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BACKGROUND: Gastric cancer, a prevalent malignancy, poses a severe threat to the health of residents in China. Timely intervention in early stages can extend patients' survival. AIM: To analyze clinical characteristics of patients with early gastric cancer and efficacy and risk of complications associated with endoscopic resection. METHODS: This study included 175 patients with early gastric cancer treated at our hospital, with no restrictions on sex or age. General data, pathological information, and endoscopic biopsy results were obtained. The clinical characteristics of early gastric cancer were analyzed, and endoscopic resection was performed. Postoperative efficacy and incidence of complications were monitored. Statistical analysis was performed using SPSS 26.0 and GraphPad Prism 8.0 software. RESULTS: A total of 175 patients with early gastric cancer were included, with 75.43% (n = 132) males and 24.57% (n = 43) females. 38.29% (n = 67) and 35.43% (n = 62) of patients had a history of smoking and alcohol consumption, respectively. Comorbidities included diabetes (8.57%, n = 15), coronary heart disease (10.29%, n = 18), and hypertension (43.43%, n = 76), which was highly prevalent. A history of abdominal surgery and family history of digestive system cancer accounted for 21.14% and 17.14%, respectively. The most common lesion location was the antral part of the stomach (52.00%, n = 91), followed by the gastric angle, body, and fundus. The pathological types were predominantly high-grade intraepithelial neoplasia (28.00%, n = 49) and well-differentiated adenocarcinoma (26.86%, n = 47), followed by moderately differentiated adenocarcinoma, high-moderately differentiated adenocarcinoma, and moderate-lowly differentiated adenocarcinoma. 89.14% of the patients had intestinal metaplasia and 85.14% had atrophy. After endoscopic resection, re-examination revealed that 13 patients had cancer cells at the tissue margin, with a positive margin rate of 7.43%. Postoperative complications included no cases of gastrointestinal obstruction, but incisional infection (2.86%, n = 5), gastric perforation (1.14%, n = 2), and gastric bleeding (4%, n = 7) were present, with an overall incidence of 8.00%. CONCLUSION: Analysis of the clinical characteristics indicated that early gastric cancer is more prevalent in males with a history of hypertension, with lesions most commonly occurring in the antral region of the stomach. The pathological types are often high-grade intraepithelial neoplasia and well-differentiated adenocarcinoma, with over 85% of patients having comorbid intestinal metaplasia and atrophy. Despite endoscopic resection, a positive margin rate persisted, indicating a probability of residual cancer at the margins. Postoperative complications, such as gastrointestinal obstruction, incisional infection, gastric perforation, and gastric bleeding can occur and require timely symptomatic treatment.
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To construct an efficient regulating layer for Zn anodes that can simultaneously address the issues of dendritic growth and side reactions is highly demanded for stable zinc metal batteries (ZMBs). Herein, we fabricate a hydrogen-bonded organic framework (HOF) enriched with zincophilic sites as a multifunctional layer to regulate Zn anodes with controlled spatial ion flux and stable interfacial chemistry (MA-BTA@Zn). The framework with abundant H-bonds helps capture H2O and remove the solvated shells on [Zn(H2O)6]2+, leading to suppressed side reactions. The HOF layer also helps form electrolyte-philic surfaces and expose Zn (002) crystal planes which benefit for rapid conduction and uniform deposition of Zn2+, and weakened sides reactions. Additionally, the electrochemically active zincophilic sites (C=O, -NH2 and triazine groups) favor the targeted guidance and penetration of Zn2+ and provide advantageous sites for uniform Zn deposition. High Young's modulus of the HOF layer further contributes to a high interfacial flexibility and stability against Zn plating-associated stress. The MA-BTA@Zn symmetric cells thereby obtain a substantially extended battery life over 1000 h at 4 mA cm-2. The MA-BTA@Zn||Cu half-cell demonstrates a highly reversible Zn stripping/plating process over 1500 cycles with impressive average Coulombic efficiency (CE) of 99.5% at 10 mA cm-2.
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Redox-active porous organic polymers (POPs) demonstrate significant potential in supercapacitors. However, their intrinsic low electrical conductivity and stacking tendencies often lead to low utilization rates of redox-active sites within their structural units. Herein, polyimide POPs (donated as PMTA) are synthesized in situ on multi-walled carbon nanotubes (MWCNTs) from tetramino-benzoquinone (TABQ) and 1,4,5,8-naphthalene tetracarboxylic dianhydride (PMDA) monomers. The strong π-π stacking interactions drive the PMTA POPs and the MWCNTs together to form a PMTA/MWCNT composite. With the assistance of MWCNTs, the stacking issue and low conductivity of PMTA POPs are well addressed, leading to the obvious activation and enhanced utilization of the redox-active groups in the PMTA POPs. PMTA/MWCNT then achieves a high capacitance of 375.2 F g-1 at 1 A g-1 as compared to the pristine PMTA POPs (5.7 F g-1) and excellent cycling stability of 89.7% after 8000 cycles at 5 A g-1. Cyclic voltammetry (CV) and in situ Fourier-Transform Infrared (FT-IR) results reveal that the electrode reactions involve the reversible structural evolution of carbonyl groups, which are activated to provide rich pseudocapacitance. Asymmetric supercapacitors (ASCs) assembled with PMTA/MWCNTs and activated carbon (AC) offer a high energy density of 15.4 Wh kg-1 at 980.4 W kg-1 and maintain a capacitance retention of 125% after 10,000 cycles at 5 A g-1, indicating their good potential for practical applications.
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As a prevalent spine disorder, Lumbar disc herniation (LDH) has been affecting more than 2 % of the worldwide population and is characterised by uncertain causes and recurring episodes. Studying the brain activity of patients could potentially provide insights into its pathogenesis and significantly enhance therapy. Therefore, we here examined brain function in patients under Spinal Manipulative Therapy (SMT). By analysing regional homogeneity (ReHo) at different frequency bands, we identified the discrepancies in brain activity between LDH patients and healthy people, highlighting the frequency dependence of spontaneous low-frequency oscillations among patients with LDH. Choosing seeds based on the peak ReHo differences helped to elucidate the functional connectivity alterations in the brain regions of LDH. Overall, this study showed that SMT significantly reduced pain, improved dysfunction, and partially rectified aberrant local consistency and functional connection in patients with LDH, not only offering insights into the pathophysiology of LDH from a neurological standpoint, but also providing inspiration for the development of new therapies based on neurobiology.
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Sirtuin 1 (SIRT1) is a key upstream regulator of lipid metabolism; however, the molecular mechanisms by which SIRT1 regulates milk fat synthesis in dairy goats remain unclear. This study aimed to investigate the regulatory roles of SIRT1 in modulating lipid metabolism in goat mammary epithelial cells (GMECs) and its impact on the adipose triglyceride lipase (ATGL) promoter activity using RNA interference (RNAi) and gene overexpression techniques. The results showed that SIRT1 is significantly upregulated during lactation compared to the dry period. Additionally, SIRT1 knockdown notably increased the expressions of genes related to fatty acid synthesis (SREBP1, SCD1, FASN, ELOVL6), triacylglycerol (TAG) production (DGAT2, AGPAT6), and lipid droplet formation (PLIN2). Consistent with the transcriptional changes, SIRT1 knockdown significantly increased the intracellular contents of TAG and cholesterol and the lipid droplet abundance in the GMECs, while SIRT1 overexpression had the opposite effects. Furthermore, the co-overexpression of SIRT1 and Forkhead box protein O1 (FOXO1) led to a more pronounced increase in ATGL promoter activity, and the ability of SIRT1 to enhance ATGL promoter activity was nearly abolished when the FOXO1 binding sites (FKH1 and FKH2) were mutated, indicating that SIRT1 enhances the transcriptional activity of ATGL via the FKH element in the ATGL promoter. Collectively, our data reveal that SIRT1 enhances the transcriptional activity of ATGL through the FOXO1 binding sites located in the ATGL promoter, thereby regulating lipid metabolism. These findings provide novel insights into the role of SIRT1 in fatty acid metabolism in dairy goats.
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Células Epiteliais , Ácidos Graxos , Proteína Forkhead Box O1 , Cabras , Lipase , Glândulas Mamárias Animais , Regiões Promotoras Genéticas , Sirtuína 1 , Animais , Sirtuína 1/metabolismo , Sirtuína 1/genética , Lipase/metabolismo , Lipase/genética , Células Epiteliais/metabolismo , Glândulas Mamárias Animais/metabolismo , Glândulas Mamárias Animais/citologia , Feminino , Ácidos Graxos/metabolismo , Proteína Forkhead Box O1/metabolismo , Proteína Forkhead Box O1/genética , Metabolismo dos Lipídeos , Lactação , Triglicerídeos/metabolismo , Triglicerídeos/biossíntese , Regulação da Expressão GênicaRESUMO
BACKGROUND: Cerebral ischemia-reperfusion injury (CI/RI) is a complex process leading to neuronal damage and death, with mitophagy implicated in its pathogenesis. However, the significance of mitophagy in CI/RI remains debated. HYPOTHESIS: We hypothesized that TRIM25 reduces ATAD3A expression by ubiquitinating ATAD3A, promoting mitophagy via the PINK1/Parkin pathway, and aggravating CI/RI. STUDY DESIGN: Rat middle cerebral artery occlusion (MCAO) followed by reperfusion and oxygen-glucose deprivation and reoxygenation (OGD/R) in PC12 cells were used as animal and cell models, respectively. METHODS: To evaluate the success of the CI/R modeling, TTC and HE staining were employed. The determination of serum biochemical indexes was carried out using relative assay kits. The Western Blot analysis was employed to assess the expression of ATAD3A, TRIM25, as well as mitophagy-related proteins (PINK1, Parkin, P62, and LC3II/LC3I). The mRNA levels were detected using QRT-PCR. Mitochondrial membrane potential was assessed through JC-1 staining. Mitosox Red Assay Kit was utilized to measure mitochondrial reactive oxygen species levels in PC12 cells. Additionally, characterization of the mitophagy structure was performed using transmission electron microscopy (TEM). RESULTS: Our findings showed down-regulation of ATAD3A and up-regulation of TRIM25 in both in vivo and in vitro CI/RI models. Various experimental techniques such as Western Blot, JC-1 staining, Mitosox assay, Immunofluorescence assay, and TEM observation supported the occurrence of PINK1/Parkin signaling pathway-mediated mitophagy in both models. ATAD3A suppressed mitophagy, while TRIM25 promoted it during CI/RI injury. Additionally, the results indicated that TRIM25 interacted with and ubiquitinated ATAD3A via the proteasome pathway, affecting ATAD3A protein stability and expression. CONCLUSION: TRIM25 promoted Pink1/Parkin-dependent excessive mitophagy by destabilizing ATAD3A, exacerbating CI/RI. Targeting TRIM25 and ATAD3A may offer therapeutic strategies for mitigating CI/RI and associated neurological damage.
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We report herein a photoinduced radical 1,3-dipolar cycloaddition between the 2-benzothiazolimines and tetrahydroisoquinoline derivatives with an organo-photocatalyst. A variety of benzothiazole-based hexahydroimidazo[2,1-a]isoquinoline architectures with great synthetic value were conveniently and efficiently constructed in moderate to good yields and excellent diastereoselectivities with highly tolerant functional groups. Moreover, the practicality and utility of this protocol were demonstrated by scale-up synthesis and facile elaboration. Preliminary mechanistic investigations indicated that the reaction proceeded via a visible-light-induced radical 1,3-dipolar cycloaddition pathway. This finding is expected to stimulate a more extensive exploration of the green and concise synthesis of structurally diverse heterocyclic molecules in the synthetic community.
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rAj-Tspin, a soluble recombinant peptide from Apostichopus japonicus, can inhibit the integrin ß1 (ITGB1)/FAK/AKT signaling pathway in hepatocellular carcinoma (HCC) via cell epithelial-mesenchymal transition (EMT) and apoptosis. Zyxin (ZYX) is a focal adhesion protein that is considered a novel mediator of EMT and apoptosis. However, the inhibitory mechanisms of rAj-Tspin in HCC and whether it is related to ZYX are unclear. We examined the antitumor effect of rAj-Tspin on the Huh7 human HCC cell line and on a nude mouse model generated via subcutaneous injection or orthotopic intrahepatic transplantation of Huh7 cells. Our results revealed that rAj-Tspin strikingly reduced the viability and promoted the apoptosis of Huh7 cells and inhibited HCC tumor growth in nude mice. rAj-Tspin inhibited ITGB1 and ZYX protein expression in vivo and in vitro in a dose-dependent manner. Mechanistically, the FAK/AKT signaling pathway and the proliferation and invasion of HCC cells were suppressed upon ITGB1 and ZYX knockdown. Moreover, the effect of ITGB1 overexpression on the growth of HCC cells was inhibited by rAj-Tspin. In contrast, the promoting effect of ITGB1 overexpression could be inhibited by ZYX knockdown. ZYX knockdown had no effect on ITGB1 expression. These findings suggest that ZYX is required for the indispensable role of ITGB1 in rAj-Tspin-alleviated HCC and provide an important therapeutic target for HCC. In summary, the anti-HCC effect of rAj-Tspin potentially involves the regulation of the ITGB1/ZYX/FAK/AKT pathway, which in turn impacts EMT and apoptosis.
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BACKGROUND: Cobalt (Co) is a metal which is widely used in the industrial production. The previous studies found the toxic effects of environmental Co exposure on multiple organs. However, the correlation of blood Co concentration with lung function was inconsistent in patients with chronic obstructive pulmonary disease (COPD). METHODS: All 771 stable COPD patients were recruited. Peripheral blood and clinical information were collected. The levels of blood Co and serum CC16 were measured. RESULTS: Cross-sectional study suggested that the level of blood Co was inversely and dose-dependently related to lung function parameters. Each 1 ppm elevation of blood Co was related to 0.598 L decline in FVC, 0.465 L decline in FEV1, 6.540% decline in FEV1/FVC%, and 14.013% decline in FEV1%, respectively. Moreover, higher age, enrolled in winter, current-smoking, higher smoking amount, and inhaled corticosteroids prominently exacerbated the negative correlation between blood Co and lung function. Besides, serum CC16 content was gradually reduced with blood Co elevation in COPD patients. Besides, serum CC16 was positively correlated with lung function, and inversely related to blood Co. Additionally, decreased CC16 substantially mediated 11.45% and 6.37% Co-triggered downregulations in FEV1 and FEV1%, respectively. CONCLUSION: Blood Co elevation is closely related to the reductions of pulmonary function and serum CC16. CC16 exerts a significantly mediating role of Co-related to pulmonary function decrease among COPD patients.
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Cobalto , Doença Pulmonar Obstrutiva Crônica , Uteroglobina , Humanos , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Masculino , Uteroglobina/sangue , Feminino , Cobalto/sangue , Idoso , Pessoa de Meia-Idade , Estudos Transversais , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Pulmão/metabolismo , Volume Expiratório Forçado/fisiologia , Testes de Função Respiratória/métodos , Biomarcadores/sangue , Capacidade Vital/fisiologiaRESUMO
Bacteria are becoming an increasingly serious threat to human health. The emergence of super bacteria makes clinical treatment more difficult. Vaccines are one of the most effective means of preventing and treating bacterial infections. As a new class of vaccines, killed but metabolically active (KBMA) vaccines provide the immunogenicity of live vaccines and the safety of inactivated vaccines. Herein, a promising strategy is proposed to improve the stability and immunogenicity of KBMA vaccines. KBMA vaccines were produced at low temperature (4 °C), and the bacterial surface was engineered using mesoporous silica nanoparticle (MSN) coating. Compared to vaccines prepared at room temperature, the metabolic activity of KBMA vaccines prepared at 4 °C remarkably improved. Benefiting from the induction of MSNs, the stability of KBMA vaccines was increased and the preservation time was prolonged at 4 °C. Meanwhile, metabolomics analysis showed that the metabolite spectrum of live bacteria changed after photochemical treatment and MSN coating, which interfered with organic acid metabolism pathways, lipid metabolism and biosynthesis of secondary metabolites. Furthermore, the immune response in the mice treated with KBMA/MSN vaccines was similar to that in those treated with live vaccines and stronger than that in those treated with inactivated vaccines. In comparison with the control group, bacteria tissue burdens of KBMA/MSN group were significantly reduced. CD4+ T cells dominated immune responses for the protection of mice. Thus, the current work promotes the application of KBMA vaccines, providing an alternative choice for treating bacterial infections.
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Nanopartículas , Dióxido de Silício , Vacinas de Produtos Inativados , Animais , Nanopartículas/química , Camundongos , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/química , Dióxido de Silício/química , Feminino , Vacinas Bacterianas/química , Vacinas Bacterianas/imunologia , Camundongos Endogâmicos BALB C , Temperatura Baixa , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismoRESUMO
Nano-biochar, characterized by its environmentally friendly nature and unique nanostructure, offers a promising avenue for sustainable carbon materials. With its small particle size, large specific surface area, abundant functional groups and tunable pore structure, nano-biochar stands out due to its distinct physical and chemical properties compared to conventional biochar. This paper aims to provide an in-depth exploration of nano-biochar, covering its sources, transformation mechanisms, properties, applications, and areas requiring further research. The discussion begins with an overview of biomass sources for nano-biochar production and the conversion processes involved. Subsequently, primary synthesis methods and strategies for functionalization enhancement are examined. Furthermore, the applications of nano-biochar in catalysis, energy storage, and pollutant adsorption and degradation are explored and enhanced in various fields.
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BACKGROUND: Drought stress limits significantly the crop productivity. However, plants have evolved various strategies to cope with the drought conditions by adopting complex molecular, biochemical, and physiological mechanisms. Members of the nuclear factor Y (NF-Y) transcription factor (TF) family constitute one of the largest TF classes and are involved in plant responses to abiotic stresses. RESULTS: TaNF-YB2, a NY-YB subfamily gene in T. aestivum, was characterized in this study focusing on its role in mediating plant adaptation to drought stress. Yeast two-hybrid (Y-2 H), biomolecular fluoresence complementation (BiFC), and Co-immunoprecipitation (Co-IP) assays indicated that TaNF-YB2 interacts with the NF-YA member TaNF-YA7 and NF-YC family member TaNF-YC7, which constitutes a heterotrimer TaNF-YB2/TaNF-YA7/TaNF-YC7. The TaNF-YB2 transcripts are induced in roots and aerial tissues upon drought signaling; GUS histochemical staining analysis demonstrated the roles of cis-regulatory elements ABRE and MYB situated in TaNF-YB2 promoter to contribute to target gene response to drought. Transgene analysis on TaNF-YB2 confirmed its functions in regulating drought adaptation via modulating stomata movement, osmolyte biosynthesis, and reactive oxygen species (ROS) homeostasis. TaNF-YB2 possessed the abilities in transcriptionally activating TaP5CS2, the P5CS family gene involving proline biosynthesis and TaSOD1, TaCAT5, and TaPOD5, the genes encoding antioxidant enzymes. Positive correlations were found between yield and the TaNF-YB2 transcripts in a core panel constituting 45 wheat cultivars under drought condition, in which two types of major haplotypes including TaNF-YB2-Hap1 and -Hap2 were included, with the former conferring more TaNF-YB2 transcripts and stronger plant drought tolerance. CONCLUSIONS: TaNF-YB2 is transcriptional response to drought stress. It is an essential regulator in mediating plant drought adaptation by modulating the physiological processes associated with stomatal movement, osmolyte biosynthesis, and reactive oxygen species (ROS) homeostasis, depending on its role in transcriptionally regulating stress response genes. Our research deepens the understanding of plant drought stress underlying NF-Y TF family and provides gene resource in efforts for molecular breeding the drought-tolerant cultivars in T. aestivum.
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Secas , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Fatores de Transcrição , Triticum , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Triticum/genética , Triticum/fisiologia , Triticum/metabolismo , Estresse Fisiológico/genética , Adaptação Fisiológica/genética , Genes de Plantas , Resistência à SecaRESUMO
Four new prenylated acetophenone derivatives, including one acetophenone dimer [acronyrone D (1)] and three acetophenone monomers [acronyrones E-G (2-4)], along with seven known analogues (5-11) were obtained from the leaves of Acronychia pedunculata. Their structures and absolute configurations were established by analysis of HRMS and NMR data, single crystal X-ray diffraction studies and quantum chemical calculations. In addition, the isolates were tested for their anti-proliferative acivity against HCT-116, RKO and SW480 cancer cell lines. Remarkably, compound 5 exhibited significant anti-proliferative effects on the three cell lines, with IC50 values ranging from 0.24 to 5.3 µM.
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The constitutive photomorphogenesis 9 (COP9) signalosome (CSN) typically composing of eight subunits (CSN1-8) mediates the process of deneddylation and deubiquitination. The fifth subunit of COP9 signalosome, CSN5, has special characteristics compared with the other seven subunits, and plays vital roles in the deneddylation activity and diverse cellular processes. However, the role of CSN5 in antiviral immunity is not clear. In this study, we identified 8 subunits (CSN1-8) of COP9 signalosome in shrimp Marsupenaeus japonicus. CSN1-6 were existed in all tested tissues, but CSN7-CSN8 were not detected in hepatopancreas. After WSSV challenged, the expression level of Csn1 to Csn4, and Csn6 to Csn8 were highly decreased, but the expression level of Csn5 was conspicuously increased in shrimp challenged by white spot syndrome virus (WSSV). The CSN5 was recombinantly expressed in Escherichia coli and its polyclonal antibody was prepared. The expression level of CSN5 was conspicuously increased at RNA and protein levels in the shrimp challenged by WSSV. After knockdown of Csn5 by RNA interference, the WSSV replication was obviously increased in shrimp. When injected the recombinant protein of CSN5 with the membrane penetrating peptide into shrimp, WSSV replication was inhibited and the survival rate of shrimp was significantly improved compared with control. We further analyzed the expression of antimicrobial peptides (AMPs) in Csn5-RNAi shrimp, and the results showed that the expression of several AMPs was declined significantly. These results indicate that CSN5 inhibits replication of WSSV via regulating expression of AMPs in shrimp, and the recombinant CSN5 might be used in shrimp aquaculture for the white spot syndrome disease control.
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Proteínas de Artrópodes , Complexo do Signalossomo COP9 , Imunidade Inata , Penaeidae , Vírus da Síndrome da Mancha Branca 1 , Animais , Penaeidae/genética , Penaeidae/imunologia , Complexo do Signalossomo COP9/genética , Complexo do Signalossomo COP9/imunologia , Vírus da Síndrome da Mancha Branca 1/fisiologia , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Proteínas de Artrópodes/química , Imunidade Inata/genética , Regulação da Expressão Gênica/imunologia , Perfilação da Expressão Gênica/veterinária , Alinhamento de Sequência/veterinária , FilogeniaRESUMO
BACKGROUND: The back-projection strategies such as confidence weighting (CW) and most likely annihilation position (MLAP) have been adopted into back-projection-and-filtering-like (BPF-like) deep reconstruction model and shown great potential on fast and accurate PET reconstruction. Although the two methods degenerate to an identical model at the time resolution of 0 ps, they represent two distinct approaches at the realistic time resolutions of current commercial systems. There is a lack of a systematic and fair assessment on these differences. PURPOSE: This work aims to analyze the impact of back-projection variants on CNN-based PET image reconstruction to find the most effective back-projection model, and ultimately contribute to accurate PET reconstruction. METHODS: Different back-projection strategies (CW and MLAP) and different angular view processing methods (view-summed and view-grouped) were considered, leading to the comparison of four back-projection variants integrated with the same CNN filtration model. Meanwhile, we investigated two strategies of physical effect compensation, either introducing pre-corrected data as the input or adding a channel of attenuation map to the CNN model. After training models separately on Monte-Carlo-simulated BrainWeb phantoms with full dose (events = 3×107), we tested them on both simulated phantoms and clinical brain scans with two dosage levels. For the performance assessment, peak signal-to-noise ratio (PSNR) and root mean square error (RMSE) were used to evaluate the pixel-wise error, structural similarity index (SSIM) to evaluate the structural similarity, and contrast recovery coefficient (CRC) in manually selected ROI to compare the region recovery. RESULTS: Compared to two MLAP-based histo-image reconstruction models, two CW-based back-projected image methods produced clearer, sharper, and more detailed images, from both simulated and clinical data. For angular view processing methods, view-grouped histo-image improved image quality, while view-grouped cwbp-image showed no advantage except for contrast recovery. Quantitative analysis on simulated data demonstrated that the view-summed cwbp-image model achieved the best PSNR, RMSE, SSIM, while the 8-view cwbp-image model achieved the best CRC in lesions and the white matter. Additionally, the multi-channel input model including the back-projection image and attenuation map was proved to be the most efficient and simplest method for compensating for physical effects for brain data. Applying Gaussian blur to the histo-image yielded images with limited improvement. All above results hold for both the half-dose and the full-dose cases. CONCLUSION: For brain imaging, the evaluation based on metrics PSNR, RMSE, SSIM, and CRC indicates that the view-summed CW-based back-projection variant is the most effective input for the BPF-like reconstruction model using CNN filtration, which can involve the attenuation map through an additional channel to effectively compensate for physical effects.
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We study the excitations of dark solitons in a nonlinear optical fiber with the second- and fourth-order dispersion, and find the emergence of striped dark solitons (SDSs) and some multi-dark-soliton bound states. The SDSs can exhibit time-domain oscillating structures on a plane wave, and they have two types: the ones with or without the total phase step, while the multi-dark-soliton bound states exhibit different numbers of amplitude humps. By the modified linear stability analysis, we regard the SDSs as the results of the competition between periodicity and localization, and analytically give their existence condition, oscillation frequency, and propagation stability, which show good agreements with numerical results. We also provide a possible interpretation of the formation of the existing striped bright solitons (SBSs), and find that SBS will become the pure-quartic soliton when its periodicity and localization carry equal weight. Our results provide the theoretical support for the experimental observation of striped solitons in nonlinear fibers, and our method can also guide the discovery of striped solitons in other physical systems.
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INTRODUCTION: The clinical symptoms of Lumbar Disc Herniation (LDH) can be effectively ameliorated through Lever Positioning Manipulation (LPM), which is closely linked to the brain's pain-regulating mechanisms. Magnetic Resonance Imaging (MRI) offers an objective and visual means to study how the brain orchestrates the characteristics of analgesic effects. From the perspective of multimodal MRI, we applied functional MRI (fMRI) and Magnetic Resonance Spectrum (MRS) techniques to comprehensively evaluate the characteristics of the effects of LPM on the brain region of LDH from the aspects of brain structure, brain function and brain metabolism. This multimodal MRI technique provides a biological basis for the clinical application of LPM in LDH. METHODS AND ANALYSIS: A total of 60 LDH patients and 30 healthy controls, matched by gender, age, and years of education, will be enrolled in this study. The LDH patients will be divided into two groups (Group 1, n = 30; Group 2, n = 30) using a random number table method. Group 1 will receive LPM treatment once every two days, for a total of 12 times over 4 weeks. Group 2 will receive sham LPM treatment during the same period as Group 1. All 30 healthy controls will be divided into Group 3. Multimodal MRI will be performed on Group 1 and Group 2 at three time points (TPs): before LPM (TP1), after one LPM session (TP2), and after a full course of LPM treatment. The healthy controls (Group 3) will not undergo LPM and will be subject to only a single multimodal MRI scan. Participants in both Group 1 and Group 2 will be required to complete clinical questionnaires. These assessments will focus on pain intensity and functional disorders, using the Visual Analog Scale (VAS) and the Japanese Orthopaedic Association (JOA) scoring systems, respectively. DISCUSSION: The purpose of this study is to investigate the multimodal brain response characteristics of LDH patients after treatment with LPM, with the goal of providing a biological basis for clinical applications. TRIAL REGISTRATION NUMBER: https://clinicaltrials.gov/ct2/show/NCT05613179 , identifier: NCT05613179.
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Encéfalo , Deslocamento do Disco Intervertebral , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Deslocamento do Disco Intervertebral/terapia , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Adulto , Masculino , Feminino , Encéfalo/diagnóstico por imagem , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Adulto Jovem , Degeneração do Disco IntervertebralRESUMO
BACKGROUND: Neoadjuvant chemotherapy (NACT) is routinely used to treat patients with advanced gastric cancer (AGC). However, the identification of reliable markers to determine which AGC patients would benefit from NACT remains challenging. METHODS: A systematic screening of plasma proteins between NACT-sensitive and NACT-resistant AGC patients was performed by a mass spectrometer (n = 6). The effect of the most differential plasma protein was validated in two independent cohorts with AGC patients undergoing NACT (ELISA cohort: n = 155; Validated cohort: n = 203). The expression of this candidate was examined in a cohort of AGC tissues using immunohistochemistry (n = 34). The mechanism of this candidate on 5-Fluorouracil (5-FU) resistance was explored by cell-biology experiments in vitro and vivo. RESULTS: A series of differential plasma proteins between NACT-sensitive and NACT-resistant AGC patients was identified. Among them, plasma HIST1H2BK was validated as a significant biomarker for predicting NACT response and prognosis. Moreover, HIST1H2BK was over-expression in NACT-resistant tissues compared to NACT-sensitive tissues in AGC. Mechanistically, HIST1H2BK inhibited 5-FU-induced apoptosis by upregulating A2M transcription and then activating LRP/PI3K/Akt pathway, thereby promoting 5-FU resistance in GC cells. Intriguingly, HIST1H2BK-overexpressing 5-FU-resistant GC cells propagated resistance to 5-FU-sensitive GC cells through the secretion of HIST1H2BK. CONCLUSION: This study highlights significant differences in plasma protein profiles between NACT-resistant and NACT-sensitive AGC patients. Plasma HIST1H2BK emerged as an effective biomarker for achieving more accurate NACT in AGC. The mechanism of intracellular and secreted HIST1H2BK on 5-FU resistance provided a novel insight into chemoresistance in AGC.
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The cellular endosomal sorting complex required for transport (ESCRT) system comprises five distinct components and is involved in many different physiological processes. Recent studies have shown that different viruses rely upon the host ESCRT system for viral infection. However, whether this system is involved in white spot syndrome virus (WSSV) infection remains unclear. Here, we identified 24 homologs of ESCRT subunits in kuruma shrimp, Marsupenaeus japonicus, and found that some key components were strongly upregulated in shrimp after WSSV infection. Knockdown of key components of the ESCRT system using RNA interference inhibited virus replication, suggesting that the ESCRT system is beneficial for WSSV infection. We further focused on TSG101, a crucial member of the ESCRT-I family that plays a central role in recognizing cargo and activating the ESCRT-II and ESCRT-III complexes. TSG101 colocalized with WSSV in hemocytes. The addition of N16 (a TSG101 inhibitor) markedly decreased WSSV replication. TSG101 and ALIX of the ESCRT system interact with WSSV envelope proteins. The host proteins TSG101, RAB5, and RAB7, the viral protein VP28, and DNA were detected in endosomes isolated from hemocytes of WSSV-infected shrimp. Knockdown of Rab5 and Rab7 expression reduced viral replication. Taken together, these results suggest that the ESCRT system is hijacked by WSSV for transport through the early to late endosome pathway. Our work identified a novel requirement for the intracellular trafficking and infection of WSSV, and provided novel therapeutic targets for the prevention and control of WSSV in shrimp aquaculture. IMPORTANCE: Viruses utilize the ESCRT machinery in a variety of strategies for their replication and infection. This study revealed that the interaction of ESCRT complexes with WSSV envelope proteins plays a crucial role in WSSV infection in shrimp. The ESCRT system is conserved in the shrimp Marsupenaeus japonicus, and 24 homologs of the ESCRT system were identified in the shrimp. WSSV exploits the ESCRT system for transport and propagation via the interaction of envelope proteins with host TSG101 and ALIX in an endosome pathway-dependent manner. Understanding the underlying mechanisms of WSSV infection is important for disease control and breeding in shrimp aquaculture.