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Terapia Neoadjuvante , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/tratamento farmacológico , Estudos de Coortes , Radiômica , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/tratamento farmacológico , Estudos Retrospectivos , Análise de Sobrevida
9.
Chemistry ; : e202402695, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39404653

RESUMO

The activation of N2 under mild conditions remains a significant challenge in chemistry. Understanding how the composition of ligands modulates the reactivity of metal centers is pivotal for the rational design of efficient catalysts for nitrogen fixation. Herein, the reactions between polynuclear niobium oxynitride anions Nb4N5-xOx- (x = 0-5) and N2 were investigated by employing mass spectrometry, photoelectron imaging spectroscopy, and theoretical calculations. The rate constants of Nb4N5-xOx-/N2 gradually decrease for x = 0 to x = 4, and then increase again for x = 5. The sharp increase of the rate constants of Nb4O5-/N2 corresponds to a decrease in the electron detachment energy of the Nb4O5- cluster in the photoelectron spectroscopic experiment. Theoretical calculations suggest that the low-coordinated Nb-Nb site in Nb4N5-xOx- (x = 0-5) behaves as the active center to bind N2 in the side-on/end-on manner. Mechanistic analysis reveals that raising the O/N ratio leads to higher electron densities on the active Nb-Nb center and decreased positive charge on the metal atoms, which hinders the approach of N2 to the clusters. This finding discloses fundamental insights into the impact of N/O ratios in fine-tuning the reactivity of metal centers towards N2 adsorption in related catalytic processes.

10.
BMC Cancer ; 24(1): 56, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38200411

RESUMO

BACKGROUND: The optimal reconstruction method after proximal gastrectomy remains unclear. This systematic review and meta-analysis aimed to compare the short-term outcomes and long-term quality of life of various reconstruction methods. METHODS: PubMed, Embase, Web of Science and Cochrane Library were searched to identify comparative studies concerning the reconstruction methods after proximal gastrectomy. The reconstruction methods were classified into six groups: double tract reconstruction (DTR), esophagogastrostomy (EG), gastric tube reconstruction (GT), jejunal interposition (JI), jejunal pouch interposition (JPI) and double flap technique (DFT). Esophagogastric anastomosis group (EG group) included EG, GT and DFT, while esophagojejunal anastomosis group (EJ group) included DTR, JI and JPI. RESULTS: A total of 27 studies with 2410 patients were included in this meta-analysis. The pooled results indicated that the incidences of reflux esophagitis of DTR, EG, GT, JI, JPI and DFT were 7.6%, 27.3%, 4.5%, 7.1%, 14.0%, and 9.1%, respectively. The EG group had more reflux esophagitis (OR = 3.68, 95%CI 2.44-5.57, P < 0.00001) and anastomotic stricture (OR = 1.58, 95%CI 1.02-2.45, P = 0.04) than the EJ group. But the EG group showed shorter operation time (MD=-56.34, 95%CI -76.75- -35.94, P < 0.00001), lesser intraoperative blood loss (MD=-126.52, 95%CI -187.91- -65.12, P < 0.0001) and shorter postoperative hospital stay (MD=-2.07, 95%CI -3.66- -0.48, P = 0.01). Meanwhile, the EG group had fewer postoperative complications (OR = 0.68, 95%CI 0.51-0.90, P = 0.006) and lesser weight loss (MD=-1.25, 95%CI -2.11- -0.39, P = 0.004). For specific reconstruction methods, there were lesser reflux esophagitis (OR = 0.10, 95%CI 0.06-0.18, P < 0.00001) and anastomotic stricture (OR = 0.14, 95%CI 0.06-0.33, P < 0.00001) in DTR than the esophagogastrostomy. DTR and esophagogastrostomy showed no significant difference in anastomotic leakage (OR = 1.01, 95%CI 0.34-3.01, P = 0.98). CONCLUSION: Esophagojejunal anastomosis after proximal gastrectomy can reduce the incidences of reflux esophagitis and anastomotic stricture, while esophagogastric anastomosis has advantages in technical simplicity and long-term weight status. Double tract reconstruction is a safe technique with excellent anti-reflux effectiveness and favorable quality of life. REGISTRATION: This meta-analysis was registered on the PROSPERO (CRD42022381357).


Assuntos
Esofagite Péptica , Qualidade de Vida , Humanos , Constrição Patológica , Gastrectomia/efeitos adversos , Anastomose Cirúrgica/efeitos adversos
11.
BMC Cancer ; 24(1): 1074, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39215275

RESUMO

BACKGROUND: This study was conducted to investigate the long-term outcomes of laparoscopic total gastrectomy (LTG) versus open total gastrectomy (OTG) in patients with advanced gastric cancer (AGC) after neoadjuvant chemotherapy (NACT). METHODS: Patients with AGC who received NACT before surgery were enrolled in either the LTG or OTG group. Propensity score matching (PSM) (1:2) was performed between the two groups based on the propensity score using a 0.15 calliper width. Three-year overall survival (OS) and disease-free survival (DFS) were compared between these two groups before and after PSM. OS and DFS rates were calculated by the Kaplan‒Meier method, and any differences in survival were evaluated with a log-rank test. Univariate and multivariate Cox proportional hazards analyses were used to estimate the simultaneous effects of prognostic factors on survival and the hazard ratio (HR) between LTG and OTG patients. RESULTS: A total of 144 patients completed the follow-up, with 24 patients in the LTG group and 120 patients in the OTG group. After a mean follow-up of 64.40 months, there were no significant differences in the 3-year OS or DFS rates between the two groups before (P = 0.453 and P = 0.362, respectively) or after PSM (P = 0.972 and P = 0.884, respectively). Multivariate Cox proportional hazards analysis indicated that ypN stage was an independent risk factor for worse OS (P = 0.013). CONCLUSIONS: This study showed that LTG with D2 lymphadenectomy performed by an experienced surgical team resulted in comparable 3-year OS and DFS compared with OTG in patients with AGC after NACT. TRIAL REGISTRATION: This study is not registered.


Assuntos
Gastrectomia , Laparoscopia , Terapia Neoadjuvante , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/tratamento farmacológico , Gastrectomia/métodos , Masculino , Feminino , Laparoscopia/métodos , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Estudos Retrospectivos , Idoso , Resultado do Tratamento , Adulto , Pontuação de Propensão , Estimativa de Kaplan-Meier , Intervalo Livre de Doença , Seguimentos
12.
Chemphyschem ; 25(9): e202400116, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38380870

RESUMO

Activation and transformation of methane is one of the "holy grails" in catalysis. Understanding the nature of active sites and mechanistic details via spectroscopic characterization of the reactive sites and key intermediates is of great challenge but crucial for the development of novel strategies for methane transformation. Herein, by employing photoelectron velocity-map imaging (PEVMI) spectroscopy in conjunction with quantum chemistry calculations, the Lewis acid-base pair (LABP) of [Taδ+-Nδ-] unit in Ta2N3 - acting as an active center to accomplish the heterolytic cleavage of C-H bond in CH4 has been confirmed by direct characterization of the reactant ion Ta2N3 - and the CH4-adduct intermediate Ta2N3CH4 -. Two active vibrational modes for the reactant (Ta2N3 -) and four active vibrational modes for the intermediate (Ta2N3CH4 -) were observed from the vibrationally resolved PEVMI spectra, which unequivocally determined the structure of Ta2N3 - and Ta2N3CH4 -. Upon heating, the LABP intermediate (Ta2N3CH4 -) containing the NH and Ta-CH3 unit can undergo the processes of C-N coupling and dehydrogenation to form the product with an adsorbed HCN molecule.

13.
Pharmacol Res ; 209: 107460, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39393436

RESUMO

Influenza vaccination is associated with a reduced incidence of cardiovascular events, cardiovascular death, and all-cause mortality. However, the functional role of the associated immunoglobulin remains unclear. This study identified a specific influenza-related immunoglobulin heavy chain junction region sequence (Ser-Leu-Gly-Ala-Ser-Asp, SD6) that inhibited plasma kallikrein (PKa) activity to resist thromboinflammatory responses and stroke injury. PKa is considered an attractive therapeutic target for alleviating the complications of thrombophilia-induced inflammation. In vitro, SD6 prolonged plasma recalcification and activated partial thromboplastin time, with no effects on bleeding risk-related prothrombin time, indicating selective inhibition of the intrinsic coagulation pathway. Correspondingly, at doses ranging from 0.25 to 4 mg/kg, SD6 attenuated arterial and cortical venous thrombosis in FeCl3-induced and photochemically induced mice, without impacting hemorrhage risk, and further mitigated cerebral inflammatory injury in a mouse model of transient middle cerebral artery occlusion ischemic stroke. These findings suggest that SD6 may serve as a potential therapeutic agent for the treatment of thromboinflammatory conditions.

14.
Inorg Chem ; 63(41): 19179-19187, 2024 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-39362659

RESUMO

Catalytic NO reduction by CO into N2 and CO2 is imperative owing to the increasingly rigorous emission regulation. Identifying the nature of active sites that govern the reactivity and selectivity of NO reduction is pivotal to tailor catalysts, while it is extremely challenging because of the complexity of real-life systems. Guided by our newly discovered triatomic Lewis acid-base-acid (LABA, Ceδ+-Rhδ--Ceδ+) site that accounts for the selective reduction of NO into N2 catalyzed by the RhCe2O3- cluster in gas-phase experiments, the reactivity of the RhM2O3- (M = Ta, V, and Al) clusters in catalytic NO reduction by CO was explored. We determined theoretically that the LABA site still prevails to reduce NO to N2 mediated by RhTa2O3- and RhV2O3-, and the strong M-oxygen affinity was emphasized to construct the LABA site. An overall assessment highlights that RhV2O3- functions as a more promising catalyst because the well-fitting V-O bonding strength facilitates both elementary reactions of NO reduction and CO oxidation.

15.
Inorg Chem ; 63(23): 10775-10785, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38804545

RESUMO

Gas-phase metal clusters are ideal models to explore transition-metal-mediated N2 activation mechanism. However, the effective design and search of reactive clusters in N2 activation are currently hindered by the lack of clear guidelines. Inspired by the Sabatier principle, we discovered in this work that N2 initial adsorption energy (ΔEads) is an important parameter to control the N2 activation reactivity of metal clusters in the gas phase. This mechanistic insight obtained from high-level calculations rationalizes the N2 activation reactivity of many previously reported metal clusters when combined with the known factor determining the N≡N cleavage process. Furthermore, based on this guideline of ΔEads, we successfully designed several new reactive clusters for cleaving N≡N triple bond under mild conditions, including FeV2S2-, TaV2C2-, and TaV2C3-, the high N2 activation reactivity of which has been fully corroborated in our gas phase experiments employing mass spectrometry with collision-induced dissociation. The importance of ΔEads revealed in this work not only reshapes our understanding of N2 activation reactions in the gas phase but also could have implication for other N2 activation processes in the condensed phase. The more general establishment of this new perspective on N2 activation reactivity warrants future experimental and computational studies.

16.
Surg Endosc ; 38(3): 1523-1532, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38272976

RESUMO

BACKGROUND: There is no optimal reconstruction method after proximal gastrectomy. The valvuloplastic esophagogastrostomy can reduce postoperative reflux esophagitis, but it is technically complex with a long operation time. The gastric tube anastomosis is technically simple, but the incidences of reflux esophagitis and anastomotic stricture are higher. METHODS: We have devised a modified valvuloplastic esophagogastrostomy after laparoscopy-assisted proximal gastrectomy (LAPG), the arch-bridge anastomosis. After reviewing our prospectively maintained gastric cancer database, 43 patients who underwent LAPG from November 2021 to April 2023 were included in this cohort study, with 25 patients received the arch-bridge anastomosis and 18 patients received gastric tube anastomosis. The short-term outcomes were compared between the two groups to evaluate the efficacy of the arch-bridge anastomosis. Reporting was consistent with the STROCSS 2021 guideline. RESULTS: The median operation time was 180 min in the arch-bridge group, significantly shorter than the gastric tube group (p = 0.003). In the arch-bridge group, none of the 25 patients experienced anastomotic leakage, while one patient (4%) experienced anastomotic stricture requiring endoscopic balloon dilation. The postoperative length of stay was shorter in the arch-bridge group (9 vs. 11, p = 0.034). None of the patients in the arch-bridge group experienced gastroesophageal reflux and used proton pump inhibitor (PPI), while four (22.2%) patients in the gastric tube group used PPI (p = 0.025). The incidence of reflux esophagitis (Los Angeles grade B or more severe) by endoscopy was lower in the arch-bridge group (0% vs. 25.0%). CONCLUSION: The arch-bridge anastomosis is a safe, time-saving, and feasible reconstruction method. It can reduce postoperative reflux and anastomotic stricture incidences in a selected cohort of patients undergoing laparoscopy-assisted proximal gastrectomy.


Assuntos
Esofagite Péptica , Refluxo Gastroesofágico , Laparoscopia , Neoplasias Gástricas , Humanos , Esofagite Péptica/etiologia , Esofagite Péptica/prevenção & controle , Estudos de Coortes , Estudos Retrospectivos , Constrição Patológica/cirurgia , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Refluxo Gastroesofágico/cirurgia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/complicações , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle
17.
Photodermatol Photoimmunol Photomed ; 40(3): e12974, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38728444

RESUMO

BACKGROUND/PURPOSE: Existing phototherapies are ineffective for treating patients with vitiligo with complete leukotrichia. We compared the efficacy of reverse perilesional irradiation, during which only the lesional areas are covered, with conventional narrowband ultraviolet B (NB-UVB) home phototherapy for repigmentation of non-segmental vitiligo in patients with complete leukotrichia. METHODS: This was a 12-week, open-label, double-arm, multicenter clinical trial, with a total of 121 patients with non-segmental vitiligo who were randomly divided into two groups (both received topical tacrolimus): the conventional NB-UVB irradiation (CI) and reverse perilesional NB-UVB irradiation (RI) groups. RESULTS: A statistically significant difference in improvement from baseline was observed in the RI group compared with the findings in the CI group (-30.8% ± 11.8% vs. -25.5% ± 11.05%, respectively [p = .010]; pair-wise comparison p = .900 at week 4, p = .104 at week 8, and p = .010 at week 12). At week 12, the average percentage change from baseline of leukotrichia in the irradiation area significantly decreased from 100% to 82.2% ± 13.65% in the RI group, and from 100% to 88.7% ± 9.64% in the CI group (p = .027). Adverse events were minor, including desquamation, dryness, erythema, and blisters. No severe or lasting side effects were observed during the study. CONCLUSION: RI mediated better repigmentation of vitiligo with complete leukotrichia than CI.


Assuntos
Terapia Ultravioleta , Vitiligo , Humanos , Vitiligo/terapia , Vitiligo/radioterapia , Feminino , Masculino , Adulto , Terapia Ultravioleta/métodos , Pigmentação da Pele , Pessoa de Meia-Idade , Adolescente , Tacrolimo/uso terapêutico , Tacrolimo/administração & dosagem
18.
MAGMA ; 37(3): 383-396, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38922525

RESUMO

OBJECT: To review recent advances of artificial intelligence (AI) in enhancing the efficiency and throughput of the MRI acquisition workflow in neuroimaging, including planning, sequence design, and correction of acquisition artifacts. MATERIALS AND METHODS: A comprehensive analysis was conducted on recent AI-based methods in neuro MRI acquisition. The study focused on key technological advances, their impact on clinical practice, and potential risks associated with these methods. RESULTS: The findings indicate that AI-based algorithms have a substantial positive impact on the MRI acquisition process, improving both efficiency and throughput. Specific algorithms were identified as particularly effective in optimizing acquisition steps, with reported improvements in workflow efficiency. DISCUSSION: The review highlights the transformative potential of AI in neuro MRI acquisition, emphasizing the technological advances and clinical benefits. However, it also discusses potential risks and challenges, suggesting areas for future research to mitigate these concerns and further enhance AI integration in MRI acquisition.


Assuntos
Algoritmos , Inteligência Artificial , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Neuroimagem , Humanos , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Processamento de Imagem Assistida por Computador/métodos , Artefatos , Encéfalo/diagnóstico por imagem , Fluxo de Trabalho , Interpretação de Imagem Assistida por Computador/métodos
19.
Eur Spine J ; 33(10): 3957-3968, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39134698

RESUMO

OBJECTIVE: To investigate the anatomical indexes and anatomical positional indexes of the atlantoaxial synchondroses in normal Chinese Han children aged 1-6 years, and to analyze the changing law of the atlantoaxial cartilage union with the growth and development of age and its influence on the atlantoaxial ossification in children. METHODS: A retrospective collection of CT imaging of 160 cases of normal cervical spine in children aged 1 to 6 years old was conducted. The cases were divided into six age groups, with each group representing a one-year age range. Measure the morphological anatomical indicators and anatomical positional indicators of the atlantoaxial synchondroses. Record and statistically analyze the measurements of each indicator. RESULTS: Measurements were taken on various parameters of the atlantoaxial synchondroses. TD, SD, height, area, and perimeter all gradually decreased among the groups. Distance between bilateral atlantal anterolateral synchondroses increased gradually from Group A to Group F, while the angle formed along the long axis in the cross-section showed a decreasing trend. Distance between the axoid dentolateral synchondroses and between the neurocentral synchondroses increased gradually from Group A to Group F, with the angle value in the cross-section showing a gradual decrease, and distance from the odontoid apex increasing from Group A to Group F. CONCLUSIONS: The atlantoaxial synchondroses gradually decrease in size with age, and ossification levels increase with age, with faster ossification occurring during a 1-2 years-old period. The anterolateral synchondroses, dentolateral synchondroses, and neurocentral synchondroses all gradually ossify towards the lateral direction with increasing age.


Assuntos
Articulação Atlantoaxial , Tomografia Computadorizada por Raios X , Humanos , Articulação Atlantoaxial/diagnóstico por imagem , Articulação Atlantoaxial/anatomia & histologia , Pré-Escolar , Estudos Retrospectivos , Lactente , Masculino , Feminino , Criança
20.
Psychiatry Clin Neurosci ; 78(10): 605-611, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39072968

RESUMO

AIM: Cerebello-cortical functional dysconnectivity plays a key role in the pathology of schizophrenia (SZ). We aimed to investigate the changes in cerebello-cortical directional connectivity in patients with SZ. METHODS: A total of 180 drug-naïve patients with first-episode SZ (54 reassessed after 1 year of treatment) and 166 healthy controls (HCs) were included. Resting-state functional magnetic resonance imaging was used to perform Granger causal analysis, in which each of the nine cerebellar functional systems was defined as a seed. The observed effective connectivity (EC) alterations at baseline were further assessed at follow-up and were associated with changes in psychotic symptom. RESULTS: We observed increased bottom-up EC in first-episode SZ from the cerebellum to the cerebrum (e.g. from the cerebellar attention and cingulo-opercular systems to the bilateral angular gyri, and from the cerebellar cingulo-opercular system to the right inferior frontal gyrus). In contrast, decreased top-down EC in the first-episode SZ was mainly from the cerebrum to the cerebellum (e.g. from the right inferior temporal gyrus, left middle temporal gyrus, left putamen, and right angular gyrus to the cerebellar language system). After 1 year of antipsychotic treatment, information projections from the cerebrum to the cerebellum were partly restored and positively related to symptom remission. CONCLUSION: These findings suggest that decreased top-down EC during the acute phase of SZ may be a state-dependent alteration related to symptoms and medication. However, increased bottom-up EC may reflect a persistent pathological trait.


Assuntos
Antipsicóticos , Cerebelo , Conectoma , Imageamento por Ressonância Magnética , Esquizofrenia , Humanos , Esquizofrenia/fisiopatologia , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/tratamento farmacológico , Masculino , Adulto , Cerebelo/diagnóstico por imagem , Cerebelo/fisiopatologia , Feminino , Antipsicóticos/farmacologia , Antipsicóticos/administração & dosagem , Adulto Jovem , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiopatologia , Seguimentos
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