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Background: Hepatocellular carcinoma accounts for 80% of primary liver cancers, is the most common primary liver malignancy. Hepatocellular carcinoma is the third leading cause of tumor-related deaths worldwide, with a 5-year survival rate of approximately 18%. Chemotherapy, although commonly used for hepatocellular carcinoma treatment, is limited by systemic toxicity and drug resistance. Improving targeted delivery of chemotherapy drugs to tumor cells without causing systemic side effects is a current research focus. Chitosan, a biopolymer derived from chitin, possesses good biocompatibility and biodegradability, making it suitable for drug delivery. Enhanced chitosan formulations retain the anti-tumor properties while improving stability. Chitosan-based biomaterials promote hepatocellular carcinoma apoptosis, exhibit antioxidant and anti-inflammatory effects, inhibit tumor angiogenesis, and improve extracellular matrix remodeling for enhanced anti-tumor therapy. Methods: We summarized published experimental papers by querying them. Results and Conclusions: This review discusses the physicochemical properties of chitosan, its application in hepatocellular carcinoma treatment, and the challenges faced by chitosan-based biomaterials.
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BACKGROUND: Cirrhosis leads to portal hypertension (PHT), affecting survival with limited treatment options. This study investigated Imperatorin (IMP), a furanocoumarin with anti-inflammatory and hypotensive properties, for its therapeutic role and mechanisms in cirrhotic PHT. METHODS: Hepatic stellate cells (HSCs) inhibition by IMP was evaluated using LX-2 cell line. Rat cirrhosis was induced via CCl4 for 16 weeks. Experimental group were orally administered IMP (15/25 mg/kg/day) for 4 weeks. We subsequently examined portal pressure (PP), cirrhosis, inflammation, angiogenesis, and vascular remodeling. Network pharmacology was employed for mechanistic insights. RESULTS: IMP significantly inhibited the fibrogenesis in HSCs and suppressed cell viability. CCl4 exposure induced cirrhosis, inflammation, angiogenesis, vascular remodeling and PHT. IMP significantly reduced PP from 22.85 ± 3.88 mmHg to 6.67 ± 0.6 mmHg, diminished collagen deposition and pro-fibrotic factor expression, alleviated inflammation, and improved liver function. Vessel wall thickness in superior mesenteric arteries was restored, and intra-/extrahepatic angiogenesis was inhibited via VEGF and vWF. Furthermore, IMP induced sinusoidal vasodilation by upregulating eNOS and GCH1. Enrichment analysis indicated that IMP was involved in various biological processes associated with cirrhosis, such as the regulation of blood pressure, tissue remodeling, response to inflammation, and regulation of angiogenesis, etc. Additionally, IMP suppressed hepatic expression of TGF-ß both in vitro and in vivo, which was further supported by KEGG analysis. CONCLUSION: Our research demonstrated that IMP significantly mitigated cirrhosis PHT by reducing hepatic fibrosis and inflammation, curbing angiogenesis and vascular remodeling, and promoting vasodilation. This protective mechanism appears to be facilitated through the downregulation of TGF-ß.
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Tetracloreto de Carbono , Furocumarinas , Células Estreladas do Fígado , Hipertensão Portal , Cirrose Hepática , Remodelação Vascular , Furocumarinas/farmacologia , Furocumarinas/uso terapêutico , Animais , Hipertensão Portal/tratamento farmacológico , Hipertensão Portal/fisiopatologia , Remodelação Vascular/efeitos dos fármacos , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Masculino , Ratos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Cirrose Hepática/metabolismo , Cirrose Hepática/induzido quimicamente , Humanos , Ratos Sprague-Dawley , Linhagem Celular , Transdução de Sinais/efeitos dos fármacos , Farmacologia em Rede , Neovascularização Patológica/tratamento farmacológico , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo , Fígado/irrigação sanguíneaRESUMO
Constructing highly efficient electrocatalysts is vital to enhance oxygen evolution reaction (OER) performance at industrially relevant current densities. Herein, three-phase coupled Ni3S2/r-NiS/h-NiS composites are grown in situ on Ni foam (NNSN/NF) via a one-step solvothermal approach. The as-prepared composites need overpotentials of only 377 mV, 451 mV and 476 mV at 1000 mA cm-2 for the OER in alkaline freshwater, simulated seawater and seawater, respectively. In addition, the optimized catalyst exhibited long-term durability at 300 mA cm-2. Our work clarifies designing and preparing cost-effective Ni-based sulfide electrocatalysts for the OER in alkaline freshwater/simulated seawater/seawater under industrially relevant current densities.
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AIM: Esophageal cancer is a disease with high morbidity and mortality, exploring effective treatment methods is the key to the treatment of this disease. This study aims to compare the clinical efficacy and safety of multi-band mucosectomy (MBM) and endoscopic submucosal dissection (ESD) in the treatment of single early esophageal cancer (EEC) and precancerous lesions, and whether MBM can achieve better clinical effect as an effective treatment method. METHODS: The clinical data of 70 patients with EEC and precancerous lesions who were treated with MBM and ESD in the Fourth Affiliated Hospital of China Medical University from May 2021 to May 2023 and could be followed up were retrospectively analyzed. They were divided into two groups according to different treatment methods: MBM group (31 cases) and ESD group (39 cases). The general data, perioperative conditions, endoscopic treatment effect and pathological results of the two groups were compared. RESULTS: The duration of endoscopic treatment in MBM group was shorter than that in ESD group [36 (25~39) min vs 46 (41~57) min, p < 0.05], and there was no significant difference in the intraoperative bleeding rate between the two groups (12.90% vs 7.69%, p > 0.05). There was no significant difference in the rate of intraoperative perforation between the two groups (3.23% vs 7.69%, p > 0.05), and the hospitalization time in MBM group was shorter than that in ESD group [5 (4~7) days vs 8 (7~12) days, p < 0.05]. The hospitalization cost was less [2535 (2423~2786) dollars vs 4485 (3858~5794) dollars, p < 0.05]. No postoperative bleeding occurred in both groups. There was no statistically significant difference in postoperative stenosis rate between MBM group and ESD group (3.23% vs 12.82%, p > 0.05), and no statistically significant difference in postoperative local recurrence rate (12.90% vs 5.13%, p > 0.05). There was no significant difference in the rate of additional surgery (9.68% vs 2.56%, p > 0.05). The en bloc resection rate of MBM group was lower than that of ESD group (77.42% vs 97.44%, p < 0.05), but there was no significant difference in the complete resection rate between the two groups (87.10% vs 97.44%, p > 0.05). The postoperative pathological results of MBM group showed 13 cases of low-grade intraepithelial neoplasia (LGIN), 11 cases of high-grade intraepithelial neoplasia (HGIN), and 7 cases of canceration, while the postoperative pathological results of ESD group showed 10 cases of LGIN, 14 cases of HGIN, and 15 cases of canceration, with no statistical significance (p > 0.05). CONCLUSIONS: MBM and ESD are effective methods for the treatment of EEC and precancerous lesions. MBM has the advantages of short hospital stay, quick recovery and low cost. However, compared with MBM, ESD can improve the complete resection rate of the lesion, avoid the occurrence of positive incisal margin, and reduce the risk of secondary treatment and additional surgery.
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Ressecção Endoscópica de Mucosa , Neoplasias Esofágicas , Lesões Pré-Cancerosas , Humanos , Neoplasias Esofágicas/cirurgia , Lesões Pré-Cancerosas/cirurgia , Estudos Retrospectivos , Masculino , Feminino , Ressecção Endoscópica de Mucosa/métodos , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Esofagoscopia/métodosRESUMO
Lactation mastitis is a debilitating inflammatory mammary disease in postpartum animals. Myeloid differentiation primary response protein MyD88 is the key downstream adapter for innate pattern recognition receptor toll-like receptor 4 (TLR4), which plays an important role in inflammation. However, the specific role of MyD88 in mammary epithelial cells in the progression of mastitis has not been investigated. In this study, lipopolysaccharide (LPS)-induced mouse mastitis model was used and cytokines such as Tnf-α, Il-1ß, Il-6, Cxcl1, Cxcl2 and Ccl2 were significantly increased in inflammatory mammary gland as shown by real time-qPCR. However, the mice with MyD88-deficienet in mammary epithelial cells (cKO) showed a reduction in the expression of Tnf-α, Il-1ß, Il-6, Cxcl1 and Cxcl2 in mammary gland compared with control mice, when subjected to LPS induced mastitis. Immunohistochemical staining of cleaved caspase-3 showed that the cell apoptosis induced by inflammation were decreased in MyD88 cKO mice. Furthermore, there were significantly fewer infiltrating inflammatory cells in alveolar lumen of MyD88 cKO mice, including Ly6G-positive neutrophils and F4/80-positive macrophages. RNA-seq in LPS treated mammary glands showed that MyD88 cKO mice had significantly downregulated inflammation-related genes and upregulated genes related to anti-inflammation processes and lipid metabolism compared with control mice. Thus, these results demonstrate that MyD88 in mammary epithelial cells is essential for mastitis progression. And this study not only has important implications for understanding the innate immune response in mammary epithelial cells, but also potentially helps the development of new therapeutic drugs for treating mastitis.
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This study aimed to investigate the impact of different strains of Lactiplantibacillus plantarum on malolactic fermentation (MLF), antioxidant activity, and aroma of ciders. A commercial strain of Saccharomyces cerevisiae and six indigenous L. plantarum strains were co-inoculated into apple juice to induce simultaneous alcoholic fermentation (AF) and MLF. The findings indicated that despite belonging to the same species, the different L. plantarum strains significantly differed (p < 0.05) in terms of antioxidant activity and aroma compounds in the ciders. MLF induced by L. plantarum resulted in the substantial consumption of malic acid and increased levels of lactic acid in the ciders, with strain-specific effects observed, particularly with L. plantarum SCFF284. In addition, ciders produced from mixed fermentations exhibited higher levels of antioxidant activity than those from pure S. cerevisiae fermentation (p < 0.05), especially for LAM284. Furthermore, ciders produced from mixed fermentations exhibited higher levels of aroma compounds, such as ethyl acetate and isoamyl alcohol, and also received higher sensory scores compared to ciders produced through pure S. cerevisiae fermentation (p < 0.05). These results highlight the effectiveness of MLF induced by L. plantarum in enhancing the antioxidant activity and aroma profile of ciders.
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BACKGROUND AND AIM: The compliance and timeliness of oral laxatives have always been the key factors restricting bowel preparation (BP). We have constructed a novel enhanced-educational content and process based on social software (SS) for BP to optimize these issues. METHODS: A multicenter, prospective, randomized controlled study was conducted at 13 hospitals in China from December 2019 to December 2020. A total of 1774 enrollees received standard instructions for BP and were randomly assigned (1:1) to the SS group (SSG) that received a smartphone-based enhanced-education strategy starting 4 h before colonoscopy or the control group (CG). RESULTS: A total of 3034 consecutive outpatient colonoscopy patients were assessed for eligibility, and 1774 were enrolled and randomly assigned. Ultimately, data from 1747 (SSG vs CG: 875 vs 872) enrollees were collected. The BP adequacy rate was 92.22% (95% CI: 90.46-93.98) in the SSG vs 88.05% (95% CI: 85.91-90.18) in the CG (P = 0.005), and the total Boston Bowel Preparation Scale scores (6.89 ± 1.15 vs 6.67 ± 1.15, P < 0.001) of those in the SSG were significantly higher than those in the CG. The average number of polyps detected in the SSG was considerably higher than that in the CG (0.84 ± 2.00 vs 0.53 ± 1.19, P = 0.037), and the average diameter of the polyps was significantly lower than that of the control group (4.0 ± 2.5 vs 4.9 ± 3.7, P < 0.001). CONCLUSIONS: This SS-enhanced education strategy can improve the BP adequacy rate and increase the average number of polyps detected, especially those of small diameter.
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Hazardous lead ions (Pb2+) even at a minute level can pose side effects on human health, highlighting the need for tools for trace Pb2+ detection. Herein, we present a DNAzyme-activated CRISPR assay (termed DzCas12T) for sensitive and one-pot detection of lead contamination. Using an extension-bridged strategy eliminates the need for separation to couple the DNAzyme recognition and CRISPR reporting processes. The tandem design endowed the DzCas12T assay with high specificity and sensitivity down to the pM-level. This assay has been used to detect lead contamination in food and water samples, indicating the potential for monitoring lead-associated environmental and food safety.
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Sistemas CRISPR-Cas , DNA Catalítico , Chumbo , DNA Catalítico/química , DNA Catalítico/metabolismo , Chumbo/análise , Sistemas CRISPR-Cas/genética , Técnicas Biossensoriais , Limite de Detecção , Contaminação de Alimentos/análise , Poluentes Químicos da Água/análiseRESUMO
Stress granules (SGs) are membraneless ribonucleoprotein (RNP)-based cellular foci formed in response to stress, facilitating cell survival by protecting against damage. Mammalian spermatogenesis should be maintained below body temperature for proper development, indicating its vulnerability to heat stress (HS). In this study, biotin tracer permeability assays showed that the inhibition of heat-induced SG assembly in the testis by 4-8 mg/kg cycloheximide significantly increased the percentage of seminiferous tubules with a damaged blood-testis barrier (BTB). Western blot results additionally revealed that the suppression of heat-induced SG assembly in Sertoli cell line, TM4 cells, by RNA inference of G3bp1/2 aggravated the decline in the BTB-related proteins ZO-1, ß-Catenin and Claudin-11, indicating that SGs could protect the BTB against damage caused by HS. The protein components that associate with SGs in Sertoli cells were isolated by sequential centrifugation and immunoprecipitation, and were identified by liquid chromatography with tandem mass spectrometry. Gene Ontology and KEGG pathway enrichment analysis revealed that their corresponding genes were mainly involved in pathways related to proteasomes, nucleotide excision repair, mismatch repair, and DNA replication. Furthermore, a new SG component, the ubiquitin associated protein 2 (UBAP2), was found to translocate to SGs upon HS in TM4 cells by immunofluorescence. Moreover, SG assembly was significantly diminished after UBAP2 knockdown by RNA inference during HS, suggesting the important role of UBAP2 in SG assembly. In addition, UBAP2 knockdown reduced the expression of ZO-1, ß-Catenin and Claudin-11, which implied its potential role in the function of the BTB. Overall, our study demonstrated the role of SGs in maintaining BTB functions during HS and identified a new component implicated in SG formation in Sertoli cells. These findings not only offer novel insights into the biological functions of SGs and the molecular mechanism of low fertility in males in summer, but also potentially provide an experimental basis for male fertility therapies.
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Barreira Hematotesticular , DNA Helicases , Masculino , Animais , Camundongos , Proteínas de Ligação a Poli-ADP-Ribose , RNA Helicases , Proteínas com Motivo de Reconhecimento de RNA , Grânulos de Estresse , beta Catenina , RNA , Claudinas , MamíferosRESUMO
BACKGROUND: Acute pancreatitis (AP) is a clinically common acute abdominal disease, whose pathogenesis remains unclear. The severe patients usually have multiple complications and lack specific drugs, leading to a high mortality and poor outcome. Acinar cells are recognized as the initial site of AP. However, there are no precise single-cell transcriptomic profiles to decipher the landscape of acinar cells during AP, which are the missing pieces of jigsaw we aimed to complete in this study. METHODS: A single-cell sequencing dataset was used to identify the cell types in pancreas of AP mice and to depict the transcriptomic maps in acinar cells. The pathways' activities were evaluated by gene sets enrichment analysis (GSEA) and single-cell gene sets variation analysis (GSVA). Pseudotime analysis was performed to describe the development trajectories of acinar cells. We also constructed the protein-protein interaction (PPI) network and identified the hub genes. Another independent single-cell sequencing dataset of pancreas samples from AP mice and a bulk RNA sequencing dataset of peripheral blood samples from AP patients were also analyzed. RESULTS: In this study, we identified genetic markers of each cell type in the pancreas of AP mice based on single-cell sequencing datasets and analyzed the transcription changes in acinar cells. We found that acinar cells featured acinar-ductal metaplasia (ADM), as well as increased endocytosis and vesicle transport activity during AP. Notably, the endoplasmic reticulum stress (ERS) and ER-associated degradation (ERAD) pathways activated by accumulation of unfolded/misfolded proteins in acinar cells could be pivotal for the development of AP. CONCLUSION: We deciphered the distinct roadmap of acinar cells in the early stage of AP at single-cell level. ERS and ERAD pathways are crucially important for acinar homeostasis and the pathogenesis of AP.
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Pancreatite , Humanos , Camundongos , Animais , Pancreatite/genética , Células Acinares/metabolismo , RNA-Seq , Doença Aguda , Estresse do Retículo EndoplasmáticoRESUMO
BACKGROUND: The symptoms of functional constipation (FC) were obviously affected by mental symptoms, which was consistent with somatic symptoms. However, the characteristics of FC patients with somatic symptom remains unexplored. METHODS: Clinical characteristics including somatic symptom (SOM, PHQ-15), depression (PHQ-9), anxiety (GAD-7), quality of life (PAC-QOL), constipation (KESS), demographic variables, anatomical abnormalities and symptoms were investigated. Subsequent analyses encompassed the comparison of clinical parameters between patients with SOM + group (PHQ-15 ≥ 10) and SOM- group (PHQ-15 < 10), subgroup analysis, correlation analysis, and logistic regression. Lastly, we evaluated the somatic symptom severity (SSS) among FC patients subjected to various stressors. RESULTS: Notable disparities were observed between SOM + and SOM- groups in variety of physiological and psychological variables, including gender, stressful events, sleep disorders, reduced interest, GAD-7, PHQ-15, PHQ-9, PAC-QOL, anterior rectocele, KESS, and internal anal sphincter achalasia (IASA) (P < 0.05). Subgroup analysis affirmed consistent findings across mental symptoms. Correlation analyses revealed significant associations between SSS and KESS, anterior rectocele, GAD-7, PHQ-9, and PAC-QOL (P < 0.05). Logistic regression identified PHQ-9 (OR = 7.02, CI: 2.06-27.7, P = 0.003), GAD-7 (OR = 7.18, CI: 2.00-30.7, P = 0.004), and KESS (OR = 16.8, CI: 3.09-113, P = 0.002) as independent predictors of SSS. Elevated SSS scores were significantly associated with couple, parental, and work-related stressors (P < 0.05). CONCLUSION: A marked heterogeneity was observed between SOM + and SOM- patients of FC, with SOM + accompanied by more severe constipation, anxiety and depression symptoms. This finding underscores the importance of considering somatic symptoms in diagnosis and treatment of FC.
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Sintomas Inexplicáveis , Qualidade de Vida , Humanos , Qualidade de Vida/psicologia , Estudos Transversais , Retocele , Inquéritos e Questionários , Pacientes Ambulatoriais , Ansiedade/diagnóstico , Depressão/diagnóstico , Depressão/psicologia , Constipação Intestinal/diagnósticoRESUMO
The quantum supremacy experiment, such as Google Sycamore [F. Arute et al., Nature (London) 574, 505 (2019).NATUAS0028-083610.1038/s41586-019-1666-5], poses a great challenge for classical verification due to the exponentially increasing compute cost. Using a new-generation Sunway supercomputer within 8.5 d, we provide a direct verification by computing 3×10^{6} exact amplitudes for the experimentally generated bitstrings, obtaining a cross-entropy benchmarking fidelity of 0.191% (the estimated value is 0.224%). The leap of simulation capability is built on a multiple-amplitude tensor network contraction algorithm which systematically exploits the "classical advantage" (the inherent "store-and-compute" operation mode of von Neumann machines) of current supercomputers, and a fused tensor network contraction algorithm which drastically increases the compute efficiency on heterogeneous architectures. Our method has a far-reaching impact in solving quantum many-body problems, statistical problems, as well as combinatorial optimization problems.
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In this study, we aimed to assess the analgesic efficacy of a thermoresponsive polymeric dexamethasone (Dex) prodrug (ProGel-Dex) in a mouse model of osteoarthritis (OA). At 12 weeks post model establishment, the OA mice received a single intra-articular (IA) injection of ProGel-Dex, dose-equivalent Dex, or Saline. Comparing to Saline and Dex controls, ProGel-Dex provided complete and sustained pain relief for >15 weeks according to incapacitance tests. In vivo optical imaging confirmed the continuous presence of ProGel-Dex in joints for 15 weeks post-injection. According to micro-CT analysis, ProGel-Dex treated mice had significantly lower subchondral bone thickness and medial meniscus bone volume than Dex and Saline controls. Except for a transient delay of body weight increase and slightly lower endpoint liver and spleen weights, no other adverse effect was observed after ProGel-Dex treatment. These findings support ProGel-Dex's potential as a potent and safe analgesic candidate for management of OA pain.
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Osteoartrite , Pró-Fármacos , Camundongos , Animais , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Modelos Animais de Doenças , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Osteoartrite/tratamento farmacológico , Artralgia/induzido quimicamente , Artralgia/tratamento farmacológico , Analgésicos/farmacologia , Analgésicos/uso terapêuticoRESUMO
Background: To determine the effect of different sterilization methods on shelf life and physicochemical parameters of fermented pork jerky. Methods: Various sterilization techniques, including boiling, pasteurization, medium-temperature steam sterilization, high-temperature steam sterilization, ultrasonic sterilization, and ultraviolet sterilization, were employed in this study to treat vacuum-sealed fermented pork jerky. Changes in microbial populations, physicochemical parameters, and sensory evaluations were monitored throughout the storage period. Results: The results indicated the presence of Staphylococcus aureus on the 24th, 21st, 33rd, 24th, 18th, and 15th days in pork jerky subjected to boiling (100°C, 20 min), pasteurization (85°C, 15 min), medium-temperature steam sterilization (105°C, 0.5 Pa, 30 min), high-temperature steam sterilization (121°C, 1.0 Pa, 20 min), ultrasonic sterilization (480 W, 30 kHz, 30 min), and ultraviolet sterilization (254 nm, 100 W/m2, 60 min), respectively. Coliforms, salmonella, and Shigella were not detected in any group during storage. The medium-temperature steam sterilization method yielded the most favorable microbiological results, with an aerobic plate count of less than 1.0 lg CFU/g. However, other physicochemical parameters and sensory evaluations were moderate, with total volatile basic nitrogen (TVB-N) and thiobarbituric acid reactive substances (TBARS) measuring 14.023 mg N/100 g and 0.427 mg MDA/kg, respectively, remaining within acceptable limits. Conclusion: Therefore, considering microbiological indicators as the primary determinant of shelf life and taking into account other physicochemical parameters, the medium-temperature steam sterilization method was identified as the most suitable approach for extending the shelf life of fermented pork jerky while preserving its flavor.
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Objective: To evaluate the long-term inhibition of malignant biliary tumor growth using paclitaxel (PTX)-covered polycaprolactone (PCL) electrospun membranes. Methods: A mixture of PCL, a material used to fabricate polymer stents, and PTX, a widely used chemotherapeutic agent, was synthesized by electrospinning. After preparing the drug-eluting membrane, drug release and fiber degradation were assessed in vitro under different pH conditions. The QBC939 cholangiocarcinoma cell line was cultured to establish a xenograft nude mouse model. Finally, the drug-eluting membrane was implanted into the mouse model, and the relative tumor inhibition rate was evaluated. Results: A new PTX-loaded PCL electrospun fiber membrane was developed. The drug release rate was about 20-40% in the 32-day release cycle, and the release quantity was between 20 and 170 mg. As pH decreased, the release rate increased significantly. The degradation rate of the fiber membranes in vitro was approximately 20-48%, and was positively correlated with the drug loading rate. In animal experiments, the growth of tumors in mice was suppressed using drug-eluting membranes. Conclusion: The PTX-loaded PCL electrospun fiber membrane enhanced the long-term drug release and exhibited excellent antitumor effects in vivo.
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The expression of defensive responses to alerting sensory cues requires both general arousal and a specific arousal state associated with defensive emotions. However, it remains unclear whether these two forms of arousal can be regulated by common brain regions. We discovered that the medial sector of the auditory thalamus (ATm) in mice is a thalamic hub controlling both general and defensive arousal. The spontaneous activity of VGluT2-expressing ATm (ATmVGluT2+) neurons was correlated with and causally contributed to wakefulness. In sleeping mice, sustained ATmVGluT2+ population responses were predictive of sensory-induced arousal, the likelihood of which was markedly decreased by inhibiting ATmVGluT2+ neurons or multiple downstream pathways. In awake mice, ATmVGluT2+ activation led to heightened arousal accompanied by excessive anxiety and avoidance behavior. Notably, blocking their neurotransmission abolished alerting stimuli-induced defensive behaviors. These findings may shed light on the comorbidity of sleep disturbances and abnormal sensory sensitivity in specific brain disorders.
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Nível de Alerta , Tálamo , Camundongos , Animais , Nível de Alerta/fisiologia , Tálamo/fisiologia , Vigília/fisiologia , Neurônios/fisiologia , Transmissão SinápticaRESUMO
BACKGROUND: Artificial intelligence (AI) performed variously among test sets with different diversity due to sample selection bias, which can be stumbling block for AI applications. We previously tested AI named ENDOANGEL, diagnosing early gastric cancer (EGC) on single-center videos in man-machine competition. We aimed to re-test ENDOANGEL on multi-center videos to explore challenges applying AI in multiple centers, then upgrade ENDOANGEL and explore solutions to the challenge. METHODS: ENDOANGEL was re-tested on multi-center videos retrospectively collected from 12 institutions and compared with performance in previously reported single-center videos. We then upgraded ENDOANGEL to ENDOANGEL-2022 with more training samples and novel algorithms and conducted competition between ENDOANGEL-2022 and endoscopists. ENDOANGEL-2022 was then tested on single-center videos and compared with performance in multi-center videos; the two AI systems were also compared with each other and endoscopists. RESULTS: Forty-six EGCs and 54 non-cancers were included in multi-center video cohort. On diagnosing EGCs, compared with single-center videos, ENDOANGEL showed stable sensitivity (97.83% vs. 100.00%) while sharply decreased specificity (61.11% vs. 82.54%); ENDOANGEL-2022 showed similar tendency while achieving significantly higher specificity (79.63%, p < 0.01) making fewer mistakes on typical lesions than ENDOANGEL. On detecting gastric neoplasms, both AI showed stable sensitivity while sharply decreased specificity. Nevertheless, both AI outperformed endoscopists in the two competitions. CONCLUSIONS: Great increase of false positives is a prominent challenge for applying EGC diagnostic AI in multiple centers due to high heterogeneity of negative cases. Optimizing AI by adding samples and using novel algorithms is promising to overcome this challenge.
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Inteligência Artificial , Neoplasias Gástricas , Humanos , Algoritmos , Projetos de Pesquisa , Estudos Retrospectivos , Neoplasias Gástricas/diagnósticoRESUMO
Background: The fundus of the stomach is a challenging region for endoscopic resection of gastrointestinal stromal tumors (GISTs), especially in the anterior wall of the fornix at the side of the greater curvature. This study aimed to introduce the Forward-Return Way (FRW) technique in gastric fundus operations and provide evidence of its advantages. The FRW technique allows the gastroscope to access the stomach fornix without entering the gastric antrum after passing through the gastric cardia. Using FRW, the gastroscope body makes a forward return along the wall of the posterior wall of the upper gastric body and the wall of the greater curvature. Methods: The clinical data of patients with stromal tumors in muscularis propria at the gastric fundus (STMF) at the Fourth Hospital of China Medical University between May 2020- March 2021 were reviewed. The novel FRW technique was used in the procedures, and the beneficial effects, suitability, applicable lesion site, and success rates of FRW were analyzed. Results: A total of 10 cases were reviewed, and the FRW technique was successfully performed in 7 cases (70%). The gastroscope's tip reached the area just below the gastric cardia, allowing endoscopists to successfully access all angles and sites of the stomach's fundus in all seven patients. The lesion was easily accessed, and the gastroscope was stable with good left-right and forward-backwards movements. Conclusion: The FRW technique significantly facilitates the resection of the GISTs by aligning the endoscopy body movement direction with the observation direction. Gastrointestinal Stromal Tumor; forward-return of gastroscopy along the gastric body wall; muscularis propria; gastric fundus.
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Holistic understanding of physio-pathological processes requires noninvasive 3D imaging in deep tissue across multiple spatial and temporal scales to link diverse transient subcellular behaviors with long-term physiogenesis. Despite broad applications of two-photon microscopy (TPM), there remains an inevitable tradeoff among spatiotemporal resolution, imaging volumes, and durations due to the point-scanning scheme, accumulated phototoxicity, and optical aberrations. Here, we harnessed the concept of synthetic aperture radar in TPM to achieve aberration-corrected 3D imaging of subcellular dynamics at a millisecond scale for over 100,000 large volumes in deep tissue, with three orders of magnitude reduction in photobleaching. With its advantages, we identified direct intercellular communications through migrasome generation following traumatic brain injury, visualized the formation process of germinal center in the mouse lymph node, and characterized heterogeneous cellular states in the mouse visual cortex, opening up a horizon for intravital imaging to understand the organizations and functions of biological systems at a holistic level.
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Imageamento Tridimensional , Animais , Camundongos , Imageamento Tridimensional/métodos , Microscopia Confocal/métodosRESUMO
Transition metal sulfides (TMSs) are considered as one of the promising electrode materials due to their fascinating redox reversibility and electronic conductivity. However, volume expansion during the charge/discharge process impedes their practical applications. The reasonable design of TMS electrode materials with unique morphology can improve the energy storage performance. Herein, we prepared the Ni3S2/Co9S8/NiS composite that is in situ grown on Ni foam (NF) via a one-step electrodeposition process. The optimized Ni3S2/Co9S8/NiS-7 shows a superhigh specific capacity of 2785.3 F g-1 at 1 A g-1 and remarkable rate capability. Furthermore, the as-assembled device displays a high energy density of 40.1 W h kg-1 at a power density of 799.3 W kg-1 and a satisfactory stability of 96.6% retention after 5000 cycles. This work provides a facile way to fabricate new TMS electrode materials for high-performance supercapacitors.