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Wavefront shaping allows focusing light through or inside strongly scattering media, but the background intensity also increases which reduces the target's contrast. By combining transmission or deposition matrices for different regions, we construct joint operators to achieve spatially resolved control of light in diffusive systems. The eigenmode of a contrast operator can maximize the power contrast between a target and its surrounding. A difference operator enhances the power delivery to a target while avoiding the background increase. This work opens the door to coherent control of nonlocal effects in wave transport for practical applications.
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BACKGROUND: Sildenafil (SIL) is regarded as an illegal adulterant in functional foods. Some functional foods doped with SIL have posed significant concern about their safety risks. However, the facile colorimetric detection of SIL is rarely investigated. RESULTS: Herein, we prepared a monodispersed spherical composite nanozyme (Fe3O4-NH2/GONRs), possessing excellent peroxidase-like (POD-like) and catalase-like (CAT-like) activities and strong superparamagnetic property. The enzyme-like activities of Fe3O4-NH2/GONRs can be selectively inhibited by SIL due to the synergistic effect of hydrogen bonds and π-π stacking between Fe3O4-NH2/GONRs and SIL. Leveraging this mechanism, a highly sensitive and selective colorimetric detection for SIL with a detection limit (LOD) of 0.26 ng/mL was developed. In addition, we prepared a three-dimensional paper-based analytical device (3D-PAD) for SIL colorimetric detection with naked-eyes and the semi-quantitative analysis with a LOD of 88 ng/mL. SIGNIFICANCE: The proposed colorimetric and PAD detections demonstrated the advantages of low-cost, highly sensitive and selective, thus have promise application potential in the rapid detection of adulterated functional foods.
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Colorimetria , Alimento Funcional , Grafite , Limite de Detecção , Papel , Citrato de Sildenafila , Citrato de Sildenafila/análise , Citrato de Sildenafila/química , Colorimetria/métodos , Grafite/química , Alimento Funcional/análise , Contaminação de Alimentos/análiseRESUMO
Chromoplasts are specialized plastids in plants involved in carotenoid synthesis, accumulation, and stress resistance. In tomatoes (Solanum lycopersicum), the Chromoplast-associated carotenoid binding protein (CHRC) regulates chromoplast development and carotenoid accumulation, although its precise mechanisms are not yet fully understood. To investigate the role of SlCHRC in carotenoid biosynthesis, we generated transgenic tomatoes using overexpression (oe-SlCHRC) and CRISPR/Cas9-mediated gene editing (cr-SlCHRC) techniques. The results demonstrated inhibited fruit ripening and delayed onset of color break in both transgenic lines. The oe-SlCHRC lines exhibited increased carotenoid accumulation, particularly (E/Z)-phytoene, lycopene, and γ-carotene, with abundant plastoglobules and carotenoid crystals observed via TEM. In contrast, cr-SlCHRC mutants showed a greener phenotype, reduced carotenoid content, and fewer plastoglobules at the BK + 10 stage. Transcriptome analysis indicated that SlCHRC influences key genes in carotenoid biosynthesis, such as SlNCED2, as well as genes related to chloroplast development, photosynthesis, and plastoglobule formation. Additionally, SlCHRC enhances heat stress tolerance in tomato fruits by upregulating heat shock proteins (HSPs), antioxidants, and proline accumulation. These findings indicate that SlCHRC plays a crucial role in improving tomato fruit quality under heat stress conditions.
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This research aimed to assess the validity of ultrasound scans with new features in detecting fetal anal atresia and verify the effectiveness of these new features. Additionally, we aimed at investigating the perinatal incidence of anal atresia. This multicenter prospective study recruited 94,617 normal gravidas and 84 gravidas with anal atresia fetuses. The gold standard for diagnosing perinatal anal atresia is routine neonatal anus examinations. The incidence calculation was based on the results of the gold standard. The validity of our new approach was evaluated via a diagnostic test involving all 94,701 subjects. The effectiveness of our new features was assessed through an ablation study in a randomly established new dataset, with the ratio of anal atresia to non-anal atresia cases of 1:4. The annual perinatal incidence of anal atresia between 2019 and 2023 ranges from 0.57 to 1.29. Our new method performed great regarding the Youden index, diagnostic odds ratio (DOR), area under the curve (AUC) of the receiver operating characteristic curve (ROCC), AUC of the precision-recall curve (PRC), F1-score, and Cramer's V. In the ablation study, our new approach surpassed its competitors concerning Youden index, DOR, AUC of the ROCC, and AUC of the PRC. Ultrasound scans show high validity and clinical value in detecting fetal anal atresia. Our new ultrasound features significantly promote the detection of fetal anal atresia.
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Anus Imperfurado , Ultrassonografia Pré-Natal , Humanos , Feminino , Estudos Prospectivos , Ultrassonografia Pré-Natal/métodos , Gravidez , Anus Imperfurado/diagnóstico por imagem , Curva ROC , Adulto , Recém-Nascido , IncidênciaRESUMO
Optical information processing and computing can potentially offer enhanced performance, scalability and energy efficiency. However, achieving nonlinearity-a critical component of computation-remains challenging in the optical domain. Here we introduce a design that leverages a multiple-scattering cavity to passively induce optical nonlinear random mapping with a continuous-wave laser at a low power. Each scattering event effectively mixes information from different areas of a spatial light modulator, resulting in a highly nonlinear mapping between the input data and output pattern. We demonstrate that our design retains vital information even when the readout dimensionality is reduced, thereby enabling optical data compression. This capability allows our optical platforms to offer efficient optical information processing solutions across applications. We demonstrate our design's efficacy across tasks, including classification, image reconstruction, keypoint detection and object detection, all of which are achieved through optical data compression combined with a digital decoder. In particular, high performance at extreme compression ratios is observed in real-time pedestrian detection. Our findings open pathways for novel algorithms and unconventional architectural designs for optical computing.
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Breast cancer is a malignancy caused by the abnormal proliferation of breast epithelial cells, predominantly affecting female patients, and it is commonly diagnosed using histopathological images. Currently, deep learning techniques have made significant breakthroughs in medical image processing, outperforming traditional detection methods in breast cancer pathology classification tasks. This paper first reviewed the advances in applying deep learning to breast pathology images, focusing on three key areas: multi-scale feature extraction, cellular feature analysis, and classification. Next, it summarized the advantages of multimodal data fusion methods for breast pathology images. Finally, the study discussed the challenges and future prospects of deep learning in breast cancer pathology image diagnosis, providing important guidance for advancing the use of deep learning in breast diagnosis.
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Neoplasias da Mama , Mama , Aprendizado Profundo , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico , Feminino , Mama/diagnóstico por imagem , Mama/patologia , Processamento de Imagem Assistida por Computador/métodos , Interpretação de Imagem Assistida por Computador/métodosRESUMO
Topotactic reduction is critical to a wealth of phase transitions of current interest, including synthesis of the superconducting nickelate Nd0.8Sr0.2NiO2, reduced from the initial Nd0.8Sr0.2NiO3/SrTiO3 heterostructure. Due to the highly sensitive and often damaging nature of the topotactic reduction, however, only a handful of research groups have been able to reproduce the superconductivity results. A series of in situ synchrotron-based investigations reveal that this is due to the necessary formation of an initial, ultrathin layer at the Nd0.8Sr0.2NiO3 surface that helps to mediate the introduction of hydrogen into the film such that apical oxygens are first removed from the Nd0.8Sr0.2NiO3 / SrTiO3 (001) interface and delivered into the reducing environment. This allows the square-planar / perovskite interface to stabilize and propagate from the bottom to the top of the film without the formation of interphase defects. Importantly, neither geometric rotations in the square planar structure nor significant incorporation of hydrogen within the films is detected, obviating its need for superconductivity. These findings unveil the structural basis underlying the transformation pathway and provide important guidance on achieving the superconducting phase in reduced nickelate systems.
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BACKGROUND: Endometrial cancer (EC) as one of the most prevalent malignancies in the female reproductive system, usually has a poor diagnosis and unfavorable health effects. Neferine (Nef), derived from the edible and medicinal lotus seed, has been known for its functional activity; however, its anti-cancer mechanism for EC remains elusive. PURPOSE: We explored the potential anti-cancer effects and underlying molecular mechanisms of Nef on EC. METHODS: The cytotoxicity was tested using MTT, and the cell cycle, apoptosis, Ca2+ levels, and the mitochondrial membrane potential (MMP) were observed through flow cytometry. After Nef treatment, differences in miRNA expression were identified using miRNA-seq data. Furthermore, western blot and immunohistochemistry (IHC) were employed to identify the proteins associated with apoptosis in both mice and cells. RESULTS: Nef treatment led to Ishikawa cell apoptosis and blocked cell proliferation in the G2/M phase. In total, 101 significantly different miRNA (p ã 0.05 and |logFC| ã 1) were obtained and subjected to GO and KEGG enrichment analysis, which revealed the Ca2+ and PI3K/AKT signaling pathways pertaining to apoptosis. Nef treatment significantly changed intracellular Ca2+ levels and MMP, activating the endoplasmic reticulum stress (ERS) pathway and the expression of key proteins in the mitochondrial pathway. In addition, Nef also inhibited the expression of key proteins in the PI3K/AKT pathway, causing cell apoptosis. Moreover, in mouse tumor tissues, the expression of CHOP, Bcl-2, Caspase 3, Cyto-c, and p-AKT was also consistent with the results in vitro. CONCLUSION: Nef could block the cell cycle and induce the activation of the mitochondrial apoptotic pathway involving the Ca2+-mediated ERS pathway and the PI3K/AKT pathway, thereby inducing apoptosis in EC cells, confirming the potential role of Nef in the prevention and treatment of EC.
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Apoptose , Benzilisoquinolinas , Cálcio , Neoplasias do Endométrio , Estresse do Retículo Endoplasmático , MicroRNAs , Feminino , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/metabolismo , Humanos , Apoptose/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Animais , MicroRNAs/metabolismo , MicroRNAs/genética , Cálcio/metabolismo , Linhagem Celular Tumoral , Camundongos , Benzilisoquinolinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Nelumbo/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Antineoplásicos Fitogênicos/farmacologiaRESUMO
The escalating adoption of laparoscopic surgical techniques has demonstrated their capacity to yield improved clinical outcomes. However, concomitant with the advantages of this minimally invasive approach, certain adverse complications have been reported. In this report, we present a noteworthy case involving a 72-year-old male patient who underwent laparoscopic inguinal hernia repair. The surgical procedure proceeded without noteworthy complications, and the patient maintained hemodynamic stability throughout. However, the post-anesthetic recovery was compromised by the onset of subcutaneous emphysema and bilateral tension pneumothorax. Immediate intervention was imperative, prompting the performance of an emergent needle thoracostomy, subsequently followed by the implementation of a closed drainage system within the thoracic cavity. These interventions proved efficacious in mitigating the patient's distressing symptoms. Although pneumothorax complications in the context of laparoscopic surgery are infrequent, it is imperative for anesthetists to remain vigilant regarding the potential occurrence of subcutaneous emphysema and pneumothorax in the perioperative period. This case underscores the significance of meticulous perioperative monitoring and rapid intervention, particularly in laparoscopic procedures, where the insufflation of carbon dioxide into the abdominal cavity can predispose patients to these rare yet potentially life-threatening complications. Heightened awareness among healthcare providers regarding the possibility of such events is pivotal in ensuring the safety and well-being of surgical patients.
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The dynamics of tuberculosis transmission model with different genders are to be established and studied. The basic regeneration numbers R0=RF+RM are to be defined, where RF and RM to be the basic reproduction number of tuberculosis transmission in female and male populations, respectively. The existence and global stability of the disease-free equilibrium was discussed when R0<1. The global dynamic behaviours of the corresponding limit system under some conditions are to be provided, including the existence, uniqueness, and global stability of the disease-free equilibrium and endemic equilibrium. The numerical simulation shows that the endemic equilibrium may be unique and stable when R0>1, and the system will undergo Hopf bifurcation based on some parameter values. Finally, we applied this model to analyse the transmission of tuberculosis in China, estimated the incidence of tuberculosis in China in 2035, and gave the conclusion that controlling the incidence of tuberculosis in male populations could better reduce the incidence of tuberculosis in China.
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Modelos Biológicos , Tuberculose , Humanos , Masculino , Feminino , Tuberculose/transmissão , Tuberculose/epidemiologia , China/epidemiologia , Número Básico de Reprodução , Incidência , Simulação por Computador , Fatores SexuaisRESUMO
A subfamily of conserved proteins called serpins plays crucial roles in various physiological functions, particularly in the activation pathway of the serine protease cascade, an essential component of insect innate immunity. Here, we found Bombyx mori serpin 3 (BmSerpin3) was most highly expressed in the fat body, and was up-regulated after exposure to bacteria, fungus and virus. Further, the expression of BmSerpin3 in the hemocytes, fat body, midgut of silkworm larvae, and BmN cells was up-regulated upon Bombyx mori nucleopolyhedrovirus (BmNPV) infection. Through Bac-to-Bac expression system, we obtained the active protein of BmSerpin3, and the enzyme activity assay showed that BmSerpin3 significantly inhibited the activity of both subtilisin and trypsin. In addition, BmSerpin3 could inhibit the activation of prophenoloxidase (PPO) in larvae. The knockdown of BmSerpin3 showed increased phenoloxidase (PO) activity compared to control after BmNPV infection. Ultimately, we confirmed that BmSerpin3 interacts with B. mori Serine Protease 7 (BmSP7). Hence, we hypothesize that BmSerpin3 is involved in innate immunity by interacting with BmSP7 to regulate the PPO activation cascade. Taken together, these results showed that BmSerpin3 play a role in silkworm innate immunity and lay a foundation for studying its functions.
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Long-term excessive use of fertilizers and intensive cultivation not only decreases soil organic carbon (SOC) and productivity, but also increases greenhouse gas emissions, which is detrimental to sustainable agricultural development. The purpose of this paper is to identify organic amendments suitable for winter wheat growth in the North China Plain by studying the effects of organic amendments on the economic benefits, carbon emissions, and carbon sequestration for winter wheat fields and to provide a theoretical basis for the wide application of organic amendments in agricultural fields. The two nitrogen rates were N0 (0 kg ha-1) and N240 (240 kg ha-1), and the four organic amendments were straw, manure, mushroom residue (M R), and biochar. The results showed that, compared to N0, N240 significantly increased the yield by 244.1-318.4% and the organic carbon storage by 16.7-30.5%, respectively, but increased the carbon emissions by 29.3-45.5%. In addition, soil carbon stocks increased with all three types of organic amendments compared to the straw amendment, with the biochar treatment being the largest, increasing carbon storage by 13.3-33.6%. In terms of yield and economic benefits, compared to the straw amendment, the manure and biochar amendments increased winter wheat yields by 0.0-1.5% and 4.0-13.3%, respectively, and M R slightly decreased wheat yield; only the economic benefit of the M R amendment was greater than that of the straw amendment, with an increase in economic benefit of 1.3% and 8.2% in the 2021-2022 and 2022-2023 seasons, respectively. Furthermore, according to the net ecosystem productivity (NEP), N0 was the source of CO2, while N240 was a sink of CO2. The TOPSIS results showed that N240 with a mushroom residue amendment could be recommended for increasing soil carbon stocks and economic benefits for winter wheat in the NCP and similar regions. Low-cost M R can increase farmer motivation and improve soil organic carbon, making a big step forward in the spread of organic materials on farmland.
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Introduction: The relationship between schizophrenia and violence is heterogeneous and complex. The aim of this study was to explore the characteristics and the potential risk factors for violence crime in patients with schizophrenia. Methodology: We conducted a retrospective case-control study at the Judicial Psychiatric Identification Unit of Xiangya Second Hospital of Central South University from January 1, 2013 to December 31, 2016. The case group included violent offenders diagnosed with schizophrenia, while the control group comprised non-violent individuals with the same diagnosis. Results: There were 308 individuals in the violent group [subdivided into the homicide group (n = 155) and the intentional injury group (n = 153)] and 139 individuals in the non-violent group. A risk model showed that a history of violence (odds ratio (OR) = 2.88, 95% CI [1.79-4.64]), persecutory delusions (OR = 2.57, 95% CI [1.63-4.06]), regular treatment in the previous four weeks (OR = 0.29, 95% CI [0.16-0.51]) and insight (OR = 0.30, 95% CI [0.14-0.62]) were independently associated with violence. Conclusion: This study provided useful clinical information to identify risk factors for violence and develop better strategic programs to manage violence in patients with schizophrenia.
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Esquizofrenia , Violência , Humanos , Estudos Retrospectivos , Masculino , Esquizofrenia/epidemiologia , Fatores de Risco , Violência/psicologia , Violência/estatística & dados numéricos , Adulto , Feminino , Estudos de Casos e Controles , Pessoa de Meia-Idade , Psicologia do Esquizofrênico , China/epidemiologia , Crime/estatística & dados numéricos , Crime/psicologiaRESUMO
As a continuation of our efforts to develop new agrochemicals with typical architecture and efficient bioactivity from plant natural products, natural neolignan honokiol was used as a lead compound to prepare novel analogs bearing the core 2-aminobenzoxazole scaffold. Their insecticidal potency against two representative agricultural pests, Plutella xylostella Linnaeus and Mythimna separata (Walker), were evaluated in vivo. The pesticide bioassay results revealed that compounds 7â³a, 9, 10d, and 10j exhibited prominent larvicidal activity against the larvae of P. xylostella (LC50 = 7.95, 11.85, 15.51, and 12.06 µg/mL, respectively), superior to the precursor honokiol (LC50 = 43.35 µg/mL) and two botanical insecticides, toosendanin (LC50 = 26.20 µg/mL) and rotenone (LC50 = 23.65 µg/mL). Compounds 7d, 10d, and 10j displayed a more pronounced nonchoice antifeedant effect (AFC50 = 9.48, 9.14, and 12.41 µg/mL, respectively) than honokiol (AFC50 = 54.81 µg/mL) on P. xylostella. Moreover, compounds 7b, 7â³a, 9, 10d, 10f, and 10j showed better growth inhibitory activity against M. separata (LC50 = 0.36, 0.34, 0.28, 0.16, 0.26, and 0.11 mg/mL, respectively) than honokiol, toosendanin, and rotenone (LC50 = 1.48, 0.53, and 0.46 mg/mL, respectively). A potted plant assay under greenhouse conditions illustrated that compounds 10d and 10j continued to provide good control efficacy against P. xylostella and an apparent protective effect on plants. Further cytotoxicity assay revealed that the aforementioned potent compounds showed relatively moderate toxicity and a good safety profile for non-target mammalian cells. Overall, the current work provides valuable insight into the agrochemical innovation of honokiol-derived analogs for use as natural-inspired pesticides in agricultural pest management.
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Compostos de Bifenilo , Inseticidas , Larva , Lignanas , Mariposas , Animais , Lignanas/farmacologia , Lignanas/química , Inseticidas/química , Inseticidas/farmacologia , Mariposas/efeitos dos fármacos , Mariposas/crescimento & desenvolvimento , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Compostos de Bifenilo/química , Relação Estrutura-Atividade , Benzoxazóis/química , Benzoxazóis/farmacologia , Estrutura Molecular , Compostos Alílicos , Aminas , Oxazóis , FenóisRESUMO
The purpose of this paper was to study in vitro atomization properties of the self-developed sodium sivelestat for inhalation, evaluate the feasibility of this preparation as an aerosol inhalation, and provide the guidance for the following animal administration experiment. Firstly, in order to ensure accurate, uniform and stable doses of the self-developed product after administration, its atomization performance was analyzed through the testing of fine particle mass and the total emitted dose, and the results of its atomization parameters meet the requirement of inhalation. Next, Atomization characteristics of two commonly used nebulizers, air compressed nebulizer and mesh nebulizer, were studied and compared. The results showed that mesh atomizers have a smaller and more uniform particle size distribution. And then, the experiment of acute lung injury induced by aerosol inhalation of lipopolysaccharide in mice was used to test the therapeutic effect of our self-developed formulation, and compared with the positive control (sodium sivelestat for injection). The results showed that inhalation had a lower concentration and was equally effective than injection of sodium sivelestat. All the results support that the self-developed sodium sivelestat can be used as an aerosol inhaled drug.
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Aerossóis , Glicina , Nebulizadores e Vaporizadores , Tamanho da Partícula , Sulfonamidas , Animais , Administração por Inalação , Camundongos , Sulfonamidas/administração & dosagem , Glicina/análogos & derivados , Glicina/administração & dosagem , Glicina/química , Lesão Pulmonar Aguda/tratamento farmacológico , MasculinoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Qing Chang Suppository (QCS), a traditional Chinese medicine formula, has been shown to effectively alleviate mucosal inflammation in patients with ulcerative colitis (UC). While the mechanism of QCS appears to be related to the regulation of CD4+T cell subset responses, direct evidence demonstrating that QCS inhibits Th1 and Th17 cell activation in UC (particularly based on human data) remains lacking. Additionally, the precise mechanisms through which QCS affects these cells have yet to be fully elucidated. AIM OF STUDY: This study aimed to investigate the effects of QCS on Th1 and Th17 cell responses in UC and to explore the underlying mechanisms. MATERIALS AND METHODS: Twenty-eight patients with mild-to-moderate UC were recruited and treated with QCS for 12 weeks. Symptoms were assessed every two weeks, with sigmoidoscopies performed at baseline and at week 12. Intestinal mucosal biopsies and peripheral blood (PB) were collected at these time points. At the end of the trial, patients were categorized into responder and non-responder groups based on a modified Mayo disease activity index score. Healthy controls (HCs) were defined as subjects without IBD or colorectal carcinoma but with colon polyps. The frequencies of IFN-γ+CD4+T cells and IL-17A+CD4+T cells in PB and colonic mucosa were measured using flow cytometry. The expression levels and localization of T-bet, RORγT, IFN-γ, TNF-α, and IL-17A were determined via immunofluorescence, and JNK signaling activation was assessed through immunoblotting and immunohistochemistry. All parameters were compared across the three groups. RESULTS: At week 12, responders showed a significant reduction in colonic mucosal inflammation compared to baseline, accompanied by decreased frequencies of IFN-γ+CD4+T and IL-17A+CD4+ T cells in both PB and the colonic epithelial layer. Notably, Th1 and Th17 cell activity around intestinal epithelial cells (IECs) was nearly undetectable, as evidenced by the diminished expression of T-bet, RORγT, IFN-γ, TNF-α, and IL-17A. Additionally, JNK phosphorylation in these cells was significantly reduced. In contrast, non-responders exhibited no meaningful improvement; colonic pathology remained unchanged, and elevated levels of IFN-γ+CD4+T and IL-17A+CD 4+T cells persisted in both the PB and colonic epithelial layer. The presence of Th1 and Th17 cells and their associated cytokines around IECs remained substantial, and there was no significant change in JNK activation. CONCLUSION: QCS attenuates mucosal inflammation in UC patients by inhibiting the differentiation and effector functions of Th1 and Th17 cells, primarily through the regulation of the JNK signaling pathway.
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Fructose-1,6-bisphosphatase (FBPase) is an emerging target in gluconeogenesis, inhibitors of which would be an effective treatment for elevated fasting blood glucose in patients with type 2 diabetes. Based on the lead compound G-1 (FBPase 10 µM inhibition = 64.3 %) and according to the X-ray crystal structure of FBPase, we designed and validated an innovative molecular docking method based on the dual-ligand model to explore the interactions between two identical ligands in neighboring targets. Based on the dual-ligand molecular docking model, a novel compound 45 bearing a benzimidazole scaffold was identified to show increased inhibitory activity against FBPase (IC50, 2.08 µM). An oral pyruvate tolerance test in ICR mice showed that 45 had a potent inhibitory effect on gluconeogenesis similar to that of metformin when administered as a single dose in vivo. Compound 45 did not inhibit the common subtypes of the human cytochrome P450 system, indicating that it may have a reduced propensity for drug-drug interactions. The findings of this study may pave the way for further development of FBPase inhibitors with novel structural features, improved activity, and good druggability.
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Benzimidazóis , Descoberta de Drogas , Inibidores Enzimáticos , Frutose-Bifosfatase , Camundongos Endogâmicos ICR , Simulação de Acoplamento Molecular , Frutose-Bifosfatase/antagonistas & inibidores , Frutose-Bifosfatase/metabolismo , Benzimidazóis/química , Benzimidazóis/farmacologia , Humanos , Animais , Ligantes , Camundongos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/síntese química , Relação Estrutura-Atividade , Estrutura Molecular , Relação Dose-Resposta a Droga , MasculinoRESUMO
BACKGROUND: The link between Alzheimer's disease and depression has been confirmed by clinical and epidemiological research. Therefore, our study examined the literary landscape and prevalent themes in depression-related research works on Alzheimer's disease through bibliometric analysis. METHODS: Relevant literature was identified from the Web of Science core collection. Bibliometric parameters were extracted, and the major contributors were defined in terms of countries, institutions, authors, and articles using Microsoft Excel 2019 and VOSviewer. VOSviewer and CiteSpace were employed to visualize the scientific networks and seminal topics. RESULTS: The analysis of literature utilised 10,553 articles published from 1991 until 2023. The three countries or regions with the most publications were spread across the United States, China, and England. The University of Toronto and the University of Pittsburgh were the major contributors to the institutions. Lyketsos, Constantine G., Cummings, JL were found to make outstanding contributions. Journal of Alzheimer's Disease was identified as the most productive journal. Furthermore, "Alzheimer's", "depression", "dementia", and "mild cognitive decline" were the main topics of discussion during this period. LIMITATIONS: Data were searched from a single database to become compatible with VOSviewer and CiteSpace, leading to a selection bias. Manuscripts in English were considered, leading to a language bias. CONCLUSION: Articles on "Alzheimer's" and "depression" displayed an upward trend. The prevalent themes addressed were the mechanisms of depression-associated Alzheimer's disease, the identification of depression and cognitive decline in the early stages of Alzheimer's, alleviating depression and improving life quality in Alzheimer's patients and their caregivers, and diagnosing and treating neuropsychiatric symptoms in Alzheimer. Future research on these hot topics would promote understanding in this field.
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Atherosclerosis, a major global health concern with high morbidity and mortality rates, involves complex interactions of chronic inflammation, oxidative stress, and proteolytic enzymes. Conventional imaging methods struggle to capture the dynamic biochemical processes in atherosclerotic plaques. Here, we introduce a novel unimolecular photoacoustic probe (UMAPP) designed with specific binding sites for neutrophil elastase (NE) and the redox pair O2â -/GSH, enabling real-time monitoring of oxidative stress and activated neutrophils in plaques. UMAPP, comprising a boron-dipyrromethene (BODIPY) core linked to a hydrophilic NE-cleavable tetrapeptide and dual oxidative stress-responsive catechol moieties, facilitates NE-mediated modulation of photoinduced electron transfer impacting photoacoustic intensity at 685â nm (PA685). Furthermore, oxidation and reduction of catechol groups by O2â - and GSH induce reversible, ratiometric changes in the photoacoustic spectrum (PA745/PA685 ratio). Initial UMAPP applications successfully distinguished atherosclerotic and healthy mice, evaluated pneumonia's effect on plaque composition and verified the probe's effectiveness in drug-treatment studies by detecting molecular alterations before visible histopathological changes. The integrated molecular imaging capabilities of UMAPP offer promising advancements in atherosclerosis diagnosis and management, enabling early and accurate identification of vulnerable plaques.
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The Yangtze River Delta (YRD) experienced record-breaking heat in the summer of 2022. However, the urban heat pattern and the role of urban expansion over the last two decades in this hot summer have not been explored. Using the advanced mesoscale Weather Research and Forecasting (WRF) model, we reproduced the fine spatial features and investigated the urban heat island (UHI) and dry island (UDI) effects during the two identified heatwaves in 2022. We further replace the current (2020) land use with the historical (2001) land use in WRF to evaluate the impacts of urban expansion from 2001 to 2020 on air temperature and moisture. Our finding revealed that the conversion of land use resulted in near-surface warming and drying, with pronounced diurnal variations, especially during the July heatwave. The analysis of surface energy balance demonstrated that the substantial decrease in evapotranspiration (ET) was the primary driver of daytime warming, elevating temperatures by 7 °C (July heatwave) and 2 °C (August heatwave). This ET reduction also led to the strong daytime coupling of warming and drying effects over new urban areas. At night, the release of stored heat resulted in the temperature increase of 2 °C (1 °C) during July (August) heatwave, highlighting the nighttime as a critical period for heightened thermal risk. Additionally, urban expansion at the periphery contributed modestly to the warming of urban cores, exacerbating conditions in an already hot environment. This study enhances understanding of the impacts of urban expansion on air temperature and humidity during extreme heatwaves, thereby supporting targeted adaptation and mitigation for extreme events within large cities.